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  • WCLC 2016

    17th World Conference on Lung Cancer

    Access to all presentations that occur during the 17th World Conference on Lung Cancer in Vienna, Austria

    Presentation Date(s):
    • Dec 4 - 7, 2016
    • Total Presentations: 2466

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    P1.04 - Poster Session with Presenters Present (ID 456)

    • Type: Poster Presenters Present
    • Track: Pulmonology
    • Presentations: 28
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      P1.04-001 - EGFR, EML4-ALK, ROS 1 and BRAF Testing in Austrian Patients with NSCLC: A Multicentre Study (ID 4449)

      14:30 - 14:30  |  Author(s): S. Holzer, M.J. Hochmair, U. Setinek, D. Krenbek, H. Fabikan, R. Rumbold, A. Mohn-Staudner, K. Kirchbacher, M. Arns, T. Bundalo, K. Patocka, O. Burghuber

      • Abstract
      • Slides

      Background:
      Targeted therapy is becoming increasingly important and has improved the overall survival for patients with NSCLC. EGFR and BRAF mutations, EML4-ALK and ROS1 translocations are current allocatable targets. The incidence of these druggable targets in Austria is unknown.

      Methods:
      Tumor tissue from bronchoscopy, CT- and ultrasound guided biopsies as well as surgical specimen with histological type of adenocarcinoma and NSCLC NOS (Not Otherwise Specified) were routinely analyzed independent of the tumor stage and clinical characteristics (reflex testing) for these genetic alterations. Since January 2010 the EGFR mutation detection was performed with the EGFR Mutation Test Kit from ROCHE on a COBAS4800. Since August 2011 tumor tissue was analyzed for EML4-ALK with a two-step procedure. First an immunohistochemical staining was done with the Ventana anti ALK(D5F3), OptiView DAB IHC DetectionKit and OptiViewAmplifikationKit® and further on positive cases were tested by PCR (AmoyDx®EML4-ALK FusionGeneDetectionKit) or ALK FISH (dual colour breakapart FISH/Abbott Vysis®). Since January 2014 the tumor tissue was analyzed for ROS1 with a two-step procedure. First an immunohistochemical staining was done with ROS1 D4D6, cell signaling® and further on positive cases were tested by PCR (AmoyDx®ROS1 GeneFusionDetectionKit) or ROS1 FISH (ROS1-6q22.1 dual colour breakapart probe ZytoVision®). BRAF testing was performed with the cobas®4800BRAF V600Mutation Test from Roche since March 2016.

      Results:
      An EGFR Mutation was found in 340 out of 2776 patients (12.2%). 253 patients (9.1%) carried an activated mutation (Exon 19 Deletion, Exon 21 L858R). EML4-ALK positive translocation was found in 100 out of 2212 patients (4.5%). ROS1 positive translocation was found in 5 out of 1060 patients (0.5%). BRAF mutation was found in 3 patients out of 40 (7.5%).

      Conclusion:
      Frequency of these genetic alterations in Austrian patients with NSCLC was quite similar to other Caucasian peers. Therefore reflex testing is recommended independent of any clinical characterization.

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      P1.04-002 - Positive Airway Pressure-Enhanced CT to Improve Virtual Bronchoscopic Navigation (ID 4869)

      14:30 - 14:30  |  Author(s): M. Diez-Ferrer, D. Gil, E. Carreño, S. Padrones, S. Aso, V. Vicens, N. Cubero, R. Lopez-Lisbona, C. Sanchez, A. Borras, J. Dorca, A. Rosell

      • Abstract
      • Slides

      Background:
      A main weakness of virtual bronchoscopic navigation (VBN) is unsuccessful segmentation of distal branches approaching peripheral pulmonary nodules (PPN). CT scan acquisition protocol is pivotal for segmentation covering the utmost periphery. We hypothesize that application of continuous positive airway pressure (CPAP) during CT acquisition could improve visualization and segmentation of peripheral bronchi. The purpose of the present pilot study is to compare quality of segmentations under 4 CT acquisition modes: inspiration (INSP), expiration (EXP) and both with CPAP (INSP-CPAP and EXP-CPAP).

      Methods:
      In 10 patients 320-detector row CT scans with slice thickness of 0.5 mm were performed in the 4 modes. In first 5 patients a pressure ranging 6-10 cmH~2~O was applied for 3 min immediately before CT acquisition (CPAP6-10). In following 5 a pressure of 10 cmH~2~O was applied, followed by 3 min of expiratory maneuvers and non-CPAP acquisitions (CPAP10). Segmentations were obtained and measurements manually calculated with a VBN system (LungPoint, Broncus Technologies, Inc., Mountain View, CA, USA). Comparisons for the inspiratory and expiratory models were made upon main airways area (proximal trachea, distal trachea and main bronchi) and distance of the path to the nodule (DIST-PN). Also, 2 random bronchi per lobe were selected and the number of bifurcations (BIF) and distance (DIST) from carina to the very end of the selected bronchi were manually counted and median calculated. Statistical analyses with R-3.2.3.

      Results:
      See table 1.Figure 1



      Conclusion:
      A tendency towards enlargement and improved segmentation of airways is seen with the use of CPAP in both levels of pressure. However, the power of this pilot study is limited and larger studies might be encouraged. Funded by La MaratóTV3-20133510, FIS PI09/90917, DPI2015-65286-R, 2014-SGR-1470, PROD-2014-00065, FUCAP and SEPAR.

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      P1.04-003 - Incidence of Non-Caseating Granulomas Diagnosed in PET Avid Mediastinal/Hilar Nodes in Patients with Known Breast Cancer (ID 4189)

      14:30 - 14:30  |  Author(s): T. Webb, I. Bonta, P. Thompson, C. Parks, D. Miller, R. Bechara

      • Abstract

      Background:
      Breast cancer is known to metastasize to the lung.. Most breast malignancies are clinically staged using radiographic modalities (e.g. PET scans). Importantly, many inflammatory disorders will present similar lymph node FDG-uptake on PET- as that of metastasized breast cancer. The latter confuses the treatment for individuals within whom both undiagnosed autoimmune disorders and breast cancer co-occur. We aim to examine the frequency of non-caseating granulomas diagnosed in PET avid mediastinal/hilar nodes in patients with known breast cancer.

      Methods:
      Between March 2013 and December 2015, 46 patients diagnosed with breast cancer were staged by PET-CT. Those with positive result in the mediastinum/hilum underwent linear endobronchial ultrasound (EBUS) for pathologic diagnosis and ensuing treatment

      Results:
      Of the 46 patients with avid mediastinal/hilar adenopathy, 31 (67%) had malignant cytology on EBUS; the remaining 15 had positive PET but negative cytology for malignancy. Twelve of the 15 patients with false positive PET had reactive lymph nodes, and 3 had non-caseating granulomas on cytology (table 1). . Table 1: Results from EBUS Procedure and Resulting Percentage Following Identification of Sarcoid-like Symptoms

      Total Number of patients in study: n=46 with positive PET Number of patients Percentage of total (all PET positive patients) Percentage among negative patients
      Positive EBUS 31 67.40%
      Negative EBUS 12 26.10% 80%
      Negative/Non-caseating granulomas EBUS 3 6.50% 20%
      Twenty percent of the patients with negative cytology and positive PET had non-caseating granuloma, and 6.5 % of all patients with positive PET had non-caseating granulomas.

      Conclusion:
      Conclusion: This study represents the largest cohort of breast cancer patients, where the incidence of non-caseating granulomas is investigated in PET-positive mediastinal/hilar nodes. We conclude that PET may not be sufficient for staging the mediastinum in patients with breast cancer and, in selected patients, pathologic staging should be done. In addition, the finding of non-caseating granulomas in these patients may either indicate an incidental diagnosis of early stage sarcoidosis, or an inflammatory reaction to the current treatment (sarcomatoid reaction). We also suggest that these patients should be followed for any manifestations of sarcoidosis.

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      P1.04-004 - Bronchocopic Cryosurgery with Carbon Dioxide; Experience in an Oncology Clinic in Colombia (ID 5528)

      14:30 - 14:30  |  Author(s): J. Sanchez Vallejo, J.A. Echeverri, J.C. Rojas Puentes, A. Angel Henao

      • Abstract

      Background:
      The bronchoscopic cryosurgery with carbon dioxide is a groundbreaking tool in the diagnostic treatment of respiratory diseases. It has shown to be of great usefulness at a reasonable cost, with multiple indications and few side effects. We described the experience in an oncology institution in Colombia.

      Methods:
      Medical histories, Bronchoscopies and images were reviewe from patients subjected to Bronchoscopic Cryosurgery. The procedures were performed at the "High-Tech Western Oncologist Clinic" in Pereira, Colombia with a highly trained medical staff from this clinic and from Neumovida Clinic from Armenia. Rigid and flexible Bronchoscopy video was made, and the equipment used in the cryotherapy was the Erbe Cryo 2 with the cryoprobe of 1.9 and 2.4 mm.

      Results:
      71 patients were found, 44 men, 27 women. Tracheal Recanalization to 11 patients, Bronchial Cryorecanalization to 24, Bronchial Cryobiopsy to 13, Tracheal Cryobiopsy to 7 and Pulmonary Cryobiopsy to 16 patients. Cryorecanalization was performed to 15 patients with tumors in the right lung and 9 in the left lung. Permeabilization of the Bronchial lumen was achieved to 22 patients at the same time the Bronchoscopy was being done. In 2 patients with Bronchial Obstruction the same procedure was achieved a week later. Pulmonary re-expansion and symptomatic control were achieved in 31 patients. Permeabilization of the bronchial lumen was achieved in 2 patients but not pulmonary re expansion. Silicone prosthesis were implanted to 9 patients with Tracheal lesions and 18 patients with Bronchial lesions. Differences between genders were not shown. There were not any important clinical complications associated with the procedures. Moderate bleeding with the pulmonary biopsy was control locally. In general the post operative evolution of the patients was satisfactory.

      Conclusion:
      The Bronchoscopic Cryosurgery has clear indications in patients with Central Airway Tumors, just as the diagnostic, therapeutic and palliatives purposes and in patients with interstitial compromise of presumable neoplasic or infectious origin. In our casuistry, the objective was achieved in all the patients that underwent the procedures such as tracheobronchial recanalization and extraction of tracheal, bronchial or pulmonary tissue with a significant symptomatic improvement with a low risk and low morbidity

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      P1.04-005 - Efficacy of Photodynamic Therapy Combined with a Guide Sheath Method in Lung Cancer Patients with Endobronchial Stenosis (ID 3679)

      14:30 - 14:30  |  Author(s): M. Misawa, F. Suzuki, S. Yamawaki, R. Tsuzuki, A. Otsuki, K. Nakashima, S. Noma, M. Aoshima

      • Abstract

      Background:
      Photodynamic therapy (PDT) using a second generation of photosensitizier, talaporfin sodium was useful for the curative or palliative treatment of lung cancer. However, it is required for interventional pulmonologist to perform accurate PD-laser irradiation in some lung cancer case. We hypothesized that all-direction type PD-laser probe covered with a guide sheath (GS) (GS-PDT) made it possible to secure its probe and fix its position in the endobronchial lesion, to enhance the effect of PDT by avoiding direct contact with the tumor lesion, thus preventing its probe from contact with blood.

      Methods:
      We evaluated the efficacy and safety of this irradiation technique for the lung cancer patients with endobronchial stenosis. Before the procedure, we evaluated the extent of tumor lesion by auto-fluorescence video-bronchoscope (BF TYPE-F260, Olympus, Japan). As a photosensitizer, talaporfin sodium (Laserphyrin, Meiji Pharma, Japan) was administered at 40mg/m[2 ]intravenously 6 hours before irradiation. PDT was performed by using video-bronchoscope (EB-530T, FUJI MEDICAL, Japan) to visualize PD-laser light clearly by adjusting FICE(Flexible spectral Imaging Color Enhancement)mode. We irradiated 664nm laser light to the target bronchus with endobronchial stenosis utilizing an all-direction type laser probe covered with a GS (disposable K203 guide sheath kit, Olympus, Japan) at each dose of 100J/cm[2] (150mW) for 11 minutes and 7 seconds under fluoroscopic guidance. After one month, we evaluated the endoscopic efficacy of this method.

      Results:
      Between December 2014 and April 2015, we performed GS-PDT for three patients with pathologically diagnosed lung cancer, 1 squamous cell carcinoma, 1 adenocarcinoma and 1 small cell carcinoma. Stage IA squamous cell carcinoma patient with endobronchial stenosis underwent definitive therapy. Stage IA adenocarcinoma patient with endobronchial wall spread of tumor to proximal respiratory tract underwent a combination of induction chemo-radiotherapy followed by sleeve left upper lobectomy as for definitive therapy to reduce the extent of lung resection. Stage IIIA limited-stage small-cell lung cancer patient with the stenosis of right main and upper lobe bronchus underwent palliative therapy to improve oxygenation and to prevent obstructive pneumonia. One month after GS-PDT, we confirmed the endoscopic response (1 complete response, 2 partial response). No PDT-related complications occurred.

      Conclusion:
      New GS-PDT method was safe and could be an effective technique to accurately irradiate the lung cancer patients with endobronchial stenosis.

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      P1.04-006 - Second Primary Lung Cancer: Five Years of a Single Center Experience in Its Diagnosis and Treatment (ID 4626)

      14:30 - 14:30  |  Author(s): F. Caushi, D. Xhemalaj, H. Hafizi, I. Skenduli, J. Shkurti, A. Mezini, Z. Pupla, A. Hatibi

      • Abstract
      • Slides

      Background:
      Second primary lung cancer (SPLC) constitute an important dimension of the burden of cancer survivorship that needs to be taken into account when defining strategies for surveillance, prevention and counseling. In last three decades the incidence of SPLC in patients that had a history of a prior cancer out of the respiratory system is estimated 2-8%. Relative risks of SPLC may be smaller than previously reported may benefit from increased surveillance. The goal of this study was to give an overview of SPLC regarding patients’ primary malignancy, their stage of lung cancer presentation and bringing to the light some possible risk factors. Such data will be helpful in calculation of the risk for SPLC as well as handling of risky patients for a better survival.

      Methods:
      This is a retrospective study for a period of 5 years where all the data that was gathered from clinical cartels of patients with lung cancer were analyzed using Pearson Chi-Square.

      Results:
      SPLC represents 2% of all lung cancers diagnosed during the period of study. The prior diagnose of cancer for this patients was breast cancer in 46% of cases, cervix cancer in 40% of cases and the other diagnosis 14% of cases. All the patients have been under oncologic treatment with radio or chemotherapy. 20% of these patients have been smokers prior to first malignancy. The average age of the patients with SPLC was 55 years old. The ratio male to female was 1:10. The most frequent hystotipe found was adenocarcinoma in 60% of cases meanwhile in all cases with a prior squamous cell cancer of cervix was found squamous cell carcinoma as SPLC. The average period of time from the prime cancer to the SPLC was 3.7 years. 73% of cases with SPLC underwent an anatomical resection of the tumor.

      Conclusion:
      This study shows that patients with the higher risk for a SPLC are premenopausal women with breast cancer and cervical cancer. Changes in the prevalence of risk factors and diagnostic techniques may have affected more recent risks. The relative risk of developing SPLC in smokers is unclear. SPLC after oncologic treatment is an issue that raises many questions.

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      P1.04-007 - Y Stents in Malignant Tumours - Long Time Follow up and Survival (ID 4071)

      14:30 - 14:30  |  Author(s): V. Kolek, R.-. Zittova

      • Abstract

      Background:
      Stent insertion is one of the standard methods of therapeutic bronchology. Stents can be applied to trachea or bronchi. Y stents are inserted to the tracheobronchial area around tracheal bifurcation. The most frequent indications are the central malignant tumours, less frequently benign stenosis, phistulla or tracheomalatia. The prognosis of central stenosing tumours is usually unfavourable with no specific data available.

      Methods:
      464 stents were inserted in our institution, out of them 120 were of Y type. The results of Y stent insertion in malignant tumours during the period 2001- 2015 were evaluated. Survival of patients was compared according to sex, age, tumour origin, histology and stage.

      Results:
      80 Y stents were inserted in 50 men and 30 women, mean age in the time of diagnosis was 61.6 year, in the time of stent insertion 62.8 year. There were 53 bronchial cancers, 6 tracheal cancers, 12 oesophageal cancers, 3 laryngeal cancer, 2 thyroid cancers, and 1 breast cancer, 2 lymphomas, and 1 thymoma. Since diagnosis the mean survival (MS) was 26.39 months, median of overall survival (mOS) was 10.89 (95% CI 8.10- 13.67) months. Since stent insertion MS was 18.09 m and mOS was 3.48 (95% CI 2.72-4.23) m. There were no statistically significant differences according to sex, age and type of tumour (p >0.05): tracheal cancer - mOS 6.07 m, lung cancer - mOS 3.64 m, oesophageal cancer - mOS 2.49 m, other tumours - mOS 3.54 m. Among lung cancers squamous cancer was the most frequent type (34 pts, mOS 4.20 m) and had better prognosis than adenocarcinoma (8 pts, mOS 3.64 m), small cell lung cancer (4 pts, mOS 1.18 m) and NOS (3 pts, mOS 1.80 m). Squamous cancer stage IIIB (22 pts, mOS 5.18 m) had better prognosis than stage IV (10 pts, 3.47 m), all differences were not significant.

      Conclusion:
      Y stent insertion is an effective palliative procedure in malignant stenosis of central airways. Tumours in this localisation have generally bad prognosis. In present study, squamous lung cancer was the most frequent one and had longer survival than other types of cancers. Study was supported by grant AZV 16-32318A

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      P1.04-008 - Tumor Pentaplicity - Case Report (ID 4658)

      14:30 - 14:30  |  Author(s): P. Smičková

      • Abstract
      • Slides

      Background:
      Metachronic tumor duplicity is a relatively common phenomenon, often related to mutagenic effects of some types of antitumor therapy. However, idiopathic tumor multiplicity is rare. We present the case report of a patient, who developed five different malignant tumors in fifteen years horizon.

      Methods:
      Case report

      Results:
      66-year old patient was diagnosed renal cell carcinoma in year 2001 with subsequent nephrectomy. During follow-up, a coin lesion was recognized on chest x-ray, histologically and radiologically verified as stage IA pulmonary adenocarcinoma. Patient underwent successful right lower lobectomy. In 2010 colorectal carcinoma was diagnosed followed by non-invasive papillocarcinoma of urinary bladder in 2012. All these tumors were treated curatively. In 2014 a new mass appeared on chest x-ray. Repeated bronchoscopy failed to obtain valid histological sample. The positron emission tomography revealed malignancy suspicion and excluded the disseminated disease. Surgical resection was performed. Peroperative histology reported carcinoma of uncertain type and surgeon decided for completion of pulmonectomy. However, final histological report showed small-cell lung cancer (pT2apN2Mx). Despite adjuvant chemotherapy given the patient developed distant metastases and died subsequently due to tumor progression in February 2016.

      Conclusion:
      Tumor pentaplicity is a clinical situation with rare occurrence. Our patient didn´t receive chemotherapy until 2010 (adjuvant chemotherapy after radical colorectal carcinoma surgery), so there could be no influence of the first three malignancies therapy. We did not find tumor occurrence in the family, no external risk factor, the patient fits in none of defined hereditary cancer predisposition disorder. Detection of common driver mutations in all five tumors is running. The long term survival is supporting the idea of a careful follow up and shows advances in current oncological treatment.

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      P1.04-009 - Bacterial Population Dynamics in Colonization of Airway Stents in Patients with Cancer (ID 4906)

      14:30 - 14:30  |  Author(s): M. Diez-Ferrer, L. Calatayud, C. Lopez-Delgado, R. Lopez-Lisbona, N. Cubero, N. Koufos, S. Marti, C. Ardanuy, J. Dorca, J. Liñares, A. Rosell

      • Abstract

      Background:
      Stent placement is an increasingly used treatment for malignant tracheobronchial stenosis. The main complication related to airway stents is bacterial colonization causing chronic cough and sputum, halitosis, recurrent bronchial infections, pneumonia and even sepsis. The main objectives were to describe potentially pathogenic bacteria (PPM) involved in stent colonization and to analyze PPM dynamics during follow-up.

      Methods:
      Prospective study in patients with malignant stenosis treated with stent placement. Bronchial washings (BW) were performed before and at least 1 month after stent placement. Qualitative cultures of PPM isolated in BW were performed. Statistical analyses with R-3.2.3.

      Results:
      Total of 65 patients, 56 (86%) men, mean age 64 (±10) y/o, 58 (89%) current or former smokers, 2 (3%) bronchiectasis, 28 (43%) COPD. Cancers were: primary lung cancer (n=52, 80%) followed by thyroid (n=4, 6%), esophagus (n=2, 3%) and other (n=7, 11%); stenosis were located in trachea (n=14, 21%), main carina (n=16, 25%) and main bronchi (n=35, 54%); and stent types included metal (n=30, 46%) and silicone (n=35, 54%). Isolated PPM in BW (table 1). Airway colonization was absent in 14 (21.5%) and present in 79%, of which it was persistent in 33 (50.8%) and intermittent in 16 (24.6%). Only 2 (3.1%) became negative. Median time until colonization was 35 days (IQR 28-116), with no significant differences between stent types or location. Figure 1



      Conclusion:
      The majority of patients with malignant stenosis treated with airway stents develop early and persistent colonization by PPM, regardless of stent type.

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      P1.04-010 - Neutrophil to Lymphocyte, Platelet to Lymphocyte Ratios and Systemic Inflammation in Lung Cancer Stages (ID 6169)

      14:30 - 14:30  |  Author(s): E. Ionela Mihaela, D. Stefan, S. Carmen, B. Miron

      • Abstract
      • Slides

      Background:
      Lung cancer is associated with systemic inflammation which seems to influence the prognostic of the disease. Different affordable methods may be used to evaluate the systemic inflammation: erythrocyte sedimentation rate (ESR), Neutrophil to lymphocyte ratio (Ne/Ly), Platelet to lymphocyte ratio (Pl/Ly). The aim of the study is to assess the relation between TNM lung cancer stages and the systemic inflammation estimated by Ne/Ly, Pl/Ly and ESR.

      Methods:
      Patients with lung cancer were classified according to 7[th] TNM lung cancer staging in two groups: Group A (I, II and IIIA) and Group B (IIIB, IV). A complete blood count (CBC) and ESR were determined. Ne/Ly and Pl/Ly ratios were calculated for all patients. The results were compared between the two groups.

      Results:
      73 consecutive patients (22 in Group A and 51 in group B) were analyzed. In Group A (16 males), the mean age was 63,73 ± 7,69 years, the median Ne/Ly: 2,86 (0,88-8,36), median Pl/Ly: 128,81 (21,62-416,67) and median ESR: 10 mm/h (10-120). In Group B (48 males), the mean age was 65,06 ± 10,09 years, the median Ne/Ly: 4,46 (0,70-25,6), median Pl/Ly: 204,48 (3,38-651,25) and median ESR: 40 mm/h (3-120). The values of Ne/Ly, Pl/Ly were significantly higher (p: 0,009 respectively p: 0,007) in Group B versus Group A, but no statistically significant difference was observed for ESR values.

      Conclusion:
      We found a relation between TNM lung cancer stages and the systemic inflammation assessed by neutrophil to lymphocyte (Ne/Ly) and platelet to lymphocyte (Pl/Ly) ratios. The values of Ne/Ly, Pl/Ly ratios were significantly higher in nonresectable stages (IIIB, IV).Erythrocyte sedimentation rate (ESR) seems not to be an appropriate method to evaluate this relation.

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      P1.04-011 - Demographic, Clinical and Survival Characteristics of Lung Cancer among Elderly Patients in Turkey (ID 6155)

      14:30 - 14:30  |  Author(s): G. Ak, S. Metintas, S. Yilmaz, F. Bogar, M. Metintas

      • Abstract
      • Slides

      Background:
      To determine demographic, clinical and survival data of elderly lung cancer patients.

      Methods:
      We evaluated 2,637 patients with lung cancer between January 1990 and October 2010. Elderly patients were defined as those 65 years or older. The patients were classified into two groups: younger and older group. The demographic, clinical and survival data of the groups were compared.

      Results:
      998 (37.8%) patients were in the older group and 1,639 (62.2%) were in the younger group. The female patients rate (9.1% vs 7.8%; p=0.238) and other cancer history (4.4% vs 3.3%; p=0.101), and family cancer history rate (p=0.664) were similar between two groups. Illiterate patients rate (20.1% vs 16.6%; p<0.001), occupational risks (9.2% vs 12.8%; p=0.005), current smoker and exsmoker rate (p<0.001), asbestos exposure rate (p=0.005), COPD prevalence (15.1% vs 8.6%; p<0.001), and two or more comorbidity rate (21.1% vs 10.1%; p<0.001) of older group was higher than younger group. The symptom duration of the groups were 96.4 days and 92.8 days, respectively (p=0.359). Systemic complaints and extrapulmonary intrathoracic spread complaints of older group were higher than younger group (p<0.001 and p=0.025). Karnosfky performance status was lower in older group than younger group (79.3 vs 82.2; p<0.001). Radiological findings of asbestos exposure was higher in the older group than younger group (6.9% vs 4.1%; p=0.002). There was no difference between the groups in terms of histology and stage (p=0.078 and p=0.254). The independent etiological risk factors of lung cancer in elderly patients were lower educational status, smoking, COPD and male gender by multivariable logistic regression analysis. The median survival was 8.0 ± 0.36 months (95% CI: 7,288-8,712) for older group and 9.0 ± 0.27 months (95% CI: 8,477-9,523) for younger group (log-Rank: 4.567; p=0.033). The factors affecting survival in the both groups stage, Karnofsky performance status and treatment by Cox regression analysis.

      Conclusion:
      These data indicate that lung cancer had different risk factors and short survival in elderly patients. These features should be considered in the management of these patients.

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      P1.04-012 - Single Center Experience with Nivolumab Administration in NSCLC Patients from EAP Program (ID 4862)

      14:30 - 14:30  |  Author(s): M. Pesek, J.-. Durova, G.-. Krakorova

      • Abstract

      Background:
      Immunotherapy using monoclonal antibody against PD-1 receptor (nivolumab) offers another possibility to improve tumor control in patients with advanced squamous (SQ) and non-squamous (NSQ) NSCLC.

      Methods:
      We present first experience with nivolumab in Early Access Program (EAP). Nivolumab tolerability, safety data, frequency of therapeutic responses and ADRs will be presented in 42 patients with advanced SQ and NSQ NSCLC.

      Results:
      22 patients with SQ-NSCLC entered EAP, 3 patients did not start therapy (2 early deaths and 1 refusal) and 19 patients received treatment (16 males, 3 females). Therapy was discontinued in 9 patients (7x disease progression, 2x serious ADR). Therapy is currently withold in 4 patients due to management of ADRs and 7 patients continue to receive nivolumab. 5 patients died (26%) with median follow up of 9 months in this group. 20 patients with NSQ histology were included in EAP, 2 patients from this group died before initiation of therapy and 1 patient did not receive nivolumab due to worsening of her performance status. 17 patients were treated with at least one dose of nivolumab (10 males, 7 females). Therapy was discontinued in 8 patients (7x disease progression, 1x due to gastrointestinal toxicity with grade 3 diarrhea). Treatment is currently withold in 6 patients due to management of ADRs and 4 patients continue to receive nivolumab. 5 patients (29%) in this group died with median follow up of 5 months. So far, we have seen 7 partial remissions in all 36 treated patients with NSCLC (19%) which corresponds to data from registration studies of nivolumab. Disease stabilization was reported in other 7 patients giving the disease control rate of 38%. As expected from nivolumab mechanism of action, adverse drug reactions are usually immune related. Serious ADRs were rarely observed including neurological toxicity (difficulty to swallow and diplopia), diarrhea, pneumonitis and skin toxicity (lichen ruber planus).

      Conclusion:
      In general, patients from EAP program were more pretreated compared to patients in registration studies (therapy allowed in 3rd and 4th line), also patients with PS2 were included (only PS 0 and 1 in the trials). Treatment with nivolumab was well tolerated and it brings the benefit for some patients after 1-3 lines of previous anticancer therapy. Although serious ADRs are relatively rare, management of side effects requires good cooperation with the patients as well as cooperation with highly specialized departments (gastroenterologists, endocrinologists, dermatologists).

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      P1.04-013 - Diagnostics and Treatment of ALK-Positive NSCLC Patients - A Single Center Experience (ID 5152)

      14:30 - 14:30  |  Author(s): M. Pesek, P.-. Grossmann, P.-. Mukensnabl, G.-. Krakorova

      • Abstract

      Background:
      ALK positive advanced NSCLC patients could get significant benefit of targeted therapy. In Czech Republic, targeted therapy is payed just as second-and more line treatment, required positive FISH result of ALK-positive NSCLC tumour.

      Methods:
      We investigate ALK-rearrangement in selected group of NSCLC patients starting from January 2011 via fluorescence in situ hybridization (FISH) with the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular). We evaluate frequence of positive and inconclusive results. In the group of ALK positive patients we evaluate clinical behaviour of tumours and effectivity and side effects of ALK inhibitors.

      Results:
      From January 2011 till June 2016, 798 nonsquamous NSCLC tumour samples were evaluated by FISH method. 20 (3.2 %) of evaluable 660 samples were positive, 138 tumour samples were clasified as ALK break inconclusive (17.3 %). ALK break positive group of patients consist of 13 men and 7 women, median age 68.5 years. 17 of them were adenocarcinomas, in two there were adenosquamous histology and in one NSCLC-NOS was found. The limit of ALK positivity was 10 % positive cells, the range of our positive results were 10 – 72 %. 6/20 patients were treated by crizotinib. Two of them received second ALK inhibitor ceritinib after failure of crizotinib, those patients are alive and well 5 and 8 years from diagnosis of adenocarcinoma st. IV. Three patients died before they could get an access to targeted therapy, seven others with low PS died before start of targeted therapy, in three others there is not actual need for targeted treatment. One patient on crizotinib died after 11 months of targeted treatment, two other died after one month of treatment, in one patient targeted therapy was refused due to intolerance.

      Conclusion:
      Patients suffering from advanced ALK rearranged NSCLC should have perspectives of long lasting tumour response on ALK inhibitors. ALK rearrangement investigations should be done in nonsquamous NSCLC routinely. In our departments, we have relatively high frequency of inconclusive ALK testing results. However, it is not easy to get adequate tissue sample from routine investigations. Positive results are found most frequently in adenocarcinoma patients. We consider due to rapid progression of ALK positive tumours on chemotherapy that targeted therapy should be realised as a first line option.

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      P1.04-014 - Diagnostic Yield in Patients Undergoing Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Diagnosis of Lung Cancer (ID 4791)

      14:30 - 14:30  |  Author(s): S. Touray, R.N. Sood, C. Martinez-Balzano, J. Holdorf, A.T. Lim, A. Sosa, P.J. Oliveira, S.E. Kopec

      • Abstract

      Background:
      Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) is an established diagnostic tool in the evaluation of lung cancer with a variable diagnostic yield, ranging from 62 % - 93 %[1–4]. Although the procedure can be performed under moderate sedation (MS) or general anesthesia (GA) [5], the impact of sedation type on the diagnostic yield has yielded variable results with some authors reporting a higher yield with deep sedation[6], whereas others note no difference between MS and GA[5]. We present findings of a retrospective study that looked at the diagnostic yield using an artificial airway under GA compared to conscious sedation through a natural airway in patients undergoing EBUS-TBNA .

      Methods:
      Demographic information on age, sex, race and co-morbidities were used to compute an age adjusted Charlson Co-morbidity index for each of 88 patients. Pathology reports were reviewed and an EBUS-TBNA was determined to be diagnostic if any of the sampled lymph nodes yielded a diagnosis. Assessment of the impact of using an artificial airway under GA on diagnostic yield was determined using multivariate logistic regression. Continuous variables are presented as means (± SD) and categorical variables are reported as counts and percentages. For all tests, two-sided P values < 0.05 were considered statistically significant.

      Results:
      Patients in the GA group were older (65 years versus 57.6, p= 0.005), had a higher age-adjusted Charlson comorbidity index, (3.7 versus 1.9, p < 0.001) and a higher ASA classification (3 versus 2 p=0.004). Average lymph node size was smaller in the artificial airway group (16.2 mm versus 20.7mm, p = 0.01). Despite these differences, the diagnostic yield was the same (61.4 % in each group). In multivariate analyses, female sex and lymph node size were the only predictors of a diagnostic EBUS-TBNA. OR 3.3, 95 % CI, 1.23 – 9.1 for female gender, (p= 0.02) and 1.1, 95 % CI, 1.00 – 1.18 for lymph node size (p= 0.04). Diagnoses made were: adenocarcinoma of the lung 42.6 %, Sarcoidosis 16.7 %, Small cell lung cancer 14.8 %, Squamous cell carcinoma 11.1 %.

      Conclusion:
      EBUS-TBNA performed under general anesthesia through an artificial airway was not associated with an increased diagnostic yield, and therefore concious sedation should be considered where appropriate, with general anesthesia reserved for those patients who are older, and with a higher perioperative risk. More research assessing the determinants of a positive diagnosis including physician pretest likelihood and PET/CT avidity are needed to improve diagnostic outcomes.

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      P1.04-015 - Clinical Application of Virtual Navigated Bronchial Intervention (ID 4996)

      14:30 - 14:30  |  Author(s): N. Kajiwara, J. Maeda, K. Yoshida, M. Hagiwara, T. Okano, M. Kakihana, T. Ohira, N. Ikeda

      • Abstract
      • Slides

      Background:
      Removal of endobronchial tumor is considered the first treatment of choice to improve respiratory status to dilate and maintain the airway. In patients with inoperable tumors we frequently regard endoscopic treatment as the first treatment of choice, but the indications and decisions regarding the method require careful consideration. We reported the indications and efficacy of virtual navigated bronchial intervention for the treatment of bronchial tumors. To select safer and precisely approach for patients with bronchial tumors, we evaluate virtual navigated bronchial intervention using a high-speed 3-dimensional (3D) image analysis system, Synapse Vincent (Fuji Photo Film Co., Ltd., Tokyo, Japan).

      Methods:
      We set out to clarify, based on retrospective evaluation of routine work-up data in our charts and patient treatment data, the efficacy of virtual navigated bronchial intervention for the treatment of different types of bronchial tumors, yet representative of the spectrum of conditions we encounter, in order to provide a guide to techniques available in interventional bronchology for obstructive lesions. All computed tomography (CT) must satisfy several conditions necessary to analyze images by Synapse Vincent. Synapse Vincent provides more information not only concerning tumor size and shape, but also whether the tumor invades surrounding tissue and the extent of airway and vessel involvement. Constructed images are displayed on a monitor, which can be utilized for deciding the simulation and interventional strategy and for navigation during interventional manipulation.

      Results:
      In these cases, Synapse Vincent was used to determine the best planning of virtual navigated bronchial intervention. The feasibility and safety of Synapse Vincent in performing useful preoperative simulation and navigation of interventional procedures lead to the safer, more precise, and less invasive for the patient, and easy to construct an image, depending on the purpose, in 5-10 minutes using Synapse Vincent. Moreover, if the lesion is in the parenchyma or sub-bronchial lumen, it helps to perform simulation with virtual skeletal subtraction to estimate potential lesion movement. By using virtual navigated system for simulation, bronchial intervention was performed with no complications safely and precisely.

      Conclusion:
      Preoperative simulation using virtual navigated bronchial intervention reduces the surgeon’s stress levels, particularly when highly skilled techniques are needed to operate on lesions. This task, including interventional simulation and navigation both pre- and during manipulation, could lead to greater safety and precision. These technological instruments should be helpful for bronchial intervention procedures, and are also excellent devices for educational training.

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      P1.04-016 - EBUS plus Fluoroscopy-Guided Biopsy Compared to Fluoroscopy-Guided TBB for Obtaining Samples of Peripheral Pulmonary Lesions (ID 3739)

      14:30 - 14:30  |  Author(s): J. Ye

      • Abstract

      Background:
      Early detection of peripheral pulmonary nodules and histopathologic diagnosis of biopsy samples of the nodules are key to improving survival rates of lung cancer. Steady improvement in bronchoscopic procedures during the past few decades enable detection and biopsy of much smaller nodules. We report a meta-analysis of recent reports comparing the diagnostic yields of endobronchial ultrasonography plus fluoroscopically-guided transbronchial biopsy with that of fluoroscopically-guided transbronchial biopsy without the use of endobronchial ultrasonography.

      Methods:
      We searched Medline, the Cochrane Library, PubMed, and Google Scholar and found five articles that met our inclusion criteria. One of those articles did not strictly meet our criteria, in that it was deficient in quantitation, but we included it because it contained other relevant information.

      Results:
      Meta-analysis from the 4 studies revealed a higher positive diagnostic yield in the group with endobronchial ultrasonographic guidance in addition to fluoroscopy than the group diagnosed with only conventional fluoroscopic guidance to the lesion, for large and small lesions.

      Conclusion:
      Obtaining transbronchial biopsy samples for histopathological diagnosis is enhanced by addition of endobronchial ultrasonography to conventional fluoroscopic guidance; this is especially important for patients with small peripheral lung lesions who benefit greatly from early diagnosis.

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      P1.04-017 - The Survival of Our Patients Diagnosed with Lung Cancer in 2013 (ID 5187)

      14:30 - 14:30  |  Author(s): S. Altin, C. Ozdemir, C. Kocaturk, M. Kiyik, N. Urer, M.Z. Gunluoglu, K. Kara, S. Hastürk, Y. Baser, M.A. Bedirhan, I. Dincer

      • Abstract

      Background:
      Lung cancer is an important health problem. To investigate the survival of our patients diagnosed in our hospital with lung cancer and the situations that effect.

      Methods:
      Using the data processing and archive system of our hospital , patients were examined who had operated with C34 code in 2013. The rates of survival were calculated using Kaplan-Meier Method and compared with Long-rank method. The influence of age on survival was analysed with Cox’s proportional hazards regression model. For multivariate analysis Cox’s proportional hazards regression model also used. The level of P<0.05 accepted as significant.

      Results:
      1563(83.5%) of 1871 patients were male and 308 of the were female and their average age were found as 62.5 years, the average age in male was 62.7 while 61.4 in female. Median age was 62. The rate of M/F was calculated as 5.1, but there were no difference in terms of the average age(p>0.05). We had 16 male and 11 female patients were about 27(1.4%), under the age of 40. As a histological type, 717(38.3%) were squamous carcinoma, 692(37%) were adenocarcinoma, 288(15,4%) were small cell, 174(9.3%) unidentified cell malign carcinoma. While with 42.8% in male squamous carcinoma was frequent, adenocarcinoma with 57.8% in female was frequent. The average survival was calculated as 18 months, median survival as 12 months (95& Cl 11-13 months) and the rate of 2 years survival as 33,4%. While surgical treatment were applied to 380 patients (20.3%), chemotherapy were applied to 1100 patients(58,8%) and palliative care were applied to 302(16,1%) patients. The 2 years survival time was found significantly high in patients received surgical treatment.(73% in spite of 23.3%)(p<0.0001). While the 2 years survival of patients receiving chemotherapy was calculated as 25,6%, the patients receiving palliative care was 20,5%(p=0.08).The median survival time was found 28,4 months in patients receiving surgical treatment, patients receiving chemotherapy 14 months and palliative care was 11.5 months .The patients received neoadjuvan therapy lived 31months. Evaluation made as multivariate analyses; age, gender, with histological type, the tretament variables one by one were found effective on survival as p=0.0001 level.

      Conclusion:
      It was obtained that the patients diagnosed with lung cancer in our hospital, after they diagnosed they lived averagely 16 months. The patients received surgical treatment with 73%,with 2 years time survival lived significantly more than the other treatments.

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      P1.04-018 - Occurrence of Triple Multiple Malignancies with Last Lung Squamous Cell Carcinoma - Case Reports (ID 5236)

      14:30 - 14:30  |  Author(s): A. Doboszyńska, A.M. Romaszko

      • Abstract
      • Slides

      Background:
      The incidence of multiple primary tumors (MMPNs) ranges from 0.73 to 11.7%. Most often occur double malignancies - 3-5%, much less triples - 0.5%. The aim of the study is to describe the three cases of triple metachronous multiple malignancies, the last of which was a squamous cell carcinoma of lung in all three patients.

      Methods:
      A retrospective analysis of all medical histories (1163) patients who were hospitalized in the Pulmonary Hospital Hospital in Olsztyn, Poland in the period from January 2013 to October 2015, with a diagnosis of at least one neoplasm was performed. We selected only these patients who were diagnosed with histologically confirmed three independent malignancies.

      Results:
      The incidence of tumors of triple malignancies was 0.52%. Of all cases of triple malignancies, we selected 3 cases - 2 men and 1 woman, whose last-growing cancer, histopathologically confirmed, was squamous cell lung cancer. Case No. 1 - 54-year-old man with COPD (GOLD 2), who gave up smoking, melanoma of the scalp treated surgically and by chemotherapy (6xDTIC) at the age of 19, Hodgkin NS II at the age of 38 treated with 6xABVD, at the age of 53 years diagnosed with squamous cell carcinoma of the left lung in stage T2N1M0. Due to the low value of spirometry disqualified from surgery, qualified for radiotherapy. Case No. 2 67-year-old man with a history of hypertension, colon cancer at the age of 56, after a laryngectomy because of laryngeal squamous cell carcinoma at the age of 63, diagnosed with asymptomatic squamous cell carcinoma of the right lung in a stage T2N0M0 at the age of 65. Case No. 3 74-year-old woman with atrial fibrillation, stable ischemic heart disease, tongue cancer at the age of 67, and its recurrence in the age of 72, after a right-sided mastectomy and chemotherapy for breast cancer at the age of 69, at the age of 74 diagnosed with squamous cell carcinoma of the left lung. The average age of first cancer was 47, the second 57 years, the third 64 years.

      Conclusion:
      1. Lung cancer often occurs as a subsequent malignancy 2. Another primary malignancy may develop even 30 years later, and therefore the possibility of development the third or another cancer should be considered for all cancer patients. 3. Development of synchronous or metachronous neoplasms should be considered in any case in patients with previous oncological treatment.

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      P1.04-019 - Final Analysis of Lung Microbiome from Patients Undergoing Bronchoscopy (ID 4201)

      14:30 - 14:30  |  Author(s): G.J. Weiss, J. Cocking, C. Bilagody, H.M. Hornstra, E. Kaufman, D.A. Nader, J.F. Turner, S. Chandrika, J.G. Caporaso, P. Keim, B. Harmon, H. Barilla, T. Pearson

      • Abstract
      • Slides

      Background:
      Recent studies have demonstrated diversity in the lung microbiomes of chronic obstructive pulmonary disease and healthy individuals. Lung microbial communities may not just serve as a predictor of cancer development, but also as a target of pharmacological cancer prevention strategies. We sought to characterize the lung microbiome diversity within patients with lung cancer for comparison to those with other cancers and those without cancer.

      Methods:
      Signed informed consent was obtained from patients ages ≥18 years undergoing a clinically indicated bronchoscopy. A bronchial lavage (BAL) was collected for research purposes after completing routine bronchoscopic procedures. Samples were prepped and DNA was extracted and 515F/806R 16S rRNA primers used to amplify Variable Region 4. Amplicons were sequenced and grouped into 100% operational taxonomic units (OTUs) using vsearch. Taxonomy was assigned, a phylogenetic tree was constructed, and sequences aligned for phylogenetic diversity calculations, including Faith's Phylogenetic Diversity and weighted and unweighted UniFrac. OTUs that were significantly different across sample categories were identified using DESeq2.

      Results:
      There were 137 unique BAL samples collected. One patient had an adverse research procedure event that resolved after temporary supplemental oxygen and overnight observation. BALs were from 68 non-small cell lung cancer (NSCLC), 12 small cell lung cancer (SCLC), 52 other cancers, and 5 non-cancer patients. 58 NSCLC were current/former smokers (average 43 pack-years), while all the SCLC were current/former smokers (average 56 pack-years). 22 other cancers were current/former smokers (average of 27 pack-years). Overall, 51 samples (37.2%) had sufficient sequencing reads (>20,000) for subsequent analyses. There were multiple bacterial taxonomic groups in each sample, however, phylogenetic diversity was low compared to other body sites. There were no statistical differences in alpha/beta diversity between ever-smokers and never-smokers, NSCLC vs SCLC, lung cancer vs non-cancer, and location of BAL collection (upper vs lower airways and right vs left lung). There were a number of statistically significant differences by taxonomy (False Discovery Rate adjusted p<0.01 and listing genus only). Adenocarcinoma vs non-adenocarcinoma had more Streptococcus and Veillonella; less Haemophilus. For NSCLC vs SCLC, Rothia was more prevalent in SCLC. BALs from the upper airways had more prevalent Streptococcus. BALs from the right lung had more prevalent Capnocytophaga and Parvimonas; less Moraxella and Selenomonas.

      Conclusion:
      We report significant taxonomic differences by tumor type and location of BAL sampling and overall low phylogenetic diversity. Future validation of this work can be used to modify bacterial colonization in a lung cancer prevention strategy or for early diagnostics/therapeutics.

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      P1.04-020 - Management of Lung Cancer in Patients with past Pulmonary Tuberculosis and Their Possible Causative Link (ID 4170)

      14:30 - 14:30  |  Author(s): F. Caushi, J. Shkurti, D. Xhemalaj, I. Skenduli, A. Mezini, H. Hafizi, A. Hatibi, I. Bani

      • Abstract
      • Slides

      Background:
      Lung cancer and tuberculosis cause significant morbidity and mortality worldwide. In the past, it was well known that lung cancer is a specific epidemiological successor of pulmonary tuberculosis (PTB) and that it often develops in scars caused by PTB. In recent years, the relevance of the two diseases has drawn attention in terms of the close epidemiological connection and chronic inflammation-associated carcinogenesis. Although studies have found a relationship between PTB and lung cancer, results for the long-term risk and the role of confounding factors remain inconclusive. Therefore, it is important to delineate the relationship between PTB and lung cancer.

      Methods:
      Clinical files of all patients diagnosed with lung malignancy between 2011 and 2016 were investigated retrospectively in terms of patient characteristics, definite histopathological diagnosis and stage of tumor, operation methods, and associated complications.

      Results:
      Mean age was 56.4 years. Past PTB was detected in 3% of operated carcinoma patients and in 6% of all patients diagnosed with lung malignancy. Central lung cancer was diagnosed in 80% of cases and peripheral in 20%. Epidermoid cancer was diagnosed in 51% of cases, adenocarcinoma in 24% and adenoepidermoid carcinoma in 25%. All cases of operable lung cancers were in stage I and II, while inoperable lung cancers were in stage IIIB and IV. Lobectomy was performed in 100% of the operated cases. None of the patients received anti-TB treatment preoperatively or postoperatively because by the time they were diagnosed with lung cancer, their sputum culture for M.Tuberculosis had converted negative. No postoperative mortality or reactivation of TB was seen.

      Conclusion:
      PTB is an important risk factor for lung cancer, possibly related to chronic inflammation and shared risk factors. Our study adds to the evidence that implicates chronic inflammation and pulmonary scarring in the etiology of lung cancer. However, further studies are needed to clarify whether there is a direct causative link between PTB and lung cancer. Surgery is the method of choice in treatment of lung cancer in subjects with past PTB history.

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      P1.04-021 - Medical Thoracoscopy for the Diagnosis and Management of Pleural Effusions: Results of a Retrospective Analysis (ID 4057)

      14:30 - 14:30  |  Author(s): S. Tsagouli, E. Kapetanakis, C. Kampolis, P. Tomos, K. Potaris, E. Kainis, I. Gkiozos, K. Syrigos

      • Abstract
      • Slides

      Background:
      Medical thoracoscopy is a minimally invasive procedure utilized mainly by pulmonologists for the diagnosis and management of pleural effusions. The aim of this study was to evaluate the efficacy and safety of medical thoracoscopy when performed by a combined team of pulmonologists and thoracic surgeons in a tertiary university hospital.

      Methods:
      This is a retrospective cohort analysis of all patients with pleural effusion whο underwent medical thoracoscopy at “LAIKO” Athens General Hospital from June 2013 to December 2014.

      Results:
      Our study population included 36 patients, 18 males and 18 females, with a mean age of 61 years. All patients were submitted to medical thoracoscopy for the diagnostic evaluation of pleural effusion. Twenty-six patients (26/36, 72.2%) presented with an undiagnosed pleural effusion, six (16.7%) with known malignant, recurrent pleural effusion, three (8.3%) with parapneumonic effusion/empyema and one (2.8%) with idiopathic pleural effusion due to nephritic syndrome. Eighteen patients (18/36, 50%) underwent drainage and pleural biopsy, 9 patients (9/36, 25%) underwent drainage, pleural biopsy and talc pleurodesis, 6 patients (6/36, 16.7%) underwent drainage and talc pleurodesis due to known malignant pleural effusion and 3 patients (3/36, 8.3%) underwent drainage of their parapneumonic effusion/empyema. Among all patients (n=27) who underwent diagnostic pleural biopsy, 2 patients (7.4%) were diagnosed with primary non-small cell lung cancer, 4 (14.8%) with malignant pleural mesothelioma, 3 (11.1%) with metastatic disease of non-thoracic primary origin and 3 (11.1%) with lymphoma, while 1 patient each (3.7%) was diagnosed with tuberculosis, systemic lupus eryhtematosus, chronic inflammation, chronic pleural fibrosis and nephritic syndrome. In 3 patients (3/27, 11.1%) the biopsy was negative. Medical thoracoscopy was non-diagnostic in one patient only (1/27, 3.7%), thus producing a diagnostic yield of 97.3%. With the notable exception of one patient (1/36, 2.8%) who died due to empyema and subsequent sepsis, the remaining post procedural complications were mild, and included subcutaneous emphysema in 6 cases (6/36, 16.7%) and minor bleeding in 3 cases (3/36, 8.3%).

      Conclusion:
      When performed by a combined team of pulmonologists and thoracic surgeons in a tertiary level hospital, medical thoracoscopy is a relatively safe and efficacious technique for the diagnosis and management of pleural effusions in patients unable to undergo or not requiring surgical intervention.

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      P1.04-022 - Use of Alternative Therapy in Patients with Lung Cancer (ID 6212)

      14:30 - 14:30  |  Author(s): K.K. Krpina, M.J. Jakopović, M.R. Roglic

      • Abstract
      • Slides

      Background:
      Background: Lung cancer has the highest mortality among all malignant diseases due to advanced stage of diseases at diagnosis, but also due to modest response to therapy. For that reasons an increasing proportion of population use alternative therapy. Most often those are drugs that are alleged immunomodulators However, for systemically administered complementary and alternative medicine (CAM), there are significant risks of adverse drug interactions with conventional treatments, which may result in either increased drug toxicity or therapeutic failure.

      Methods:
      Methods: We performed a retrospective analysis of alternative therapies used during oncology treatment in lung cancer. Data were collected from medical documentation. Total of 246 patients diagnosed with lung cancer at Department of pulmonary diseases Jordanovac were tracked during a two-year period. General information, sociodemographic characteristics and alternative therapies were extractes from documentation and statistically analised.

      Results:
      Results: Total of 76 out of 246 patients (31%) admitted to using alternative therapy. Women use it more often than male (38% vs 28%). No difference was observed according to age o geographic location. Yet there was a small, but significant difference according to level of education. Among patient with university degree 36% used alternative therapy in contrast to 30% among those with high school education. Use of chemotherapy and advanced stage of disease correlated with more frequent CAM use (58% vs 42%). Most often used alternative therapy was aronia (46%) and then cannabis and its derivatives (mostly oil) in 36% of patients, while beta-glucan (11%) and other comprised smaller percentages.

      Conclusion:
      Conclusion: Use of alternative therapies is increasing among patients with lung cancer and it is imperative for physicians to know about this. So far there is no scientific or clinical evidence for positive effects of this therapy, but it is known that it can collide with chemotherapy. Because of that it is imperative to expand our knowledge of use of alternative therapy, as well as its effects.

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      P1.04-023 - Thrombomodulin Inhibits the Growth and Angiogenesis of Human Lung Cancer via Blocking VEGFR2-Mediated JAK/STAT3 Signaling Pathway (ID 4520)

      14:30 - 14:30  |  Author(s): Y. Yi, S. Lu

      • Abstract
      • Slides

      Background:
      Angiogenesis has been an attractive target for drug therapy because of its key role in the growth and metastatic spread of malignant tumor. Thrombomodulin has been shown to possess anti-inflammatory and vascular endothelial protection activities. However, its roles in tumor angiogenesis are unknown. The aim of this study was to investigate the roles of thrombomodulin in tumor angiogenesis and its anticancer activities.

      Methods:
      ex vivo aortic ring angiogenesis sprouting assay was used to detect neo-vascularization. Western blotting was performed to examine STAT3 signaling cascade.

      Results:
      Thrombomodulin significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, migration and tube formation in vitro and blocked vascular endothelial growth factor (VEGF)-triggered neo-vascularization. VEGF receptor (VEGFR) 2 mediated-Janus Kinase 2/STAT3 signaling pathway was significantly inhibited by thrombomodulin in endothelial cells. In addition, the constitutively activated STAT3 protein, and the expression of STAT3-dependent target genes, including cyclin D1, c-Myc, Bcl-xL, and VEGF were also down-regulated in response for thrombomodulin in human lung cancer cells. Consistent with the above findings, thrombomodulin inhibited tumor cell cycle progression and induced cell apoptosis in vitro.

      Conclusion:
      Therefore, our provided the first evidence that thrombomodulin inhibited tumor angiogenesis and growth via inhibiting VEGFR2-mediated JAK/STAT3 signaling pathway with the potential of a drug candidate for cancer therapy.

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      P1.04-024 - Molecular Profiling and Survival of Primary Pulmonary Neuroendocrine Carcinoma with Completely Resection (ID 4517)

      14:30 - 14:30  |  Author(s): G. Lou, Z. Song, Y. Zhang

      • Abstract
      • Slides

      Background:
      According to the 2015 World Health Organization classification of lung tumors, pulmonary Large cell neuroendocrine carcinoma (PLCNC) is grouped with the small cell lung cancer (SCLC) and carcinoid as pulmonary neuroendocrine carcinoma(PNC) for the common features of neuroendocrine characteristics . Molecular profiles and prognosis of primary pulmonary neuroendocrine carcinoma(PNC) are not well investigated currently. We conducted present study to evaluate genomic abnormality and survivals in patients with primary PNC.

      Methods:
      Tumor samples of PNC after completely resection from Zhejiang Cancer Hospital were collected from 2008 to 2015. Nine driver genes including six mutation (EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2) and three fusions (ALK, ROS1, RET) were evaluated by RT-PCR. Survival analysis was evaluated using the Kaplan-Meier method.

      Results:
      Totally, 108 patients with pathologic confirmed PNC were enrolled. Samples included 52 PLCNC, 44 small cell lung cancer (SCLC) and 12 carcinoid. Twelve patients were found to harbor genomic aberrations (11.1%). The most frequent gene abnormality was PIK3CA (n=5,4.6%),followed with EGFR (n=3,2.8%), KRAS (n=2,n=1.9%), ALK (n=1,0.9%), RET (n=1,0.9%). No ROS1,BRAF,NRAS and HER2 mutations were observed. The frequencies of gene aberrations in PLCNC, SCLC and carcinoid were 15.4%,6.8% and 8.3%,respectively. Sixty-seven patients were with recurrence or metastasis after surgery, including 32 PLCNC, 33 of SCLC, and two of carcinoid (both were atypical carcinoid). Among the 32 patients with PLCNC,none received molecular targeted treatment,28 received first-line chemotherapy,including 18 of etoposide/platinum regimen and 10 of other platinum-based treatment. The progression free survival in patients with etoposide/platinum regimen was longer than patients with non-etoposide/platinum treatment (4.8 vs.3.4 months,P=0.019) . Survival difference was observed among the PLCNC,SCLC and carcinoid group (37.0 vs. 34.0 vs.not reached, P=0.035), but no difference existed between the PLCNC and SCLC group (P=0.606) .

      Conclusion:
      Common genomic abnormality is rare in PNC patients and most frequently observed in PLCNC. Patients with carcinoid had a superior survival than PLCNC and SCLC.

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      P1.04-025 - The Impact of Emergency Presentation on Survival of Lung Cancer Patients (ID 5964)

      14:30 - 14:30  |  Author(s): M. Jakopovic, D. Fedza, L. Bitar, I. Markelić, F. Seiwerth, A. Hecimovic, B. Čučević, I. Mazuranic, G. Redzepi, A. Vukic Dugic, M. Jankovic, M. Samarzija

      • Abstract

      Background:
      A significant proportion of lung cancer patients are diagnosed through emergency department (ED), which is usually associated with poorer prognosis. We investigated the assocation between diagnosis of lung cancer after presentation through emergency department due to symptoms associated to lung cancer.

      Methods:
      Medical charts of patients with lung cancer patients newly diagnosed in Department for Respiratory Diseases Jordanovac, University Centre Zagreb in years 2012 and 2103 were reviewed. Overall survival was calculated and was compared between groups.

      Results:
      The medical charts of 951 males and 407 females, mean age 64 years (males 64.5, females 62) were reviewed. 292 out od 1359 patients (21,5%) were diagnosed with lung cancer after initial presentation through ED. The most common reasons for ED admissions were hemopytsis (in 31% of patients), pneumonia (16%), brain metastasis (15%), dyspnea (10%) and superior vena cava syndrome in 8% of patients. There were no differences in histology subptypes between two different routes of presentation (most common histology subtype was adenocarcinoma followed by squamous histology). Significantly higher proportion of patients diagnosed after initial diagnosis through ED were at presentation in stage IV (61 vs 44%, p<0.0001), poorer performance status (ECOG 3-4 vs ECOG 0-1, p<0.0001), significantly less patients underwent surgical resection (14 vs 5%, p<0.0001) and radiotherapy (56 vs 73%, p<0.0001). Median overall survival (mOS) was significantly lower in patients diagnosed through ED (6.0 vs 10.0 months, p<0.0001). In patients with non-small cell lung cancer (NSCLC) results were similar (mOS 6.0 vs 10.0 months, p<0.0001). In patients with small cell lung cancer (SCLC) mOS was also significantly worse (7.0 vs 9.0 months, p<0.0001) in patients diagnosed through ED.

      Conclusion:
      Higher stage, reduced access to surgical resection and radiotherapy, and significantly lower overall survival regardless of histology subtypes among lung cancer patients who presents through emergency department, stress out the importance of earlier diagnosis of lung cancer patients so that initial presentation through emergancy department can be reduced.

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      P1.04-026 - Coexisting Lung Cancer and Interstitial Lung Disease: A Challenge in Clinical Practice (ID 5611)

      14:30 - 14:30  |  Author(s): A. Linhas, D. Machado, S. Conde, S. Campainha, A. Barroso

      • Abstract

      Background:
      Lung cancer (LC) risk is increased in patients with interstitial lung disease (ILD), and the two diseases sometimes occur concomitantly. Cigarette smoking is a recognised risk factor for development of both pathologies but the aetiology and pathogenesis of LC in patients with ILD is still unclear. The benefit of chemotherapy or radiotherapy for LC in cases of ILD remains unknown. Objective: To analyse characteristics and outcomes of patients with ILD and LC.

      Methods:
      A retrospective analysis of all patients presenting with concomitant ILD and lung cancer to our centre, between 1[st] January 2011 and 30[th] June 2016, was performed. Diagnosed lung cancer patients with suspected ILD, but not confirmed, were excluded, as well as patients who developed ILD in the setting of lung cancer therapy. Clinical, radiological and pathological characteristics of this cohort were described. Outcomes were also reported.

      Results:
      Eleven patients were included (mean age 63±12years). Most patients were men (82%) and heavy smokers (64% had a smoking history >30pack/year). The majority ILD cases were related to connective tissue disease (45%) and combined pulmonary fibrosis and emphysema (CPFE) (18%). The most prevalent lung cancer histological type was adenocarcinoma (45%); most patients were diagnosed at advanced stages (63%) and mainly during the clinical and radiological follow-up for the fibrosis. The mean time from the onset of ILD to the onset of LC was 39.4 months. On chest CT, the tumours were predominantly peripheral. Surgical resection was performed in 3 patients with stage I or II LC; chemotherapy and/or radiotherapy were given to 6 patients with advanced disease (stage III and IV). One patient was refused for radiotherapy due to considerations of the adverse effects on the prognosis. The median survival since the diagnosis of LC was 6.7months. Two patients died of respiratory failure due to progression of pneumonitis after the therapy and three patients died due to progression of LC.

      Conclusion:
      Patients with LC and ILD might benefit from chemotherapy and radiotherapy, but pre-existing ILD could influence negatively the prognosis. Therapy for LC should be considered in patients presenting both LC and ILD and interdisciplinary evaluation of therapeutic options is mandatory. When planning radiotherapy it is important determinate the radiation pneumonitis risk. More studies are needed to clarify the role of LC treatment in the management of ILD patients.

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      P1.04-027 - Changes in Pulmonary Function in Lung Cancer Patients after Thoracic Surgery (ID 5619)

      14:30 - 14:30  |  Author(s): A. Linhas, S. Campainha, A. Barroso, S. Conde

      • Abstract

      Background:
      Surgery is considered the first line treatment for patients with resectable early non-small cell lung cancer (NSCLC). Many of these patients present limited lung function which is caused by a common etiologic factor - cigarette smoking. The evaluation of pulmonary function preoperatively is important to identify candidates at risk of postoperative respiratory complications and may assist in operability decision. However, lung function after surgical resection may be affected by several factors. Objective: To evaluate changes in pulmonary function after thoracic surgery, in patients with solitary nodules or lung cancer.

      Methods:
      Retrospective study of patients diagnosed with operable lung cancer and solitary nodules followed in our centre between 1[st] January 2011 and 31[th] December 2014. Patients presenting pulmonary function tests (PFTs) until one year after surgery were included. Patients without PFTs after surgery were excluded.

      Results:
      Forty three patients were included. The results are presented in the table:

      Mean age 62±9 years
      Gender 67,4% (n=29) male
      Indications for surgery Adenocarcinoma Carcinoid tumour Squamous cell carcinoma Solitary pulmonary nodule 44,2%(n=19) 14%(n=6) 11,6% (n=5) 25,6% (n=11)
      Clinical staging in lung cancer patients IA IB IIA IIIA 43,7% (n=14) 15,6% (n=5) 12,5% (n=4) 18,7% (n=6)
      Location of the lesion Superior right lobe Superior left lobe 34,9% (n=15) 25,6% (n=11)
      Neoadjuvant chemotherapy Neoadjuvant radiotherapy 20,9% (n=9) 4,7 (n=2)
      Open surgery Video-assisted thoracic surgery (VATS) 83,7% (n=36) 16,3%(n=7)
      Comorbidities Chronic Obstructive Pulmonary Disease (COPD) Ischemic Heart Disease (IHD) 30,3% (n=13) 4,7% (n=2)
      Smoking habits Smoker Ex-smoker Non-smoker 37,2% (n=16) 32,6% (n=14) 30,2% (n=13)
      The mean values of FVC (L), FEV1 (L), FEV1/FVC and DLCO decreased after surgery (p=0.010, p=0.001, p=0.011 and p=0.037, respectively). FVC (L) and FVC (%) values decreased more significantly in patients submitted to pneumonectomy (p=0.004 and p=0,047). There was, though, an improvement of FVC (%) in patients submitted to VATS and wedge resection (p=0.005 and p=0.034). FEV1 (L) mean values increased in patients submitted to wedge resection (p=0.017) and decreased in patients submitted to pneumonectomy (p=0.04). There was no significant association between histological type, clinical stage, local of the lesion, COPD and CVD and lung function parameters before and after surgery.

      Conclusion:
      The postoperative pulmonary function varied according to the type of surgery, therefore the surgical procedure adopted may help us predict changes in lung function after lung surgery. Clinicians should be aware of these changes when determining the surgical method, especially in high-risk patients.

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      P1.04-028 - Collection of ICHOM-Defined Patient-Reported Outcome Measures (PROMs) during Routine Lung Cancer Treatment: A Pilot Study (ID 5476)

      14:30 - 14:30  |  Author(s): J.P. Van Meerbeeck, L. De Backer, A. Janssens, B. Hiddinga, G. Vanhoutte

      • Abstract

      Background:
      PROMs -including symptoms, health related quality of life, well-being and functional status- are commonly measured in clinical trials. They are used in a variety of ways, including therapy decisions on individual patient level or research into disease progression. Optimizing how patients feel is a goal of good oncology practice and a quality performance indicator of care. Therefore it is important to implement the collection of PROMs during routine lung cancer treatment without disturbing the routine workflow. The International Collaboration on Health Outcomes Measures (ICHOM) has proposed a standard set of uniform PROMs for lung cancer (Mak et al, ERJ 2016).

      Methods:
      A pilot study is set up to establish an operational workflow and to identify trouble shooting to the collection of PROMs in standard of care. Self-reporting by the patient is conducted via a web-based interface using questionnaires and individual case-mix variables according to the ICHOM standard set. At baseline, during treatment and in follow up patients receive electronic invitations. Computer-inexperienced patients have the opportunity to complete paper forms.

      Results:
      A gap analysis was done and a swim lane algorithm constructed which will be presented at the meeting. From February 2016 onwards, 24 patients were screened of whom 11 consented. The other 13 patients were screen failures because of language barrier, previous therapy start or mental confusion. From the enrolled patients, 2 are currently in follow up and 5 patients choose to complete PROMs on paper forms. Updated results on compliance and outcome in 50 patients will be brought at the meeting.

      Conclusion:
      Participants’ profile reflect a tertiary setting hospital with many referrals and patients, unable to complete the PROM’s. To optimize the inclusion rate, several adaptations in the implementation workflow have been introduced. Although the registration of PROMs is not very time-consuming, real-time monitoring requires a user-friendly online tool and dedicated staff. Lessons from this pilot study will be applied when rolling out other ICHOM standard sets.

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    P1.05 - Poster Session with Presenters Present (ID 457)

    • Type: Poster Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 79
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      P1.05-001 - Creation and Early Validation of Prognostic miRNA Signatures for Squamous Cell Lung Carcinoma by the SPECS Lung Consortium (ID 6088)

      14:30 - 14:30  |  Author(s): D. Harpole, R. Bueno, W.G. Richards, D. Beer, K.V. Ballman, M.S. Tsao, F.A. Shepard, D.T. Merrick, A. Van Bokhoven, W.A. Franklin, R. Govindan, M. Watson, D.R. Gandara, G. Chen, Z.H. Chen, L. Chirieac, H. Chui, C. Genova, M. Joshi, A. Kowalewski, M. Onaitis, C.J. Rivard, T. Sporn, F.R. Hirsch

      • Abstract

      Background:
      Despite overall favorable prognosis for operable early stage non-small cell lung cancer, predicting outcome for individual patients has remained challenging. Small retrospective studies have reported potential non-coding micro(mi)RNAs that might have prognostic significance; however, these studies lacked statistical power and validation. To refine these initial findings to clinical application, the investigators have undertaken a collaborative, structured evaluation of multiple signatures putatively prognostic for lung squamous cell carcinoma (SCC) under a NCI/SPECS (Strategic Partnerships fo Evaluating Cancer Signatures) award. The study design specifies a primary validation cohort comprising institutional cases, and additional validation cohorts of Cooperative Group cases, all profiled via a common pipeline.

      Methods:
      Completely resected SCC (confirmed by central pathology review) meeting clinical (Stage I-II; complete 3-year follow-up) and specimen quality criteria (Tumor cellularity ≥ 50%;necrosis ≤ 20%) were submitted by 6 institutions. Clinical, pathological and outcome data were uploaded to a central database. Lysates from 5 um sections of FFPE SSC tumor samples were run on the HTG EdgeSeq Processor (HTG Molecular Diagnostics, Tucson, AZ) using the miRNA whole transcriptome assay in which an excess of nuclease protection probes (NPPs) complimentary to each miRNA hybridize to their target. S1 nuclease then removes un-hybridized probes and RNA leaving behind only NPPs hybridized to their targets in a 1-to-1 ratio. Samples were individually barcoded (using a 16-cycle PCR reaction to add adapters and molecular barcodes), individually purified using AMPure XP beads (Beckman Coulter, Brea, CA) and quantitated using a KAPA Library Quantification kit (KAPA Biosystems, Wilmington, MA). Libraries were sequenced on the Illumina HiSeq platform (Illumina, San Diego, CA) for quantification. Standardization and normalization was provided to the project statistical core for validation of two pre-existing signatures and generation of new models (MCP clustering).

      Results:
      Among 224 cases with miRNA data, median age was 70 (43-92), 143 (64%) male, with 67% former (67%) and current (26%) smokers. All patients were completely resected stage I or II. . At follow-up, 59 (26%) had documented recurrence and 129 (58%) were deceased. To date, we have been unable to validate the previous models, but have created a novel signature of three miRNAs (see Figure) that is being validated in the second phase of the project using an independent, blinded multi-institutional cohort.

      Conclusion:
      The Squamous Lung Cancer SPECS Consortium has established well-annotated and quality-controlled resources for validation of prognostic miRNA signatures. A new candidate 3-miRNA signature has been identified for further development as a clinically useful biomarker.

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      P1.05-002 - The Prognostic Impact of EGFR Mutation Status and Mutation Subtypes in Patients with Surgically Resected Lung Adenocarcinomas (ID 3932)

      14:30 - 14:30  |  Author(s): K. Takamochi, S. Oh, T. Matsunaga, K. Suzuki

      • Abstract

      Background:
      EGFR mutation status is a well-established predictor of the efficacy of EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer. Recently, the differences in EGFR mutation subtypes were also reported to be associated with the efficacy of EGFR TKIs. However, the prognostic impact of EGFR mutation status and mutation subtypes remains controversial.

      Methods:
      We retrospectively reviewed 945 consecutive patients with surgically resected adenocarcinomas who had their EGFR mutation status analyzed between January 2010 and December 2014. Overall survival (OS) and recurrence-free survival (RFS) were analyzed in three cohorts (all patients, pathological stage I patients, and patients with exon 21 L858R point mutation or exon 19 deletions) using Kaplan-Meier methods and Cox regression models.

      Results:
      The median follow-up time was 42 months. The results for EGFR mutation status, mutation subtype, and the comparison data of OS/RFS are summarized in the attached Table. Positive EGFR mutation status was significantly associated with longer OS/RFS in all patients and was also associated with longer OS in pathological stage I patients. However, no significant differences were observed in OS/RFS between patients with exon 21 L858R point mutation and those with exon 19 deletions. In a Cox regression model for OS, the EGFR mutation status was a significant prognostic factor that was independent of well-established prognostic factors such as age, pathological stage, vascular invasion, lymphatic permeation, and serum CEA level.

      3y-RFS 5y-RFS P 3y-OS 5y-OS P
      All Pts 0.009 < 0.001
      EGFR mut+ (N = 423) 84.6% 76.7% 95.2% 89.0%
      EGFR mut- (N = 522) 78.8% 71.2% 84.9% 76.5%
      p stage I Pts 0.102 < 0.001
      EGFR mut+ (N = 352) 93.4% 85.4% 98.2% 94.5%
      EGFR mut- (N = 392) 90.6% 82.8% 92.6% 85.9%
      Subtypes 0.385 0.507
      Ex 21 L858R (N = 224) 84.8% 79.6% 95.2% 90.0%
      Ex 19 del (N = 164) 84.7% 74.3% 97.5% 95.8%


      Conclusion:
      Positive EGFR mutation status is a favorable prognostic factor in patients with surgically resected lung adenocarcinomas. However, EGFR mutation subtypes (exon 21 L858R point mutation or exon 19 deletions) have no prognostic impact.

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      P1.05-003 - Coexpression of CD8a and PD-L1 Frequently Observed in Resected NSCLC Tumors from Smokers (ID 4764)

      14:30 - 14:30  |  Author(s): A. Lisberg, E.B. Garon, R. McKenna, J. Dering, H. Chen, N. Kamranpour, D. Hou, M. Velez, R.B. Cameron, J.M. Lee, S.M. Dubinett, D. Slamon

      • Abstract

      Background:
      With the approval of anti-programmed cell death-1 (PD-1) therapy in advanced non-small cell lung cancer (NSCLC), identifying patients with early stage disease most likely to benefit from therapy has become a priority. It has been hypothesized that patients whose tumors show evidence of PD-1 mediated T cell exhaustion, via the presence of both tumor infiltrating lymphocytes (TILs) and PD-L1 expression, are more likely to respond to anti-PD-1 therapy (Teng et al, 2015). The current study utilized microarray analysis to evaluate the relationship between both clinicopathologic features and overall survival (OS) with tumor microenvironment (TME) composition.

      Methods:
      Gene expression microarray analysis was performed using the Agilent Whole Human Genome 4x44K 2-color platform for 319 NSCLC and 15 normal resection specimens. The reference sample was an equal mixture of 258 of the NSCLC samples. Rosetta Resolver and Statistica 13.0 were used for analysis. Samples with PD-L1 expression levels greater or unchanged from reference level were classified as positive, while those significantly lower [log (ratio)<0 and p<0.01] than the reference were classified as negative. CD8a expression was used as a surrogate for TILs as previously described by Ock et al. (2016), and categorized in the same manner as PD-L1. Relationships between TME composition and clinicopathologic features were evaluated with the chi-square test. Survival analysis was performed using the Kaplan-Meier method and compared using the log-rank test.

      Results:
      In the 319 NSCLC samples the incidence of a Type I TME (+CD8a/+PD-L1) was 45%, Type II TME (-CD8a/-PD-L1) 12%, Type III (-CD8a/+PD-L1) 25%, and Type IV (+CD8a/-PD-L1) 18%. When assessing for survival, patients with a PD-L1 negative/CD8a positive (Type IV) TME had improved OS compared to patients with PD-L1 negative/CD8a negative (Type II) TME (p=0.02). When assessed for smoking, ever smokers were more likely to evidence a PD-L1 positive/CD8a positive (type I) TME compared to never smokers, 49% vs 32%, while never smokers more frequently evidenced a PD-L1 positive/CD8a negative (Type III ) TME compared to ever smokers, 37% vs 22% (P=0.05). Interestingly, 75% of normal lung samples evidenced a PD-L1 positive/CD8a positive microenvironment.

      Conclusion:
      Evidence of both TILs and PD-L1 expression was observed in the majority of normal lung specimens and also more frequently in tumors from smokers compared to non-smokers. Patients whose tumors showed evidence of CD8a, but not PD-L1, had improved OS compared to patients without evidence of either. Future studies will utilize immunohistochemistry to corroborate these findings and investigate other components of the TME.

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      P1.05-004 - Surfactant Protein C is a Prognostic Marker in Resected Non-Small Cell Lung Cancer (ID 4393)

      14:30 - 14:30  |  Author(s): I. Macía, J. Moya, G. Aiza, R. Ramos, I. Escobar, F. Rivas, A. Ureña, G. Rosado, P. Rodríguez-Taboada, S. Aso, S. Padrones, C. Déniz, E. Nadal, G. Capella

      • Abstract
      • Slides

      Background:
      The lung cancer cells express genes involved in key points of the lung development. The objective of this study was to determine the prognostic value of expression of embryonic markers in tumour tissue samples from patients with surgically-treated non-small cell lung cancer (NSCLC).

      Methods:
      Study based on 129 primary tumour samples from 102 patients with surgically-treated NSCLC (99% R0) and 27 lung samples. Expression of the following markers was evaluated by mRNA RT-qPCR assay: CEACAM5, FGFR2b, FRS2, MYCN, SFTPC, SHH, SHP2, and SOX17 in the tumour and lung samples. Statistical analyses included chi-squared tests, non-parametric tests, Kaplan Meier curves, log-rank and Cox regression tests.

      Results:
      Patients' characteristics were: mean age 67 ± 8 years, squamous carcinoma (49%), adenocarcinoma (43%), pathological staging: I: 56%, II: 32%, III: 11% and IV: 1%. 18% received adjuvant chemotherapy, 1% radiotherapy and 7% both. CEACAM5 and MYCN were overexpressed in tumour samples related to lung samples (p<0,05), FGFR2b showed similar expression and FRS2, SFTPC, SHH, SHP2 and SOX17 were underexpressed (p<0,05). The squamous carcinomas expressed more FGFR2b, FRS2 and SFTPC (p<0,10), while adenocarcinomas expressed more CEACAM5 (p>0,05). Lymph node involvement was associated with SHH underexpression (p<0,05), intratumoral vascular invasion with CEACAM5 or FGFR2b underexpression (p<0,05) and relapse with SHH (p<0,05) or SFTPC (p=0,09) underexpression. Kaplan-Meier curves of SFTPC were plotted in figure 1. Underexpression of SFTPC in the tumour sample was associated with a 7-fold (7.3; 1.3-40.9) greater active risk of recurrence and a nearly 5-fold (4.9; 1.04-23.2) greater risk of death. Underexpression of SHP2 was associated with a shorter disease-free survival interval (DFS) and overall survival (OS) (p=0.055). Overexpression of FGFR2b or SHH was associated with longer DFS and OS (p<0.05; for SHH, p=0.07 for OS). Combining markers did not provide any additional information. Figure 1



      Conclusion:
      Underexpression of SFTPC in tumour samples was independently associated with worse prognosis.

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      P1.05-005 - Programmed Death-Ligand 1 (PD-L1) in Resected Lung Adenocarcinomas (LA) in a University Hospital (ID 6101)

      14:30 - 14:30  |  Author(s): M. Álvarez, S. Vicente, A. Cebollero, I. Pajares, E. Millastre, J. Hernando, T. Puértolas, R. Álvarez, M.Á. Artal Cortés, A. Antón

      • Abstract

      Background:
      The role of monoclonal antibodies inhibiting of the Programmed Death-1 and its ligand (PD-1/ PD-L1) pathway have been described in advanced disease. The knowledge of the role of this pathway in early stages of lung cancer is still limited. We assessed the incidence of PD-L1 expression in tumour cells of samples of resected lung adenocarcinomas and its prognostic role.

      Methods:
      A retrospective analysis of patients (p) with lung adenocarcinomas radically resected at our Institution between 2004 and 2011 has been conducted. PD-L1 was determined by Immunohistochemistry (SP263, Ventana® assay). A cut-off value of 5% of positive tumour cell was chosen.

      Results:
      112 tumours from 107 p were included. Median age was 62 years. 81% were male, 88% had exposure smoking, baseline performance status was 0 – I – II (62,5% - 26,8% - 10,7%) and pathological stage was I – II – III – IV (49,1% - 26,8% - 23,2% - 0,9%). Fourteen p (12%) expressed PD-L1>5%. They were mostly male (71%), smokers (93%), baseline performance status was 0 – 1 – 2 (64% - 29% - 7%), the most common histological subtype was poorly differentiated adenocarcinoma (64%) and pathological stage was I – II – III (28% - 21% - 50%). One p (7,7%) harboured EGFR mutation, none (0%) were ALK positive and 6 p (46,2%) had a K-RAS mutation. With a follow-up of 52 months median disease free survival (DFS) was 49 months and overall survival (OS) 58 months. Median DFS was shorter in p with expression of PD-L1 (27 months) that in negative tumours (49 months) (p=0,45). Median OS showed a similar pattern (32 vs 66 months respectively) also favouring PD-L1 negative p (p=0,05).

      Conclusion:
      In our series, patients with resected adenocarcinomas expressing PD-L1 in >5% of cells showed a worse disease free and overall survival than patients without such expression.

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      P1.05-006 - Identification of miRNAs and mRNAs Associated with Metastasis in Early-Stage Non-Small Cell Lung Cancer (NSCLC) (ID 5829)

      14:30 - 14:30  |  Author(s): S. Tam, N. Pham, S. Sakashita, E. Kaufman, M. Pintilie, N. Liu, G. Liu, F. Shepherd, M.S. Tsao

      • Abstract

      Background:
      Early-stage NSCLC patients whose tumours can form primary xenografts (XG) in immune deficient mice have significantly shorter disease-free survival and are at a greater risk of early metastasis compared with patients whose tumours do not form xenografts (non-XG). Genomic and proteomic characterization of XG and non-XG-forming primary patient tumours may reveal clinically relevant genetic aberrations that are associated with early metastasis.

      Methods:
      miRNA-seq and RNA-seq data of 100 early-stage NSCLC patients with known engraftment status were acquired. The cohort includes 62% adenocarcinoma (ADC) and 38% squamous cell carcinoma (SQCC). Least absolute shrinkage and selection operator (LASSO) was applied to identify features associated with XG status using integrated miRNA and mRNA abundance profiles. Gene Ontology (GO) annotation was subsequently performed to elucidate biological processes that may be altered between the two patient groups.

      Results:
      Using miRNA and mRNA data alone, ADC patients were classified as XG and non-XG with 88.7% and 95.2% accuracy. The integration of these two data types classified the patients with 100% accuracy using 20 features (7 miRNAs and 13 mRNAs). While less is known regarding the roles of the identified miRNAs in lung ADC, several of the genes have been suggested to affect the metastatic ability of lung cancer cells; these include PITX1, GPNMB and KRT14. In SQCC, both the miRNA and mRNA data alone and the integrated profiles were able to classify patients into XG and non-XG-forming groups with 100% accuracy. However, the roles of the selected features (1 miRNA and 11 mRNAs) in the metastasis of SQCC are not well defined. GO annotation of the identified mRNAs in ADC revealed enrichment of biological processes related to B cell differentiation, wound healing and regulation of the immune response and signalling pathway, while catabolic and metabolic processes were enriched in SQ.

      Conclusion:
      The use of single-dimensional data to classify patients into different prognostic groups may not be sufficient in the presence of heterogeneous patient populations. Integrative analysis of multi-omic data can provide greater insights into clinically relevant genetic aberrations, which can be used to improve the molecular classification of NSCLC.

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      P1.05-007 - Analysis of RNA Sequencing Data along with PET SUV-max Can Discover Novel Gene Sets Which Can Predict Surgical Outcome of NSCLC (ID 5404)

      14:30 - 14:30  |  Author(s): Y. Hwang, Y.J. Jung, S.B. Lee, Y.H. Kim, K. Hyun, S. Park, H.J. Lee, I.K. Park, C.H. Kang, Y.T. Kim

      • Abstract
      • Slides

      Background:
      Recent development of NGS technology provides a better understanding on the molecular mechanism of the cancer. A comprehensive analysis algorism of NGS data along with various clinical phenotypes and clinical outcome may lead discovery of novel molecular mechanism of cancer biology. It has been suggested that the preoperative SUV of the PET-CT is related to the aggressiveness of the cancer. We hypothesized that the identification of genes that were related to the PET SUV-max would lead a discovery of novel genes which could predict long-term outcomes of patients of non-small cell lung cancer.

      Methods:
      We set a 51 adenocarcinoma and a 101 squamous cell carcinoma patients cohort, whose cancer and normal tissue whole transcriptome sequencing data were available. The RNA sequencing fastq files were aligned on the reference genome (http://grch37.ensembl.org/) and the differential expressions were analyzed using tuxedo protocol (TopHat 2.0, Cufflinks 2.2.1). Visualizations of differential expressions were presented with CummeRbund R-package.

      Results:
      Based on the preoperative PET-CT SUV-max, patients were classified as "Low" (SUV≤3), "Intermediate" (SUV 3-10), and "High" (SUV>10) groups. Using the tuxedo RNA analysis tools, we selected 31 genes which showed significantly different expression of RNAs between "Low" and "High" groups in adenocarcinoma and between “Intermediate” and “High” groups in squamous cell carcinoma. By comparing expression levels of those 31 genes according to the development of recurrence, we could identify two sets of genes (COL2A1, BPIFB2, RYR2, F7, HPX, AC022596.6 and H19 for adenocarcinoma; BPIFB2, AC022596.6, ANKRD18B, GCLC, HHIPL2, COL2A1 and DPP10 for squamous cell carcinoma) which were related to the development of recurrence. Figure 1



      Conclusion:
      Our results suggest that it is necessary to set a comprehensive analysis algorithm of the NGS data along with various clinical phenotypes of the patients, for the discovery of clinically meaningful molecular mechanisms of the cancer.

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      P1.05-008 - Detection of EGFR Mutations in Pulmonary Vein and Peripheral Blood Plasma Cell-Free DNA for Analysis of Surgical Treatment in Early-Stage NSCLC (ID 4372)

      14:30 - 14:30  |  Author(s): C. Yang, D. Yang, B. Dong, X. Meng, Y. Liu

      • Abstract

      Background:
      Free circulating DNA (cfDNA) has been known for several decades. These small DNA fragments are released into the circulation from nucleated cells through necrosis, apoptosis and/or active secretion. Use of blood plasma cfDNA to detect mutations has spread widely as a form of liquid biopsy. However, it remains unclear which types of samples are appropriate for detecting tumor cell-free DNA in these biopsies. We compared the abundance of EGFR mutations in peripheral blood and pulmonary vein plasma cell-free DNA from patients with early-stage NSCLC.

      Methods:
      In this study, primary lung tumors and matched presurgery peripheral blood plasma samples and intraoperative pulmonary vein blood samples were collected from patients with early-stage NSCLC (n=89). We detected EGFR mutations (exon19 deletion, L858R, G719X, S768I and T790M) in 89 early-stage lung cancer samples using droplet digital PCR (ddPCR) and amplification refractory mutation system (ARMS). EGFR mutation abundance was determined and analyzed to reveal potential impact of samples types.

      Results:
      Presurgery peripheral blood plasma samples (n=89) and intraoperative pulmonary vein blood samples (n=89) matched tumor tissue samples (n=89) were analyzed for EGFR mutations using ddPCR and ARMS respectively. Of the 41 EGFR mutations detected in tumor tissues by ARMS, 37 of the corresponding mutations were detected in presurgical peripheral blood plasma cfDNA and intraoperative pulmonary vein cfDNA , whereas 4 mutations were found in plasma from patients with EGFR wild-type tumors (sensitivity 80.49%, specificity 91.67%).Free circulating DNA was identified in the plasma of pulmonary venous blood and peripheral blood in thirty-seven patients. Of the 37 cases of EGFR mutation positive plasma samples, ddPCR identified a higher mutation abundance of pulmonary venous samples than peripheral blood (1.05% vs. 0.12%, p = 0.007).

      Conclusion:
      This study demonstrates accurate mutation detection in plasma using ddPCR, and that cfDNA can be detected in presurgical peripheral blood and intraoperative pulmonary vein in patients with early-stage lung cancer. Our results suggest that pulmonary venous blood can be obtained from the resected specimen, thus facilitating the detection of cfDNA. Future studies can now address whether monitoring the change of EGFR mutation abundance after surgery identifies patients at risk for recurrence, which could guide therapy decisions for individual NSCLC patients.

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      P1.05-009 - Clinical Value of Circulating Tumor Cell in the Differential Diagnosis of Solitary Pulmonary Nodule (ID 4977)

      14:30 - 14:30  |  Author(s): L. Wang, L. Qiao, W. Yu, J. Lou

      • Abstract
      • Slides

      Background:
      The diagnosis of lung cancer suffers from the lack of accurate, noninvasive and early diagnostic tests. Low-dose helical computed tomography (LDCT) identifies millions of solitary pulmonary nodules (SPN) annually, many of which are undiagnosed as either malignant or benign. When removed surgically, 18%-25% of the nodules are benign, which leads to unnecessary treatment procedures for surgeons, stress and panic for patients and waste of medical resources for government. Therefore, an accurate noninvasive test that can discriminate benign SPN from malignant is urgently needed. Circulating tumor cells (CTCs) are cells shed from either primary or secondary tumors that migrate into the circulatory system and exist at the early stage of cancer. In recent years, CTC has become the research hotspot because of its great significance in the early diagnosis of cancer, disease monitoring, prognosis evaluation and guiding individualized treatment. In this study, we evaluated the application value of CTC in the differential diagnosis of SPN.

      Methods:
      Peripheral blood samples were collected from 134 patients with solitary pulmonary nodule in Shanghai Chest Hospital from September 2013 to January 2015, including 80 patients with malignant nodule and 54 with benign nodule. CTC levels of the above subjects were detected by LT-PCR (ligand-targeted polymerase chain reaction, LT-PCR) assay, and serum CEA and CYFRA21-1 were detected by flow fluorescence assay.

      Results:
      The CTC levels of malignant SPN patients were significantly higher than that of benign SPN patients (P<0.001). The area under the Receiver Operating Characteristic (ROC) curves of CTC and CEA were 0.817(95% CI: 0.743~0.891) and 0.613(95% CI: 0.508~0.718) respectively, while the CYFRA21-1 had no significant meaning in the differential diagnosis of SPN. The positive and negative predictive value (PPV and NPV) in differential diagnosis of SPN for CTC were 89% and 74%. Then the patients were divided into three groups according to the nodule diameter to evaluate the diagnostic value of CTC in SPN with different size. For SPN with diameter less than 8 mm, the PPV and NPV of CTC were 86% and 57%; For SPN with diameter between 8 mm and 20 mm, the PPV and NPV of CTC were 88% and 81%; For SPN with diameter greater than 20 mm, the PPV and NPV of CTC were 92% and 68%.

      Conclusion:
      Compared with traditional tumor marker, CTC detection could provide more clinical value in differential diagnosis of solitary pulmonary nodule.

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      P1.05-010 - Aberrant Promoter Methylation of ESR1 and CDH13 Gene Are an Independent Prognostic Marker in Surgically Resected Non-Small Cell Lung Cancer (ID 3840)

      14:30 - 14:30  |  Author(s): M. Kontic, D. Jovanovic, S. Bojic, H. Nelson, S. Ognjanovic

      • Abstract
      • Slides

      Background:
      Aberrant promoter hypermethylation of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine the correlation between the aberrant promoter methylation of multiple genes and 5-year survival rate in patients with nonsmall cell lung carcinoma (NSCLC) after a surgical resection.

      Methods:
      Primary tumor samples (n=65) and corresponding nonmalignant lung tissues (n=65) were obtained from NSCLC patients who underwent curative surgery. The methylation status of seven genes (SOX1, RASSF1A, HOXA9, CDH13, MGMT, ESR1 i DAPK) was quantified using bisulfite pyrosequencing. Cox proportional hazards models were used to analyze the associations between gene methylation status and overall patient survival.

      Results:
      In the Cox proportional hazards model, ESR1 methylation in tumor tissue was associated with significantly poorer survival, with hazard ratio of 1.09 (95% confidence interval 1.02-1.16, p=0.01). This effect was independent of TNM stage, which was also a predictor of survival. We also found that aberrant methylation in CDH13 gene in tumor tissue was associated with inferior survival in surgically resected NSCLC pateints. In contrast, there were no significant survival differences noted between the methylation-positive and methylation-negative tumors for the other genes tested.

      Conclusion:
      Our study shows that aberrant promoter methylation of ESR1 and CDH13 genes may be associated with inferior survival, showing promise as a useful prognostic biomarker in patients with NSCLC.

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      P1.05-011 - Comparative Analysis of TTF-1 Copy Number Alterations and Protein Expression in Patients with Non-Small Cell Lung Cancer (ID 5133)

      14:30 - 14:30  |  Author(s): K. Yoshimura, Y. Inoue, N. Kurabe, T. Kahyo, A. Kawase, M. Tanahashi, H. Ogawa, N. Inui, K. Funai, K. Shinmura, H. Niwa, T. Suda, H. Sugimura

      • Abstract
      • Slides

      Background:
      TTF-1 (also known as NKX2-1) is located at chromosome 14q13.3. TTF-1 is a master regulator for the development of normal lung, and is also both a lineage oncogene and a suppressor gene in non-small cell lung cancer (NSCLC). TTF-1 expression is associated with a favorable prognosis. In contrast, the clinical significance of increased TTF-1 gene dosage has yet to be fully elucidated. We explored the relationship of TTF-1 copy number alterations with TTF-1 protein expression as well as patients’ prognoses in a relatively large cohort.

      Methods:
      We assessed TTF-1 gene copy number and protein expression in microarrayed 636 NSCLC, including 421 adenocarcinomas and 173 squamous cell carcinomas (SCCs), and 42 other histologies, using fluorescent in situ hybridization and immunohistochemistry. TTF-1 copy number alterations were divided into three categories; amplification (TTF-1/CEP14 ≥2), polysomy (TTF-1/CEP14 <2 and TTF-1 signals ≥4 copies per nucleus), and disomy (the others). Their associations with clinical data were retrospectively analyzed.

      Results:
      Among the entire cohort, TTF-1 amplification and polysomy were observed in 5.6% (36/636) and 8.3% (53/636), respectively. Tumors with copy number alterations (amplification and polysomy) were detected in 14.5% (61/421) among adenocarcinomas, 9.3% (17/173) among squamous cell carcinomas, and 26.2% (11/42) among other histologies (P = 0.012). TTF-1 expression was almost exclusively observed in adenocarcinomas (P < 0.001). In the adenocarcinoma cohort, the frequency was 6.7% (28/421) for TTF-1 amplification and 7.8% (33/421) for polysomy. TTF-1 positivity was 84.8% (357/421). A multivariate Cox hazards model analysis demonstrated that TTF-1 amplification was an independent worse prognostic factor (hazard ratio (HR), 3.84; 95% confidence interval (CI), 2.18-6.71) for overall survival, but TTF-1 expression was adversely an independent better prognostic factor (HR, 0.49; 95% CI, 0.28-0.85). In the SCC cohort, there were few cases of TTF-1 amplification (1.7%, 3/173), polysomy (8.1%, 14/173), and TTF-1 expression (3.7%, 10/273). Interestingly, any case of adenocarcinoma and SCC with TTF-1 amplification harbored positive TTF-1 expression.

      Conclusion:
      Both TTF-1 amplification and TTF-1 expression were more common in adenocarcinoma. However, they had distinct prognostic roles: TTF-1 amplification was an independent poor prognostic factor in adenocarcinoma, whereas TTF-1 expression was a favorable prognostic factor.

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      P1.05-012 - The Impact of EGFR Mutations on the Prognosis of Patients with Resected Stage I Lung Adenocarcinoma (ID 4753)

      14:30 - 14:30  |  Author(s): J. Kitamura, L.F. Tapias, D.J. Mathisen, M. Lanuti

      • Abstract
      • Slides

      Background:
      Recent studies have reported that epidermal growth factor receptor (EGFR) mutations are potential predictive factors for prognosis as well as for the response to the treatment of EGFR tyrosine kinase inhibitors in patients with advanced lung adenocarcinoma. However, the prognostic role of EGFR mutations has not been well studied in treatment-naïve stage I lung adenocarcinoma. In this study, we evaluated the pure prognostic value of EGFR mutations in patients with stage I lung adenocarcinoma who underwent complete resection.

      Methods:
      We retrospectively reviewed the medical records of treatment-naïve patients who underwent complete resection of stage I lung adenocarcinoma between January 2008 and December 2014. Mutation testing was performed on resected tumor using multiplex (SNaP Shot) polymerase chain reaction assay. Survival curves were generated with Kaplan-Meier method and compared using a log-rank test. A Cox proportional hazards model was used for multivariate analysis.

      Results:
      Of 583 patients, 127 (21.8%) patients had EGFR-mutations. Median follow up period after surgery was 36.9 months (range: 0.1-95.8). Patients with EGFR mutations showed a better 5-year recurrence-free survival (RFS, 89.4% vs 77.8%, p=0.0053) and 5-year overall survival (OS, 99.1% vs 87.7%, p=0.0044) than those with EGFR wild-type (Figure). Multivariate analysis demonstrated that the presence of EGFR mutation (HR=0.4875, p=0.0388) and pathological stage 0 or IA (HR=0.4590, p=0.0016) were independent prognostic factors for better RFS. The presence of EGFR mutations (HR=0.1878, p=0.0443), lobar resection (HR=0.4076, p=0.0123), and ECOG performance status 0 (HR=0.4061, p=0.0259) were independent prognostic factors for better OS. Figure 1



      Conclusion:
      Patients harboring an EGFR-mutation in completely resected stage I lung adenocarcinoma had a much improved prognosis compared to those patients whose tumors expressed EGFR wild-type. The presence of an EGFR mutation was a significant positive prognostic factor in this cohort.

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      P1.05-013 - Lung Tumorspheres as a Platform for Testing New Therapeutic Strategies in Non-Small Cell Lung Cancer (ID 4848)

      14:30 - 14:30  |  Author(s): E. Munera Maravilla, A. Herreros Pomares, S. Calabuig Fariñas, E. Escorihuela, E. Duréndez, A.I. Martinez, M. Martorell, A. Blasco, E. Jantus-Lewintre, C. Camps

      • Abstract

      Background:
      Resistance to treatment is one of the causes influencing the high mortality of lung cancer. This feature seems to be linked to a subpopulation known as Cancer Stem Cells (CSCs), which are able to grow as spheroids (suspension culture). The aim of the study was to obtain tumorspheres from lung cancer cell lines and to use them as an in vitro platform for drug screening.

      Methods:
      Cells from lung cancer cell lines (A549, H1650, PC9, H460 and H358) were grown in monolayer and as spheroids. Cultured cells were used: (i) to compare the cytotoxic effect of anticancer drugs in adherent vs lung-tumorspheres (ii) to perform a high-throughput screening with a commercial chemical library (Prestwick) and (iii) to analyze the citotoxicity of specific inhibitors of Wnt, Hedgehog and Notch pathways. Briefly, cells were plated at the desired density in 200 μl of medium in 96-well plates and compounds were added at 4 different concentrations (n=3). Cell viability was measured after 48 and 72h, using MTS Assay. Cell viability was normalized to the respective mock-treated control cells and presented as percentage of control.

      Results:
      Cells cultured in serum-free conditions were able to form spheroids, such as stem-like cells. Under these culture conditions, classical anticancer drugs (cisplatin, paclitaxel, vinorelbine and pemetrexed) exhibited mild or null cytotoxic effects on A549, H1650, PC9, H460 and H358 spheroids. Moreover, we performed a high-throughput screening with Prestwick library and remarkably, three compounds reduced the number of viable cancer cells. As regards ‘stemness’ inhibitors, Wnt (IWP2 and XAV939) and Hedgehog inhibitors (Vismodegib) show high activity against tumorspheres (p<0.05), suggesting them as possible therapeutic strategies in NSCLC

      Conclusion:
      Our data suggest that lung-tumorspheres showed resistance to classical anticancer drugs, strengthening its possible use as a short-term culture platform for a simple, and cost- effective screening to investigate novel therapeutic approaches. In this setting, some compounds were identified as promising therapeutic agents on lung tumorspheres, but confirmatory data are still necessary. This project was supported by [RD12/0036/0025] from RTICC, SEOM 2012, [PI12-02838 and PI15-00753] from ISCIII

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      P1.05-014 - Stemness Gene Expression Profile of Tumorspheres from Non-Small Cell Lung Cancer (ID 4748)

      14:30 - 14:30  |  Author(s): A. Herreros Pomares, S. Calabuig Fariñas, E. Munera Maravilla, A. Blasco, A.I. Martinez, E. García Del Olmo, E. Jantus-Lewintre, C. Camps

      • Abstract

      Background:
      Lung cancer features like chemoresistance, tumor progression or metastasis have consolidated lung cancer as the first cause of death cancer-related worldwide. Cancer stem cells (CSCs) are small subpopulations of stem-like cells that have been associated to these traits, constituting a promising target, but remaining largely unknown. In this study, we isolated CSCs from lung cancer cell lines and tumor tissue of resectable NSCLC patients using a sphere-forming assay and analyzed their gene expression profile.

      Methods:
      The investigation was carried out on cells from seven NSCLC tumor samples and six cell lines (H1650, H1993, H358, A549, PC9, H460) grown in monolayer and as spheroids. The expression of CSC-markers (CD133, EPCAM1, ALDH1A1, CD166, ABCG2, CD44, MUC1, BMI1, THY1), pluripotency promoters (KLF4, OCT4, NANOG, SOX2, MYC, CCND1), cell cycle regulators (CDKN1A, CDKN2A, MDM2, WEE1), invasiveness-related genes (CDH1, VIM, SNAI1, MMP2, MMP9, CEACAM5, ITGA2, ITGA6, ITGB1), Notch pathway (NOTCH1, NOTCH2, NOTCH3, JAG1, DLL1, DLL4, NUMB, HEY1, HES1), Wnt pathway (WNT1, WNT2, WNT3, WNT5A, CTNBB1, DKK1, FZD7) and Hedgehog pathway (SMO, PTCH1, SHH, GLI1) components were analyzed by quantitative real time PCR (RTqPCR). ACTB, CDKN1B and GUSB genes were used as housekeeping controls for the relative expression calculation.

      Results:
      Lungspheres showed significantly higher expression of the CSC-markers EPCAM1, CD44 and ALDH1A1 (p= 0.028, p= 0.021 and p= 0.043, respectively) and the quiescence promoter CDKN1A (p= 0.021) in comparison with their paired-monolayer cells. The epithelial to mesenquimal transition (EMT) inducer, SNAI1, as well as integrins ITGA2, ITGA6 and ITGB1 were overexpressed in tumorspheres (p= 0.011, p= 0.018, p= 0.016 and p= 0.013, respectively). Regarding the Notch signaling pathway, most ligands (JAG1 and DLL4) and receptors (NOTCH1 and NOTCH2) analyzed had increased expression in spheroids (p= 0.021, p= 0.028, p= 0.038 and p= 0.036, respectively). In Wnt pathway, we found higher expression levels of WNT3, CTNBB1 and GSK3B (p= 0.021, p= 0.008 and p= 0.021, respectively) in tumorspheres. No significant results were found for the rest of genes analyzed.

      Conclusion:
      Lung cancer spheroids from primary tumors and cell lines showed increased levels of genes related to CSCs properties. Genes belonging to Notch and Wnt signaling pathways were found to be more expressed in tumorspheres, suggesting that these pathways could be interesting lung-CSC targets. This work was supported in part, by grants RD12/0036/0025 from RTICC, and PI12-02838/PI15-0753 from ISCIII.

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      P1.05-015 - Genomic Characterisation of Non-Small Cell Lung Cancer in an Australian Population (ID 4052)

      14:30 - 14:30  |  Author(s): B. Parris, D. Irwin, M. Daniels, L. Franz, F. Goh, L. Passmore, E. McCaul, D. Courtney, R. Bowman, I. Yang, K. Fong

      • Abstract

      Background:
      Lung cancer is a heterogeneous disease with poor prognosis. Genomic variants may predict sensitivity to targeted drug therapies or assist in prognostication. We sought to determine the frequency of driver mutations and gene rearrangements in non-small cell lung cancer (NSCLC) and evaluate the feasibility of the MassARRAY system for multiplexed mutational profiling.

      Methods:
      A cohort study of 419 fresh-frozen NSCLC tumours was performed (AC, n=370; SCC, n=39; ASC, n=7; LCC, n=3). High-throughput and multiplexed mutational profiling was performed using the MassARRAY genotyping system (Agena Bioscience) (n=419). The OncoFOCUS+KIT panel was used for detecting genomic variants in EGFR, BRAF, KRAS, NRAS and KIT (n=413) and the LungFusion panel for fusion genes involving ALK, RET and ROS1 (n=371). Clinico-pathological associations were evaluated using Fisher’s exact test for categorical data, and T test for continuous data. A p-value of <0.05 (two-tailed) was considered statistically significant.

      Results:
      At least one genomic variant was detected in 196 (46.8%) cases (n=419). EGFR mutations were identified in 42 cases (10.2%), KRAS in 133 (32.3%), BRAF in 11 (2.7%), NRAS in 4 (1.0%) and no KIT mutations were detected. Gene rearrangements involving ALK, RET and ROS1 were identified in 2 (0.5%), 1 (0.3%) and 5 (1.3%) cases respectively. Based on current clinical guidelines for NSCLC, 28 patients would qualify for tyrosine kinase inhibitor therapy, and 4 for targeted therapy available for other cancers (BRAF V600E). EGFR mutations were significantly associated with adenocarcinoma histology and female never smokers (p<0.001) and KRAS mutations predominated in smokers (p<0.001).

      Conclusion:
      Driver mutations were detected in 46.8% of NSCLC cases resected at TPCH. Rapid, multiplexed mutation testing can guide treatment as well as assist in patient stratification for clinical trials.

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      P1.05-016 - Circulating BARD1 Antibodies for Early Detection of Lung Cancer (ID 4193)

      14:30 - 14:30  |  Author(s): I. Irminger-Finger, M. Pilyugin, A. Bianco, B. Hegedus, S. Sardy, P. Descloux, G. Laurent

      • Abstract

      Background:
      In a study of more than 100 NSCLC cases we previously showed that the expression of BARD1 isoforms is correlated with poor patient survival. BARD1 is a tumor suppressor acting with BRCA1 as ubiquitin ligase. BARD1 has also functions in mitosis and poly(ADP)-ribose signaling for DNA repair. In cancer cells BARD1 isoforms are generated by alternative splicing. SNP affecting splicing and cancer predisposition were identified in neuroblastoma. The alternatively spliced isoforms lack tumor suppressor functions and act as oncogenes. As the domain composition of cancer-associated isoforms predicts altered tertiary structures, we investigated whether BARD1 isoforms act as cancer antigens.

      Methods:
      ELISA assays were performed to detect antibodies generated against BARD1 isoforms in the serum of lung cancer patients. We used BARD1 protein fragments and short peptides for capturing autoimmune antibodies. Using fitted Lasso logistic regression methods, we developed an algorithm for the prediction of lung cancer based on a blood test for detection of BARD1 antibodies.

      Results:
      Modeling values from 200 samples, shows a distinction of lung cancer and healthy controls with high sensitivity and specificity (AUC=0.961; Figure 1). Splitting the samples randomly and repeatedly into training sets and validation sets, confirmed an average AUC=0.964 for the training sets and AUC=0.861 for the validation sets. ROC curves for early and late stage lung cancers showed no difference in their AUCs. The BARD1 lung cancer test is highly specific and does not cross-react with other cancers.

      Conclusion:
      Lung cancer has a very long latent phase and is often discovered at an advanced and untreatable stage. Currently the detection by low dose CT scan is relatively expensive and not very specific. Therefore a blood test, such as the BARD1 test could i) help to detect cancers earlier, in particular by screening of risk groups, and ii) become a diagnostic aid in combination with CT scan.Figure 1



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      P1.05-017 - The Prognostic Impact of EGFR, KRAS and TP53 Somatic Mutations in Curatively Resected Early-Stage Lung Adenocarcinomas (ID 4527)

      14:30 - 14:30  |  Author(s): B.E. Gould Rothberg, R. Das, L.K. Jackson, H. Lazowski, Y. Bai, D. O'Neill, S.H. Roberts, J.M. Rothberg, R. Herbst, A.W. Kim, D. Boffa, D. Rimm, F. Detterbeck, L.T. Tanoue

      • Abstract

      Background:
      As the 5-year survival among individuals undergoing curative-intent resection for early-stage lung cancer approaches 50%, identification of prognostic biomarkers useful for risk stratification is a priority. While somatic mutation profiling drives treatment choice in advanced disease, its usefulness among early-stage patients is not well-established.

      Methods:
      From May 2011 through December 2014, The Yale Lung Cancer Biorepository enrolled 192 individuals who underwent curative-intent complete resection for Stage IA-IIIA adenocarcinoma. Demographics and lifestyle choices were ascertained by interview using validated questionnaires. Pathologic characterization of index tumors, including CLIA Laboratory-assayed EGFR/KRAS status, was extracted from the medical record. A custom targeted resequencing panel covering all coding exons from 93 lung adenocarcinoma-related genes was designed. Buffy coat-derived germline DNA and tumor DNA, extracted from the FFPE surgical specimen, were sequenced on the Ion Torrent platform with >90% of the assayed amplicons achieving >30x coverage in both tumor and germline from each case. Somatic nonsynonymous tumor variants were identified using the Torrent Variant Caller. Bivariate associations were evaluated by Chi-square or ANOVA. Survival analyses were conducted using Cox modeling.

      Results:
      181/192 (94.3%) participants underwent EGFR/KRAS somatic mutation profiling with 43 EGFR mutations and 71 KRAS mutations detected. EGFR mutations were more common among well- and moderately-differentiated lesions (p=0.06) and among never or former light smokers (p=0.0007). Seventy-two percent of EGFR and 81.7% of KRAS mutations were found among female patients (p=0.0008). The joint distribution between smoking and gender favored EGFR mutations among female never/former smokers, KRAS mutations among female ever-smokers and EGFR/KRAS wild-type status among male ever-smokers (p=0.0002). After adjustment for AJCC 7[th] edition Tstage, Nstage and presence of lymphovascular invasion, KRAS mutations (HR=2.14; 95% CI:1.04-4.43; p=0.04) but not EGFR mutations (p=0.63) were prognostic for poorer disease-free survival. Targeted resequencing data is available on 148 cases. The nonsynonymous mutation burden ranged from 0-7 with 84% of cases having ≤3. In addition to KRAS and EGFR, frequent mutations were noted in p53 (n=40; 27.0%), STK11 (n=10; 6.8%) and PIK3CA (n=7; 4.7%) with 4 genes mutated in 6 cases. TP53 mutations were associated with high nonsynonymous mutation burden (p<0.0001) and the joint distribution with EGFR/KRAS status revealed the highest burden among KRAS[mut]/TP53[mut] (3.94±1.57) followed by EGFR[mut]/TP53[mut] (3.07±1.61) and EGFR_KRAS[wt]/TP53[mut] (2.20±1.40; p<0.0001).

      Conclusion:
      KRAS[mut], like EGFR[mut], is associated with female gender but only KRAS[mut] is prognostic following curative-intent resection. Elevated mutation burden observed among KRAS[mut]/TP53[mut] may offer novel therapeutic options following recurrence.

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      P1.05-018 - LncRNA16 is a Potential Biomarker for Early-Stage Lung Cancer That Promotes Cell Proliferation by Regulating the Cell Cycle (ID 4693)

      14:30 - 14:30  |  Author(s): N. Wu, H. Zhu, L. Zhang, Y. Yang, X. Wang

      • Abstract
      • Slides

      Background:
      Early diagnosis of lung cancer greatly reduces mortality; however, the lack of suitable plasma biomarkers presents a major obstacle. Recent studies showed that long noncoding RNAs (lncRNAs) play important roles in cancer initiation and development.

      Methods:
      Here, we identify differential expressed lncRNAs by using custom designed microarray on 20 lung cancer samples and evaluate the expression by Real-time PCR (qRT-PCR) on 118 lung cancer samples.The role of lncRNA16 in lung cancer was studied in vitro and in vivo, utilizing the lung cancer cell line PC9 ,A549 and xenograft mouse models.

      Results:
      lncRNA16 (ENST00000539303) expression level was highly in lung cancer (80/118) and in plasma (32/42) of lung cancer patients. In early stage, lncRNA16 expression levels were significantly higher compare to that in adjacent matched normal tissues (Figure 1C-1F) . Importantly, this increase was mirrored in plasma samples of early stage lung cancer patients (Figure 2A) . Our study reveals that knockdown of lncRNA16 inhibited proliferation of PC9 cells in vitro and also inhibited tumor growth in xenograft mouse models. Specifically, we show that lncRNA16 promotes G2/M transition through regulating cyclin B1 transcription.

      Conclusion:
      In conclusion, lncRNA16 was identified as a potential biomarker for lung cancer diagnosis, as it displayed significantly elevated levels in cancer patient over baseline. Furthermore, we showed that the false-negative rate is significantly lower compared to markers those widely used for lung cancer assessment.

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      P1.05-019 - Two Inflammatory Biomarkers MDC/CCL22 and BLC/CXCL13 Are Independently Associated with the Significant Risk of Early Stage Lung Adenocarcinoma (ID 3966)

      14:30 - 14:30  |  Author(s): Y. Zhang, K. Yu, S. Hu, Y. Lou, C. Liu, J. Xu, R. Li, X. Zhang, H. Wang, B. Han

      • Abstract
      • Slides

      Background:
      This prospective study was designed to investigate the association between multiple inflammatory biomarkers in circulation and the risk for early stage lung adenocarcinoma.

      Methods:
      We measured 10 inflammatory biomarkers in 228 early stage lung adenocarcinoma patients and 228 age, sex and smoking matched healthy controls by using the Luminex bead-based assay.

      Results:
      Only two biomarkers were significantly associated with early stage lung adenocarcinoma risk after Bonferroni correction: the multivariate odd ratio or OR (95% confidence interval or CI) was 0.29 (0.16-0.53) for MDC/CCL22 (P<0.0001) and 4.17 (2.23-7.79) for BLC /CXCL13 (P<0.0001) for the comparison of 4[th] quartile with 1[st] quartile. When analysis was restricted to never smokers (196 patients/196 controls), MDC/CCL22 and BLC/CXCL13 were still significantly associated with early stage lung adenocarcinoma risk (OR; 95% CI; P: 0.37; 0.21-0.66; P<0.0001 for MDC/CCL22 and 2.78; 1.48-5.22; P =0.001 for BLC/CXCL13). Additionally, significance persisted after restricting analysis to 159 stage IA lung adenocarcinoma patients and 159 matched controls for MDC/CCL22 (OR; 95% CI; P: 0.37; 0.21-0.66; <0.0001) and BLC/CXCL13 (2.78; 1.48-5.22). Furthermore, elevated BLC/CXCL13 was associated with a 2.90-fold (95% CI: 1.03-8.17; P=0.037) increased risk of subcentimeter lung adenocarcinoma, and there was an increasing trend for BLC/CXCL13 with the progression of subcentimeter lung adenocarcinoma.

      Conclusion:
      Our findings demonstrated that MDC/CCL22 and BLC/CXCL13 were independently associated with the significant risk of early stage lung adenocarcinoma, and this association persisted even in non-smokers and in stage IA patients. Moreover, BLC/CXCL13 was identified to play a carcinogenic role in the progression of lung adenocarcinoma.

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      P1.05-020 - Opposing Prognostic Roles of CD73 and A2A Adenosine Receptor in Non-Small-Cell Lung Cancer (ID 5139)

      14:30 - 14:30  |  Author(s): Y. Inoue, K. Yoshimura, N. Kurabe, T. Kahyo, A. Kawase, M. Tanahashi, H. Ogawa, N. Inui, K. Funai, K. Shinmura, H. Niwa, T. Suda, H. Sugimura

      • Abstract
      • Slides

      Background:
      CD73 (otherwise known as ecto-5’-nucleotidase) is an important molecule in the adenosine pathway because it generates adenosine by enzymatically dephosphorylating extracellular AMP, which results in immunosuppressed niche within the tumor microenvironment. A2A adenosine receptor (A2AR) acts as a predominant receptor for adenosine in immune cells and can also be expressed in lung tumor cells. However, the clinical impact of the adenosine pathway in non-small-cell lung cancer (NSCLC) has yet to be uncovered, although the pathway has been shown to have a pivotal role in the regulation of anti-tumor immunity and is considered as one of the promising future treatment targets.

      Methods:
      We investigated CD73 and A2AR protein expression profiles using immunohistochemistry in tissue microarrays containing 642 resected NSCLC specimens. The expression levels were assessed using the H-score method that ranged from 0 to 300, and cutoffs were determined using the minimum P-value method for overall survival (OS). The associations between their expression levels and clinicopathological and molecular characteristics as well as patients’ prognoses were retrospectively analyzed.

      Results:
      The median age of patients was 68 years old (range, 23–88) and 440 (68.5%) patients were male. 438 (68.2%) patients had smoking history and 420 (65.4%) patients had adenocarcinoma histology. Significantly higher expression of both CD73 and A2AR was observed in female than male, in never smokers than ever smokers, and in adenocarcinomas than squamous cell carcinomas. Among adenocarcinomas, both high CD73 and A2AR expression were significantly associated with TTF-1 positivity and EGFR mutations. ALK-positive adenocarcinomas showed significantly higher expression levels of CD73 than ALK-negative tumors. High CD73 expression was an independent indicator of a poor prognosis for NSCLC patients in multivariate Cox regression analyses for OS (hazard ratio (HR), 2.19; 95% confidence interval (CI), 1.38–3.47) and disease-specific survival (DSS) (HR, 2.97; 95% CI, 1.78–4.95). Contrary, high A2AR expression was an independent favorable predictor of prognosis for OS (HR, 0.69; 95% CI, 0.49–0.97) and DSS (HR, 0.51; 95% CI, 0.33–0.79). Among adenocarcinomas, high CD73 expression was an independent poor prognostic marker for OS (HR, 2.73; 95% CI, 1.61–4.63) and DSS (HR, 4.57; 95% CI, 2.54–8.23), whereas high A2AR expression was an independent favorable prognostic marker for DSS (HR, 0.56; 95% CI, 0.32–0.98).

      Conclusion:
      Both CD73 and A2AR expression was associated with TTF-1-positive and EGFR-mutant adenocarcinoma. Nonetheless, they had opposing prognostic significance in resected NSCLC.

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      P1.05-021 - circRNAs: Potential Novel Biomarkers for the Early Detection of Lung Cancer (ID 5020)

      14:30 - 14:30  |  Author(s): R. Lin, G. Reid, L. Mutti, A.W. Ryan, S. Nicholson, N. Leonard, V. Young, R. Ryan, S.P. Finn, S. Cuffe, S.G. Gray

      • Abstract

      Background:
      Lung cancer is the leading cancer killer globally. Cancers such as colon, breast, and prostate all have relatively reliable early detection tests. In contrast, lung cancer does not. If caught early, lung cancer has a much better prognosis. Non-invasive or minimally invasive tools to improve early detection of lung cancer represents a critical unmet need. Analysis of the human transcriptome indicates that a mere 2% of the genome corresponds to protein coding transcripts, yet ~ 75% of the genome is transcribed. It is now well established that these non-coding RNAs (ncRNAs) play important regulatory functions within the cell and their expression are often altered in cancer. Circular RNAs (circRNAs) are a species of ncRNAs. They are abundant, conserved and demonstrate cell-type specific expression patterns. Moreover, they are extremely stable with half-life’s greater than 48 hours, are resistant to degradation by RNA exonucleases, and have been shown to play important roles in cancer. Taken together these suggest that circRNAs could potentially be important biomarkers in early lung cancer diagnosis.

      Methods:
      Total RNAs isolated from a panel of matched normal/tumour NSCLC adenocarcinoma (Stage IA/IB) samples (n=6) were probed for circRNAs using the Arraystar circRNA microarray. Survival was assessed on linear mRNAs with associated circRNAs using KM-Plot.

      Results:
      Interim analysis of the data has identified n=206 circRNAs with a 2-fold difference in expression between their matched normal vs. tumour counterparts. Principal Component Analysis (PCA) demonstrated a clear separation of the samples (Tumour vs. Normal). Self-Organizing Maps (SOMs) analysis generated distinctive SOMS clusters of circRNAs, while associated linear pathway enrichment for microRNA and transcriptional binding motifs identified several additional potential networks. Moreover, an analysis of linear mRNAs associated with 10 circRNAs with altered expression in adenocarcinomas found that these mRNAs were linked to overall survival, and that the majority were adenocarcinoma specific.

      Conclusion:
      Altered levels of a number of circRNAs were associated with lung adenocarcinoma. A separate cohort of squamous cell carcinomas is currently being assessed for circRNAs. At present we are validating the expression of these circRNAs in a larger cohort of specimens, and assessing whether or not these are detectable in plasma/serum from the same individuals. Overall, circRNAs may represent novel potential biomarkers for the detection of NSCLC, and may provide additional critical basic knowledge regarding the development and biology of NSCLC.

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      P1.05-022 - Circulating Tumor Cell Isolation to Monitor NSCLC Patients over the Course of Treatment (ID 5975)

      14:30 - 14:30  |  Author(s): J. Herrmann, J. Pfannkuche, T. Lesser

      • Abstract
      • Slides

      Background:
      Compared to the investigation of the primary tumor or a biopsy taken from a distant metastasis, the investigation of a patient’s blood is relatively simple, less invasive and can be performed repeatedly. Thus, CTC (circulating tumor cells) investigation can be used as a real-time marker for staging, disease progression and therapy responsiveness. Cancer mortality might be reduced dramatically when the disease and its metastatic spread are detected and characterized early and can therefore be treated in an optimal fashion. The GILUPI CellCollector[® ]offers medical personnel at any point-of-care with the unique opportunity to enrich these CTCs in vivo. Here, we conducted a study using this effective device, to monitor CTC counts before as well as on different time points after surgery in non-small cell lung cancer (NSCLC) patients and further to characterize the CTCs on a molecular level.

      Methods:
      In total, 20 NSCLC patients (different stages) were screened for CTCs at different time points: preoperative, 30 minutes after tumor resection, 1 week postoperative as well as in 3-monthly intervals up to 2 years. In addition, 1 patient with a benign lung disease were included in this study.

      Results:
      CTCs were isolated independent from tumor stages and even in quite early cases CTCs could be detected. Moreover, a difference between CTC occurrence before and after surgery was seen and a correlation between CTC enumeration and clinical lack of recurrence could be detected.

      Conclusion:
      The GILUPI CellCollector® overcomes blood volume limitations of other diagnostic approaches and thereby increases the diagnostic sensitivity of CTC analysis. Future implementation into clinical practice may improve early detection, prognosis and therapy monitoring of cancer patients. Besides enumeration, captured CTCs are ready for molecular characterization and will help to establish more personalized treatment regiments since knowledge of the molecular make-up of the cancer cells to be defeated is an indispensable prerequisite to use targeted therapies efficiently.

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      P1.05-023 - Induction of Patient-Derived Xenograft Formation and Clinical Significance for PD-L1 in Lung Cancer Patients (ID 4668)

      14:30 - 14:30  |  Author(s): P. Zhang, Y. Ma, J. Si

      • Abstract
      • Slides

      Background:
      The relevance of programmed cell death ligand 1 (PD-L1) to patient-derived xenograft (PDX) formation and clinicopathological characteristics in early stage lung cancer was studied

      Methods:
      Cell counting kit-8 and flow cytometry were carried out to examine proliferation and apoptosis in PC9 and H520 cells transfected with siRNAs. Nod-scid mice were used to establish PDX. Immunohistochemistry was done to investigate PD-L1 expression in tumor tissues.

      Results:
      Proliferation was reduced and apoptosis was induced when PD-L1 was inhibited in the cells. Higher PD-L1 expression rate was observed in the primary tumors with PDX formation than in the tumors without PDX formation. Moreover, PD-L1 was found to be related to smoking, histological types, stages and overall survival in 209 of lung cancer patients.

      Conclusion:
      This study suggests that PD-L1 promotes PDX formation ability and is an independent prognostic marker for the early stage lung cancer patients.

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      P1.05-024 - Preoperative Neuron-Specific Enolase to Albumin Ratio is a Prognostic Biomarker for Patients with Operable Non-Small-Cell Lung Cancer (ID 5273)

      14:30 - 14:30  |  Author(s): H. Ren, X. Li, B. Zhang, Y. Zhang, L. Yang, G. Xiao, X. Gao, G. Huang, P. Wang, H. Wang, C. Yang, S. Qin

      • Abstract
      • Slides

      Background:
      Neuron-specific Enolase (NSE) is a widely used tumor biomarker in small-cell lung cancer (SCLC) diagnosis, and serum albumin (Alb) levels are commonly used as indicators of the nutritional status of cancer patients. However, the prognostic value of these markers in combination has not been examined. This study was designed to explore the value of the combination between NSE and Alb in non-small-cell lung cancer (NSCLC).

      Methods:
      We retrospectively evaluated the prognostic value of the preoperative NSE to albumin ratio (NAR) in 319 patients with operable NSCLC. We analyzed associations among the NAR, clinicopathological characteristics, and inflammatory biomarkers. Univariate and multivariate analyses were performed to identify the clinicopathological characteristics associated with OS. Furthermore, we compared the prognostic value of the NAR with other established prognostic indexes by evaluating the area under the curves (AUC).

      Results:
      The optimal NAR cutoff level was found to be 3.2×10[-7]. We found that a higher NAR was associated with more advanced TNM staged cancers (P=0.041) and higher tumor stage (P=0.011).The NAR was also associated with the inflammatory biomarker albumin/globulin ratio (AGR, P=0.032), but not the neutrophil/lymphocyte ratio (NLR, P=0.295) or platelet/lymphocyte ratio (PLR, P=0.260). In multivariate analyses, the NAR was an independent prognostic factor for NSCLC patients (P<0.001). The AUC of the NAR was higher than the NLR, PLR or AGR at 24 and 36 months of follow-up.

      Conclusion:
      The preoperative NAR might be an independent prognostic factor for patients with operable NSCLC, and a higher NAR indicates a poorer prognosis.

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      P1.05-025 - Prognostic Significance of Hepatitis B Virus to Stage IB Non-Small Cell Lung Cancer Patients in China (ID 5474)

      14:30 - 14:30  |  Author(s): S. Lu, Z. Li

      • Abstract

      Background:
      Hepatitis B virus (HBV) is considered to be a major cause of hepatocellular carcinoma. However, little is known about the role of chronic HBV infection in other malignancies. We aimed to determine HBV infection with other well established prognostic factors and performed multivariate survival analyses to evaluate its value in Chinese non-small cell lung cancer (NSCLC) patients.

      Methods:
      It is a retrospective evaluation of the impact of HBV infection status in 366 patients who underwent complete surgical resection for stage IB NSCLC NSCLC patients in Shanghai Chest Hospital from 1998 to 2008. All the patients were Shanghai Niece and all the stage IB NSCLC patients didn’t receive adjuvant chemotherapy. The patients’ blood samples were tested with chemiluminescent immunoassay for the presence of HBV surface antigen (HBsAg), antibodies against HBV core antigen (anti-HBc), and antibodies against HBsAg (anti-HBs) before operation. Other variables in the analysis included age, gender, history of smoking and pathologic type. HBsAg positive was definite as HBV infection.

      Results:
      Figure 1 51 HBV infection cases (13.93%) were positive in stage IB NSCLC. The 5-year overall survival of patients without or with chronic HBV infection were 71.25% and 50.98% (P=0.028). Multivariate analyses revealed that gender, chronic HBV infection were significant predictive factors for overall survival (P< 0.05).



      Conclusion:
      The chronic HBV infection is a significant independent prognostic factor in stage IB non-small cell lung cancer.

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      P1.05-026 - High Resolution Metabolomics on Exhaled Breath Condensate to Discover Lung Cancer's Biomarker (ID 5617)

      14:30 - 14:30  |  Author(s): C.Y. Park, A. Khan, A.D. Pamungkas, E.J. Sim, K.H. Kang, S.Y. Lee, Y.H. Park

      • Abstract
      • Slides

      Background:
      Early and non-invasive detection of lung cancer is a desirable prognostic tool for prevention of lung cancer at early stages. Previously, unusual human breath smell of lung cancer patients detected by trained dogs played an important role in early detection of lung cancer. Which suggests that exhaled breath condensate (EBC) is a promising source for searching potential biomarkers in lung cancer patient.

      Methods:
      EBC sample collected using specific device called R-tube, containing both the volatile organic compounds (VOCs) and non-volatile organic compounds (NVOCs), were obtained from patients with lung cancer (n = 20) and control healthy individuals (n = 5). The EBC samples were applied to high resolution metabolomics (HRM) based LC-MS for comparison of metabolic differences among healthy people and lung cancer patients in order to detect potential biomarkers. The multivariate statistical analysis was performed, including a false discovery rate (FDR) of q=0.05, to determine the significant metabolites between the groups. 2-way hierarchical clustering analysis (HCA) was done for determining the classification of significant features between the control healthy and lung cancer patients. The significant features were annotated using Metlin database (metlin.scripps.edu/) and the identified features were then mapped on the human metabolic pathway of the Kyoto Encyclopedia of Genes and Genomes (KEGG). This study was approved by Korea University Guro Hosipital Institutional review board (KUGH14273)

      Results:
      Using metablomics-wide associated study (MWAS), metabolic changes among healthy group and lung cancer patients were determined. The 2-way HCA identified the different metabolic profile in lung cancer patients from healthy control. The identified potential biomarkers are Acetophenone (m/z 103.0542, [M+H-H~2~O][+]), P-tolualdehyde (m/z 138.0914, [M+NH4][+]), 2,4,6-Trichlorophenol (m/z 218.9134, [M+Na][+]) and 11(R)-HETE (m/z 343.2233, [M+Na][+]). The top 5 of affected KEGG pathways are Arachidonic acid metabolism, Glycerophospholipid metabolism, Bile secretion, Inflammatory mediator regulation of TRP channels and Tyrosine metabolism.

      Conclusion:
      Our result shows that Acetophenone, P-tolualdehyde, 2,4,6-Trichlorophenol and 11(R)-HETE are significantly higher in lung cancer patients. Acetophenone and 2,4,6-Trichlorophenol are classified as a Group D human carcinogen approved by US Environmental Protection Agency (EPA), while 11(R)-HETE is associated with Arachidonic acid metabolism and P-tolualdehyde is related to xylene degradation pathway and degradation of aromatic compounds pathway. Our identified metabolites can be the potential biomarkers in EBC for the early and non-invasive detection of lung cancer.

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      P1.05-027 - Novel Prognostic Gene Expression Signatures for Squamous Cell Lung Carcinoma: A Study by the SPECS Lung Consortium (ID 4490)

      14:30 - 14:30  |  Author(s): R. Bueno, W.G. Richards, D. Beer, K.V. Ballman, M.S. Tsao, F.A. Shepard, D.T. Merrick, A. Van Bokhoven, W.A. Franklin, R. Govindan, M. Watson, D.R. Gandara, D. Harpole, Z.H. Chen, G. Chen, L. Chirieac, H. Chui, C. Genova, M. Joshi, A. Kowalewski, M. Onaitis, C.J. Rivard, T. Sporn, F.R. Hirsch

      • Abstract

      Background:
      A multi-institutional squamous lung cancer consortium of investigators is developing prognostic signatures through the US NCI Lung SPECS (Strategic Partnership for Evaluation of Cancer Signatures) program. Six institutions contributed tumor specimens and published/unpublished expression-based prognostic signatures for validation using standardized sample cohorts (a primary validation cohort comprising institutional cases, and additional validation cohorts from two prospective cooperative group studies) and quality controlled assessment in independent laboratory and statistical cores. Here, we report on de novo prognostic signatures derived using the pooled institutional dataset.

      Methods:
      Highly quality-controlled cases of primary SCC from the pooled cohort (N=249) were analyzed to generate de novo prognostic signatures from among the 147 genes comprising pre-existing signatures, and from among all profiled genes. Minimax Concave Penalty (MCP) selection and Ward’s minimum variance clustering yielded survival analyses with 2 clusters that were evaluated using Cox regression and bootstrap cross validation (bCV; 500 iterations).

      Results:
      Two significantly prognostic models were generated (see Figure): Pooled Model A (PMA) was the optimal 2-cluster model using probesets representing 6 genes selected from components of pre-existing signatures: CASP8, MDM2, SEL1L3, RILPL1, LRR1, COPZ2. Pooled Model B (PMB) was the optimal 2-cluster model using probesets representing 6 genes selected from among all those profiled: SSX1, DIAPH3, LOC619427, CASP8, EIF2S1, HSPA13. PMA and PMB each remained independently prognostic in multivariable analyses incorporating an a priori baseline model (age, sex, stage; c-index = 0.641).

      Conclusion:
      Two de novo prognostic signatures were derived using a pooled multi-institutional cohort of SCC assembled for validation of pre-existing signatures. PMA and PMB were each found to be independently prognostic, accounting for established clinical predictors. Both now move forward, along with validated pre-existing signatures, to additional assessment of discrimination, calibration and clinical usefulness using additional independent prospective US co-operative group cohorts of cases. Figure 1



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      P1.05-028 - Phenotypic and Functional Profiling of Tumor-Infiltrating Lymphocytes (TIL) in Early Stage Non-Small Cell Lung Cancer (NSCLC) (ID 6044)

      14:30 - 14:30  |  Author(s): L. Federico, C. Haymaker, M. Forget, L.M. Vence, I. Team, P. Sharma, J. Allison, B. Fang, J. Zhang, H. Wagner, E. Bogatenkova, I. Wistuba, B. Sepesi, J. Heymach, D.L. Gibbons, C. Bernatchez

      • Abstract

      Background:
      The ICON study aims to perform a comprehensive immunogenomic characterization of early stage localized non-small cell lung cancer (NSCLC) and lay the foundation for the identification of barriers to tumor immunity that may be targeted in future trials. Earlier work has demonstrated the prognostic significance of TIL in localized NSCLC. This work evaluates the functional status of T cells infiltrating the NSCLC tumors and their capacity to expand ex-vivo and perform effector function in the first 22 patients enrolled.

      Methods:
      Patients enrolled on the ICON study underwent surgery. Fresh tumor samples were mechanically disaggregated and immediately stained for flow cytometry. Panels consisted of markers of T cell subsets, differentiation status, T cell function, activation and exhaustion. PD-L1 expression was assessed on malignant cells as well as CD68+ tumor-associated macrophages (TAMs) by IHC. Fragments from the tumor tissue were also placed in culture in media containing IL-2 for ex-vivo TIL expansion. TIL cultures were maintained for 3-5 weeks and subsequently underwent phenotypical and functional characterization.

      Results:
      Analysis of freshly disaggregated tumor tissue (n=22) from NSCLC tumor or adjacent normal tissue by flow cytometry demonstrated that effector CD8[+] T cells found in the tumor were less functional than T cells infiltrating normal tissue, revealed by a decrease in the co-expression of the cytotoxic effector molecules perforin and granzyme B (p=0.0004) together with an enhanced expression of the inhibitory receptor PD-1 (p<0.0001). Immunohistochemistry analysis showed PD-L1 expression on malignant cells and/or CD68+ TAMs on all tumor samples except one, strongly suggesting that the PD-1/PD-L1 inhibitory axis was engaged contributing to decreased T cell functionality. TIL could be expanded from the majority of samples (68.2%, n=22). The degree of infiltration predicted the ability to grow TIL ex-vivo (median CD3+ infiltrate of 15.25% of live cells in disaggregated tumor tissue for samples from which TIL could be grown versus 2.9% when TIL could not grow p = 0.015). Immunophenotyping following expansion showed an enrichment in CD8+ aβTCR+ T-cells expressing both perforin and granzyme B indicating that TILs propagated with IL-2 regained functionality (p=0.016). Lastly, NSCLC TIL were rapidly expanded using anti-CD3 antibody, feeder cells and IL-2 over two weeks (n=6) and reached clinically relevant numbers for TIL ACT (range 381-1282 fold expansion).

      Conclusion:
      Overall, while TILs present in NSCLC are functionally inhibited, they can be expanded ex-vivo from most tumor samples and regain a functional phenotype for potential use in adoptive T-cell therapy.

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      P1.05-029 - SABRTOOTH-A Feasibility Study of SABR Compared to Surgery in Patients with Peripheral Stage I NSCLC Considered to Be at Higher Risk from Surgery (ID 4432)

      14:30 - 14:30  |  Author(s): K.N. Franks, M.P. Snee, B. Naidu, D. Sebag-Monterfiore, M. Callister, J. Ferguson, R. Booton, M. Kennedy, C. Lowe, F. Collinson, L. McParland, R. Naylor, J. Webster, W. Gregory, J. Bestall, J. Hewison, D. Baldwin

      • Abstract
      • Slides

      Background:
      Stereotactic Ablative Radiotherapy (SABR) is a well established treatment for medically inoperable peripheral stage I NSCLC. Previous non-randomised evidence supports SABR as an alternative to surgery, but high quality randomised control trial (RCT) evidence is lacking due to low recruitment. The UK SABRtooth study aims to see if a large RCT is feasible.

      Methods:
      The trial management group includes pulmonologists, thoracic surgeons, nurses, patient representatives, oncologists and statisticians. Patients considered at higher-risk of operative mortality and morbidity with a peripheral stage I (<5cm) NSCLC are eligible. Defining “higher-risk” patients considers multiple criteria, but the final decision is left to the individual tumour boards. Equipoise in presenting the two interventions to patients was considered key. Bias is minimised by ensuring the initial approach is by the pulmonologist with subsequent counseling by the research nurse and randomisation occurring before consultation with a surgeon or oncologist . Patients who decline the trial or do not proceed with their allocated treatment are invited to take part in qualitative interviews. The trial is open in 4 thoracic oncology centres and their referral units. The aim is to recruit on average 3 patients/month to demonstrate that a phase III RCT would be feasible.

      Results:
      Following a launch meeting in April 2015 the trial opened in July (all centres opened October 2015). To help train research staff with introducing the trial to patients, mock patient consultations were recorded. Recruitment was initially slow. Specific research nurse meetings have taken place (December 2015 and June 2016) to understand the barriers to recruitment, centre-specific issues and provide additional education to improve nurses’ confidence in recruiting patients. Regular updates are provided with monthly emails and In February 2016, the Chief Investigator and Trial Manager visited each site to promote the trial and help with any local barriers to recruitment. In response to feedback, changes to the protocol to aid patient recruitment, additional promotional and patient information provided and a video for patients were produced. The study has also been presented at various oncology/thoracic meetings. As a result recruitment has increased with 15 patients successfully randomised into the trial.

      Conclusion:
      Whether SABR is an alternative to surgery is a key question in stage I NSCLC. However, SABRtooth is a challenging study but with a novel trial design and continual adaptive feedback we hope to be able to meet recruitment targets and demonstrate that a definitive phase III RCT is feasible.

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      P1.05-030 - Lung SABR for Early Stage Lung Cancer: Outcomes and Toxicity of 803 Patients Treated at the Leeds Cancer Centre (ID 5874)

      14:30 - 14:30  |  Author(s): P.F. Murray, K. Clarke, K.N. Franks, J. Lilley, P. Dickinson, M.P. Snee, P. Jain

      • Abstract
      • Slides

      Background:
      SABR is an established treatment for early peripheral stage non-small cell lung cancer (NSCLC) in medically inoperable patients We present the outcomes 803 patients, a large prospective series of patients, with a minimum 12 months follow-up after undergoing SABR treatment in Leeds, UK, between May 2009 and May 2015.

      Methods:
      Patients with a pathological or clinical diagnosis of peripheral stage I lung cancer, and deemed medically inoperable, were treated with SABR at the Leeds Cancer Centre, using a dose fractionation of 54Gy/3#, 55Gy/5#, or 60Gy/8# depending on proximity of organs at risk. Patient follow-up was assessed using an electronic patient record and radiology reports. Survival analysis was performed using Kaplein-Meier estimation and log rank test was used to compare survival distibutions including performance status, histology, tumour T stage, tumour location, post-SABR fibrosis, and toxicity.

      Results:
      803 patients were treated with SABR and had at least 12 months follow-up. Mean age at treatment was 73.9 years (39 to 94 years). Median follow-up was 23.3 Months, from time of last treatment fraction to last medical contact or death. Median overall survival estimate was 33.3 Months (95% C.I. 29.54-27.1 Months) 1 year OS – 80.1% (SE 1.4%), 3 year OS – 46.4% (SE 2%), 5 year OS – 29.5% (SE 2.6%) Local control (LC) 1 year LC – 99.2% (SE 0.3%), 2 year LC – 97.2% (SE 0.7%), 3 year LC – 95.1% (SE 0.9%) Both performance status and tumour size were associated with a worse overall survival, Log rank p<0.001 (PS), p=0.035 (T stage). Toxicity Only 4 patients had documented grade 3 toxicity. 3 pneumonitis requiring admission, and 1 patient developed a bronchopulmonary fistula 2 years post-treatment. 44 Patients had a rib fracture recorded, of these 16 patients were symptomatic, and were treated with analgesia or neuropathic adjuncts. 156 patients had documented radiological pneumonitis (gd 1), with 331 developing fibrotic change in the treatment area. Of interest the presence of radiological pneumonitis and fibrotic changes was associated with an improved overall survival, Log rank P=0.009 (Rad pneum), P<0.001 (Fibrosis).

      Conclusion:
      SABR for early stage lung cancer is a safe and effective treatment even in medically inoperable patients, with excellent local control. In our cohort, we found radiological pneumonitis and fibrosis was associated with an improved overall survival, which may be indicative of the patient response to SABR, and will need further evaluation. Performance status and tumour size were associated with a poorer overall survival.

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      P1.05-031 - Primary Results of Dose Escalated Stereotactic Body Radiotherapy for Stage IA Non-Small Cell Lung Cancer (ID 4606)

      14:30 - 14:30  |  Author(s): T. Komiyama, K. Kuriyama, K. Marino, S. Aoki, M. Araya, H. Onishi

      • Abstract
      • Slides

      Background:
      JCOG 0403 showed excellent overall survival in stereotactic body radiotherapy (SBRT) for stage IA non-small cell lung cancer (NSCLC). In Japan, 48Gy/4Fr for isocenter have been the standard dose fractionation of SBRT for stage IA NSCLC. JCOG0702 showed that dose escalation of 55Gy for PTVD~95%~ was feasible in SBRT for peripheral small (PTV volume 100cc or less) NSCLC. Intensification of local treatment with dose escalation is considered to be one of the measures for improvement of overall survival. In 2011, we adopted dose escalated regimen (50Gy/4Fr for PTVD~95%~) for SBRT for stage IA NSCLC, expected improvement of local control and overall survival. The purpose of this study was to review and report the primary results of dose escalated SBRT for stage IA NSCLC.

      Methods:
      From August 2011 to April 2015, 31 patients with stage IA NSCLC were treated with dose escalated SBRT at the University of Yamanashi. The patients' ages ranged from 61 to 86 (median 79) years. Twenty two patients were male, 9 were female. Performance status was 0 in 26, 1 in 5 patients. Tumor histology was squamous cell carcinoma in 6 and adenocarcinoma in 23, other NSCLC in 2 patients. Clinical stage was T1a in 19, T2b in 12 patient. A multiple static ports radiation planned by a radiation treatment planning system (Pinnacle[3] Version 9.2-9.8) was performed with linac using 6MV x-ray beams. The Breath hold technique and CT image guided set-up were used in all cases. A total dose of 50Gy was delivered in 4 fractions over 4-5days. Radiation doses were prescribed to the 95% of planning target volume (PTVD~95%~). A superposition algorithm with heterogeneity correction was used for dose calculations.

      Results:
      The follow-up period for all patients was 3.3-43.1 (median 23.7) months. The overall survival rate at one year and two years were 87.1%, 79.3%, respectively. The local control rate at one year and two years were both 96.4%. Local recurrence, regional lymph node metastases, and distant metastases were observed in 1, 4 and 3 patients, respectively. Regarding to the toxicities, grade 3 radiation pneumonitis were observed in 3 patients. Grade 2 rib fracture were observed in 3 patients. There were no Grade 4 or greater adverse events in the follow-up period.

      Conclusion:
      The toxicity was considered to be acceptable. The local control effect was considered to be sufficient. Longer follow- up durations are needed to validate the clinical benefits of dose escalated SBRT for stage IA NSCLC.

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      P1.05-032 - Quality of Life after Stereotactic Body Radiotherapy and Surgery in Patients with Early Stage Non-Small Cell Lung Cancer (ID 4947)

      14:30 - 14:30  |  Author(s): E.A. Kastelijn, S.Y. El Sharouni, F.N. Hofman, P. Zanen, F.M.N.H. Schramel

      • Abstract
      • Slides

      Background:
      Several studies have shown that the clinical outcomes after stereotactic body radiotherapy (SBRT) are not inferior compared to surgery in patients with early stage non-small cell lung cancer (NSCLC). Quality of life (QoL) after treatment is an important parameter for patients which receives raising interest. We compared the QoL during the first year after treatment in patients with early stage NSCLC.

      Methods:
      Patients diagnosed with early stage NSCLC and treated with SBRT or surgery in the Sint Antonius Hospital between 2013 and 2015 were included. QoL assessments were performed before treatment, and at three, six and 12 months after treatment. QoL was evaluated by using the 30-item European Organization for Research and Treatment of Cancer Quality of life Core questionnaire and its corresponding 13-item lung cancer supplement. A linear mixed model was used to analyse the data and a change of more than five points was determined as minimal clinically important difference .

      Results:
      Ninety-three patients were included (SBRT n = 39, surgery n = 54). Patients who underwent SBRT were significantly older, had a higher ECOG performance status and a lower pulmonary function. The compliance for SBRT and surgery at baseline were 97% and 98% (p = 0.8), at three months 74% and 71% (p = 0.8), at six months 62% vs 78% (p = 0.1), and at 12 months 45% and 73% (p = 0.04). The ECOG performance status was not significantly different between the patients who were compliant and those who were not compliant. During the 12 months after treatment different significant changes were observed: QoL remained stable in SBRT patients and increased in surgical patients (p = 0.012) Role functioning increased in SBRT patients and decreased in surgical patients (p = 0.005) Cognitive functioning increased in SBRT patients and remained stable in surgical patients (p = 0.045) Social functioning remained stable in SBRT patients and decreased in surgical patients (p = 0.001) Pain increased in SBRT patients and decreased in surgical patients (p = 0.001) SBRT patients had a decrease in effect of pain medication and surgical patients had an increase in effect of pain medication (p = 0.0001).

      Conclusion:
      We showed that in patients with early stage NSCLC treated with SBRT or surgery the QoL scores showed different changes after treatment. In the light of the comparable clinical outcomes after both treatments these QoL aspects should be discussed with the patient before making a treatment-decision.

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      P1.05-033 - Comparison of Single- and Five-Fraction Schedules of Stereotactic Body Radiation Therapy for Central Lung Tumors (ID 4394)

      14:30 - 14:30  |  Author(s): S.J. Ma, Y. Syed, C. Rivers, J.A. Gomez Suescun, A.K. Singh

      • Abstract
      • Slides

      Background:
      Stereotactic Body Radiation Therapy (SBRT) is a treatment option for patients with early-stage non-small cell lung cancer (NSCLC) who are medically inoperable or decline surgery. The safety of 20 Gray (Gy) x 3 fractions of SBRT within 2 cm of the proximal bronchial tree is unclear. Here we compare the clinical outcome of patients with centrally located lung tumors who underwent either single fraction (SF)- or five-fraction (FF-) SBRT at a single institution over 5 years.

      Methods:
      Between January 2009 and October 2014, 11 out of 42 patients received 26-30 Gy in 1 fraction, while the remaining 31 patients received 52.5-60 Gy (median 55 Gy) in 5 fractions. Data were retrospectively collected using an institutional review board-approved database. Kaplan-Meier method, competing risks method, and Cox regression model were used. Toxicities were graded using Common Terminology Criteria for Adverse Events version 4.0. R version 3.3.1 was used for statistical analysis.

      Results:
      After a median follow-up of 12 months for SF-SBRT and 17 months for FF-SBRT groups (p=0.64), 1-year overall survival rates for SF- and FF-SBRT groups were 82% and 87%, respectively. There was no statistically significant difference in overall survival (p=0.061), progression-free survival (p=0.47), local failure (p=0.43), nodal failure (p=0.42), and distant failure (p=0.45) at 18 months. No primary tumor failure was seen in both groups at 18 months. Distant failure rates at 18 months were 9.1% for SF-SBRT group and 54.5% for FF-SBRT group. Among the patients with distant failure (n=4 in SF-SBRT and n=6 in FF-SBRT), median time to distant failure was 29.5 months and 8.9 months for SF- and FF-SBRT groups, respectively (p=0.0095). 3 out of 11 patients in SF-SBRT group and 2 out of 32 patients in FF-SBRT group experienced grade 3-4 toxicities. No grade 4-5 toxicities were observed in the FF-SBRT group. SF-SBRT group showed higher cumulative incidence of grade 3+ toxicity at 18 months (p=0.018). However, univariate analysis showed SF-SBRT alone was not a significant factor that increased risk for grade 3+ toxicities (HR=5.50, p=0.063). 4 out of 5 toxicities occurred at least 12 months after SBRT.

      Conclusion:
      SF- and FF-SBRT showed no significant difference in overall survival and local control. No grade 4-5 toxicities were observed in our FF-SBRT group. The onset of distant failure was significantly delayed in the SF-SBRT compared to the FF-SBRT group. The majority of toxicities occurred late. Having SF-SBRT itself was not significantly associated with severe toxicity.

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      P1.05-034 - Neutrophil-To-Lymphocyte and Platelet-To-Lymphocyte Ratios as Prognostic Biomarkers in Early NSCLC Patients Treated with SABR (ID 6102)

      14:30 - 14:30  |  Author(s): S. McKay, K. Moore, J. Macphee, J. Hicks, G. Lumsden, V. Maclaren, P. McLoone, S. Harrow

      • Abstract

      Background:
      Inflammation may play an important role in cancer progression. High Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) have been reported to be poor prognostic indicators in several malignancies. In this study we quantify the prognostic impact of these biomarkers for overall survival (OS) among early stage NSCLC patients treated with Stereotactic Ablative Body Radiotherapy (SABR).

      Methods:
      102 consecutive patients who received SABR between October 2011 and May 2014 at the Beatson West of Scotland Cancer Centre (BWoSCC) were identified from a prospectively maintained electronic database. NLR and PLR were derived from blood results obtained within 60 days prior to SABR. Receiver Operator Characteristic (ROC) curves were generated to calculate the optimal thresholds for NLR and PLR.

      Results:
      The median age of patients was 72 (range 47-91) years. 60 (59%) were female. Maximum tumour diameter ranged from 10-42mm (median 18mm). Median follow up was 37.1 months. Overall survival at 2 and 4 years was 75.5% (95%CI 65.9-82.7%) and 51.4% (38.8-62.6%) respectively. There was strong association between NLR and PLR levels (r=0.803, p<0.001). ROC Curves indicated a threshold value for NLR of 3.155 (AUC 0.74) and PLR of 155.15 (AUC 0.70) respectively. Median OS for ‘low’ NLR and PLR was not yet reached compared with 33.9 months for ‘high’ NLR (p<0.0001) and 35.4 months for ‘high’ PLR (p=0.002). Multi-variable analysis indicated a stronger independent effect of NLR (p<0.0001), whilst taking account of gender, age, tumour size, histological confirmation and performance status. No association was found between elevated NLR or PLR and loco-regional or distant recurrence.

      Conclusion:
      Neutrophil-to-Lymphocyte Ratio appears to be a prognostic biomarker for patients with early stage NSCLC receiving SABR. Platelet-to-Lymphocyte ratio acts as a linear co-variant. We found no association between elevated NLR or PLR and loco-regional or distant recurrence.

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      P1.05-035 - SABR for Medically Inoperable Early Stage NSCLC at the Beatson West of Scotland Cancer Centre: Outcomes and Toxicity (ID 4798)

      14:30 - 14:30  |  Author(s): S. McKay, K. Moore, J. Macphee, J. Hicks, G. Lumsden, V. Maclaren, A. Aitken, D. Stobo, G. Cowell, P. McLoone, S. Harrow

      • Abstract

      Background:
      SABR is now an established therapeutic option for patients with medically inoperable early stage NSCLC. It is well tolerated and associated with low rates of Grade 3+ toxicity. Here we present the outcomes and toxicity data for the SABR service based at the Beatson West of Scotland Cancer Centre (BWoSCC).

      Methods:
      All 102 consecutive patients (median age 72 (range 47-91) years, 60 (59%) female) who received SABR between October 2011 and May 2014 at the BWoSCC were identified from a prospectively maintained electronic database. Toxicity data was collected at pre-determined intervals in a dedicated follow-up clinic. Radiological evidence of pneumonitis was scored on follow-up CT imaging at 3 months post-SABR. Outcomes were collated from electronic records.

      Results:
      Median and minimum follow-up were 37.1 and 24.1 months respectively. Histological confirmation of NSCLC was available for 33 (32.4%) patients. Local and regional control rates at 2 years were 95.1% and 94.1% respectively. 8.8% of patients developed metastases within 2 years with a median time to detection of metastases of 6.9 months. Overall survival (OS) at 1, 2, 3 and 4 years post-SABR was 88.2% (95%CI 80.2-93.1%), 75.5% (65.9-82.7%), 59.8% (48.2-69.7%) and 51.4% (38.8-62.7%) respectively. No difference in OS was apparent between histologically confirmed and unconfirmed subgroups (p=1.0). On multi-variable analysis, tumour size >= 20mm was negatively associated with OS (p=0.003) whilst gender, age, performance status, deprivation index and histological confirmation were not associated. Radiological scoring of post-SABR pneumonitis was available for 69 patients. A total of 33 of these patients (48%) had radiological evidence of pneumonitis. No association between V5 or V20 and radiological pneumonitis was identified. One death occurred that was potentially related to radiation pneumonitis. Otherwise, only 1 patient experienced grade 4 toxicity (fatigue) and 5 patients (4.9%) reported grade 3 toxicity (4x dyspnoea, 1x fatigue) within 12 months of SABR. There were 4 instances of rib fracture with no association with maximum chest wall dose.

      Conclusion:
      Within the Beatson West of Scotland Cancer Centre the use of SABR for early stage NSCLC is associated with high rates of loco-regional control. Our overall survival and toxicity data compare favourably with published series.

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      P1.05-036 - A Propensity-Matched Study of Multi-Port versus Single-Port Video-Assisted Thoracoscopic Surgery for Early Lung Cancer (ID 4595)

      14:30 - 14:30  |  Author(s): K. Hirai, S. Takeuchi, J. Usuda

      • Abstract
      • Slides

      Background:
      Several thoracic surgeons have already reported the beneficial effects of single-port (SP) video-assisted thoracoscopic surgery (VATS) for the patients with lung cancer. We also analyzed surgical outcomes between SP VATS and multi-port (MP) VATS, which was defined as surgery through 3-4 ports alone, and showed the inhibitory effect of postoperative wound pain in the SP VATS (Eur J Cardiothorac Surg 2015 ). In this study, we aimed to compare the effectiveness of SP and MP video-assisted thoracoscopic surgery for stage I lung cancer.

      Methods:
      A total of 212 patients with non-small cell lung cancer underwent lobectomy via SP and MP procedure between April 2008 and June 2015 in our institute. We examined the a propensity-matched analysis, perioperative variables and short-term outcomes of both operations.

      Results:
      Propensity matching produced 80 pairs in each group. The clinical outcomes of SP /MP group were as follows. The mean Fev1.0 and maximum size of tumor was 1.88±0.32/1.65±0.41 liter and 2.8±0.3/2.7±0.3 cm, respectively. The median operation time, intraoperative blood loss was 165±35/172±26 min. and 85±25/75±26 ml. The median drainage duration and postoperative hospital stay were 1.8±0.7/1.9±0.8 and 7.5±1.9/7.2 ±1.8 days and the mean number of dissected lymph nodes was 19.8±3.8/17.5± 3.1. The number of days that was used with analgesic agents within a month after surgery was 8.1±1.2/12.5±2.5 (P<0.05). Conversion rate to open thoracotomy was 3.9/3.6 %. The overall 3-year disease free survival rate was 92/88%. As for mortality and morbidity, there was no significant difference in both groups.

      Conclusion:
      SP VATS lobectomy, showing alomost as effective as the MP VATS should be considered as a new treatment option for stage I lung cancer.

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      P1.05-037 - Histopathologic Results of Surgically Resected Pure Ground-Glass Opacity Lung Nodules (ID 6269)

      14:30 - 14:30  |  Author(s): G.D. Lee, C.H. Park, Y.W. Do, S. Lee

      • Abstract

      Background:
      Little is known about the histopathology of persistent pure ground-glass opacity lung nodules (GGNs).

      Methods:
      We reviewed preoperative chest computed tomography (CT) in patients who underwent surgery for GGNs between Mar. 2015 and May 2016. A total of 58 surgically resected pure GGNs persistent more than 3 months and their diameter at CT scan less than 15 mm in 41 patients were included. Then pathologic reports of 58 GGNs were retrospectively reviewed.

      Results:
      Median age of the patients was 58 years (range, 33 – 75) and 34 patients (83.3%) were female. Median preoperative follow-up duration of GGNs was 11 months (range, 3–114). In spite of all patients were asymptomatic, the reasons of check-up the chest CT included to follow-up for other malignant disease in 29 patients (70.1%), routine health check-up in 10 (25.0%), and to follow-up of other benign disease in 2 (4.9%). Among a total 45 operations, preoperative CT-guided localization was performed in 31 operations (68.9%). Extents of resection included wedge resection in 29 patients (64.4%), segmentectomy in 7 (15.6%), and lobectomy in 9 (20.0%). Lymph node sampling or dissection was performed in 27 operations (60.0%). Among 58 resected GGNs, median diameter of GGNs was 8mm (range, 3-15mm), median number of resected GGN per operation was 2 (range, 1-5). The distribution of pathologic diagnosis included benign disease in 3 GGNs (5.2%), atypical adenomatous hyperplasia (AAH) in 4 (6.9%), adenocarcinoma in situ (AIS) in 17 (29.3%), minimally invasive adenocarcinoma (MIA) in 19 (32.8%), and invasive adenocarcinoma (IA) in 15 (25.9%). The diameter of GGNs classified into 3 categories (0 – 5mm, 6 – 10mm, 11 – 15mm) were associated with pathologic invasiveness (Cochran-Amitage test, p = 0.005). However, follow-up duration of GGNs classified into 3 categories (3 - 12 months, 13 - 24 months, more than 25 months) was not associated with diameter of GGNs (p = 0.453) or pathologic invasiveness (p = 0.893). Among 18 GGNs tested, epidermal growth factor receptor (EGFR) mutations were detected in 5 GGNs (27.7%).

      Conclusion:
      The prevalence of lung adenocarcinoma (AIS, MIA, IA) was 87.9% in surgically resected pure GGNs persistent more than 3 months and their diameter at CT scan less than 15 mm. A diameter of GGNs diameter was associated with pathologic invasiveness. Further studies are needed for persistent pure GGNs not affected by partial-volume effect of CT in non-selected patients.

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      P1.05-038 - Patterns of Recurrence in Curatively Resected Stage I Lung Cancer (ID 6300)

      14:30 - 14:30  |  Author(s): K. Lee, D.K. Kim, S. Park, Y. Kim, H.R. Kim, S.H. Choi, H.P. Lee, B.K. Chong, J.S. Bok, S.K. Hwang

      • Abstract
      • Slides

      Background:
      The patterns of recurrence after curative resection for pathologically stage I non-small cell lung cancer(NSCLC) were investigated according to the cell type.

      Methods:
      The medical records of stage I NSCLC patients who undergone curative resection at Asan Medical Center between 2000 and 2009 were reviewed.

      Results:
      Total 940 patients with pathologically proven stage I NSCLC were included. Patients with lepidic-type adenocarcinoma(LTA) were 74, other adenocarcinoma(ADC) 580, and squamous cell carcinoma(SCC) 246. Median length of follow-up was 62 months(3~189), median survival was 146 months, and median disease-free survival(DFS) was 109 months. During follow-up, recurrence occurred in 221 patients(23.5%). Number of recurrence is grouped by every 6 months. Incidence of recurrence was peaked within 2 years after resection, then gradually decreased thereafter. Recurrence LTA(AIS/MIA) group was significantly rare(13.5%) throughout the all follow-up period(median DFI of 60months), and its distribution shows relatively even distribution. Comparing ADC and SCC, ADC seemed to show better 5-year OS in univariate analysis(p=0.003), but not in multivariate analysis. Furthermore, there were no significant difference in 5-year DFS(p=0.331). ADC shows higher proportion of distant metastasis, even though ADC group has lower T-stage. SCC shows higher incidence of local recurrence. Figure 1



      Conclusion:
      Recurrence of ADC occured within 2 years after resection, and shows higher proportion of distant metastasis(74.0% Vs. 57.2) even though ADC group has lower T-stage. Most of recurrence of both ADC and SCC groups were peaked within 2 years after resection. LTA group shows significantly delayed pattern of recurrence.

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      P1.05-039 - Recurrence and Survival Outcome after Segmentectomy for Non-Small Cell Lung Cancer: A Long-Term Follow-Up Study at a Single Institute (ID 5011)

      14:30 - 14:30  |  Author(s): T. Koga, K. Fujino, K. Yoshimoto, K. Ikeda, Y. Sato, T. Ito, T. Mori, M. Suzuki

      • Abstract

      Background:
      This study aimed to investigate the factors associated with long-term outcomes of segmentectomy for non-small cell lung cancer (NSCLC) carried out at a single institute.

      Methods:
      179 patients with stage I NSCLC who underwent a segmentectomy between 2005 and 2009 were investigated. Histological classification was reassessed according to the criteria of the 2015 WHO.

      Results:
      179 patients with stage I NSCLC (159 adenocarcinomas (ADCs), 14 squamous cell carcinomas (SQCs), 4 adenosquamous carcinomas, and 2 typical carinoids) who underwent segmentectomy between 2005 and 2009 were investigated.The mean follow-up was 73 months. The 5-year overall survival (5-OS) and 5-years disease-free survival (DFS) were 91.8% and 90.2%, respectively. Seven cases of distant recurrence and 8 local-regional recurrence occurred. Multivariate analysis revealed that lymphovascular invasion (LVI) was the independent predictor of 5-OS (P=0.005), and part-solid GGO (GGO ratio < 50%) and LVI were that for 5-DFS (P=0.043, P<0.001). Among invasive ADC patients, micropapillary pattern (MIP) ≧ 5% was identified as an independent predictor of recurrence (P=0.005) and survival (P=0.007). There were five local recurrences in patients with MIP more than 5 years after segmentectomy. Figure 1



      Conclusion:
      LVI was an independent predictor of the recurrence and overall survival. In patients with invasive ADC, MIP≧5% was a multivariable predictor of recurrence and overall survival. In the patients who underwent a segmentectomy, 5 years without recurrence is not sufficient to conclude that patients with NSCLC is cured.

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      P1.05-040 - Prognostic Factor of Node Involvement Pattern in Completely Resected pN1 Squamous Cell Carcinoma Patients (ID 3971)

      14:30 - 14:30  |  Author(s): K. Tane, K. Miura, H. Okuma, Y. Kitamura, W. Nishio, M. Yoshimura

      • Abstract
      • Slides

      Background:
      In patients with non-small cell lung cancer, the degree of regional lymph node involvement is an important prognostic factor. The prognostic significance of lymph node involvement pattern is unclear in the seventh edition of TNM classification. Squamous cell carcinoma (SCC) often arises in the central way and directly invades intrapulmonary and hilar lymph nodes. In this study, we reviewed our population of operated SCC patients classified as pathologically N1 (pN1) to evaluate the association between N1 lymph node involvement patterns and the prognosis.

      Methods:
      From our institutional database of 3,264 consecutive patients underwent surgical resection for NSCLC at our hospital between January 1987 and December 2010, we examined 152 patients with completely resected pN1 squamous cell carcinoma. We performed reassessment of the data according to the seventh edition of TNM classification of lung cancer. We divided the patients into two groups based on lymph node involvement pattern; direct and separate pattern. The direct pattern was defined as lymph node metastasis by the primary tumor directly with continuity, separate pattern as metastasis without continuity. Survival curves were generated by the Kaplan-Meier method and multivariate analysis was based on the Cox proportional hazards model.

      Results:
      In the lymph nodes metastasis pattern, 75 (49%) patients were the direct group, 77 (51%) patients were the separate group. The percentage of sleeve lobectomy was significantly higher in the direct group and lobectomy without bronchoplastic procedure was higher in the separate group. The median follow-up period was 50 months. The 5-year survivals of the direct and separate group were 54% and 41% (p = 0.01). The 5-year survival of patients with the direct group was as good as pN0 patients (p = 0.78). No survival difference between the separate group and pN2 patients was noted (p = 0.06). Overall recurrence rate of the direct group (44% [33/75]) was lower than the separate group (50% [39/77]), but there was no significant difference among them (p = 0.09). No significant difference was noted in recurrence pattern (distant or locoregional) when comparing the direct group or separate group (p = 0.27). By multivariate analyses of survival, lymph node involvement pattern (p = 0.02) and lymphatic infiltration (p = 0.02) was independent prognostic factor.

      Conclusion:
      Lymph node involvement pattern of patients with pN1 squamous cell carcinoma is significant prognostic factor. Survival of the direct pattern is higher than the separate pattern.

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      P1.05-041 - Dynamics of Brain Metastasis for Curatively Resected Stage I or II Non-Small Cell Lung Cancer Patients (ID 5933)

      14:30 - 14:30  |  Author(s): S. Shin, B.J. Park, J.H. Cho, H.K. Kim, Y.S. Choi, J.I. Zo, Y.M. Shim, J. Kim

      • Abstract

      Background:
      Development of brain metastasis results in a significant impairment in overall survival. The aim of this study to investigate the timing and manifestation of brain recurrence event during follow-up in patients undergoing surgery for stage I or II non–small-cell lung cancer (NSCLC).

      Methods:
      Between 2008 and 2012, medical records for patient who underwent curative surgery for stage I or II NSCLC at our institution were reviewed retrospectively. Event dynamics including brain metastasis, distant metastasis and non-brain distant metastasis, based on the hazard rate, were evaluated.

      Results:
      A total of 2389 eligible patients were identified. At a median follow-up of 50.6 months (IQR, 37.8–60.3 months), 573 patients developed recurrence. Among those, 457 patients had distant metastasis including 70 patients had brain metastasis as the first relapse site. The hazard rate curve for brain metastasis is similar from those of all distant metastasis and non-brain distant metastasis. The distinct surge was noted in 8.3 months in the brain metastasis. Subgroup analysis according to pathologic stage revealed that patients with stage II have distinct surge in 10 months, while the surge of stage I patients is more gradual and low. Hazard rate for brain metastasis is similar for each stage since 34months.

      Conclusion:
      Brain recurrence dynamics of resected stage I or II early-stage NSCLC displays a similar pattern compared to other distant metastasis. The overall risk reached high less than 1 year postoperative period regardless of stage. Our findings would be helpful to make a strategy to surveillance for brain metastasis after surgical resection for early stage NSCLC.

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      P1.05-042 - Treatment Strategy of Limited Surgery for Early Lung Cancer (ID 4497)

      14:30 - 14:30  |  Author(s): K. Kojima

      • Abstract
      • Slides

      Background:
      The standard surgical procedure for operable lung cancer is lobectomy with lymph node dissection. However early lung cancer cases have been increasing in Japan and they have been able to be candidates for limited operation. We have predicted early lung cancer depending on image findings and performed a limited operation positively.

      Methods:
      The advisability of the limited operation is evaluated with computed tomography (=CT) and positron emission tomography (=PET) for the cases in which we have diagnosed a lung nodule as c-Stage IA by staging of lung cancer. We have judged surgical indication for limited operation when the tumor diameter in mediastinal window setting of high resolution CT is 5mm or less and SUVmax level in tumor portion is 1.5 or less even if it exceeds 5mm. We decided the orientation as follows: Wide wedge resection is performed for pure GGO (=ground glass opacity) based on expectation to be Adenocarcinoma in situ (=AIS). Segmentectomy with lymph node dissection is performed for mixed GGO to deal when it is difficult to distinguish whether that the lesion is AIS, Minimally Invasive Adenocarcinoma (=MIA) or Invasive Carcinoma. We examined whether each surgery method was appropriate compared with the postoperative pathological result.

      Results:
      Surgical treatment for lung cancer was performed to 453 cases in our hospital between Apr.2010 and Jun.2016. 115 cases were diagnosed as early cancer suspected in preoperation by the above criteria. Wide wedge resection was performed to 27 cases (31 lesions). 30 lesions were AIS and 1 lesion was MIA pathologically. We underwent left S9 segmentectomy with lymph node dissection in addition for 1 case of mucinous adenocarcinoma. Segmentectomy with lymph node dissection was performed to 58 cases (61 lesions). 26 lesions were AIS, 29 lesions were MIA, 5 lesions were invasive adenocarcinoma and 1 lesion was squamous cell carcinoma pathologically. In all cases of invasive adenocarcinoma and squamous cell carcinoma, both lymph node metastasis and lymphovascular invasion was negative, so we did not perform completion lobectomy in addition. We performed lobectomy to 23 cases in spite of our expectation as early cancer due to a lesion of the middle lobe, a lesion near pulmonary hilum or the request of the patients and pathological results were 7 AIS, 7 MIA and 9 invasive adenocarcinoma with no lymphovascular invasion and no lymph node metastasis.

      Conclusion:
      We can operate for the appropriate extent of resection for early lung cancer by making full use of image findings.

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      P1.05-043 - Survival Following Surgical Resection of Lung Adenocarcinoma Stratified According to Morphological Sub-Type (ID 4494)

      14:30 - 14:30  |  Author(s): H. Balata, T. Edwards, C. Tennyson, P. Foden, A. Chaturvedi, P. Crosbie, R. Booton, M. Evison

      • Abstract
      • Slides

      Background:
      Lung adenocarcinoma is the commonest histological sub-type of Non-small cell lung cancer (NSCLC) and a leading cause of death worldwide. Identifying factors that may influence survival or the risk of recurrence following resection of lung adenocarcinoma may inform adjuvant strategies and the intensity of surveillance programs. The aim of this study was to assess the effect of morphological sub-type on survival following surgical resection.

      Methods:
      Patients who underwent surgical resection for non-small cell lung cancer between 2011 and 2014 at a tertiary thoracic surgical and lung cancer centre were identified from pathological records (n=1387). Patients with adenocarcinoma (n=705) were selected and the predominant morphological subtyping was recorded. Survival data was obtained from national death registries.

      Results:
      Of the 705 adenocarcinomas, Acinar (n=325), Lepidic (n=133) and Solid (n=131) were the most frequent histological subtypes identified. Numbers for other subtypes were small and therefor 3 year survival was not always possible to calculate.

      Survival by histological subtypes
      Histology No. of Deaths during follow-up 1 year survival 2 year survival 3 year survival
      Acinar (N=325) 93 90.5% 79.2% 68.3%
      Glandular (N=17) 5 94.1% - -
      Lepidic (N=133) 32 92.5% 84.4% 76.6%
      Micropapillary (N=3) 1 - - -
      Mixed (N=26) 9 84.6% 71.3% -
      Papillary (N=38) 11 78.9% 76.3% -
      Solid (N=131) 50 81.7% 67.1% 59.7%
      Unknown (N=31) 10 93.5% 71.5% -


      Conclusion:
      A difference in survival can be seen between the three commonest adenocarcinoma subtypes (Acinar, Lepidic and Solid) at 1, 2 and 3 years following surgical resection. Interpreting results on other sub-types is limited by small numbers. Lepidic and Solid have the best and worst survival rates respectively. Limitations include a lack of adjustment for pathological stage or co-morbidities and a lack of cancer-specific mortality data. Future studies may evaluate if the morphology of lung adenocarcinomas could have a role in defining adjuvant and surveillance strategies.

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      P1.05-044 - The Impact of IASLC 8th Edition Updates for T-Classification for Lung Cancer in a US Population-Based Surgical Resection Cohort (ID 6241)

      14:30 - 14:30  |  Author(s): M.P. Smeltzer, N.R. Faris, C. Fehnel, C. Houston-Harris, M.A. Ray, Y. Lee, M.B. Meadows, S. Signore, C. Mutrie, E.T. Robbins, R.U. Osarogiagbon

      • Abstract
      • Slides

      Background:
      Accurate staging of non-small cell lung cancer (NSCLC) is vital for prognostication and treatment selection. We evaluated the impact of the 8[th] Edition TNM (8E) T-classification in a US regional NSCLC resection database.

      Methods:
      Curative-intent NSCLC resections from 11 hospitals in 4 contiguous Dartmouth Hospital Referral Regions within 3 US states from 2009-2016 were re-staged based on 8E T-categorization. Survival analyses were conducted using the Kaplan-Meier method and proportional hazards models with adjusted hazard ratios (aHR) controlling for age, histology, grade, pN-category, and comorbidities. M1 patients and those who received neoadjuvant therapy were excluded.

      Results:
      The 2245 patients had a median age of 65, were 48% female, 78% white, 21% black. The 961 pT1 (8E) distribution was 10% pT1a, 52% pT1b, and 39% pT1c. The 793 pT2 (8E) patients were 82% pT2a and 18% pT2b. Of the 318 patients with pT3 (8E), 134 (42%) were pT2b based on the 7[th] Edition TNM (7E); of the 152 with pT4 (8E), 107 (70%) were pT3 based on 7E. There was no survival difference between pT1a and pT1b (p=0.83); pT1c had worse survival than pT1b (p<0.01; Figure 1a). Of the 145 patients previously classified as pT2b by 7E, 134 (92%) were upstaged to pT3. They had similar survival to those classified as pT3 in 7E (p=0.75). Of the 296 patients previously classified as pT3, 107 (36%) were upstaged to pT4. The upstaged patients had worse survival than 7E pT3 patients who were not upstaged, although not statistically significant (aHR:1.32, Figure 1b). Adjusted models confirm an increasing trend in the hazard of death with increasing stage, with the exception of pT1b. (aHR: pT1a=1.00, pT1b=0.89, pT1c=1.15, pT2a=1.38, pT2b=1.54, pT3=1.86, pT4=2.44). Figure 1



      Conclusion:
      This analysis independently corroborates the 8E re-classification for late stage patients in the US. However, we found no survival differentiation between tumors less than 2cm.

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      P1.05-045 - Adjuvant Chemotherapy for Patients with Stage IB Non Small Cell Lung Cancer (ID 4565)

      14:30 - 14:30  |  Author(s): J. Wang, Y. Yue

      • Abstract
      • Slides

      Background:
      The prognosis of stage Ib non-small cell lung cancer (NSCLC) remains poor, there’re much controversy over the necessity of adjuvant chemotherapy to them. The aim of this study is to investigate the clinical characters influencing prognosis of the stage Ib non-small cell lung cancer (NSCLC) and to explore the indication of postoperative chemotherapy.

      Methods:
      In total, 569 stage IB patients with NSCLC who underwent surgical resection with or without adjuvant therapy were included in this study. Cox proportional-hazards ratios were used to identify independent prognostic factors for survival. Kaplan-Meier survival curves were calculated to estimate survival rates.

      Results:
      Adjuvant chemotherapy, tumor size and performance status were independent prognostic factors in the univariate and multivariate analyses. Patients with tumor greater than 4 cm and patients with good performance status benefitted from adjuvant chemotherapy. On the contrary, to the patients with tumor less or equal to 4 cm or patients without good performance status, giving adjuvant chemotherapy is not better than giving surgery alone. Figure 1 Figure 2





      Conclusion:
      Adjuvant chemotherapy, tumor size and performance status were closely correlated with survival in the stage Ib NSCLC, patients with tumor greater than 4 cm and patients with good performance status benefitted from adjuvant chemotherapy.

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      P1.05-046 - Randomized Study of Adjuvant Docetaxel vs. Observation for Completely Resected StageⅠB-Ⅲa NSCLC with 11 Years' Median Follow-Up (ID 5722)

      14:30 - 14:30  |  Author(s): W. Zhong, X. Yang, H. Yan, R. Liao, Q. Nie, S. Dong, B. Jiang, Q. Zhou, J. Yang, Y.-. Wu

      • Abstract

      Background:
      Although previous meta-analyses have verified the significance of adjuvant chemotherapy, the role of adjuvant carbopatin plus docetaxel(DC) among patients with completely resected NSCLC with long periods of follow-up remains unclear.

      Methods:
      Eligible patients were randomly assigned to 4 cycles of DC or observation after complete resection. The primary end point was DFS; secondary ones were OS, the toxicity and safety of drugs. An increase of 15% in 1-year survival rate (observation arm 70%) with a sample size of 270 patients was considered significant.

      Results:
      This trial was suspended prematurely in June 2005 due to the negative survival benefits from chemotherapy in stage IB patients in the JBR10 trial. 82 patients were enrolled between 2002 to 2005(43 and 39 in each arm).Two arms were well-balanced on age, gender, histology, smoking history and staging. Median follow-up was 11 years(10.5-13y). DFS was marginally significantly longer in DC arm than observation (10.4 vs. 3.7y; HR=0.58; 95% CI, 0.33-1.03; P=0.06), as was 5-year DFS rates(63% vs. 41%, P=0.057). No statistical significance existed in OS (NR vs. 7.1y; P=0.103) or 5-year survival rates(76% vs. 61%; P=0.148). Multivariable analysis revealed patients receiving adjuvant DC(HR=0.54,95%CI 0.30-0.96,P=0.036) and with stage IB disease(HR=0.34,95%CI, 0.19-0.61,P<0.001) bore lower recurrence risk. In DC arm, 84% of patients received at least one cycle of DC, and 53% of patients finished four. Grades 3 adverse events occurred in 5%(2/43) in chemotherapy group. The time-varying endpoints showed adjuvant DC could delay the recurrence and mortality in the first postoperative 5ys, while two arms tended to be equivalent after 5ys. Figure 1



      Conclusion:
      This is the first randomized trial used DC as adjuvant chemotherapy suggesting a potentially significant role for completely resected early stage NSCLC with safety and compliance. Additionally, at least 10ys’ follow-up for each patient was vital to investigate the long-term time-varying recurrence and mortality pattern.

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      P1.05-047 - Early Mortality in Patients with Non-Small Cell Lung Cancer Undergoing Adjuvant Chemotherapy (ID 5523)

      14:30 - 14:30  |  Author(s): D. Morgensztern, P. Samson, S.N. Waqar, L. Du, S. Devarakonda, A. Masood, C. Robinson, V. Puri, R. Govindan

      • Abstract

      Background:
      Although adjuvant chemotherapy improves survival in patients with completely resected non-small-cell lung cancer (NSCLC) compared to surgery alone, it is also associated with potentially disabling or lethal adverse events. Since there is limited information on the early mortality among patients undergoing adjuvant chemotherapy, we used the National Cancer Data Base (NCDB) to calculate the percentage of deaths within the first 6 months from starting chemotherapy.

      Methods:
      The NCDB was queried for patients aged 18 or older, diagnosed with stage IB to IIIA NSCLC (AJCC 7[th] edition) from 2004 to 2012, who underwent surgery with negative margins followed by multi-agent chemotherapy, starting within 120 days from the surgical resection. Patients who received radiation therapy were excluded. Age groups were divided into <50, 51-60, 61-70, 71-80 and >80 years. Early mortality from months 1 to 6 were calculated and multivariate logistic regression was performed to identify clinical variables independently associated with mortality at six months from the date of initiation of adjuvant chemotherapy.

      Results:
      A total of 19,791 patients met the eligibility criteria. The median age was 65 (range 19-89). The percentage of deaths at 1, 2, 3, 4, 5 and 6 months were 0.6%, 1.3%, 1.9%, 2.6%, 3.3% and 4.2% respectively. The percentages of death at 6 months for each age group from < 50 years to > 80 years were 2.7%, 3.2%, 4.1%, 5.3% and 7.8% respectively. Factors independently associated with increased 6-month mortality included increased age, male gender, higher Charlson-Deyo co-morbidity score (CDCS), type of surgery, length of stay (LoS) > 6 days and 30-day readmission (Table).

      Conclusion:
      There is a high risk for early mortality among patients undergoing adjuvant chemotherapy for NSCLC, particularly in patients older than 70, with high co-morbidity score and a more complicated post-operative period.

      Table. Multivariable analysis
      Variable OR (95% CI) P-value
      Age
      ≤ 50 Reference Reference
      51-60 1.08 (0.74-1.60) 0.68
      61-70 1.33 (0.91-1.95) 0.15
      71-80 1.59 (1.06-2.38) 0.03
      > 80 2.27 (1.29-3.98) 0.004
      Gender
      Male Reference Reference
      Female 0.70 (0.59-0.82) < 0.001
      CDCS
      0 Reference Reference
      1 1.13 (0.95-1.34) 0.15
      2 1.58 (1.26-1.98) < 0.001
      Surgery
      Sub-lobar Reference Reference
      Lobectomy 0.72 (0.53-0.97) 0.03
      Pneumonectomy 0.97 (0.68-1.39) 0.87
      Stage
      IB Reference Reference
      II 1.29 (1.04-1.59) 0.02
      IIIA 2.28 (1.81-2.87) < 0.001
      LoS
      ≤ 6 days Reference Reference
      > 6 days 1.24 (1.06-1.46) 0.008
      30-day readmission
      No Reference Reference
      Yes 1.54 (1.20-1.99) 0.001


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      P1.05-048 - Effect of Adjuvant Chemotherapy on the Patterns and Dynamics of Recurrences in Resected Stage II(N1) Lung Adenocarcinoma (ID 4990)

      14:30 - 14:30  |  Author(s): B.J. Park, Y.S. Choi, J.H. Lee, H.K. Kim, J.H. Cho, J.I. Zo, Y.M. Shim, S. Shin, M. Ahn, J.S. Ahn, K. Park, J. Kim

      • Abstract
      • Slides

      Background:
      Although the complete surgical resection in most cases of the non-small cell lung carcinoma with N1 involvement is feasible, a considerable number of patients develop recurrence and the disease course is highly variable. Timing and pattern of recurrence are essential to explain strong prognostic heterogeneity, however, research focusing on these subjects have rarely been reported. We investigated the patterns of recurrences and event rates over time in patients with completely resected N1-stageII lung adenocarcinoma.

      Methods:
      We retrospectively reviewed the medical records of 333 patients who underwent a complete surgical resection for N1-stage II lung adenocarcinoma. Survival curves were generated using the Kaplan-Meier method, and the event dynamics was estimated using the hazard function.

      Results:
      The median recurrence-free survival was 36.8 months. The life table survival analysis showed that the 1-year, 3-year and 5-year recurrence free survival rates were 85.1%, 50.2% and 36.6%, respectively. Approximately 151(45.2%) patients experienced recurrence, and the patterns of recurrences included loco-regional in 41 patients (27.2%), distant in 68 (45.0%), and both in 42 (27.8%). Most commonly involved organs were the lung (n=77, 47.0%), followed by lymph nodes (n=41, 27.2%), bone (n=31, 20.5%), and brain (n=30, 19.9%). There were 228 patients received adjuvant chemotherapy. Patients treated with adjuvant chemotherapy showed better recurrence free survival (chemotherapy group vs non-chemotherapy group; median survival 42.5 months vs 25.4 months), and post-recurrence survival(chemotherapy group vs non-chemotherapy group; median survival 39.8 months vs 22.6 months) compared to those of patients without adjuvant chemotherapy. The multivariate analysis revealed that adjuvant chemotherapy was significantly correlated with recurrence free survival (p=0.004) and post recurrence survival (p=0.001). Patients underwent adjuvant chemotherapy had less distant (p=0.014) and less lung (p=0.045) recurrence, while there is no difference in loco-regional (p=0.837) and brain (p=0.997) recurrence. The recurrence hazard curve demonstrated similarly shaped and sized initial and second peak at 16 and 24months, followed by a smaller peak at 40months. The temporal distribution of the recurrence risk varied depending on adjuvant chemotherapy. A visual inspection of the hazard curves suggested that the patients without adjuvant chemotherapy exhibited earlier and higher first peaks with higher hazard rate over time.

      Conclusion:
      In the patients who underwent completely resected N1-stageII lung adenocarcinoma, adjuvant chemotherapy not only reduced the recurrence hazard, but also delayed the recurrence, altered pattern of recurrence and improved post-recurrence survival.

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      P1.05-049 - Neoadjuvant Erlotinib Treatment in Patients with Resectable Non-Small Cell Lung Carcinoma (ID 3788)

      14:30 - 14:30  |  Author(s): M.H. Van Gool, H.M. Klomp

      • Abstract

      Background:
      The value of neo-adjuvant therapy in patients with resectable non-small cell lung carcinoma (NSCLC) is limited. Recent advances in targeted therapy have provided novel treatment options for NSCLC with promising results. The Epidermal Growth Factor Receptor (EGFR) is over expressed or may harbour activating mutations in adenocarcinoma in particular. Inhibition of EGFR with tyrosine-kinase inhibitor (TKI) therapy has a favourable outcome in advanced stage patients with activating mutations. The purpose of this study was to prospectively evaluate 18F-FDG-PET metabolic response to neoadjuvant erlotinib, in patients with resectable NSCLC.

      Methods:
      This study was designed as a multicentre open-label phase II trial, performed in the Netherlands. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. Metabolic response evaluation was performed using FDG-PET/CT scan. Tumour FDG uptake and changes were measured by standardized uptake values (SUV). Metabolic response was classified using EORTC criteria. Metabolic response was compared to the histopathological response and survival.

      Results:
      From December 2006 until November 2010, 60 patients were enrolled in this study. In 43 patients (18 male, 25 female), FDG-PET/CT scans and histopathologic response monitoring were available. 14 patients (33%) showed a metabolic response. Histopathologic examination showed a response in 13 patients (30%). In predicting histopathologic response FDG-uptake showed an area under the curve of 72%. Metabolic responders show an improved overall and progression free survival in comparison to patients without metabolic response.Figure 1



      Conclusion:
      FDG-PET/CT may be used as a predictive tool to identify patients with advantage of neoadjuvant EGFR-TKI treatment in resectable NSCLC.

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      P1.05-050 - External Validation of a Prognostic Model for Squamous-Cell Lung Cancer and Impact of Adjuvant Treatment in >1,300 Patients (ID 5297)

      14:30 - 14:30  |  Author(s): E. Bria, S. Pilotto, I. Sperduti, G. Leuzzi, M. Chiappetta, F. Mucilli, G.B. Ratto, F. Lococo, P.L. Filosso, L. Spaggiari, S. Novello, M. Milella, P. Visca, A. Santo, A. Scarpa, M.V. Infante, G. Tortora, F. Facciolo

      • Abstract
      • Slides

      Background:
      A risk classification model able to powerfully discriminate the prognosis of resected squamous-cell lung cancer (R-SqCLC) patients (pts) was developed (Pilotto JTO 2015). Herein, we validate the model in a larger multicenter series of >1,300 R-SqCLC pts (AIRC project 14282).

      Methods:
      R-SqCLC pts in 6 different institutions (01/2002 - 12/2012) were considered eligible. Each patient was assigned with a prognostic score to identify the individual risk of recurrence, on the basis of the clinico-pathological data according to the develop model (age, T-descriptor according to TNM 7th edition, nodes, and grading). Kaplan-Meier analysis for disease-free/cancer-specific/overall survival (DFS/CSS/OS) was performed according to the published 3-class risk model (Low: score 0-2; Intermediate: score 3-4; High: score 5-6). Harrell’s C-statistics was adopted for model validation. The effect of adjuvant chemotherapy (ACT) was adjusted with the Propensity Score (PS).

      Results:
      Data from 1,375 pts from 6 institutions were gathered (median age: 68 years; male/female: 86.8%/13.2%; T-descriptor 1–2/3–4: 73.3%/26.7%; nodes 0/>0: 53.4%/46.6%; stages I-II/III-IV: 71.7%/28.3%); 384 pts (34.5%) underwent ACT. With a median follow-up of 55 months (95% CI 51-59), pts at Low-Risk had a significantly longer DFS in comparison with Intermediate- (HR 1.67, 95% CI 1.40-2.01) and High-Risk (HR 2.46, 95% CI 1.90-3.19) pts, as well as for CSS (HR 1.79, 95% CI 1.48-2.17; HR 2.33, 95% CI 1.76-3.07) and OS (HR 2.46, 95% CI 1.80-3.36; HR 4.30, 95% CI 2.92-6.33). C-statistics was 68.3 (95% CI 63.5-73.1), 68.0 (95% CI 63.2-72.9), and 66.0 (95% CI 61.6-71.1), for DFS, CSS and OS, respectively. 60-months DFS for Low-, Intermediate- and High-Risk pts was 51.0%, 33.5% and 25.8%, respectively (p<0.0001). 60-months CSS for Low-, Intermediate- and High-Risk pts was 82.7%, 64.7% and 53.3%, respectively (p<0.0001). 60-months OS for Low-, Intermediate- and High-Risk pts was 56.7%, 37.9% and 30.9%, respectively (p<0.0001). A significant benefit in DFS was found in favor of ACT (p=0.005), with no difference in CSS (p=0.57), although a trend in OS (p=0.16). Overall, no significant differences for ACT were found in DFS, CSS and OS when survival was corrected with PS analysis, although CSS and OS curves visually separate with a trend for ACT in Intermediate- and High-Risk pts.

      Conclusion:
      The prognostic performance of the previously developed model was validated in a larger R-SqCLC pts’ series. Considering the overall dismal prognosis of such disease, the efficacy of ACT requires to be clearly established for Intermediate- and High-Risk pts, as well as that should be questioned for Low-Risk pts.

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      P1.05-051 - Safety and Compliance Data of the Phase III Study of Adjuvant Chemotherapy in Completely Resected P-Stage I Non Small Cell Lung Cancer: JCOG0707 (ID 3877)

      14:30 - 14:30  |  Author(s): H. Kunitoh, H. Sakurai, M. Tsuboi, M. Wakabayashi, M. Okada, K. Suzuki, N. Ikeda, M. Takenoyama, Y. Ohde, M. Takahama, K. Yoshiya, I. Matsumoto, M. Yamashita, T. Marutsuka, H. Date, Y. Saito, Y. Yamashita, N. Okumura, S. Watanabe, H. Asamura

      • Abstract
      • Slides

      Background:
      Post-operative UFT (tegafur/uracil) has been shown to prolong survival of Japanese patients (pts) with completely resected, pathological (p-) stage I (T1> 2 cm) non small cell lung cancer (NSCLC). This trial aimed at estimating the efficacy of S-1 (tegafur/gimeracil/oteracil) compared to UFT as adjuvant therapy in this population.

      Methods:
      Eligible pts had undergone complete resection with lymph node dissection for p-stage I (T1-2N0M0, T1> 2 cm, by 5[th] Edition UICC TNM) NSCLC, within 56 days of enrollment. Pts were randomized to receive either oral UFT 250mg/M2/d for 2 years (Arm A), or oral S-1 80mg/M2/d for 2 weeks followed by 1 week of rest, for 1 year (Arm B). The initial primary endpoint was overall survival (OS). Based upon the results of monitoring in Jun. 2013, which showed the combined OS of the 2 arms better than expected (4-year OS of 91.6% vs. presumed 5-year OS of 70-76.5%), the study was judged to be underpowered. The study protocol was amended so that the primary endpoint was relapse-free survival (RFS). With a calculated sample size of 960, this study would detect the superiority of Arm B over Arm A with power 79% and a one-sided type I error of 0.05, assuming the 5-year RFS of 75% in Arm A and the hazard ratio of 0.75.

      Results:
      From Nov. 2008 to Dec. 2013, 963 pts were enrolled: median age 66 (range: 33 to 80), male 58%, adenocarcinoma 80%, p-T1/T2 46%/54%. Only 2 pts received pneumonectomy. All pts had completed protocol therapy. >Grade 3 toxicities (hematologic/nonhematologic) were observed in 15.9 (1.5/14.7) % in Arm A, and in 14.6 (3.6/11.9) % in Arm B, respectively. In Arm A, 59.5% of the pts completed protocol therapy, and 70.7% received UFT for >1 year, which was comparable to prior studies. In Arm B, 54.7% completed protocol therapy, and 69.9% received S-1 for > 6 months. There were 4 cases of on-protocol deaths, probably of cardio-vascular origin: 1 in Arm A and 3 in Arm B. Based on the 2[nd] interim analysis in Sep. 2015, the data and safety monitoring committee recommended the follow-up of pts without unmasking of treatment arms. Estimated combined 2-year OS and RFS were 97.3% and 89.6%, respectively.

      Conclusion:
      Both post-operative adjuvant therapies were feasible, with similar compliances. Main results will be available in 2019.

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      P1.05-052 - An Exploratory Analysis of Postoperative Adjuvant Chemotherapy with Tegafur-Uracil on Survival for Lung Adenocarcinoma (ID 4551)

      14:30 - 14:30  |  Author(s): M. Tsuboi, C. Hamada, H. Kato, M. Ohta

      • Abstract
      • Slides

      Background:
      The Eighth Edition of the TNM Classification (TNM 8[th]) for non-small cell lung cancer (NSCLC) proposes a more detailed classification of primary tumor diameter (T). Tegafur-uracil (UFT) improves survival in patients with stage I adenocarcinoma of the lung based on the results of Japan Lung Cancer Research Group (JLCRG: Kato H, et al. N Engl J Med. 2004). However, it is controversial whether the effect of UFT on survival in each T category be the same when TNM[8th] is adopted.

      Methods:
      This exploratory analysis was performed on the subgroup of 979 eligible patients in JLCRG study. The hazard ratio and the 95% confidence interval (CI) for overall survival in each T category of TNM 8[th] were estimated using stratified Cox proportional hazards models, stratified by sex and age. The overall survival in each T category was estimated by the Kaplan-Meier method.

      Results:
      The UFT group and the observation group were reanalyzed based on the new classifications of T category defined by TNM[8th], T1a (T, ≤1 cm), T1b (T, >1 to ≤2 cm), T1c (T, >2 to ≤3 cm), T2a (T, >3 to ≤4 cm), T2b (T, >4 to ≤5 cm), and T3 (T, >5 to ≤7 cm). The major prognostic factors did not differ significantly between these two groups in each T category. The benefits of UFT on overall survival varied in each T category (Table 1). Figure 1



      Conclusion:
      UFT tended to improve survival in each T category defined by TNM[8th], except for T1b, when compared to surgery alone.

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      P1.05-053 - Impact of Gender Difference on Adjuvant Chemotherapy after Radical Resection in Patients with Non-Small Cell Lung Cancer (ID 4081)

      14:30 - 14:30  |  Author(s): L. Yang, X. Zhai, W. Ziping

      • Abstract
      • Slides

      Background:
      Gender was an important prognostic factor in patients with advanced non-small cell lung cancer (NSCLC). However, there are few studies reporting the impact of gender difference on the efficacy of adjuvant chemotherapy (ACT) in NSCLC patients.

      Methods:
      900 patients (584 men and 316 women) who received post-operative ACT in the Cancer Hospital of the Chinese Academy of Medical Sciences between 2001 and 2013 with complete records in the database of the hospital were analyzed in this study for analysis. The primary end point was disease-free survival (DFS) in terms of gender. Survival analysis was performed using Kaplan–Meier estimates, log-rank tests and Cox’s proportional hazards regression analysis. Propensity score matching (PSM) was used, and survival analysis of the match data were carried out.

      Results:
      There was no significant difference in DFS between the two groups in terms of gender before propensity score was matched (105.857 weeks [95%CI 86.699, 125.015] vs. 95.714 months [95%CI 81.905, 109.523], P=0.575). Furthermore, no significant impact of gender on DFS was observed between the PS-matched groups (102.429 weeks [95%CI 80.078, 124.779] vs. 99.143 weeks [95%CI 66.539, 131.746], P=0.893).

      Conclusion:
      The results suggest that gender was not a prognostic factor on ACT after radical resected NSCLC. However, these conclusions are limited by the nature of this retrospective study, and therefore prospective trials are required for further verification.

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      P1.05-054 - Adjuvant Chemotherapy Uptake in Patients with NSCLC after Complete Resection: Single Institution/Single Area Experience (ID 3914)

      14:30 - 14:30  |  Author(s): V. Kolek, I. Grygarkova, J. Kultan, P. Jakubec, M. Szkorupa, J. Klein, C. Neoral, J. Skarda, T. Tichy, Z. Kolar

      • Abstract

      Background:
      Adjuvant chemotherapy (AC) is recommended in patients (pts) with stages IB (tumour of ≥4 cm in diameter), IIA, IIB, and IIIA of non-small cell lung cancer (NSCLC) after complete resection. According to metaanalyses it prolongs survival of pts in good PS and age less than 75 years. The selection of patients is influenced by the limited profit of AC, possible toxicity and the lack of predictive biomarkers. There are only few retrospective studies describing routine utilization of AC in specified areas. Presented AC uptake in stages II and III varies from 20 % to 24% in Canada and USA. .

      Methods:
      A retrospective study of AC uptake in pts with NSCLC from a Moravian region with 600.000 inhabitants was conducted, evaluation period was 2006-2013. Treatment strategy of all patients was discussed by surgeons and pneumo-oncologists on the interdisciplinary tumour boards before and after surgery. Uptake and compliance of AC was evaluated according to age, sex, TNM stages, type of surgery and other cofactors. AC was given in regimens using doublets of platinum with vinorelbine (rarely gemcitabine or paclitaxel). Vinorelbine was applied both intravenously (25 mg/m[2]) and orally (60 - 80 mg/m[2]). The choice of cisplatinum (80mg/m[2]) or carboplatinum (AUC 5) was based on patient preference, PS and comorbidities. .

      Results:
      Out of all 1557 pts with lung cancer, NSCLC was present in 1293 pts. 308 pts underwent curative-intent surgery and complete resection was achieved in 295 pts. 226 pts were pts with stages IB, II and IIIA and AC was applied in 183 pts (80.1%), in 34 (18.6 %) pts together with neoadjuvant chemotherapy. AC was not applied in 43 (19.9 %) pts after radical surgery due to worse PS, comorbidities, complications after surgery or patient´s refusal. The mean age of pts with AC was 65 years, 66,7% were men, 48,9 % women, 49,9 % were current smokers, 40,0% ex-smokers and 10,1 % non-smokers. Age, sex and smoking habits were not statistically different between pts with and without AC. Compliance with AC was very good, 82% of pts accomplished planned therapy.

      Conclusion:
      The optimal uptake of AC in routine practice depends on the intensive communication between the patient, surgeons and pneumoocologists. The individual decision is important in a context to the patients´ health status, tumour parameters and the potential risk/ benefit of therapy. Study was supported by grant AZV 16-32318A

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      P1.05-055 - Risk Factors of Postoperative Recurrence in Stage IA and IB Patients (ID 5606)

      14:30 - 14:30  |  Author(s): F. Hoshi, A. Sakurada, T. Hasumi, T. Sado, M. Noda, Y. Matsuda, S. Eba, H. Mitomo, T. Togo, M. Katahira, Y. Okada

      • Abstract

      Background:
      The 5-year survival rates of the patients with pathological stage IA and IB NSCLC have been reported 86-93% and 67-84%, respectively. Among stage I disease, patients with stage IA of tumor diameter over 20 mm as well as stage IB are recommended to take oral UFT as adjuvant chemotherapy for 2 years in Japan. Even after complete resection and such adjuvant therapy, we still observe recurrence at a certain rate. Identifying clinicopathological factors which is associated with recurrence would be beneficial to establish alternative strategy. The purpose of this study is to identify the predictive factors for recurrence in the patients with stage I NSCLC.

      Methods:
      A total of 742 stage I NSCLC patients who underwent complete resection in our hospital from 1996 to 2012 were retrospectively analyzed. Medical records of these patients were reviewed carefully. The median age was 66.4 years with 512 stage IA and 281 stage IB. Histopathologically, there were 590 adenocarcinoma, 150 squamous cell carcinoma, 32 large cell carcinoma, and 21 other histology cases. Surgical procedure was segmentectomy, lobectomy, and pneumonectomy for 46, 588, and 8 patients, respectively. Clinicopathological factors such as smoking history, histology, pathological vascular invasion (v), and lymphatic vessel invasion (ly) were analyzed.

      Results:
      Recurrence occurred in 132 cases. Multivariate analysis showed that T factor, v(+), ly(+), and smoking history have statistical significance with recurrence. n pT1a and T2a cases, there were no statistical significance between recurrence and pathological ly(+) and/or v(+). But only in T1b cases, ly(+) and/or v(+) had statistical significance with recurrence.

      Conclusion:
      We identified that T factor, v, ly, and smoking history were predictive factors for recurrence in stage IA and IB NSCLC patients. Because of good prognosis, pT1b patients whose both v and ly were negative may not take UFT as adjuvant chemotherapy.

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      P1.05-056 - Increased Risk of Postoperative Recurrence in EGFR-Positive Stage IA to IB Invasive Lung Adenocarcinoma (ID 4811)

      14:30 - 14:30  |  Author(s): M. Ito, Y. Miyata, K. Kushitani, T. Yoshiya, Y. Tsutani, K. Konishi, Y. Takeshima, M. Okada

      • Abstract
      • Slides

      Background:
      Somatic mutations of EGFR represent one of the most frequent genetic aberrations in lung adenocarcinoma and response to tyrosine kinase inhibitors (TKIs) has been favourable in EGFR-positive and advanced lung adenocarcinoma patients. The prognostic significance of EGFR mutations as oncogenic driver mutations in early-stage lung adenocarcinoma has yet to be determined. We aimed to evaluate the oncological significance of EGFR mutations in early-stage lung adenocarcinoma

      Methods:
      Four hundred and seventy-three consecutive lung adenocarcinoma patients who underwent surgical resection for pathological N0M0 disease, between January 2007 and December 2013, were retrospectively reviewed. The prognostic significance of EGFR mutation status was evaluated in 407 cases from these patients. Overall survival (OS) and recurrence-free interval (RFI) curves were estimated using the Kaplan-Meier method and compared using a log-rank test. Univariate and multivariate analyses were performed using a Cox proportional hazards model.

      Results:
      There was no statistical significance in the 5-year OS (89.3 vs. 95.3%, P = .20, HR = 1.605) or RFI (86.5 vs. 93.5%, P = .06, HR = 1.956) rates between the EGFR-positive (n=183) and EGFR-negative (n=224) groups. Considering the risk of recurrence and positive EGFR mutation status, OS and RFI rates were subsequently calculated among specific histological subtypes. After adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive mucinous adenocarcinoma (IMA) cases were excluded, all analysed cases were ≤5.0 cm in tumour diameter and were classified as pathological Stage IA-IB. Among specific histological subtypes, the 5-year RFI (81.5 vs. 92.4%, P = .04, HR = 2.160) but not OS rate (86.8 vs. 94.3%, P = .31, HR = 1.499) was significantly poorer in EGFR-positive cases compared to EGFR-negative cases. Univariate analysis, excluding AIS, MIA, and IMA, identified a pathological tumour size of >3.0 cm, a highly malignant subtype (micropapillary or solid predominant adenocarcinoma), pleural/lymphatic/vascular invasion, and a positive EGFR mutation status as significant negative predictive factors for RFI. Multivariate analysis confirmed pleural invasion and a positive EGFR mutation status as independent negative predictive factors for RFI.

      Conclusion:
      EGFR mutation status is a predictive factor for postoperative recurrence in early-stage lung adenocarcinoma, with the exception of AIS, MIA, and IMA. The risk of recurrence should be considered with EGFR mutation status and predominant histological subtype in resected early-stage lung adenocarcinoma patients.

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      P1.05-057 - Prediction of Early Recurrence in Patients with Stage I and II Non-Small Cell Lung Cancer Using FDG PET Quantification (ID 4872)

      14:30 - 14:30  |  Author(s): M. Arvanitakis, I.A. Burger, S. Steiger, B. Sick, W. Weder, S. Hillinger

      • Abstract

      Background:
      Although surgical resection remains the optimal treatment for early-stage NSCLC, up to 50% of patients with stage I and II relapse and die within 5 years after curative resection. Therefore prognostic markers are important as these patients might benefit from adjuvant therapy. The goal of this study was to evaluate established PET quantification metrics including: maximal standard uptake volume (SUV~max~), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) as prognostic markers for early recurrence and overall survival in resected early stage lung cancer.

      Methods:
      Between January 2003 and December 2010 182 surgically resected patients with stage I-II NSCLC who underwent 18 F FDG PET/CT less than one month prior to surgery have been evaluated. All patients had at least 5 years of follow-up. Cox proportional hazard model was used to determine the association between variables and survival respectively time to recurrence. For the multivariate analysis the following variables have been included: tumor size on CT, age tumor stage, histology, SUV~max~, TLG (for TLG~42%~ (threshold at 42% SUV~max~) and TLG~2.5 ~(cut-off at SUV 2.5) and MTV~42%~ and MTV~2.5~). To identify high-risk patients we used survival trees.

      Results:
      133 patients were included, 71 with adeno carcinoma, 62 with squamous cell carcinoma. TLG~2.5~ and MTV~2.5~ values have been a significant prognostic factor for recurrence (P<0.0001). Patients with a MTV2.5 above 42 cm[3] had a mean recurrence time of 0.8±0.9 years, while patients with MTV2.5 ≤ 42 cm[3 ]recurred within 2.8±1.3 years. Using the survival tree models TLG~42%~ has been the first choice variable for discriminating high risk patients for DOD (dead of disease) independent from histological type, whereas MTV~2.5~ has been the first choice for DOD in adeno carcinoma patients.

      Conclusion:
      TLG and MTV may be useful prognostic variables in stage I-II NSCLC depending on the tumor type. Using a cut-off at 42 cm[3 ]for early stage adenocarcinoma patients a high risk of recurrence within one year might be identified and adjuvant therapy following surgical resection could improve outcome for those patients.

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      P1.05-058 - Prognostic Factors of Post-Recurrence Survival in Resected Stage I Non-Small Cell Lung Cancer (ID 3819)

      14:30 - 14:30  |  Author(s): Y. Kubouchi, Y. Kidokoro, T. Oono, Y. Yurugi, M. Wakahara, K. Miwa, K. Araki, Y. Taniguchi, H. Nakamura

      • Abstract
      • Slides

      Background:
      Recurrence after surgical resection is a major obstacle in the cure and long term survival, and has become the most common cause of death. However prognostic factors and efficacy of the therapy after recurrence remain controversial. We evaluated the prognostic factors of post-recurrence survival (PRS) in patients of resected stage I NSCLC.

      Methods:
      Of the 551 patients who underwent a complete resection for stage I NSCLC between 2005 and 2013, 89 (16.2%) patients who experienced a postoperative recurrence were selected for this retrospective study. Case of preoperative therapy and death within 30 days of operation were excluded. Clinicopathological factors were analysed for PRS by univariate and multivariate analyses. Univariate and multivariate analyses were performed by using the Cox proportional hazards model.

      Results:
      89 patients experienced recurrence during a median follow-up period of 54.0 months. The median recurrence free interval (RFI) was 16.0 months. The 1-year PRS and 3-year PRS were 65.6% and 44.7%, respectively. The pattern of recurrence was loco-regional in 24(27.0%), and distant in 65(73.0%). The most common organ sites of recurrence were contralateral lung in 42 patients, the ipsilateral thorax in 24, bone in 24, brain in 12, liver in 9. Univariate analysis indicated that male sex (p=0.035), smoking history (p=0.034), larger tumor size over 25mm (p=0.008), stage IB (p=0.044), squamous cell carcinoma (p=0.001), RFI within 16 months (p=0.011), presence of symptoms (p=0.001), bone metastasis (p=0.001), liver metastasis (p=0.009) and not having received any treatment (p<0.001) were significant prognostic factors of worse PRS. Multivariate analysis revealed that larger tumor size over 25mm (p=0.05), RFI within 16 months (p=0.05) and no treatment for recurrence (p<0.001) were the independent prognostic factors for poor PRS. The result of multivariate analysis of PRS determined that post-recurrence therapy had a strong impact on PRS. Therefore, we further examined PRS in 61 patients who underwent any post-recurrence therapy. For patients receiving treatment for recurrence, bone metastasis (p=0.042) was a significant predictive factor of worse PRS, while treatment with EGFR-TKIs (p=0.045) was a good prognostic factor.

      Conclusion:
      This study showed that tumor size, RFI, and post-recurrence therapy were prognostic factors for PRS. In the patients who underwent treatment for recurrence, bone metastasis and treatment with EGFR TKIs were independent prognostic factors. Although further validation is needed, this information is important for future design of clinical trials for therapy after recurrence.

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      P1.05-059 - Factors Associated with Recurrence and Survival in Patients with Curatively Resected Stage IA Adenocarcinoma of the Lung (ID 5990)

      14:30 - 14:30  |  Author(s): M. Harada, H. Horio

      • Abstract

      Background:
      Even when meticulously clinically and pathologically studied, completely resected stage IA adenocarcinoma of the lung does recur. However, there are few data regarding the patterns of recurrences and their risk factors in this population. Therefore, this study characterizes cancer recurrence and its risks and assesses recurrence-free survival in patients with curatively resected stage IA adenocarcinoma.

      Methods:
      Between January 1990 and December 2005, a total of 214 patients were given a final diagnosis of pathologic stage IA (UICC-7) adenocarcinoma of the lung. The medical records of these patients were retrospectively reviewed with regard to patient characteristics, tumor pathologic findings and follow up status. Survival was analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis.

      Results:
      The median follow up after curative resection was 83 months. Cancer recurred in 28 patients (13%). Among them, local recurrence occurred in 10 patients (5%), whereas distant recurrence occurred in18 patients (8%). Recurrence earlier and later than 5 years after surgery was in 15 patients (7%) and in 13 patients (6%), respectively, with nearly constant risk. At 5 years after index resection, 175 patients (82%) were alive without evidence of cancer recurrence, 11 patients (8%) had experienced recurrence of cancer but still alive and 11 patients (5%) had died with non-cancer causes. Recurrence-free 5- and 10-year survival rates were 92.5 and 70.0%, respectively. Univariate analysis revealed five significant prognostic factors: gender (p=0.0177); lepidic component (p =0.0007); tumor location (p=0.0099); pleural invasion (p=0.0274) and lymphatic or vascular vessel invasion (LVI) (p< 0.0001). Multivariate analysis revealed lepidic component, tumor location, and LVI as significant factors. Hazard ratios for recurrence were 0.381 for having lepidic component (95% CI, 0.147-0.979; p= 0.0451), 0.361 for right sided tumor (95% CI, 0.188-0.692; p= 0.0022), and 2.785 for having LVI (95% CI, 1.392-5.555; p= 0.0038).

      Conclusion:
      Surgically “cured” stage IA adenocarcinoma of the lung recurs. Our analyses indicate no-lepidic component, tumor location, LVI as an independent indicator for cancer recurrence. Identifying high-risk patients for recurrence will simplify decision making for postoperative treatment strategies.

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      P1.05-060 - Adherence to Surveillance Guidelines in Resected NSCLC: Physician Compliance and Impact on Outcomes (ID 4624)

      14:30 - 14:30  |  Author(s): C. Ho, J. Siegfried, K. Remo, J. Laskin

      • Abstract

      Background:
      Guidelines on resected NSCLC have varying recommendations on appropriate post-operative surveillance. There is general consensus that patients require follow up q6m with clinic visits or CT scans for the first 2 y. This study evaluated compliance with surveillance guidelines and the impact on outcomes.

      Methods:
      The BC Cancer Agency provides comprehensive cancer control for a population of 4.5 million. Inclusion criteria included referred patients from 2005-2010, resected stage Ib/II NSCLC, minimum 2 y f/u at the BCCA, no prior lung cancer diagnosis. Retrospective chart review collected baseline parameters, follow up visits, CT imaging, recurrence and death.

      Results:
      479 were referred and 263 were eligible. Baseline characteristics median age 68, male 52%, current/former/never smoker 38/52/10%, stage Ib/II 51/49%, squamous/non 30%/70%, wedge/lobectomy/pneumonectomy 8/76/16%, adjuvant chemotherapy 46%. Adherence to 4 interventions in 2 y: clinic visits 62%, CT scans 18%, visit and/or CT 67%. Multivariate analysis (MVA) for predictors of guideline adherence demonstrated only stage was significant. Recurrence rate was 46% at 2 y with patterns of recurrence and treatment in table 1. Surveillance below vs per/above guidelines; PFS 26.6 m vs 22 m (p=0.54), OS 47 m vs 41.8 m (p=0.27).

      Follow up visits and/or CT scans below guidelines n=87 Follow up visits and/or CT scans per or above guidelines n=176 p value
      Recurrence within 2 years 32 (37%) 88 (50%)
      Method of detection 0.41
      Surveillance 18 (56%) 41 (47%)
      Patient 14 (44%) 47 (53%)
      Distribution of recurrence 0.16
      Second primary 1 (3%) 2 (2%)
      Locoregional recurrence only 10 (31%) 14 (16%)
      Metastatic 21 (66%) 73 (82%)
      Curative intent treatment at recurrence 5 (16%) 6 (7%) 0.16
      Palliative chemotherapy 7/27 (26%) 32/82 (39%) 0.25


      Conclusion:
      Compliance with follow up recommendations for resected NSCLC was 67% in our study. Guideline conformity did not increase the rate of curative intent therapy at recurrence due to metastatic presentation nor did it increase the proportion of patients treated with palliative chemotherapy. Better adjuvant treatment and surveillance options need to be developed for resected NSCLC.

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      P1.05-061 - Increased Treatment-Related Toxicity in Patients with Early-Stage Non-Small Cell Lung Cancer and Co-Existing Interstitial Lung Disease (ID 4622)

      14:30 - 14:30  |  Author(s): H. Chen, A.V. Louie, E.J. Nossent, G. Boldt, D. Palma, S. Senan

      • Abstract
      • Slides

      Background:
      Treatment options for early-stage non-small cell lung cancer (ES-NSCLC) are generally well-tolerated. Minimally-invasive surgical techniques, stereotactic ablative radiotherapy (SABR) and radiofrequency ablation (RFA) can all achieve post-treatment mortality of <1% in clinical trial settings. There has been increasing evidence to suggest that patients with interstitial lung disease (ILD) suffer severe toxicity after treatment for NSCLC. Treatment-related toxicity may result in death and may take the form of acute exacerbations of existing ILD following surgery or RFA, or severe radiation pneumonitis following SABR.

      Methods:
      We performed a systematic review of literature in compliance with PRISMA guidelines to investigate the rate of treatment-related toxicity and mortality following treatment for ES-NSCLC. The Medline and EMBASE databases were queried from respective dates of inception to January 2016. Treatment modalities included in the search strategy were surgery, SABR, RFA, particle beam therapy and conventionally-fractionated radiotherapy. Results were summarized with weighted statistics according to the sample size of individual studies.

      Results:
      A total of 3,054 unique records were screened and 282 full texts were reviewed. Forty-nine journal articles were included in the final analysis, with 92% of studies being retrospective in design. Thirty surgical studies with 1716 patients, 13 SABR studies with 122 patients, 3 RFA studies with 46 patients, 2 proton beam therapy (PBT) studies with 17 patients and one carbon ion beam therapy (CIBT) study with 5 patients were included. Most patients in non-surgical studies were medically inoperable. Treatment-related or 30-day post-operative mortality was 2.3%, 15.5%, 8.7%, 5.8% and 0%, respectively, for surgery, SABR, RFA, PBT and CIBT. Treatment-related acute exacerbation of ILD or radiation pneumonitis > grade 3 was 12%, 25%, 25%, 12.5% and 20%, respectively. For patients treated with surgery, 5-year overall survival (OS) was 31.4% to 61.6% (median 54.2%) for patients with ILD and 70.5% to 88.3% (median 83.0%) for patients without ILD. For medically inoperable patients treated with SABR, 2 to 3-year OS was 0% to 53.8% (median 48.8%) for patients with ILD and 54% to 86.7% (median 70.8%) for patients without ILD. Studies that included only patients with idiopathic pulmonary fibrosis reported higher treatment-related toxicity compared to other studies.

      Conclusion:
      An elevated level of treatment-related toxicity is observed in patients treated for ES-NSCLC with co-existing ILD. Medically inoperable patients experienced high levels of treatment-related mortality. For surgery and SABR, overall survival was worse for patients with ILD compared to those without ILD.

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      P1.05-062 - Is Lung Microwave Thermoablation a Valid Alternative to Surgery in High Risk Patients? A Propensity Match Analysis (ID 5648)

      14:30 - 14:30  |  Author(s): P. Mendogni, D. Tosi, A. Palleschi, L. Rosso, I. Righi, M. Montoli, F. Damarco, C. Bareggi, C. Marenghi, M. Nosotti

      • Abstract

      Background:
      Surgery is considered the best treatment in Stage I non small cell lung cancer. Local non–surgical therapies (radiotherapy, thermoablation) are becoming valid alternative to surgery in high risk patients (poor cardiac or pulmonary function, elderly patients).

      Methods:
      Patients submitted in our Department to Microwave thermoablation (MW) were compared with a cohort of patient submitted to lung lobectomy in the same period of time, abstracted from our database with a propensity match method. The study was retrospective on data recorded prospectively. Primary endpoint was overall survival.

      Results:
      From June 2009 to October 2014 in our Department, 36 patients underwent MW for Stage I non-small cell lung cancer (NSCLC) or lung metastasis. From our database were abstracted 41 patients with a propensity match method, submitted to lung lobectomy. Two groups were comparable by age, diagnosis, stage and gender. MW group resulted elder than Surgery group (75,5 vs 72,2 years; p<0,001). Lesion diameter was greater in MW group (20,9 vs 26,5 cm; p<0,001). Overall survival, analyzed by actuarial survival curve, was comparable (Logrank test p=0,2).

      Conclusion:
      In our experience, in a propensity match evaluation, lung MW thermoablation resulted non inferior than lung lobectomy in terms of overall survival. Even though surgery is still considered the first choice in patients affected by Stage I NSCLC or lung metastasis, lung MW thermoablation is confirmed as a valid alternative treatment in high risk patients. Randomized prospective studies are mandatory.

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      P1.05-063 - Multicenter Observational Study of Patients with Resected Early-Staged NSCLC, Who Were Excluded from an Adjuvant Chemotherapy Trial (ID 4713)

      14:30 - 14:30  |  Author(s): T. Hishida, M. Tsuboi, K. Yoh, K. Takamochi, H. Sakurai, Y. Goto, T. Shukuya, Y. Ohashi, H. Kunitoh

      • Abstract
      • Slides

      Background:
      From Nov. 2008 to Dec. 2013, the Japan Clinical Oncology Group (JCOG) conducted a randomized phase III trial (JCOG0707), which compared the survival benefit of UFT and S-1 for completely resected pathological (p-) stage I (T1>2 cm and T2 in the 6th TNM classification) NSCLC and a total of 963 patients were enrolled. Recently, there is a growing concern that those who participated in clinical trials are highly selected and do not represent the “real-world” population. Hereby, we conducted a multicenter observational study of patients excluded from JCOG0707 trial during the study period.

      Methods:
      We retrospectively collected and analyzed the patients’ backgrounds, tumor profiles, post-surgical treatment of the patients who underwent R0 resection of p-stage I (T1>2cm and T2 in TNM 6th) NSCLC by lobectomy or larger lung resection but were excluded from JCOG0707 from Japanese multi-centers.

      Results:
      Of the 48 institutions which took part in JCOG0707, 34 (enrolling 917 or 95.2% of all JCOG0707 patients) participated in this multicenter study, and 5006 patients were enrolled. Among them, 2617 (52.3%) patients fulfilled the eligibility criteria, but were not enrolled to JCOG0707 mainly due to patients’ decline (69.2%), or physicians’ discretion (20.5%). The accrual rate to JCOG0707 was various by institutions (4.1 to 46.1%), but was 25.9% (917 / [917+2617]) as a whole. Total number of p-stage I and eligible patients at each institution did not correlate the accrual rate (R2=0.003 and 0.046). In the remaining 2389 (47.7%) patients, main ineligible reasons included the existence of active multiple cancer (29.1%), physicians’ decision based on the patients’ comorbidities (19.4%), delayed recovery from surgery (14.1%), and high age ≥81 years (10.7%). Majority of patients received no adjuvant chemotherapy (n = 3338, 66.7%). This proportion differed according to p-T factor (T1: 75.3% vs. T2 : 57.8%, p<0.001) and the JCOG0707 eligibility (ineligible population: 77.6% vs. eligible population: 56.7%, p<0.001). Standard UFT and experimental S-1 were given in 1550 (31.0%) and 21 (0.4%) patients, respectively. Among those who received adjuvant UFT, 971 (62.6%) took UFT for one year or longer.

      Conclusion:
      Only selected population of candidate patients, even if they met the eligibility criteria, were enrolled to JCOG0707 adjuvant chemotherapy trial for early-stage NSCLC. The “excluded” patients were mainly treated with observation alone or standard UFT treatment. Further analysis of this “excluded” population, including long-term survival, should be necessary for external validation of the randomized trial results.

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      • Abstract

      Background:
      Multifocal lung cancer (MFLC) is a clinical scenario that is more frequently diagnosed with the increased utilization of computed tomography of the chest. The management of MFLC is limited by the difficulties in accurately staging a patient and understanding whether lesions represent separate primaries or metastatic disease. We sought to understand the global practice patterns of MFLC.

      Methods:
      A questionnaire was developed and sent to members of the International Association for the Study of Lung Cancer through REDCap electronic data capture tools to assess how a hypothetical patient with synchronous MFLC would be evaluated and treated. Responses were compared by specialty using the χ[2] test.

      Results:
      We received 221 responses from multiple specialists (74 Thoracic Surgeons, 68 Medical Oncologists, 32 Pulmonologists, 22 Radiation Oncologists and 25 others) primarily from Europe (n=76) and North America (n=62). Over 87 respondents reported 20 or more years of experience in the field. Most respondents recommended surgery (n=140, 63%), but many others did not (n=39, 18%) or were uncertain (42, 19%). Surgeons (n=60/74, 81%) were significantly more likely to recommend surgery than medical oncologists (n=37/68, 54%), pulmonologists (n=21/32, 66%) or radiation oncologists (n=10/22, 45%; p=0.01). Lobectomy of the primarily involved lobe (n=42, 30%) and various combinations of segmentectomies (n=48, 34%) were the most commonly recommended surgical approaches. Of those who recommended surgery, most would obtain a PET/CT to rule out distant metastasis (n=135, 97%) and an MRI to rule out brain metastases (n=76, 55%) but in the absence of radiographic lymph node involvement most would not stage the mediastinum by bronchoscopy or mediastinoscopy prior to resection (n=90, 65%). Many preferred obtaining multiple biopsies of separate lesions (n=139, 63%) and genetic testing of these lesions (n=146, 66%) to assess their histologic and genetic agreement. In the case that surgery was not offered or declined, more respondents recommended radiation (n=114, 52%) than those who did not (n=50, 23%) or were uncertain (56, 26%). Similarly, in the absence of surgery or radiotherapy, slightly more respondents recommended systemic chemotherapy (n=83, 38%) than those who did not (n=79, 36%) or those who were uncertain (n=59, 27%).

      Conclusion:
      Although most respondents favored surgery when feasible for MFLC, many were uncertain as to the optimal approach for this disease. Optimal management of MFLC requires greater evidence from studies which is currently lacking, and current strategies are strongly influenced by specialty bias.

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      P1.05-065 - Usage of Chest Radiography or Computed Tomography in Post-Treatment Surveillance for Stage I and II NSCLC: Influence on Survival (ID 5524)

      14:30 - 14:30  |  Author(s): L. Alberts, R. Karzijn, F.N. Hofman, S.Y. El Sharouni, E.A. Kastelijn, F.M.N.H. Schramel

      • Abstract

      Background:
      Survivors of stage I and II non-small-cell lung cancer (NSCLC) have higher risk of developing a recurrence of disease or a second primary lung cancer compared to the general population. Post-treatment surveillance (visits and radiological imaging) is needed for early recognition. Although a myriad of international guidelines exist regarding post-treatment surveillance no consensus has derived yet. The aim of this study was to further establish the appropriate follow-up modality: chest radiography with or without a computed tomography (CT) scan.

      Methods:
      In this retrospective study all patients diagnosed with a recurrence of previously treated stage I and II NSCLC between 2008 and 2014 at St Antonius Hospital, Nieuwegein the Netherlands, were included. We categorized patients after treatment in two imaging modality groups: one group received only chest radiographs (CR group) and the other group received ≥ one thoracic CT scan (CT group). The overall survival (OS), 1- and 3-yearssurvival and progression free survival (PFS) were compared between the groups by using the Kaplan-Meier survival, the log rank-test and the Cox proportional hazard model.

      Results:
      73 patients were enrolled; 50 patients in the CR group and 23 patients in the CT group. The median overall survival was 22.1 months (interquartile range (IQR) = 14.2-39.2 months) in the CR group compared to 27.2 months (IQR= 18.5-53.2 months) in the CT group (p = 0.12). After adjustment for the Eastern Cooperative Oncology Group (ECOG) performance score and morphology was made, both the overall survival (hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 0.76-2.70, p = 0.27) and the progression free survival (HR = 1.16, 95% CI = 0.65 – 2.07, p = 0.63) were not different in the CR group compared to patients in the CT group. There was no significant difference in the 1- and 3-yearssurvival either. The 1-yearssurvival was 80% in the CR group versus 91% in the CT group (HR = 5.50, 95% CI = 0.52-58.01, p = 0.16) and the 3-yearssurvival was 30% versus 39% (HR = 1.50, 95% CI = 0.74-3.01, p = 0.29).

      Conclusion:
      We showed that follow-up with a chest radiography, in patients with earlier diagnosed and curative treated stage I and II NSCLC, did not give inferior clinical outcomes compared to follow-up with a CT scan. Although more investigation is needed, this study might indicate that there is no need for a CT scan as standardized follow-up.

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      P1.05-066 - Impact of Micropapillary Pattern in Nodal Upstaging of Lung Adenocarcinoma 2cm or Less (ID 5189)

      14:30 - 14:30  |  Author(s): H. Yamazaki, Y. Kondo, M. Naito, H. Nakashima, Y. Matsui, K. Shiomi, Y. Satoh

      • Abstract

      Background:
      Clinical and pathological determinations of lymph node staging are critical in the treatment of lung cancer. However, upstaging of nodal status frequently is necessitated by postoperative findings. It is now being recognized that lung adenocarcinoma (LAC) with tumor cells arranged in a micropapillary pattern (MPP) is more malignant than those without such pattern. Thus, this study was conducted to evaluate clinicopathologic features that impact nodal upstaging in patients with small-sized(≦2cm) LACs with MPP(LAC-MPP).

      Methods:
      We retrospectively reviewed the 182 radically resected lung adenocarcinomas at the Kitasato University Hospital, Japan, from January 2005 to December 2015. MPP was defined as a small papillary tumor cell tuft without an obvious fibrovascular core. Tumors with ≧1% of their tumor cells arranged in a MPP were diagnosed as LAC-MPP, while the remainders were diagnosed as conventional LAC. The histological subtypes and differentiation grade of LAC were determined according to the 4th WHO classification. The registry date of the patients with LAC and LAC-MPP were analyzed, and the clinicopathologic profiles and surgical outcomes of the patients were evaluated.

      Results:
      One hundred and sixty (88%) of the total 182 were LAC whereas 22(12%) were LAC-MPP. Among the two groups, there is no significant difference in age, sex, smoking habit, preoperative serum CEA level, or surgical procedures. Compared with the LAC, the LAC-MPP had worse statuses for lymphatic invasion (p=0.0096), pleural invasion (p=0.002), postoperative lymph node metastases (p<0.001) and postoperative recurrence (p=0.002). On the other hand in clinical stages, pleural lavage cytology, and postoperative stages, there is not significant deference statistically. Median follow up time was 48 months. The five-year overall survival rates were 92% in LAC group and 85% in LAC-MPP, statistically not significant deference (p=0.98). Also with regarding to the median relapse free survival rates, no significant difference was found between two groups (p=0.14).

      Conclusion:
      The follow-up term of patients was limited in this study. But, we concluded that LAC-MPP should be considered as an aggressive disease showing nodal upstage. Although lymph node metastasis and lymphatic infiltration should be usually reported in LAC-MPP patients, these are difficult to detect by preoperative imaging tools such as CT and PET canning. Therefore, MPP could be important factor to determine the indications for limited resection for LAC patients even if small-sized(≦2cm) LAC- MPP.

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      P1.05-067 - Consultation with Medical Oncology Less Common in Elderly Patients with Resected Stage II Nonsmall Cell Lung Cancer (ID 4679)

      14:30 - 14:30  |  Author(s): S. Li, G. Darling, A. Farrelly, K. Forster, K. Woltman, J. Stiff, W. Evans

      • Abstract

      Background:
      Adjuvant chemotherapy (AC) is guideline recommended standard of care for resected Stage II NSCLC patients in Ontario. Despite evidence of a significant survival benefit, uptake of AC has been lower than expected and has remained unchanged since 2008 at 50-55%. Factors that may preclude use of chemotherapy include comorbid medical conditions, socioeconomic and demographic factors and the opportunity for consultation with a medical oncologist (MO). This study evaluated: 1) patient opportunity for a consultation with a MO, and 2) differences between patients who had a consultation and those who did not.

      Methods:
      Stage II NSCLC adult patients diagnosed between 2010 and 2013 were identified using the Ontario Cancer Registry. Complete surgical resections and consultation with a MO were identified using multiple administrative databases. Receipt of guideline-recommended AC within 120 days after resection, and consultation with MO within 30 days prior and 90 days after resection were determined. Guideline-recommended AC includes platinum based regimens, including receipt outside a Regional Cancer Center (RCC). Alternative treatments were defined as non-platinum based chemotherapy or radiotherapy. Socioeconomic and demographic characteristics were compared between patients who received a consultation and those who did not. Characteristics associated with receiving a consultation were assessed using univariable analysis and multivariable logistic regression.

      Results:
      Of 778 Stage II resected NSCLC patients who survived at least 120 days, 40.9% (n=318, CI: 37.40–44.42) received guideline-recommended AC, 3.0% (n=23, CI: 1.70-4.40) received alternative treatment in an RCC, 11.2% (n=87, CI:8.95-13.50) received chemotherapy outside of an RCC hospital, and 45.0% (n=350, CI:41.45-48.56) of patients did not have systemic treatment after surgery. Overall, 72.9% (n=567) of patients had a consultation with a MO within 30 days prior or 90 days after resection. Of 350 patients who did not receive AC, 219 (62.6%) had a MO consultation. Median time from resection to consultation was 29 days, and did not differ between treatment groups (p=0.35). Age was a significant determinant for MO consultation. Adjusting for sex, patients aged 41-60yrs (OR 2.38, CI:1.25-4.56) and 61-70yrs (OR 2.46, CI:1.35-4.49) were significantly more likely to have a consultation versus patients >80 yrs. Other characteristics were not significantly associated with having a consultation.

      Conclusion:
      Although uptake of guideline-recommended AC is lower than expected (52.1%, CI:48.48-55.62), the majority of patients had an opportunity to discuss this treatment option with a MO. Patients over 80yrs were significantly less likely to have this consultation.

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      P1.05-068 - Elderly Patients with Resected Stage II Nonsmall Cell Lung Cancer Are Less Likely to Have a Consultation with a Medical Oncologist (ID 4814)

      14:30 - 14:30  |  Author(s): G. Darling, S.X.L. Li, A. Farrelly, K. Forster, K. Wortman, J. Stiff, W.K. Evans

      • Abstract
      • Slides

      Background:
      Adjuvant chemotherapy (AC) is guideline recommended standard of care for resected Stage II NSCLC patients in Ontario. Despite evidence of a significant survival benefit, uptake of AC has been lower than expected and has remained unchanged since 2008 at 50-55%. Factors that may preclude use of chemotherapy include comorbid medical conditions, socioeconomic and demographic factors and the opportunity for consultation with a medical oncologist (MO). This study evaluated: 1) patient opportunity for a consultation with a MO, and 2) differences between patients who had a consultation and those who did not

      Methods:
      Stage II NSCLC adult patients diagnosed between 2010 and 2013 were identified using the Ontario Cancer Registry. Complete surgical resections and consultation with a MO were identified using multiple administrative databases. Receipt of guideline-recommended AC within 120 days after resection, and consultation with MO within 30 days prior and 90 days after resection were determined. Guideline-recommended AC includes platinum based regimens, including receipt outside a Regional Cancer Center (RCC). Alternative treatments were defined as non-platinum based chemotherapy or radiotherapy. Socioeconomic and demographic characteristics were compared between patients who received a consultation and those who did not. Characteristics associated with receiving a consultation were assessed using univariable analysis and multivariable logistic regression.

      Results:
      Of 778 Stage II resected NSCLC patients who survived at least 120 days, 40.9% (n=318, CI: 37.40–44.42) received guideline-recommended AC, 3.0% (n=23, CI: 1.70-4.40) received alternative treatment in an RCC, 11.2% (n=87, CI:8.95-13.50) received chemotherapy outside of an RCC hospital, and 45.0% (n=350, CI:41.45-48.56) of patients did not have systemic treatment after surgery. Overall, 72.9% (n=567) of patients had a consultation with a MO within 30 days prior or 90 days after resection. Of 350 patients who did not receive AC, 219 (62.6%) had a MO consultation. Median time from resection to consultation was 29 days, and did not differ between treatment groups (p=0.35). Age was a significant determinant for MO consultation. Adjusting for sex, patients aged 41-60yrs (OR 2.38, CI:1.25-4.56) and 61-70yrs (OR 2.46, CI:1.35-4.49) were significantly more likely to have a consultation versus patients >80 yrs. Other characteristics were not significantly associated with having a consultation.

      Conclusion:
      Although uptake of guideline-recommended AC is lower than expected (52.1%, CI:48.48-55.62), the majority of patients had an opportunity to discuss this treatment option with a MO. Patients over 80yrs were significantly less likely to have this consultation.

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      P1.05-069 - Stage II NSCLC Treated with Non-Surgical Approaches: A Multi-Institution Report of Outcomes (ID 4552)

      14:30 - 14:30  |  Author(s): S. Dudani, X. Zhu, D.W. Yokom, A. Yamada, C. Ho, J. Pantarotto, N.B. Leighl, T. Zhang, P. Wheatley-Price

      • Abstract
      • Slides

      Background:
      Standard management of stage II non-small cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some patients do not undergo surgery for various reasons. The optimal non-surgical management of stage II NSCLC is undefined, with a paucity of data to guide decision making in this setting. We examined outcomes of stage II NSCLC patients who were treated with curative, non-surgical approaches.

      Methods:
      We performed a multi-institution review of stage II NSCLC patients treated non-surgically with curative intent between January 2002 and December 2012, across three major Canadian academic cancer centres. Data on demographics, comorbidities, staging, treatment, and outcome were collected. The primary endpoint was overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for factors associated with choice of therapy and OS.

      Results:
      158 patients were included for analysis. Median age 74 years (range 50-91); 44% female; 94% current/former smokers; 67% performance status (PS) 0-1. Stage II groupings: T2b-T3 N0 in 55%; N1 in 45%. The commonest reasons for no surgery were inadequate pulmonary reserve (27%) and medical comorbidities (24%). All patients received radical radiotherapy (RT) (median 60 Gy [range 48-75]). 73% received RT alone; 24% and 3% of patients received concurrent and sequential chemoradiotherapy (CRT), respectively. Of those who received RT only, 39% received conventional (1.8-2 Gy/day), 51% received hypofractionated (2.5-4 Gy/day) and 10% received stereotactic body RT (≥7.5 Gy/day). In multivariate analyses, CRT was less likely in patients ≥70 years old (OR 0.28, 95% CI 0.11-0.70, p=0.006), as well as in those with higher (>5) Charlson comorbidity scores (OR 0.34, 95% CI 0.13-0.90, p=0.03) or low (<10x10[9]/L) white blood cell (WBC) counts (OR 0.26, 95% CI 0.09-0.73, p=0.01). At time of analysis, 74% have died. Median OS was 22.9 months (95% CI 17.1-26.6 months). Patients receiving CRT had significantly longer median OS than those receiving RT alone (39.1 vs 20.5 months, p=0.0019). RT fractionation schedule (p=0.16) and nodal status (p=0.14) did not influence survival. After adjusting for possible confounders, treatment with CRT was associated with improved survival (HR 0.38, 95% CI 0.21-0.69, p=0.001), while elevated WBC (HR 2.45, 95% CI 1.48-4.04, p=0.0005) and poor PS (ECOG 2-3) (HR 1.87, 95% CI 1.16-3.01, p=0.01) were poor prognostic factors.

      Conclusion:
      Non-surgical approaches to management of stage II NSCLC are varied. Treatment with CRT was associated with significantly longer survival compared to RT alone, and a randomized trial may be warranted in this population.

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      P1.05-070 - Diagnostic Yield and Efficacy of EBUS TBNA in Molecular Testing for NSCLC Mutations (ID 4401)

      14:30 - 14:30  |  Author(s): S. Nuguru, S. Raad, E. Bendaly, H. Oueini, K. Diab

      • Abstract

      Background:
      Non-small cell lung cancer (NSCLC) can be further defined at the molecular level by recurrent driver mutations including ALK, BRAF, EGFR, HER2, KRAS, MEK1, MET, NRAS, PIK3CA, RET, and ROS1. Genetic testing has become a routine part of diagnosis and staging for patients with NSCLC. The presence of mutations can influence response to targeted therapy; tailoring therapy accordingly has become standard practice.

      Methods:
      Sixty-nine patients referred to Indiana University Hospital with suspected or confirmed lung adenocarcinoma underwent EBUS-TBNA of lung masses or lymph nodes using a 21-gauge Olympus[TM] needle without suction. Samples were first reviewed by a pathologist, and if suspicious for NSCLC, were sent for different types of molecular testing based on the clinical scenario. At least 6 extra passes were placed in cell block. For Paradigm testing, 10 passes were sent. EGFR and KRAS testing were performed using the FDA approved Thera screen RGQ PCR Kit. Testing for ALK rearrangement was done using fluorescent in situ hybridization. In some cases, testing for these mutations in addition to ROS1, BRAF, and HER2 was done using the Paradigm Cancer Diagnostics test.

      Results:
      Sixty-nine samples from patients with NSCLC obtained by EBUS-TBNA were sent for molecular testing for EGFR. All samples were sufficient for analysis (Yield=100%). EGFR mutations were found in 3 patients (4.3%) vs. 66 wild-type (95.7%). 60 samples were sent for molecular testing for KRAS (yield = 100%), of which 10 had mutations (16.7%) vs. 50 wild-type (83.3%). 51 samples were sent for ROS1 testing (0 mutant, 48 wild-type); tissue samples were inadequate for testing in 3 patients (yield=94.1%). 64 samples were sent for ALK testing (3 (4.7%) mutant, 55 (85.9%) wild-type; yield = 90.6%). Ten samples were sent for BRAF testing and two samples were sent for HER2 testing, all of which were negative for mutations (yield = 100%). No complications were associated with EBUS TBNA.

      Conclusion:
      EBUS TBNA with a 21-gauge needle is a safe and efficient method for molecular mutational analysis in patients with NSCLC. It can be used effectively for diagnosis, staging and guiding treatment decisions for NCSLC. Adequate samples for mutational analysis can be obtained and placed in cell block without suction. Improving the yield of this technique and comparing the yield with and without suction is important as we start testing for a greater number of mutations.

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      P1.05-071 - A Review of Quality of Life Measures Used in Lung Cancer Surgical Outcomes (ID 6175)

      14:30 - 14:30  |  Author(s): R. Yip, E. Taioli, R. Schwartz, K. Li, K. Tam, Y.M. Htwe, D.F. Yankelevitz, C.I. Henschke

      • Abstract

      Background:
      With the increased life expectancy following surgery for early stage non-small-cell lung cancer (NSCLC), concern about the quality of life (QoL) of patients after surgery has gained attention. Previous QoL studies were limited by small sample size, inclusion of late-stage cancers and non-surgical treatments. This review summarized the existing literature on QoL in early stage lung cancer patients who underwent surgical treatment.

      Methods:
      PubMed and PsycINFO were searched for articles published between 1995 (year of the last published meta-analysis) and March 21, 2016. All English articles reported on quality of life for Stage I NSCLC were included. Data extraction was performed by two independent reviewers using pre-specified criteria.

      Results:
      Ten articles from nine studies were identified. Of the nine studies, four reported on the SF-36, one on the SF-12, one on the EORTC QLQ-C30, one on POMS-TMD, one on EQ-5D, and one on SGRQ. One study reported only on pre-surgical QoL, six only on post-surgical QoL and two studies reported on both pre- and post- surgical QoL. Timing for the administration of post-surgical QoL survey varied, from time at discharge to up to six years post-surgery. Two studies included only NSCLC patients with COPD. Due to the heterogeneity of these studies, comparison between studies and traditional meta-analysis were not possible.

      Conclusion:
      The literature on QoL in Stage I NSCLC patients is very sparse. As CT screening for lung cancer becomes more widespread with a consequent shift from late to early stage NSCLC, additional research is needed to explore the impact of different NSCLC surgical approaches on QoL.

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      P1.05-072 - Predictors and Patterns of Lymph Node Metastasis in Small Peripheral Non Small Cell Lung Cancer (ID 4268)

      14:30 - 14:30  |  Author(s): J. Lin, X. Yang, L. Yan, S. Wang, W. Zhong, Q. Nie, R. Liao, S. Dong, B. Jiang, Y.-. Wu

      • Abstract
      • Slides

      Background:
      Lobectomy is the standard treatment of early stage non-small cell lung cancer (NSCLC) and wheather sublobar resection is appropriate for small peripheral small NSCLC or not is unclear. PET-CT is a powerful imaging modality for the detection of lymph node metastasis with a relatively low false-negative rate. We identified predictors and patterns to identify false-negative N(+) disease in PET-CT.

      Methods:
      A total of 435 consecutive cN0 peripheral NSCLC underwent curative-intent resections following PET-CT scans from January 2008 to December 2014 in our hospital, we analysed patients’ clinicopathological data retrospectively. 171 patients with tumour size≤2cm were enrolled to identify predictors and patterns of lymph node metastases by multivariable analysis. The cut‑off values, sensitivity and specificity for the predictors were calculated using a receiver operating characteristic curve. The patterns of lymph node metastases were also analysed.

      Results:
      In total, 9.4% (16/171) PET-CT-diagnosed N0 NSCLC cases were pathologically N1/N2 disease. The preoperative CEA was a unique independent risk factor for lymph node metastasis (OR = 0.914, 95 CI% = 0.85–0.98, P = 0.009). According to ROC curve, we divided the patients into two groups by CEA: the N(+) rates in the CEA ≤1.67 and CEA> 1.67 groups were 1.6% (1/64) and 14.0% (15/107), respectively (P =0.007). In 16 patients with lymph node metastasis, 7 were N1 disease, and 6 out of 9 N2 diseases were skip N2 disease. 93.5%(15/16) lymph node metastases were found in adenocarcinoma and 11 of them were single station metastases. The metastases rates in solid and subsolid lesions were 12.8%(16/125) and 0%(0/46)(P=0.007), retrospectively. Solid/mucinous/ micropapillary predominant adenocarcinoma were associated with LN metastases(31.2% vs 7.1%, P=0.01).

      Conclusion:
      The preoperative CEA was an independent risk factor for lymph node metastases in cN0 NSCLC with T ≤ 2cm. In patients with CEA>1.67, sublobar resection should be avoided before thorough lymph node sampling that include intrapulmonary lymph node while patients with CEA ≤ 1.67 may be candidate for sublobar resection, especially in GGO lesions. In patients with solid/mucinous/ micropapillary predominant adenocarcinoma, sublobar resection should be avoided due to high LN metastases rate.

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      P1.05-073 - Evaluation of Stage 1 Sub-Solid Lung Nodules Using PET Imaging (ID 4287)

      14:30 - 14:30  |  Author(s): B.V. Tran, D.G. Nicastri, R. Yip, K. Li, D. Xu, M.B. Beasley, M. Salvatore, D.F. Yankelevitz, C.I. Henschke, R. Flores

      • Abstract

      Background:
      Positron emission tomography (PET) scans are valuable in the evaluation of lung nodules. Subsolid (SS:<80% solid) lung nodules, however, often have low levels of metabolic activity and rare metastases. The purpose is to assess PET in the evaluation of SS nodules.

      Methods:
      Between 2009-2015, 892 patients had a chest computed tomography (CT) with a SS finding and PET within 6 months, with pathology specimen, at our institution. 50 patients had clinical stage IA/B lung cancer and were retrospectively analyzed. CT analysis further classified these subsolid lesions as nonsolid(NS) and part-solid(PS).

      Results:
      26 patients had NS nodules and 24 PS. Mean maximal tumor dimension was not statistically significantly different between the groups (mean±SD; NS- 16.8±6.9; PS- 16.9±6.2). PET positive nodules (SUV>2.5) were larger in maximal tumor dimension than PET negative on CT though the difference was not statistically significant (mean±SD; PET Neg, n=42- 16.1±5.7; PET-pos, n=8- 20.9±8.8). Among the 39 patients in which lymph node pathology was obtained, sensitivity and specificity of PET in identifying N1 disease was 0% and 92.9%; and 0% and 100% for N2 disease. Recurrence and overall survival were 0% and 100%, with median follow-up of 34 months. Figure 1



      Conclusion:
      The use of PET for the evaluation of SS nodules in stage I lung cancer may have limited value in detecting metastases and affecting current clinical decision making for these patients.

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      P1.05-074 - Factors Predicting Discordance between Clinical and Surgical-Pathologic Staging in Operable Non-Small Cell Lung Cancer (ID 4083)

      14:30 - 14:30  |  Author(s): I. Koukis, D. Grapsa, P. Tomos, A. Papazafiropoulou, A. Karakatsani, I. Kotteas, A. Charpidou, K. Syrigos

      • Abstract
      • Slides

      Background:
      Accurate clinical staging is of the utmost importance for the optimal management of patients with non-small cell lung cancer (NSCLC). The aim of this study was to identify factors associated with discordance between clinical and pathologic staging in patients with operable NSCLC.

      Methods:
      The medical records of 85 patients with early-stage NSCLC, who had been submitted to thoracotomy followed by surgical resection of the primary tumor and systematic lymph node dissection, were retrospectively reviewed. All patients were staged according to the 7th edition of the TNM staging system. The presence of postoperative upstaging or downstaging was correlated with various demographic and clinicopathological factors, including age, sex, smoking history, tumor histology, tumor size and location.

      Results:
      Discordance between clinical and surgical-pathologic staging was found in 45/85 cases (52.9%), and the majority of these patients were upstaged (35/85 cases, 41.2%). Patients with IIB and IB clinical stage had the highest (77.8%) and lowest (48.1%) probability of discordance, respectively. With regard to T stage, disagreement between clinical and surgical-pathologic T stage was noted in 22/85 patients (25.9%), including 16 upstaged patients (16/85, 18.8%) and 6 downstaged patients (6/85, 7.1%). Nodal status was altered postoperatively in 39/85 cases (45.9%), including 29 upstaged patients (29/85, 34.1%) and 10 downstaged patients (10/85, 11.8%). The rate of unsuspected mediastinal lymph node involvement (pathologic stage N2) was 14.1% (12/85 patients), despite negative mediastinoscopy findings. Age was the only statistically significant factor independently associated with staging discordance (odds ratio 0.93; 95% confidence interval, 0.87 to 0.99).

      Conclusion:
      Postoperative upstaging or downstaging was observed in a relatively high percentage of our patient population, and was significantly and independently correlated with patient’s age. These observations warrant confirmation in larger prospective series of patients with early-stage NSCLC.

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      P1.05-075 - The Correlation between the Prognoses of Patients with Non-Small Cell Lung Cancer and Preoperative Platelet- Lymphocyte Ratio (ID 5137)

      14:30 - 14:30  |  Author(s): S. Ishihara, M. Shimomura

      • Abstract
      • Slides

      Background:
      The platelet- lymphocyte ratio (PLR) is a prognostic factor that correlates immunity or inflammation with tumor invasion. We retrospectively investigated the correlation between prognosis and preoperative PLR in patients with non-small cell lung cancer who underwent anatomical lung resection in our hospital.

      Methods:
      We conducted a retrospective study of 116 patients with primary lung cancer who underwent anatomical lung resection in our hospital from January 2009 to May 2014. We excluded patients who underwent previous lung resection or had intraoperative malignant pleural effusion or positive surgical margins. We analyzed 105 patients (65 with adenocarcinoma, 25 with squamous cell carcinoma, 9 with large cell carcinoma, and 2 with adenosquamous carcinoma). We constructed a ROC curve with PLR values calculated preoperative blood analyses and determined that the threshold was 160. We divided the patients into high and low PLR groups. We analyzed these two groups with respect to background, pathological findings, and cancer-specific survival. Additionally, we investigated factors that correlated with cancer-specific survival with.

      Results:
      The median patient age was 71 years (range, 50-88 years). There were 75 male patients and 25 female patients. The median follow-up duration was 43 months (range, 0-85 months). Regarding surgical techniques, 101 patients underwent lobectomy, 3 underwent segmentectomy, and 1 patient underwent sleeve lobectomy. A total of 47, 34, 8, 9, 6, and 1 patients were diagnosed with pathological stage IA, IB, IIA, IIB, IIIA, and IIIB cancer. The overall survival rate was 71.3%. When examining background characteristics, tumor size was larger and T factor was more elevated in the high PLR groups, and pathological stage was more advanced in the high PLR group. N factor was not significantly different between the two groups. Cancer-specific survival was significantly poorer in the high PLR group than in the low group (p=0.0007). Considering tumor types, patients with adenocarcinoma in the high PLR group had poorer prognosis compared to the patients with adenocarcinoma in the low PLR group (p=0.0002), but for squamous cell carcinoma and in the other tumor types, there was no significant difference (p=0.20 and p=0.86, respectively). Multivariate analysis revealed that PLR was an independent prognosis factor for the cancer-specific survival.

      Conclusion:
      In the patients who underwent anatomical resection with lung cancer, PLR was correlated with prognosis.

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      P1.05-076 - Risk Factors in Patients with Pathological Stage I Non-Small Cell Lung Cancer (ID 4256)

      14:30 - 14:30  |  Author(s): Y. Tokunaga, T. Okamoto, S.S. Chang

      • Abstract

      Background:
      Patients with pathological (p-) stage I non-small cell lung cancer (NSCLC) can have good prognosis with complete resection, whereas some patients die from disease recurrence. The aim of this study was to investigate the risk factors for p-stage I NSCLC.

      Methods:
      We retrospectively reviewed 234 patients with completely resected p-stage I NSCLC from March 2005 to December 2015. Patients with synchronous or metachronous multiple lung cancer or malignancies from other organs were excluded. Clinicopathological factors were analyzed, including age, sex, serum carcinoembryonic antigen (CEA) levels, histology, surgical procedure, tumor size, pleural invasion, lymphatic invasion, vascular invasion, and histological grade. Univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed.

      Results:
      The study group included a total 234 patients, with 119 men and 115 women, ranging in age from 22 to 88 years (mean 68±10.4 years). The median follow-up period was 50.7 months. The preoperative serum CEA level was elevated in 37 patients. Complete resection was performed in all patients, comprising pneumonectomy in one patient, and bilobectomy in two, lobectomy in 192, segmentectomy in 17, and wedge resection in 22. Adenocarcinoma, squamous cell carcinoma, and other histology were observed in 187, 38 and nine patients, respectively. The maximum tumor diameter exceeded 30 mm in 63 patients and tumor diameter was 30 mm or less in 171 patients. There were 38 patients with pleural invasion, 24 patients with lymphatic invasion, and 34 patients with vascular invasion. Multivariate analysis showed that pleural invasion and lymphatic invasion were independent factors for recurrence, whereas older age (>70 years), high serum CEA levels, pleural invasion, lymphatic invasion and vascular invasion were independent factors for poor survival. The 5-year DFS and OS in patients without pleural invasion and without lymphatic invasion were 88.5% and 93.5%, respectively, compared with 29.1% and 33.2% in patients with pleural invasion and with lymphatic invasion (p < 0.001).

      Conclusion:
      Pleural invasion and lymphatic invasion were independent factors for recurrence and poor survival in p-stage I NSCLC. Adjuvant chemotherapy should be considered for patients with lymphatic invasion.

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      P1.05-077 - Outcome of N2 Disease in NSCLC - A Single Institution Experience (ID 5041)

      14:30 - 14:30  |  Author(s): L. Bitar, F. Seiwerth, I. Markelić, M. Koršić, S. Pleština, B. Čučević, S. Kukulj, M. Roglić, M. Samarzija, M. Jakopović

      • Abstract

      Background:
      There are many different therapy options available for stage IIIA-N2 NSCLC patients that were set by the NCCN guidelines. That is why we decided to evaluate outcome of different management strategies.

      Methods:
      Medical records of the patients diagnosed with lung cancer in Clinical hospital center Zagreb, Department for respiratory diseases Jordanovac during the year 2012 and 2013 were retrospectively collected and reviewed. Median overall survival (mOS) was measured and analyzed using the Kaplan-Meier and log-rank test.

      Results:
      There were 147 patients diagnosed with stage IIIA–N2 NSCLC, out of which 105 were male (71.4%), with median age 63 (40-102). Most of them were ex-smokers (54.4%), while only 9.5% never smoked cigarettes. Most of them had very good performance status at the time of diagnosis (ECOG 0-1 91.9%). 78 (53.1%) of the patients were diagnosed with adenocarcinoma, 62 (42.2%) with planocellular carcinoma, 6 (4.1%) with NSCLC-NOS and only 1 (0.7%) with adenosquamous carcinoma. mOS for all diagnosed lung cancer patients was 9 months and for NSCLC 8 months. mOS for IIIA-N2 NSCLC was 14 months. Our patients were treated with chemotherapy in 40.8% of the cases (mOS 11 months); sequential chemotherapy and irradiation in 25.2% (mOS 17 months); surgery, sequential chemotherapy and irradiation in 14.3% (mOS 26 months); surgery and adjuvant chemotherapy in 4.1% (mOS 15 months) and neoadjuvant chemotherapy and surgery in 1.4% (mOS 34 months) of the cases, while only 1.4% of all patients were treated with only surgical resection (mOS 4 months); (p=0.001).

      Conclusion:
      We analyzed the data collected at our department to assess the difference in outcomes of different strategies in IIIA – N2 management. The most of our patients were treated with platinum-based doublets only, followed by sequential chemotherapy and irradiation as a second most frequent therapy option. Only 21.8% of the patients were treated with surgery only or surgery combined with other forms of treatment. Only 1 patient underwent concurrent chemoradiation. The difference in overall survival between different therapy options showed highest mOS in patients treated with neoadjuvant chemotherapy and surgery followed by surgery and sequential chemotherapy and irradiation. Sequential chemotherapy and irradiation was superior to chemotherapy. The limitation of our study was a small number of patients in this specific subgroup, as well as small number of patients who underwent concurrent chemoradiation.

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      P1.05-078 - The Relationship between IASLC/ATS/ERS Grading System of Adenocarcinoma of the Lung and Quantitive PET Parameters (ID 5338)

      14:30 - 14:30  |  Author(s): Ü. Yılmaz, Ö. Özmen, F. Demirağ, T. İnal Cengiz, P. Akın Kabalak, D. Kızılgöz, İ.O. Alıcı, G. Fındık

      • Abstract

      Background:
      There are differences in terms of survival even in early stage adenocarcinomas and subtypes of tumor are the most particular factor. The aim of the study was to investigate the relationship between International Association for the Study of Lung Cancer (IASLC)/ American Thoracic Society (ATS)/ European Respiratory Society (ERS) grading system of the adenocarcinoma and quantitative PET parameters in terms of survival.

      Methods:
      179 operated adenocarcinoma patients categorized according to grade, histological subtypes (Table 1). All patients underwent complete resection and lymph node resection. Invasive adenocarcinoma (MIA) and adenocarcinoma in situ (AIS) were excluded. PET/CT images were re-evaluated and MTV, TLG and SUV-max of primary tumors were calculated. Correlations between quantitative PET parameters and both tumor and overall survival were analysed.

      Results:
      A strong correlation was detected in terms of tumor size between pathologic tumor size and PET-BT (p<0.001, r=0.816). If the SUV-max of tumor/ lymphadenopathy (LAP) ratio cut-off is taken as <2.5, it is significantly higher to detect metastatic lymph node (p<0.001). SUVmax value had weak negative correlation with survival (p=0.004 r= - 0,220). 49.6 was determined as cut-off value for TLG and 9.68 cm3 was for MTV. 1, 2, 3 and 5 years survival rates were indicated in Table 1 There were significant relation between survival and SUVmax, tumor size (PET-BT and CTT) and TLG (p<0,05). In this study over-all survival rates for 1, 2, 3 and 5 years were 88.9%, 77.8%, 76.4% and 66.1%.

      Survival rates 1 year 2 years 3 years 5 years p value
      TLG<49.6 88.9 70.4 69 51.6 p=0.0051
      TLG>49.6 91.5 87.3 85.9 82.2
      MTV<9.68 89.5 72.1 70.8 53.3 p=0.002
      MTV>9.68 89.6 85.1 83.6 79.9


      Conclusion:
      Although, there was no correlation between tumor grade and PET parameters, PET/CT is an important imaging modality for a more accurate T staging and prediction of lymphatic metastasis and survival. To our opinion quantitative PET parameters can help to decide on treatment options and it is possible to avoid unnecessary treatment and to decrease treatment related morbidity rate.

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      P1.05-079 - Lung Cancer in the Elderly: Factors Affecting Long-Term Survival Following Resection (ID 5802)

      14:30 - 14:30  |  Author(s): P. Balakrishnan, S. Galvin, B. Mahon, J. Riordan, J. McGiven

      • Abstract

      Background:
      Lung Cancer remains the most common cancer in the world . It has progressively become a disease of older people , with the median age at diagnosis now exceeding 65 years . As population grows older demographically , it poses various distinct treatment & management challenges . Thus , we looked into factors associated with long-term survival following pulmonary resections for lung cancer in the elderly patients 70 years or older

      Methods:
      All medical records for these elderly patients with lung cancer who under went pulmonary resections , between years 2000 to 2010 , were reviewed . These data was cross-referenced & checked with the operating theatre ORSOS & national mortality data .

      Results:
      Patients were stratified into various groups . Gender , Median age at diagnosis , patient characteristics , assocciated medical co-morbidities , Pre-operative lung functions tests , extend of pulmonary resections & overall 1 , 2 & 5 years survival was calculated

      Conclusion:
      Stringent & proper selection criterias in elderly patient with lung cancer undergoing pulmonary resections will identify groups of patients that will benefit from these surgeries . Thus , identifying these elderly sub-groups will give new lease of life in survivability following pulmonary resections for lung cancer .

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    P1.06 - Poster Session with Presenters Present (ID 458)

    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 47
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      P1.06-001 - Incidence of Molecular Testing and Outcomes of Treatment with Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer in a Dutch Population (ID 6151)

      14:30 - 14:30  |  Author(s): R. Sluga, F.M.N.H. Schramel

      • Abstract

      Background:
      Introduction: Tyrosine kinase inhibitors (TKIs) for treatment of advanced EGFR mutated adenocarcinoma were shown in many studies to be superior to chemotherapy in terms of progression-free survival. Since most data is derived from studies on Asian populations, there is a lack of data from other ethnicities. In the Netherlands the guidelines recommend that EGFR-mutation analysis should be performed in all patients with stage IIIb and IV adenocarcinoma and a non-small cell lung cancer-not otherwise specified(NSCLC- NOS). The aim of this study was to investigate the compliance to the guidelines in terms of determination of EGFR mutations, prevalence of EGFR mutations and the outcomes of treatment with the TKIs in a cohort of European patients with advanced NSCLC harboring an EGFR mutation.

      Methods:
      Methods: Data was obtained by retrospective analysis of the medical records of patients with a stage IIIb and IV non-small cell lung cancer between 2009 and 2014 in the two top-clinical hospitals in the Netherlands.

      Results:
      Results: The total number of patients included in the study was 1022. Molecular diagnostic tests were performed in 57.8% of patients with advanced adenocarcinoma or NSCLC-NOS. The prevalence of performing molecular diagnostic tests improved significantly between 2009 and 2014 (25,2% to 74,4% respectively). Positive EGFR mutation was found in 43 patients (in 9,1% of all molecular diagnostic tests performed). 72,1% of patients harboring an EGFR mutation were treated with TKIs.A significant overall survival benefit with a mean survival of 763 days was seen in EGFR positive patients treated with TKIs (with or without prior/subsequent chemotherapy) versus 435 days in patients treated with conventional chemotherapy (hazard ratio (HR): 0.719. 95% confidence interval (CI): 0.587-0.881). A large fraction of the patients with EGFR-mutated tumors were either initially or after progression treated with chemotherapy. EGFR positive patients who were prior to TKI treatment treated with chemotherapy had significantly longer survival in comparison to patients treated only with chemotherapy (1201 days vs 435 days respectively (HR: 3.289, 95% CI: 1.551-6.997). 10 patients were not treated with TKIs, either because of poor performance status (40%), patient’s refusal (30%), rapid disease progression (20%) or T790M mutation (10%).

      Conclusion:
      Conclusion: This study showed that incidence of molecular testing improved significantly over the course of the last years, leading to more effective targeted therapy. Overall survival was significantly prolonged in patients harboring an EGFR mutation treated with chemotherapy prior to TKIs, compared to patients without EGFR mutation treated only with conventional chemotherapy

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      P1.06-002 - Contralateral Axillary Lymph Node Metastasis of a Lung Cancer: A Case Report (ID 5382)

      14:30 - 14:30  |  Author(s): O.G. Intepe, M. Yildirim, R. Ustaalioglu, T. Okay

      • Abstract
      • Slides

      Background:
      Primary lung cancer metastasis to axillary lymph node is rare. Routine examination of the axilla is useful way to detect suspicious nodes.

      Methods:
      We evaluated retrospectively medical and pathological records of a male patient at our division who had a primary lung cancer with M1b axillary lymph node metastasis.

      Results:
      A 66-year-old male presented with shortness of breath. His chest x-ray showed a large opacity in the lower one-half of the right lung field. Computed tomography (CT) imaging revealed a solid mass in the right hemithorax measuring 50x50 mm. Positron emission tomography/Computed tomography (PET/CT) demonstrated increased fluorodeoxygucose uptake (Standard uptake value: 9,9) by the mass. Fiberoptic bronchoscopy was performed and transbronchial biopsy was consistent with squamous cell carcinoma. Mediastinoscopy was performed to evaluate the stage of the tumor and biopsies from 2R, 2L, 4R, 4L, 7. mediastinal lymph nodes had negative results. Right lower lobectomy was planned and due to invasion of the right middle lob vein and bronchus, right lower bilobectomy and mediastinal lymph node dissection were performed. Pathological evaluation of the tumor and lymph nodes showed that staging of the tumor was T2b N1 (11. lymph node had metastasis, although 2,4,7,9. lymph nodes were metastasis free). Patient was discharged on post-operative 7. days and received chemotherapy 12 cycles. During follow-up PET/CT revealed increased FDG uptake by mass in the residual right lung(SUV:9.3) and axillary subcentimetric nodule(SUV:11.1). Physical examination of the patient revealed a palpable nodule in the right axilla. Ultrasound guided needle biopsy was performed to this nodule but it had negative result. Before performing pulmonary resection, we decided to dissect this lymph node. 30 months after right lower bilobectomy, axillary lymph node dissection was performed and frozen section procedure demonstrated squamous cell lung carcinoma metastasis to axillary lymph node. Pulmonary resection was cancelled and patient was discharged post operatively 3.day and received chemotherapy again. After 6 month follow-up the patient was dead.

      Conclusion:
      Routine physical examination of axilla is recommended even if mediastinal lymph nodes are metastasis free either at initial presentation or at follow-up of patients. In this case metastatic axillary lymph node was subcentimetric, although according to Austin et al. 14 mm or larger axillary lymph nodes are suggestive of adenopathy. Fishman et al. considered 15mm or larger single axillary lymph node without fatty center as abnormal. Without mediastinal lymph nodes metastasis, contralateral axillary lymph node metastasis could be of systemic origin.

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      P1.06-003 - Anamorelin in Cachectic Patients with Advanced NSCLC, a Post-Hoc Pooled Efficacy Data Analysis of Two Phase 3 Trials (ID 4878)

      14:30 - 14:30  |  Author(s): D. Currow, J. Temel, A. Abernethy, J. Friend, K. Fearon

      • Abstract
      • Slides

      Background:
      Anorexia-cachexia is a multifactorial syndrome frequently experienced by patients with non-small cell lung cancer (NSCLC). It is characterized by decreased body weight (mainly due to muscle loss) and is associated with worsen morbidity, poor tolerance of chemotherapy and reduced survival. The randomized, double-blind ROMANA 1 and ROMANA 2 phase 3 trials in cachectic NSCLC patients, demonstrated that the ghrelin receptor agonist anamorelin was well tolerated, improved body weight, lean body mass (LBM), fat mass (FM) and anorexia/cachexia symptoms and concerns, with no difference in handgrip strength compared to placebo. Here we assessed pooled efficacy and numbers needed to treat (NNT) from ROMANA 1 and ROMANA 2 studies.

      Methods:
      Stage III/IV NSCLC patients with cachexia (≥5% weight loss during prior 6 months or BMI<20 kg/m[2]) were randomized (2:1) to daily oral 100 mg anamorelin or placebo for 12 weeks. Endpoints included changes in LBM, FM, total body mass (TBM) and in self-reported anorexia/cachexia symptoms and concerns. We present the pooled efficacy data from a post-hoc analysis from both trials (anamorelin, N=552; placebo, N=277); treatment differences, 95% CI, NNT and nominal p values from baseline to end of study.

      Results:
      At the end of study, compared with placebo, anamorelin-treated patients significantly increased body composition parameters (LBM, appendicular LBM, FM and TBM), and a greater proportion of patients showed improvements in these parameters (Table). The anamorelin group also significantly improved anorexia/cachexia symptoms and concerns, and compared to placebo, more patients in the anamorelin arm achieved the minimally important difference of 4 points. Figure 1



      Conclusion:
      Anamorelin has anabolic activity while improving symptom burden in cachectic patients with NSCLC. A significantly greater proportion of patients increased lean mass, fat mass and improved anorexia/cachexia symptoms and concern score in the anamorelin arm versus the placebo arm, with favorable NNT.

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      P1.06-004 - Evaluating the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ): Preliminary Results from the Quantitative Pilot Study (ID 5217)

      14:30 - 14:30  |  Author(s): A.M. Liepa, D.M. Bushnell, T.M. Atkinson, K. Debusk, K.P. McCarrier, M.L. Martin, S.J. Coons

      • Abstract
      • Slides

      Background:
      In collaboration with the US Food and Drug Administration (FDA), the Patient-Reported Outcome (PRO) Consortium’s NSCLC Working Group has developed the 7-item NSCLC-SAQ. Content includes cough, pain (2 items), shortness of breath, fatigue (2 items), and appetite. A quantitative pilot study is underway to evaluate the NSCLC-SAQ’s item-level and scale-level performance.

      Methods:
      Eligible subjects with clinically-diagnosed advanced NSCLC from US-based clinical sites completed a questionnaire battery (demographics, NSCLC-SAQ, NCCN/FACT Lung Symptom Index-17 [FLSI-17], Patient Global Impression of Severity [PGIS]) using a tablet computer. For this interim analysis, items were evaluated for response distribution, ceiling/floor effects, missing data, and item-to-item correlations. Exploratory factor and Rasch analyses were examined. Internal consistency reliability was estimated using Cronbach’s coefficient alpha. Construct validity was assessed with Pearson correlations between the NSCLC-SAQ and FLSI-17 Disease-Related Symptom (DRS) subscale. The PGIS was used to assess the NSCLC-SAQ’s known-groups validity.

      Results:
      For this interim analysis, 117 (of the anticipated 150) subjects from nine sites were included. Subjects’ mean age was 64 years old (range 40-85), 55% were female, and 84% were white (non-Hispanic), ECOG performance status at enrollment was: 0 (33%), 1 (50%), and 2 (17%). NSCLC staging was: Stage IIIB (15%) and IV (85%). A total of 34% were treatment-naïve, 32% had received first-line treatment only, and 34% had received second- or third-line treatment. Mean scores for the 7 items of the NSCLC-SAQ ranged from 0.9 to 2.2 using a response scale between 0 (“No at all” or “Never”) to 4 (“Very Severe ” or “Always”). Subjects used the full range of responses (i.e., 0, 1, 2, 3, and 4) and provided answers for all NSCLC-SAQ items. Rasch analyses showed the items were ordered and the person-to-item distribution was acceptable. Factor analysis indicated a single component accounting for 47% of the variance, which supports a unidimensional scale structure and the ability to calculate a total symptom score. Cronbach’s alpha was 0.80. The NSCLC-SAQ total symptom score correlated highly (r=0.87) with the FLSI-17 DRS and was able to discriminate levels of overall symptom severity as assessed by the PGIS (p<0.001).

      Conclusion:
      The NSCLC-SAQ has been developed in accordance with the FDA’s PRO Guidance. This study provides quantitative evidence of adequate item and scale performance. These data will be submitted to the FDA to support qualification of the NSCLC-SAQ as a measure to assess a symptom endpoint for efficacy evaluation and product labeling.

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      P1.06-005 - An International Cohort of Patients with Small Cell Lung Cancer after a Non-Small Cell Lung Carcinoma Oncogene or Non-Oncogene Addicted (ID 4531)

      14:30 - 14:30  |  Author(s): M. Giaj Levra, S. Novello, L. Ferrer, F. Barbieri, J. Mazieres, V. Westeel, N. Girard, M. Poudenx, J. Le Treut, M.R. Migliorino, C. Audigier Valette, A. Madroszyk, C. Leduc, M. Locatelli- Sanchez, A.C. Toffart, D. Moro-Sibilot

      • Abstract
      • Slides

      Background:
      Phenotypic transformation from Non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a resistance mechanism in tyrosine kinase inhibitors (TKIs) treated EGFR mutant tumors. SCLC is also however less frequently diagnosed in patients without EGFR mutations treated with chemotherapy. These transformations are rare and little is known about the clinical and therapeutic characteristics of these patients. In this study we describe and compare the characteristics of SCLC arising from mutant or non mutant NSCLC.

      Methods:
      We performed a multicentric retrospective collection (27 centers in France and Italy) of cases. Between 2005 and 2015, patients with stage III or IV NSCLC with a secondary transformation to SCLC with histological proof were included.

      Results:
      Forty seven cases of SCLC transformation were collected, 34 in EGFR mutant and 13 in non. Most of the patients (n=37, 82%) were stage IV, (n=27, 57%) female and (n=26, 76%) had an exon 19 mutation. The last treatment before transformation was a TKI in 23 (68%) cases in the mutant group and in 3 (23%) patients (erlotinib) in the non-mutant. Median time to SCLC transformation was 17 [IQR, 11-29] months in the mutant group and 26 [IQR 23-36] months in the other (p=0.03). Molecular analyses were not performed in the non mutant group, 25 (74%) had molecular analyses in the EGFR mutant. A driver mutation was identified in 22/25 (88%) patients: in most of the cases the same as the initial, 1 case of ALK fusion and 1 of PI3K mutation. Thirty patients (88%) received at least one line of treatment after transformation in the mutant group, in all cases a platinum-etoposide (P-E) chemotherapy. Median survival from initial diagnosis in the EGFR mutant group was significantly worse 28 [17-41] months vs 49 [36-118] months in the non EGFR mutant group (p=0.01). After transformation, the same tendency was observed with a median survival of 8 [3-12] months for the EGFR mutated patients vs 13 [6-15] months for the non EGFR mutated patients (p=0.06).

      Conclusion:
      SCLC that occurs in EGFR mutant treated by TKIs is more aggressive than classic SCLC, and differs on epidemiological characteristics. These transformed SCLC are not fully explained and we need to define the molecular characteristics of this cohort, before and after transformation and if funded the whole genome sequencing of the tumors to understand this TKIs mechanism of resistant.

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      P1.06-006 - Treatment beyond Progression in Patients with Advanced Squamous NSCLC Participating in the Expanded Access Programme (EAP) (ID 5450)

      14:30 - 14:30  |  Author(s): F. Cappuzzo, A. Delmonte, S. Capici, L. Crinò, A.F. Logroscino, P. Sandri, L. Livi, F. Vitiello, D. Signorelli, L. Calabrò, D. Turci, S. Quadrini, P. Antonelli, S. Giusti, F. Di Costanzo, F. Rastelli, P. Marchetti, G. Finocchiaro, E. Cortesi, A. Ardizzoni

      • Abstract
      • Slides

      Background:
      Response patterns of immunotherapies differ from those seen with other therapies approved for the treatment of tumors. Due to this reason, immunotherapy protocols generally allow patients (pts) to continue treatment beyond investigator-assessed radiographic progressive disease (PD) as long as there is ongoing clinical benefit, but to date no data has been reported regarding treatment beyond PD in routine clinical practice. Here we report the analysis about the subgroup of pts treated beyond initial PD in the italian cohort of nivolumab EAP for pts with squamous non small cell lung cancer (Sq-NSCLC).

      Methods:
      Nivolumab was available upon physician request for pts aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months. Pts included in the analysis had received ≥ 1 dose of nivolumab and were monitored for adverse events (AE) using Common Terminology Criteria for Adverse Events. Patients were allowed to continue treatment beyond initial PD as long as they met the following criteria: investigator-assessed clinical benefit, absence of rapid PD, tolerance of program drug, stable performance status and no delay of an imminent intervention to prevent serious complications of PD.

      Results:
      With a median follow-up of 5.2 months (range 0-12.9), 363 pts were evaluable for response. Prior to first progression, the objective response rate (ORR) was 14%, with 1 complete response (CR) and 50 (14%) partial responses (PR), and the disease control rate (DCR) was 41%. Sixty-six pts were treated beyond RECIST defined progression, with 23 pts obtaining a non-conventional benefit, meaning a subsequent tumor reduction or stabilization in tumor lesions. In particular, 17 pts obtained a SD and 6 pts obtained a PR. As to July 2016, median overall survival in these pts had not been reached (95% CI: 3.2-4.6) and 6 months and 12 months OS were 75% and 53%, respectively. The safety profile was consistent to what already observed in the general population.

      Conclusion:
      As already observed in clinical trials, these preliminary EAP data seem to confirm that a proportion of pts who continued treatment beyond PD demonstrated sustained reduction or stabilization of tumor burden, with an acceptable safety profile. Further investigations are warranted in order to better define and identify pts who can benefit from treatment beyond progression.

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      P1.06-007 - Radical Treatment of Synchronous Oligometastatic Non-Small Cell Lung Cancer (NSCLC) (ID 6283)

      14:30 - 14:30  |  Author(s): O. Arrieta, R.L. Luna Palencia, O. Macedo-Pérez, F. Barron, J.F. Corona Cruz, L.A. Chinchilla Trigos, M. Blake Cerda, F. Maldonado Magos

      • Abstract
      • Slides

      Background:
      Cancer represents a large biological spectrum of disease ranging from localized to multisystem involvement with multiple intermediate stages. Oligometastatic NSCLC is thought to carry a better overall survival (OS) but there are few prospective studies that evaluate it.

      Methods:
      Prospective cohort study with NSCLC patients treated at the Instituto Nacional de Cancerologia of Mexico, with stage IV and oligometastatic disease (≤ 5 metastatic lesions). Patients were enrolled to receive, after 4 cycles of systemic treatment with platinum-doublet chemotherapy or 4 months of tyrosine kinase inhibitors in patients with driver mutations, local consolidative treatment for the primary lesion and their metastases with chemoradiotherapy, surgery, radiotherapy, stereotactic radiosurgery or radiofrequency ablation based on the decision of the Multidisciplinary Thoracic Committee of the institution. The primary outcome was overall survival. The study was approved by de Institutional Ethics Committee and registered in clinical trials NCT02805530.

      Results:
      Up to this moment, we have evaluated 29 patients with NSCLC and oligometastatic disease. Of these, 62% males with a median age of 58 years (IQR 52.5-64.5), median CEA 10.2 (IQR 3.25-55), 59% former or currently smokers (median 37.5 package/year), wood-smoke exposure 28%. Overall 90% of the patients presented adenocarcinomas, 28% EGFR mutation (50% deletion of exon 19, 38% mutation on exon 21). At diagnosis 93% of the patients had symptoms mainly cough (48%), dyspnea (30%), neurologic symptoms (26%), weight loss (18%) and dysphonia (15%). We evaluated the oligometastatic disease status with PET-CT and MRI in 66% of the patients and the remaining with CT scan plus MRI. At diagnosis 66% had one or two metastases, 14% three to four metastases and 20% five metastases. For metastatic sites CNS was the main site of metastases in 52% of patients, 28% contralateral lung, 17% bone metastases and 7% at suprarenal. For radical treatment to the primary tumor, 59% chemoradiotherapy, 21% radiotherapy, 28% surgery and 3% radiofrequency. For definite treatment for the metastases, 45% received radiotherapy, 14% chemoradiotherapy and 17% surgery. The mean dose of radiotherapy received for the control of the primary tumor was 56.3 Gy (SD 11.28 Gy) and 29.5 Gy (SD 3.84Gy) for metastases. After multimodal treatment 24% had radiologic complete response. The median OS were 18.26 months (95%CI:10.89-25.64), the median OS for those with and without radiologic complete response were 28.58 months (95%CI:12.98-44.18) and 14.45 months (95%CI:10.40-18.51) respectively.

      Conclusion:
      Patients with oligometastatic NSCLC with agressive treatment have a large OS regardless their mutational status.

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      P1.06-008 - Non-Small Cell Lung Cancer in Octogenarians: Real-Life Clinical Practice; Characteristics, Therapy and Survival (ID 4034)

      14:30 - 14:30  |  Author(s): H. Koyi, G.N. Hillerdal, D. Brodin, K.G. Kölbeck, E. Brandén

      • Abstract

      Background:
      Globally, more people are surviving to older age; consequently, an increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue. We performed a retrospective study of our patients to demonstrate how octogenarians with non-small cell lung cancer (NSCLC) are treated in real-life clinical practice.

      Methods:
      A retrospective observational study of all elderly (>80 years) patients with NSCLC referred to Department of Respiratory Medicine and Allergy, Karolinska Hospital, Sweden, 2003-2010 and followed until June, 2016.

      Results:
      During the period 2662 patients were newly diagnosed with lung cancer. 485 (12.2%) were 80 years or older. 33 (6.8%) hade small cell lung cancer and were excluded, leaving 452 for the study. 216 (47.8%) were male. Mean, median, and range age for males were 83.8, 83, and 80-96 years, respectively. These figures for females were 83.7, 83, and 86-95. 28 (6.2%) of the population were 90 years old or older. 77.8% patients were current or former smokers with significant differences between the genders (p<0.001). There was no difference in performance status (PS) between the genders (p<0.93), with PS 0-1 in 45%, PS2 in 26% and PS3-4 in 29%. 33.9% of patients were diagnosed in stages 1-II, 34.1% in stage III and 31.9% in stage IV. Most of the patients, 45.6%, had adenocarcinoma, 18.1% squamous cell carcinoma, while histological diagnosis was unavailable in 23.2%. There were significant differences in treatment modalities (p=0.040). Chemotherapy was given in 9.5%, local radiotherapy in 17%, stereotactic body radiotherapy (SBRT) in 10.6%, 6.9% underwent surgery and 209 (46.2%) were not given any therapy. Second-line chemotherapy was given in 4% and third-line in 1.5%. Only one patient received fourth line. Median overall survival was 115 days in patients given no therapy and 362 days in patients given any therapy. Patients who underwent surgery had a median overall survival of 5,6 years compared to 3,5 years for patients given SBRT (p=0.0187). There were no significant differences in survival between genders.

      Conclusion:
      Treatment of NSCLC patients 80 years and older with any modality is feasible with a good PS. Survival is fairly good with surgery or SBRT.

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      P1.06-009 - Determining Optimal Array Layouts for Delivering TTFields to the Lungs Using Computer Simulations (ID 4530)

      14:30 - 14:30  |  Author(s): N. Urman, Z. Bomzon, U. Weinberg, H.S. Hershkovich, Y. Palti, E. Kirson

      • Abstract
      • Slides

      Background:
      Tumor Treating Fields (TTFields) are low intensity, alternating electric fields in the intermediate frequency range. TTFields disrupt mitosis by interfering with formation of the mitotic spindle. The therapy is FDA approved for the treatment of glioblastoma (GB). A study to assess the efficacy of TTFields in combination with chemotherapy for the treatment of mesothelioma is underway, and a pivotal study testing the efficacy of TTFields in NSCLC is planned. TTFields are delivered through two pairs of transducer arrays applied to the patient's skin. In-vivo and In-vitro studies suggest that treatment efficacy increases with field intensity. Therefore personalizing the array placement to deliver optimal field distributions is important and is a prerequisite when treating GB patients. However, optimal array layouts for lung cancer patients have not yet been determined. Here we present a finite element simulations-based study investigating optimal array layouts in male and female anatomic models.

      Methods:
      The study was performed using the Sim4Life software package and the DUKE and ELLA computational models (ZMT, Zurich, Switzerland). To represent individuals with a variety of body dimensions, the models were linearly scaled. The distribution of TTFields within the thorax of these models was calculated for a set of array layouts. The layouts were ranked with highest scores for those that conformed well to body contours and delivered uniform high intensity fields to the lungs.

      Results:
      Uniform field distributions within the lungs are obtained when the arrays are axially-aligned with the parenchyma as much as anatomically possible. Generally, the layouts that received the highest scores were those in which one pair of arrays delivered an electric field from the anterolateral to the posterior-contralateral aspect of the patient, with the second pair inducing the field from the antero-contralateral to the posterolateral aspect of the patient. However, due to body contours, this type of layout does not adhere well to smaller females, potentially hampering the efficient delivery of TTFields. Therefore, for smaller females, a layout in which one pair of arrays is placed on the lateral and contralateral aspects of the patients, and a second set of arrays is placed on the anterior and posterior aspects of the patient is preferred.

      Conclusion:
      This study provides important insights into how TTFields distribution in the lungs is influenced by the array layout. These results should be accounted for when developing guidelines for transducer array placement on the thorax.

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      P1.06-010 - Analysis of the Incidence of Cancer Cachexia in Patients with Advanced Lung Cancer at Referral to a Dietitian (ID 4871)

      14:30 - 14:30  |  Author(s): A. Hug, I. Phillips, L. Allan, J. Mendis, V. Ezhil

      • Abstract

      Background:
      Lung cancer is the second most common cancer diagnosed in men and women in the UK with a very poor 5 year survival (10%). There is a lack of robust data on the stage of cachexia in which patients with lung cancer present. The severity of cachexia can influence overall outcomes and a patient’s quality of life. Refractory (irreversible) cachexia indicates a poor prognosis.

      Methods:
      We reviewed all patients diagnosed with metastatic primary lung cancer that were referred to the Macmillan Oncology Dietitians over a 4 year period at the Royal Surrey County Hospital. Reasons for referral commonly included: weight loss, glycaemic control in diabetes, decreased oral intake and food texture modification. We compared self-reported usual body weight (UBW) to weight at referral. Patients were defined as cachectic if weight loss was >5% and refractory cachexia if survival was <90 days from dietitian review.

      Results:
      Figure 1 310 patients with incurable lung cancer were reviewed by the dietitian. Mean age was 68.8 (range 36-89). 42% were female, 58% were male. Mean weight loss was 10%. 76% of patients had lost >5% of usual body weight. Mean pre-cancer body mass index (BMI) was 26.9 (kg/m2), mean BMI at referral was 23.0 (kg/m2). Median survival of non-cachectic and cachectic cohorts were different (299 vs 188 days respectively, p=0.0078). 24% (73 patients) had refractory cachexia.



      Conclusion:
      Our study shows cachexia is very common (76%) in lung cancer and affects survival. A quarter of patients had refractory cachexia. BMI is an insensitive measure of weight loss. Early symptom control improves survival in lung cancer and this data suggests patients are routinely being referred too late to a dietitian. Cachexia in lung cancer is a significant clinical problem. Could upfront assessment of cachexia improve outcome in patients with advanced lung cancer? We propose to investigate this further.

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      P1.06-011 - Altered Body Composition and Fat Loss in Advanced Non-Small Cell Lung Cancer (ID 4212)

      14:30 - 14:30  |  Author(s): A. Mohan, R. Poulose, A.A. Ansari, R. Guleria, K. Madan, V. Hadda, G.C. Khilnani

      • Abstract

      Background:
      Assessment of body composition, including fat mass and fat%, is a useful measure of nutritional status in cancer and may help guide nutritional interventions. However, these abnormalities have not been well documented in lung cancer. We aimed to study alterations in parameters of body composition in Non small cell lung cancer (NSCLC).

      Methods:
      A retrospective chart review was conducted of all newly diagnosed patients with NSCLC. Age and sex matched healthy controls were recruited prospectively. Disease staging was done according to the American Joint Committee on Cancer (7th edition). Performance status was asssessed using the Karnofsky performance Scale(KPS), and the Eastern Cooperative Oncology Group (ECOG). Details of body composition including basal Metabolic Rate (BMR), total body water (TBW), fat mass, and Fat-free mass (FFM) were calculated by bioelectric impedance method using TANITA TBF 300 body composition analyzer.

      Results:
      A total of 256 patients (83.6% males) and 211 controls (81.5% males) were studied. The mean (SD) age of patients was 54.5(9.0) years, median smoking index was 598 (range, 0-2500) and mean duration of symptoms was 158.3(91.7) days. Median KPS was 80 (range, 40-100). Majority had Stage IV disease (54.7%), followed by Stage III (41.4%) and Stage II (3.9%). All measured components of body composition were significantly lower in NSCLC compared to controls (Table).Among patients with normal body weight (BMI 18.5 – 25 kg/m[2]), the TBW and FFM were significantly lower compared to their healthy counterparts. Figure 1



      Conclusion:
      NSCLC is associated with significant malnutrition and altered body composition, especially reduction in the percentage of body fat. Nutritional interventions must, therefore, be tailored accordingly for these patients.

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      P1.06-012 - Central and Peripheral Lung Adenocarcinomas Exhibit Different Timing and Predilection for Distant Metastasis (ID 5649)

      14:30 - 14:30  |  Author(s): T. Klikovits, Z. Lohinai, K. Fabian, M. Gyulai, A. Fodor, J. Varga, E. Baranya, O. Pipek, I. Csabai, Z. Szallasi, J. Tímár, B. Hegedus, B. Dome, J. Moldvay

      • Abstract

      Background:
      Although distant metastases are major factors for unfavorable prognosis in lung adenocarcinoma (ADC), metastatic patterns have not been widely analyzed in this malignancy.

      Methods:
      Clinicopathological data of 1126 ADC patients (541 men, 585 women, mean age: 62.1 ± 9.4 years, 32-88 years) were studied retrospectively, focusing on the localization of primary tumor and distant metastases. Metastases diagnosed at the time of primary tumor diagnosis were defined as early metastases. For statistical analyses, Fisher's exact test and a chi-squared independence test were performed.

      Results:
      At time of diagnosis, 621 patients had stage IV disease. 435 of them had a solitary organ metastasis, mainly in the contralateral lung (n=187), in the brain (n=66), or in the bone (n=59). During the follow up period another 242 patients developed distant metastasis. 39% of all patients had central (i.e. endobronchially visible) tumor. In cases with early-, late-, and non-metastatic disease, the proportions of central tumors were 43%, 35% and 31%, respectively. Central primary tumors were significantly more likely to give rise to early metastases than peripheral ones (p=0.021). When comparing central and peripheral lung cancers according to their metastatic sites, in central tumors lung metastases appeared significantly earlier (p=0.017), while in peripheral ones bone metastases appeared significantly later (p=0.015). There were significant differences in the metastatic organ distributions of central vs. peripheral primary tumors for early (p=0.025) and late (p=0.009) metastases. There was no significant difference in the metastatic organ distributions of right vs. left lung primaries both for early and late metastases. In right lung tumors brain metastases appeared later (p=0.047). No significant difference was observed in the metastatic organ distributions of primary tumors of the upper vs. lower lobes for early (p=0.051), and late (p=0.528) metastases. Early appearance was characteristic for lung, pleural, and adrenal involvement (p<0.001 in all comparisons), while late development was typical for brain metastasis (p=0.002). Bone, liver, subcutaneous, and pericardial metastases showed no such tendencies.

      Conclusion:
      There are significant differences in metastatic organ distributions of central vs. peripheral lung cancers both for early and late metastases. Central primary tumors are more likely to give rise to early metastases than peripheral ones. Results of molecular subgroup analyses will be presented during the Conference.

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      P1.06-013 - Patient Characteristics and Survival: A Real-World Analysis of US Veterans With Stage IV Adenocarcinoma vs Squamous NSCLC (ID 4737)

      14:30 - 14:30  |  Author(s): M.I. Patel, M. Parisi, M. Patel, C. Pelletier, C.L. Bennett, P. Georgantopoulos

      • Abstract

      Background:
      5-year survival rate in patients with stage IV NSCLC was 1%. Stage IV adenocarcinoma (ADENO) and squamous (SCC) account for 44% and 18% of stage IV NSCLC diagnoses, respectively. Patient characteristics and survival in US veterans with stage IV ADENO vs SCC NSCLC were examined.

      Methods:
      Patients with a unique diagnosis of stage IV NSCLC between 1/1/2010 and 12/31/2015 from the US Veterans Affairs (VA) health system database were included. Lung cancer diagnoses were confirmed by VA Central Cancer Registry and Veterans Health Administration National Patient Care Database. Patients were excluded if they did not have 1 VA visit within 1 year before diagnosis.

      Results:
      13,956 patients with stage IV NSCLC were included (ADENO: n=6525 [47%]; SCC: n=3421 [25%]). Baseline characteristics were similar for ADENO vs SCC, including age at diagnosis (mean, 68.8 vs 69.2 y), married at diagnosis (43.9% vs 42.2%), had known Agent Orange exposure (17.4% vs 16.3%), and the majority were white (60.8% vs 63.8%). For ADENO vs SCC, more patients were former smokers (39.5% vs 34.3%), but fewer were current smokers (53.9% vs 61.1%). For ADENO vs SCC, occurrence of brain or bone metastases were higher and incidence of chronic obstructive pulmonary disease or chronic pulmonary disease were lower (Table); age at death (mean, 69.3 vs 69.7 y) and time from diagnosis to death (TDD; mean, 0.56 vs 0.55 y) were similar. More ADENO vs SCC patients received chemotherapy (48.5% vs 44.1%). Mean TDD was longer in patients treated with chemotherapy vs not (ADENO: 0.86 vs 0.31 y; SCC: 0.84 vs 0.35 y).Figure 1



      Conclusion:
      ADENO was more prevalent than SCC in veterans with stage IV NSCLC, similar to the overall population; stage IV SCC prevalence was higher in the veterans than in the overall population. Mean TDD was longer in chemotherapy-treated patients regardless of histology.

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      P1.06-014 - What Factors Determine Treatment Satisfaction in Patients with Advanced NSCLC Receiving Chemotherapy? (ID 6025)

      14:30 - 14:30  |  Author(s): S. Visser, M. De Mol, N. Van Walree, J. Van Toor, B. Den Oudsten, B. Stricker, J.G. Aerts

      • Abstract
      • Slides

      Background:
      In advanced non-small cell lung cancer (NSCLC) treatment decisions regarding palliative chemotherapy are complex due to limited survival gain and treatment-related toxicities. Insight into determinants of patients’ treatment satisfaction may impact decision-making and patient care. We determined the relation of patient- and treatment-related variables to treatment satisfaction.

      Methods:
      In a prospective observational multi-center study, patients with stage IIIB or IV NSCLC receiving pemetrexed (PEM)-based chemotherapy as first- or second-line treatment were enrolled. After four cycles of chemotherapy, patients completed the WHO Quality of Life-BREF (WHOQoL-BREF), which contains one item measuring overall QoL on a 1-5 scale, and the Cancer Therapy Satisfaction Questionnaire (CTSQ). The CTSQ was recently validated (Cheung et al, Qual Life Res. 2016;25(1):71-80). It consists of 16 items scored on a 1-5 scale and contains three domains. Only satisfaction with therapy (SWT) and feelings about side effects (FSE) were used. The domain scores range between 0-100, with higher scores representing better SWT and more positive FSE. We collected sociodemographic information and ECOG performance status at baseline. Adverse events (cancer- or therapy-related) during treatment were weekly registered (CTCAE 3.0). Tumor response measurements were obtained (RECIST 1.1). Patient- and treatment-related determinants univariably associated with SWT (p<0.05) were analyzed using multivariable linear regression (method: Enter).

      Results:
      Of the 95 patients receiving four cycles of chemotherapy, 69 patients completed the CTSQ. The majority of these patients had stage IV NSCLC (87.7%) and received PEM-based therapy as first-line treatment (92.3%). Treatment resulted in stable disease (SD; 53.8%), partial response (PR; 40.0%) and progressive disease (PD; 6.2%). The mean SWT domain score was 79.6±13.1. Univariably, higher patients’ age (p=0.034), tumor response (PR vs. SD or PD, p=0.040), overall QoL (p=0.008) and FSE (p=0.004) were significantly related to SWT. The frequency of (severe) adverse events was not associated with SWT (p=0.546). After including these variables in the multivariable analysis, only age (β=0.44; 95%CI (0.09-0.79)) and FSE (β=0.13; 95%CI (0.00-0.26) were independently related to SWT.

      Conclusion:
      Importantly, higher SWT in elderly supports the opinion that palliative chemotherapy should not be reserved for younger age groups. Although symptomatic adverse events are known key contributors to QoL, the frequency of (severe) adverse events was not related with SWT. However, in patients with better FSE treatment satisfaction was higher. Therefore, patients’ education about and management of adverse events may have added value in maintaining patients’ well-being during chemotherapy, ultimately resulting in higher treatment satisfaction. This study is funded by ZonMw, the Netherlands.

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      P1.06-015 - Designing Transducer Arrays for the Delivery of TTFields Whilst Maximizing Patient Comfort and Field Intensity in the Thorax (ID 4897)

      14:30 - 14:30  |  Author(s): Z. Bomzon, H.S. Hershkovich, U. Weinberg, E. Kirson, S. Strauss

      • Abstract
      • Slides

      Background:
      Tumor Treating Fields (TTFields) are an anti-mitotic therapy that utilizes low intensity electric fields in the intermediate frequency range to disrupt cell division. A study to test the efficacy of TTFields in combination with chemotherapy for the treatment of mesothelioma is underway, and a pivotal study testing the efficacy of TTFields in treating NSCLC is planned. TTFields are delivered via two pairs of transducer arrays placed on the patient's skin. The transducer arrays comprise a set of ceramic disks that make electric contact with the skin through a thin layer of conductive medical gel. The disks in the arrays currently in use are arranged in an almost rectangular pattern. One pair of arrays is placed on the posterior and anterior sides of the patient’s thorax. The other pair is placed on the lateral and contralateral aspects of the patient. This configuration has several limitations: The array placed on the chest may not adhere well to body curvature, leading to sub-optimal electric contact that reduces field intensity in the tumor. In females and obese individuals, fields generated by arrays placed on the anterior and posterior have to traverse thick layers of adipose in the breast. The high resistivity of these layers damps the intensity of TTFields in the lungs. Here we present novel array designs intended to overcome these limitations.

      Methods:
      Multiple concepts for arrays designed to adhere comfortably to the body, whilst avoiding regions of high adipose were proposed. Finite element simulations using realistic computational phantoms were used to evaluate the field distribution generated by these arrays, and optimize their design.

      Results:
      Novel array designs for delivering TTFields to the lungs were developed. These arrays are not designed as large patches, but comprise sets of interconnected small patches that adhere to the natural contours of the patient's bodies. Simulations showed that these arrays deliver uniform field distributions to the lungs. A particularly noteworthy design is a pair of arrays in which one array was shaped as a circular ring placed around the neck and shoulders, and the second array was shaped as a belt placed on the lower torso. This design yielded a highly uniform and intense field directed longitudinally throughout the torso.

      Conclusion:
      The arrays presented in this study deliver high field intensities to the thorax whilst maintaining patient comfort. These designs could help to improve the outcome of TTFields therapy.

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      P1.06-016 - Pulmonary Tuberculosis among Newly Diagnosed-Therapy Naive Advanced NSCLC  in Persahabatan Hospital Jakarta Indonesia (ID 5886)

      14:30 - 14:30  |  Author(s): J. Zaini, S.L. Andarini, R.R. Ramadhani, E. Syahruddin, A. Hudoyo

      • Abstract

      Background:
      The prevalence of lung cancer increased in the recent years in Indonesia, meanwhile pulmonary tuberculosis (TB) is still a major public health problems in this community. Malignancy such as lung cancer increase the risk of tuberculosis infection and reactivation, therefore evaluation of tuberculosis among lung cancer patients is needed

      Methods:
      Newly diagnosed, therapy-naive advanced NSCLC subjects were enrolled from a referral respiratory hospital Persahabatan Hospital Jakarta Indonesia between 2014-2015. Active pulmonary tuberculosis were diagnosed by Xpert MTB/ RIF from induced sputum and LPA M. TB culture. Latent Tuberculosis Infection (LTBI) was determined by Quantiferon-TB Gold-In-Tube (QFT-GIT). Demographic and clinical characteristics were evaluated.

      Results:
      Of 50 lung cancer subjects enrolled, 30 (60%) men with mean of age 55 years old (31- 74 years old). Eighty five percents were adenocarcinoma (42 subjects) and 15% squamous cell lung cancer. Most of them were at end stage (87% stage IV and 13%stage IIIB) with WHO performance status (PS) 1 to 3 (20 % PS 1, 70% PS 2 and 10% PS 3). Comorbidities among this group were COPD (3 ssubjects), diabetes mellitus (2 subjects), hypertension (4 subjects), congestive heart failure (1 subjects). Active tuberculosis were diagnosed in 2 % (1 subject). Based on Quantiferon results, 14 % were positive (7 subjects) and classified as latent tuberculosis infection (LTBI); 60% (30 subjets) classified as non-LTBI (negative Quantiferon result) but 12 (24%) indeterminate cases. The characteristics of LTBI patients were 67% men, two third were adenocarcinomas, 80% stage IV of lung cancer, 80% having WHO PS 2 and 3, 50% were underweight (body mass index (BMI) < 17.5.

      Conclusion:
      Active pulmonary tuberculosis and latent tuberculosis infection is common among newly diagnosed therapy naive advanced NSCLC in this population. Most of them are men, adenocarcinoma, PS 2-3, and half of them were underweight.

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      P1.06-017 - Observational Study on Prolonged Disease Stabilization in Advanced NSCLC EGFR WT/Unknown Patients Treated with Erlotinib in Second Line (ID 4998)

      14:30 - 14:30  |  Author(s): F. Grossi, A. Montanino, M.R. Migliorino, A. Santo, M. De Tursi, A. Delmonte, F. Vitiello, M. Mencoboni, V. D'Alessandro, G. Romano, E. Rijavec, A. Misino, A. Chella, M. Roselli, S. Cavuto

      • Abstract
      • Slides

      Background:
      In advanced NSCLC, erlotinib treatment was shown to improve survival independently of EGFR status and induce high rates of prolonged stable disease (SD). It has previously been reported that, after second-/third-line erlotinib, PFS and OS are long-lasting and similar between patients with SD ≥8 months and those attaining partial/complete response (PR/CR). The present study investigated the clinical value of SD in a real-world setting of advanced NSCLC.

      Methods:
      This Italian multicenter observational study enrolled patients with stage IIIB-IV NSCLC on second-line erlotinib and wild-type/unknown EGFR mutational status, with SD, CR or PR per RECIST v1.1 lasting for ≥4 weeks. Patients were observed from the beginning of erlotinib for approximately 8 months or until death. Primary end-points were the rate and duration of SD (i.e. time interval from erlotinib start to the last evidence of SD by RECIST) or CR+PR. Secondary end-points were OS and PFS (i.e. time interval from the erlotininb start to the first evidence of progression), estimated by the Kaplan-Meier method and calculated by response duration or disease stabilization. Adverse events occurring during the observation period were also recorded.

      Results:
      At the cut-off date of 30/04/16, 144/172 (83.7%) enrolled patients were evaluable for response (mean age 69.1 years, 61.8% males). At the start of erlotinib treatment, 85.4% were non-smokers, 89.6% had an ECOG-PS of 0-1, and 84.7% had stage IV NSCLC (83.3% adenocarcinoma and 11.8% squamous cell carcinoma). Following second-line erlotinib, 82.6% (119/144) of patients achieved SD and 17.4% (25/144) PR. Notably, SD was maintained for ≥8 months in 27% (39/144) of cases. At the end of the observation period, 12 (8.3%) patients had deceased, none with SD ≥8 months. Median OS had not been reached by the entire population. According to SD duration, median OS was 4.3 months if <2 months, 6.8 if between 2 and 5 months, and not reached if ≥5 months or if PR. Median PFS was 9.0 months in the entire population, 8.7 among patients with SD and 10.8 with PR. According to SD duration, PFS was 1.4 if <2 months, 4.4 months if between 2 and 5 months, 7.5 if between 5 and 8 months and 10.5 if ≥8 months. No unexpected toxicities were observed.

      Conclusion:
      In advanced NSCLC, second-line erlotinib yielded a high rate of SD, lasting ≥8 months in 27% of cases, with PFS similar to PR patients and low mortality rate.

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      P1.06-018 - Treatment Patterns and Clinical Practices of Advanced (Stage IV) Non-Small Cell Lung Cancer (NSCLC) in Europe - A Structured Literature Review (ID 4369)

      14:30 - 14:30  |  Author(s): T. Brodowicz, D. Niepel, E. Booth, R.K. Hernandez, G. Braileanu, M. Cawkwell, J. Amelio

      • Abstract

      Background:
      Non-small cell lung cancer (NSCLC) is associated with high mortality and a poor five-year survival. Novel therapies in the pipeline hold promise to address these unmet needs and improve prognosis. Furthermore, their introduction is expected to bring considerable changes to the European treatment landscape. The aim of this review is to provide an overview of the current treatment patterns for advanced (stage IV) NSCLC across five European countries (EU5; France, Germany, Italy, Spain and the UK).

      Methods:
      A structured literature search was conducted in electronic databases for studies published between January 2010 and February 2016 to identify publications reporting on treatments for stage IV NSCLC in European populations. Additional literature searches of relevant European conferences and internet-based sources were performed to ensure the most up-to-date evidence and published clinical guidelines in the EU5 countries were captured.

      Results:
      A total of nine relevant articles (five full-text studies and four conference abstracts) as well as ten clinical guidelines were eligible for inclusion in the literature review. All publications identified were observational studies of advanced NSCLC treatment patterns in the EU5 with data collected between 2005 and 2014. The most commonly reported first-line treatments were cisplatin, carboplatin and pemetrexed, a trend supported by data from individual countries where platinum-based regimens were the most widely prescribed. Other systemic treatments received included non-platinum based regimens, bevacizumab and investigational drugs. The most common second- and third-line treatment options were docetaxel, erlotinib and gemcitabine. There was limited published literature on lines of treatment prescribed in the UK whereby only information on second-line prescribed therapies was available. These included docetaxel, erlotinib, and pemetrexed. Based on this data, treatment patterns appear to be in-line with recommendations from European and national guidelines of NSCLC treatments with the exception of crizotinib and afatinib, which were not approved at the time of the data collection for the majority of studies included in the literature review.

      Conclusion:
      Treatment practices in advanced NSCLC are similar across EU5 countries with slight variations depending on the time period assessed and most notably on the approval and availability of novel therapies. Overall, treatments reported as part of clinical practices across EU5 countries prior to 2010 are still recommended by both national and European-wide guidelines. Furthermore, there is a paucity of comprehensive treatment patterns information for the UK.

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      P1.06-019 - The Possibility of the Additional Local Therapy to Systemic Chemotherapy in Advanced Lung Cancer Cases with Multiple Metastases (ID 4488)

      14:30 - 14:30  |  Author(s): T. Honda, H. Uehara, M. Natsume, Y. Fukasawa, T. Sakamoto, R. Usui, S. Ota, Y. Ichikawa, K. Watanabe, N. Seki

      • Abstract

      Background:
      In stage IV non-small cell lung cancer (NSCLC) patients with multiple metastases, a various pattern of disease progression is observed, including the growth of only primary site, the growth of only pre-existing metastatic site, or the appearance of new metastatic site. The aim of our study is to evaluate the detailed recurrence pattern in patients with stage IV NSCLC, and is also to evaluate whether a specific patient’s population exists whose disease progression is well controlled by the additional local therapy, such as surgery or radiotherapy to the primary or pre-existing metastatic site, during or after the systemic chemotherapy.

      Methods:
      NSCLC patients in stage IV admitted to our hospital from 2012 to 2014 were examined retrospectively. The recurrence pattern was classified into the following groups; the growth of primary site, the growth of pre-existing metastatic site, or the appearance of new metastatic site. Furthermore, progression-free survival (PFS), overall survival (OS), and new lesion-free survival (NFS) of these groups were examined, respectively.

      Results:
      Patients treated with chemotherapy for stage IV NSCLC were 114 cases. The median age was 70 years old, and male was 74 cases. The number of platinum-based combination regimen was 71 cases, monotherapy was 16 cases, epidermal growth factor receptor tyrosine kinase inhibitor was 25 cases, crizotinib was two cases. In the first-line chemotherapy, median PFS, median OS and median NFS in all patients were 172 days, 417 days and 270 days. Median PFS, median OS and median NFS in patients for the growth of primary site were 235 days, not reached and not reached. Median PFS, median OS and median NFS in patients for the growth of pre-existing metastatic site were 171 days, 250 days and 205 days. Median PFS, median OS and median NFS in patients for the appearance of new metastatic site were 149 days, 423 days and 149 days.

      Conclusion:
      The prognosis of the appearance of new metastatic site group seems to be worse than the growth of primary site group in the pattern of disease progression in the first-line chemotherapy. And the prognosis of the growth of pre-existing metastatic site group seems to be worse than the appearance of new metastatic site group. In the stage IV NSCLC therapy, there is a possibility that the treatment outcomes will be improved according to well controlled the pre-existing metastatic site by the additional local therapy.

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      P1.06-020 - Prevalence of Autoimmune Disease in US Veterans With Non-Small Cell Lung Cancer (NSCLC) (ID 4745)

      14:30 - 14:30  |  Author(s): M.I. Patel, M. Parisi, C. Pelletier, C.L. Bennett, P. Georgantopoulos

      • Abstract

      Background:
      Immunotherapy has emerged as an effective treatment strategy in cancer; patients with preexisting autoimmune diseases are often restricted from use. The prevalence of autoimmune disease was 12.5% worldwide (Lerner, Int J of Celiac Disease, 2015) and 24.6% in US patients with lung cancer (LC) (Khan, JAMA Oncol 2016). We report autoimmune disease prevalence in veterans with NSCLC in a real-world setting.

      Methods:
      Patients with a unique diagnosis of NSCLC between 1/1/2010 and 12/31/2015 were included. Diagnoses were confirmed by VA Central Cancer Registry and Veterans Health Administration National Patient Care Database. Patients were excluded if they had <1 VA visit within 1 year prior to diagnosis. Baseline autoimmune diseases were identified using ICD-9 codes for 36 organ-specific and 7 systemic autoimmune diseases. Autoimmune disease was defined as having ≥1 claim of any type (broad definition) or having ≥1 inpatient claim or ≥2 outpatient claims ≥30 days apart (narrow definition).

      Results:
      40,371 patients with NSCLC were included (stage IV adenocarcinoma n=6525, stage IV squamous cell carcinoma (SCC) n=3421). Almost all patients were male (99.9%). Autoimmune disease prevalence was greater per broad vs narrow definition in all patients (15.7% vs 13.6%), adenocarcinoma patients (13.4% vs 11.0%), and SCC patients (15.0% vs 12.3%). By broad definition, 13.4% of all patients, 11.7% of patients with stage IV adenocarcinoma, and 13.0% of patients with stage IV SCC had 1 autoimmune disease; 2.3%, 1.7% and 2.0% had >1 autoimmune disease, respectively. The most common autoimmune diseases in all 3 patient populations were psoriasis, chronic rheumatic heart disease (CRHD), rheumatoid arthritis (RA), Addison disease, and ulcerative colitis (Table).Figure 1



      Conclusion:
      Prevalence of autoimmune disease was lower in the predominantly male US veterans with NSCLC than the general population with LC; the prevalence was similar regardless of stage or histology. The most frequent autoimmune diseases were psoriasis, CRHD, and RA.

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      P1.06-021 - Treatment Patterns and Healthcare Resource Use from a Retrospective Cohort of Japanese Patients with Advanced Non-Small Cell Lung Cancer (ID 4632)

      14:30 - 14:30  |  Author(s): T. Kato, K. Mori, K. Minato, H. Katsura, K. Taniguchi, A. Arunachalam, S. Kothari, X. Cao, H. Isobe

      • Abstract
      • Slides

      Background:
      The treatment landscape for advanced/metastatic non-small cell lung cancer (NSCLC) has changed with the advent of targeted therapies and the use of companion diagnostics.

      Methods:
      The primary objective of this multi-site, retrospective, chart review study was to describe the treatment patterns, Biomarker (Bmx) testing practices and health care resource use (HCRU) in patients who initiated first line therapy (1LT) for newly diagnosed Stage IIIB/IV NSCLC between January 2011 - July 2013 in Japan. Data were analyzed descriptively. Overall survival (OS) was estimated using the Kaplan-Meier method.

      Results:
      Of the 175 Japanese patients 70% were male, 19% non- smokers, mean age of 68.8 years (SD=7.75), 83% stage IV and 74 % (n=129) with non-squamous (NSq) histology. 60% (n=105) received second line therapy (2LT) and 31% (n=55) received third line + therapy (3L+T). 85% (n=110) of the NSq and 40% (n=17) of the squamous (Sq) patients received at least one Bmx test. 81% (n=105) and 19% (n=25) of NSq patients, and 40% (n=17) and 24% (n=4) of Sq patients received an EGFR and ALK test, respectively. EGFR Tyrokinase Inhibitors were most commonly used among NSq EGFR mutated patients (n=44) across all lines. 86% (n=38) of the patients used Gefitinib in 1LT and Erlotinib was used in 2LT (n=11 of 30, 37%) and 3LT (n=9 of 15, 60%) patients. All ALK positive patients (n=2) in 1L received anti-ALK therapy (Crizotinib). Among NSq EGFR/ALK negative or unknown patients (n=83), 89% (n=74) received platinum combinations, most commonly carboplatin+paclitaxel (n=22, 26.5%). Single agents (n=29, 67% and n=11, 50%) were commonly used in NSq EGFR/ALK negative or unknown patients receiving 2LT (n=43) and 3LT (n=22); most commonly docetaxel (n=15, 35% & n=5, 23%). Majority of the 1LT patients with Sq histology (36/43, 84%) received platinum combinations therapy; most commonly carboplatin+paclitaxel (51%). Among 2LT, 67 % (n=20) received a single agent, most commonly docetaxel (n=14, 47%). Single agents were commonly used in 73% (n=11) of the patients receiving 3L+T. Overall, the average length of stay, regardless of line of therapy, was 24.6 days per admission. Duration of treatment was longest for 1LT (mean [SD] 140 [175] days), followed by 2LT (66 [129] days) and 3L+T (65 [83] days).Median OS for Japan from start of 1LT & 2LT was 9.9 and 4.7 months, respectively.

      Conclusion:
      NSq patients are frequently tested for Bmx in Japan. Treatment is personalized according to mutation status and is in concordance with recommended guidelines.

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      P1.06-022 - Clinical Characteristics of Survival Outliers in Stage IV Adenocarcinoma Lung Cancer Patients (ID 4304)

      14:30 - 14:30  |  Author(s): A. Fung, A. D'Silva, H. Li, S. Otsuka, D..G. Bebb

      • Abstract
      • Slides

      Background:
      Lung cancer is the leading cause of cancer deaths among men and women in Canada. Many lung cancer patients are diagnosed at advanced stages of disease, which is associated with poor survival outcomes. The mean survival of stage IV non-small cell lung cancer (NSCLC) patients is typically less than 12 months; however, there appears to be a small subset of patients with advanced disease that live substantially longer than the norm. Our study aims to determine whether certain clinical characteristics correlate with longer survival in stage IV NSCLC patients.

      Methods:
      Data on 1803 stage IV NSCLC patients (1291 adenocarcinoma, 512 squamous cell carcinoma) from 1999-2011 were extracted from the Glans Look Lung Cancer database. Adenocarcinoma data is presented here; squamous cell carcinoma data analysis is ongoing. Clinical characteristics such as age, gender, ethnicity, smoking history, histology, molecular testing, metastatic disease, treatments, and socioeconomic factors were compared between survival outliers and patients with average survival. Survival outliers were defined as those patients who lived > 5 years, or greater than 2 standard deviations from mean survival (42.1 months).

      Results:
      In the survival outlier group, there were 25 patients who lived >5 years, and 59 who lived >42.1 months. Survival outliers included a higher percentage of females, had a smaller smoking history, smaller tumour size at diagnosis, received more treatment lines, and had lower metastatic disease burden at diagnosis (P<0.05 in the outlier group with survival >42.1 months). Upon further characterization of metastatic disease, there appears to be survival outliers associated with no liver metastases and less sites of metastases at diagnosis, as well as with stage M1a disease compared to stage M1b.

      Conclusion:
      Adenocarcinoma patients with localized and lower metastatic disease burden and no liver metastases at the time of diagnosis appeared to live longer than their counterparts. Further statistical analysis is ongoing to determine the significance of other clinical characteristics with respect to survival. The present study will help us better understand the importance of various clinical parameters and their association with survival, in hopes of improving outcomes for lung cancer patients in the future.

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      P1.06-023 - Clinicopathological Characteristics of Axillary Lymph Node Metastasis in Lung Cancer (ID 3757)

      14:30 - 14:30  |  Author(s): Y. Kong, M. Chen

      • Abstract

      Background:
      The morbidity and mortality of lung cancer are rather high. One major metastasis pathway of lung cancer is lymph node metastasis. The incidence of axillary lymph node metastasis(ALNM) is rare, and little is known about its clinicopathological characteristics.

      Methods:
      The clinical data of 91 patients with ALNM who were treated in Zhejiang Cancer Hospital from January 1, 2007 to December 31, 2013 were retrospectively analyzed. The relevance of tumor site、local lymph node site and axillary lymph node site were checked by contingency table. Survival rates were calculated by the Kaplan-Meier method and compared by the log-rank test.

      Results:
      Lung cancer patients with ALNM were often presented with adenocarcinoma(59.3%)、peripheral tumor type(71.4%)、 pleura invasion with pleural effusion(48.4%) or chest wall invasion(52.7%). There was a relationship between tumor site(P<0.001)、local lymph node site(P<0.001) and axillary lymph node site. The median survival time of lung cancer patients with ALNM was 19.02 months, 2-year survival rate is 62.64%. Patients detected with ALNM at the initial diagnose had poorer prognosis (p=0.002). Figure 1Figure 2





      Conclusion:
      ALNM from lung cancer is rare, it may be involved through direct chest wall invasion, spread from supraclavicular and mediastinal lymph node metastasis or systemic origin. Patients detected with ALNM at the initial diagnose had poorer prognosis.

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      P1.06-024 - Distinctive Patterns of Primary Metastases and Clinical Outcomes According to the Histological Subtypes in Stage IV Non-Small Cell Lung Cancer (ID 3963)

      14:30 - 14:30  |  Author(s): D.S. Lee, S.J. Kim, Y.S. Kim, J.H. Kang

      • Abstract

      Background:
      The purpose of this study was to compare the primary patterns of metastases and clinical outcomes between adenocarcinoma (Adenoca) and squamous cell carcinoma (SQ) in initially diagnosed stage IV Non-small cell lung cancer (NSCLC).

      Methods:
      Between June 2007 and June 2013, a total of 427 eligible patients were analyzed. These patients were histologically confirmed as Adenoca or SQ and underwent systemic imaging studies, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography and brain imaging. Synchronous metastatic sites were categorized into 7 areas, and whole-body metastatic scores were calculated from 1 to 7 by summation of each involved region. We compared the patient, tumor, and metastatic characteristics according to the histological subtypes, and examined clinical outcomes.

      Results:
      The enrolled study cohort comprised 81% (n=346) Adenoca patients and 19% (n=81) SQ patients. The median age of the study population was 65 years (range, 30–94 years), and 263 (61.6%) patients were male. The most common metastatic sites were thoracic lymph nodes (LNs) (84.3%), followed by lung to lung/lymphangitic spread (59%) and bone (54.8%). The distribution of patient characteristics revealed that age 65 years (69.1% vs 50.6%; P=0.003) and male sex (84% vs 56.4%; P<0.001) were more frequently found in SQ patients. Regarding metastatic features, bone metastasis (60.4% vs 30.9%; P<0.001), lung to lung/lymphangitic metastasis (63% vs 42%; P=0.001), and brain metastasis (35% vs 16%; P=0.001) were significantly and more frequently found in Adenoca patients. Patients with high metastatic scores (score 3–6) were more frequently found to have Adenoca (91.6% vs 73.4%; P<0.001). In multivariate prognostic evaluation, sex (P=0.001), age (P<0.001), histology (P<0.001), LN status (P=0.032), pleural/pericardial metastasis (P=0.003), abdomen/pelvis metastasis (P<0.001), axilla/neck metastasis (P=0.006), and treatment factors (P<0.001) remained independent prognostic factors affecting overall survival.

      Conclusion:
      We observed distinctive patterns of primary metastases and clinical outcomes according to the histological subtypes in stage IV NSCLC. Future studies need to disclose the underlying mechanism of these unique metastatic features and tumor biologies.

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      P1.06-025 - Analysis of Risk Factors for Development of Skeletal-Related Events in Women with Bone Metastases from NSCLC and Breast Cancer (ID 4933)

      14:30 - 14:30  |  Author(s): F. Lumachi, P. Ubiali, A. Del Conte, F. Mazza, S.M. Basso

      • Abstract
      • Slides

      Background:
      Bone metastasis (BM) are common (up to 50% of cases) in patients with advanced non-small cell lung cancer (NSCLC) and other malignancies, including prostate cancer and breast cancer (BC). In patients with BMs, the onset of skeletal-related events (SREs), such as pathological fracture, malignant hypercalcemia, or spinal cord compression requiring surgery or radiation therapy, seriously affects the quality of life of patients and overall survival. The purpose of this study was to analyze the risk factors (RFs) for development of SREs in women with advanced NSCLC and BC, with the aim of highlighting the differences (if any) between the two groups of patients.

      Methods:
      The medical records of 16 women with BMs from NSCLC (Group A) and 15 women with BMs from luminal-type BC (Group B) were reviewed. The following RFs have been considered: age >65 years, ECOG performance status (PS) <2, the presence of extra-skeletal metastases (ESM) or hypercalcemia (>2.65 mmol/L), and number of BMs >1. Odds ratio (OR) estimates and the relative 95% confidence interval (CI) were calculated. A p-value level <0.05 was considered statistically significant.

      Results:
      During follow-up, 5 (33.3%) Group A and 111 (68.7%) Group B patients developed SREs (OR=4.40, p=0.04), respectively. The results are reported in the Table. No significant difference (p=NS) was found between groups in relation to ECOG-PS, ESM or hypercalcemia, and number of BMs. Only the age >65 years (OR=0.22, p=0.04) represented a weak significant risk factor.

      Parameter NSCLC BC OR 95% CI p-value
      No. of patients 15 16 - - -
      Skeletal-related events 33.3% 68.7% 4.40 0.97-19.85 0.04
      Age >65 years 73.3% 37.5% 0.22 0.05-1.01 0.04
      ECOG-Performance status >2 40.0% 18.8% 0.34 0.07-1.76 0.25
      Extra-skeletal metastases 26.7% 43.7% 2.14 0.47-9.70 0.32
      Malignant hypercalcemia 26.7% 12.5% 0.39 0.06-2.55 0.39
      Multiple bone metastases 53.5% 37.5% 0.52 0.12-2.20 0.38


      Conclusion:
      Women with BMs from NSCLC has a reduced risk for development of SREs compared to those with BC, but elderly (>65 years) patients require a closer surveillance, and a precocious bisphosphonate treatment could be suggested.

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      P1.06-026 - Adenosquamous Carcinoma of the Lung: A Single Institution Experience in the Era of Molecular Testing (ID 6103)

      14:30 - 14:30  |  Author(s): K.K. Mandalapu

      • Abstract
      • Slides

      Background:
      Adenosquamous carcinoma (ADS) lung is rare subtype of non-small cell lung cancer (NSCLC) that compromises 0.4-4% of all lung cancers and is thought to carry a worse prognosis than adenocarcinoma (AD) or squamous cell carcinoma (SC). Epidermal growth factor receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) mutations have been observed in patients (pts) with this rare subtype. In the recent years EGFR tyrosine kinase inhibitors (Gefitinib, Afatinib and Erlotinib) and ALK inhibitors (Critzotinib, Ceritinib) have prolonged progression free survival in high-stage adenocarcinomas of the lung. The current NCCN guidelines recommend EGFR and ALK mutation testing in metastatic ADS lung cancer patients. However the frequency of these mutations as well as outcomes of patients with ADS lung is not known in this era of targeted therapies

      Methods:
      We retrospectively identified all pts seen in our oncology clinic for ADS during the last 10 years (1/1/2005 - 1/1/2015). Overall survival (OS) was estimated by Kaplan-Meier methods

      Results:
      16 pts were identified, median age at diagnosis was 71y (52-85y), 63% male, 81% had a smoking history, 87% had ECOG performance status 0-1. 37% had Stage I, 18% had stage II, 18% had stage III and 25% had stage IV disease at diagnosis, 13% developed metastatic disease after treatment for stage III disease. 75% of pts diagnosed with metastatic disease after 2012 were tested for EGFR and ALK, while none diagnosed prior to 2012 were tested. All pts were negative for EGFR and ALK mutations. All pts with Stage I and II received only surgery; pts with stage III got multimodality treatment with chemotherapy, radiation, and surgery. All the pts with metastatic disease received chemotherapy, with regimens similar to those for AD or SC of lung. The median OS for pts with localized disease was 48.3 months (48.0- NA). The median OS for pts with metastatic disease was 5.4 months (2.3-9.2)

      Conclusion:
      Our small analysis showed that pts with localized ADS of lung had similar outcomes to those of historical pts with localized AD or SC of the lung. However, pts with metastatic ADS of the lung had worse outcomes than historical pts with metastatic AD or SC of the lung even with similar chemotherapy regimens. Few pts had EGFR and ALK testing, but this is becoming more routine as we have better targeted therapies if they carry mutation

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      P1.06-027 - Retrospective Study of Treatment for Postoperative Local Recurrence of Lung Cancer (ID 4690)

      14:30 - 14:30  |  Author(s): K. Miyoshi, K. Tsuruoka, N. Matsunaga, T. Nakamura, S. Yoshida, Y. Tamura, M. Imanishi, S. Ikeda, Y. Fujisaka, I. Goto

      • Abstract
      • Slides

      Background:
      There is no consensus regarding the standard treatment for postoperative local recurrence of lung cancer. In order to clarify the impact of differences in treatment on patient survival, we conducted a retrospective study of treatment outcomes for patients with postoperative local recurrence of lung cancer.

      Methods:
      The subjects of this study were patients who were diagnosed with postoperative local recurrence of lung cancer and treated at our hospital from 2008 to 2014. We divided patients according to treatment regimen, and compared patient characteristics and survival.

      Results:
      This study included 38 patients. Among them, 8 received radiation therapy (RT), 10 received chemoradiation therapy (CRT), 18 received chemotherapy (CT), and 2 received best supportive care. The patient characteristics were as follows: median age (range), 71 years (55–84); gender male/female, 30/8; pStage at operation IA/IB/IIA/IIB/IIIA/IIIB, 9/6/9/8/5/1; histology small cell carcinoma/squamous cell carcinoma/adenocarcinoma, 5/12/21. There were no significant differences in patient characteristics between each treatment group. The proportion of patients who experienced disease progression after treatment was 75.0% (6/8) in the RT group, 20.0% (2/10) in the CRT group, and 77.8% (14/18) in the CT group. Progression free survival (PFS) tended to be better in the CRT group than in the other treatment groups. The differences in median PFS (months) were; RT vs CRT: 8.0 vs 15.5, HR=0.210 (95%CI 0.042-1.047), P=0.057; CRT vs CT: 15.5 vs 14.0, HR=0.206 (95%CI 0.047-0.908), P=0.037.

      Conclusion:
      In patients with postoperative local recurrence of lung cancer, CRT yielded better outcomes than the other treatments in terms of PFS.

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      P1.06-028 - Description of the Patients with Advanced Squamous NSCLC Treated in a Single Institution (ID 6171)

      14:30 - 14:30  |  Author(s): I. Torres, J. Gimeno, I. Pajares, A. Comin, J. Hernando, P. Felices, A. Nuño, E. Millastre, A. Viñaras, A. Artal Cortes

      • Abstract

      Background:
      Squamous carcinomas are a distinct subtype of NSCLC. Even if it is no longer the most frequent one, still remains a significant percentage of NSCLC patients in our practice. Besides, clinical presentation, associated comorbidities and available therapies are different for non-squamous subtypes. Assessing their characteristics may help to optimize therapy.

      Methods:
      DAta from patients with a diagnosis of advanced (stage IV patients plus patients with lower stages but not amenable for any local therapy) squamous NSCLand treated in our Hospital between 2009-15 were reviewed.

      Results:
      209 patients (p) were found. Median age was 69 years (40-89). Gender: Male in 89.5%. PS: ECOG 0= 9.1%, 1= 45.9%, 2= 38.3%, 3= 6.7%. By stage, I= 0.5%, II 3.4%, III 27.7%, IV 68.7%. Therapy: 29.1% of p did not receive any systemic therapy and 70.9% receive chemotherapy (CT). CT included a platinum in 69p (carboplatin 47p, cisplatin 22p) and 61p received a non-platinum scheme (gemcitabine-vinorelbine 21p, monotherapy 40 p (gemcitabine 8p, oral vinorelbine 23p, other 9p). Patients with better PS (p<0.001) and stage less than IV (0.02) were more probable to receive CT and also that CT given included platinum. Overall survival (OS) was 6.5 months (5.4-7.6) for the whole group. For stage IV patients, it was significantly shorter: 5.4 months (p=0.03). OS for patients not receiving therapy was 2.7m (vs 7.7m in those treated). Within stage IV OS was shorter for female vs male (4.2 vs 5.8m), and decreased with poorer performance status: 0, 13.5, 1, 8.2m, 2, 3.8m, 3, 2.2m.

      Conclusion:
      Squamous carcinomas are still the second most frequent subgroup of NSCLC. They are more frequently male and almost half of them presented with PS ≥2. Of them, 29% did not even receive CT and out of those treated, only 60% were considered fit to receive a platinum-based therapy. OS was generally poor, but it was remarkably low in patients with PS 2 or worse. Median OS in untreated patients was under 3 months.

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      P1.06-029 - Epidemiologic, Clinical Characteristics and Therapeutic Strategy of Elderly NSCLC Patients Treated in a Single Institution (ID 5379)

      14:30 - 14:30  |  Author(s): M. Vaslamatzis, E. Patila, T. Tegos, N. Alevizopoulos, C. Zoumblios, T. Kapou, C. Stathopoulos, A. Laskarakis, C. Zisis, E. Vasili

      • Abstract
      • Slides

      Background:
      In NSCLC pts 40% are ≥ 70y with poor PS and increased comorbidities(cbs). The aim of this retrospective study is to present all data in 208 NSCLC pts stage IIIB and IV admitted in our unit between 1/2007- 3/2016.

      Methods:
      Group A(young old):51%,70-75years(y),Group B(old):49%,75-87y.Median PS:2(0-3). Histology: Adenocarcinoma(AC) 43%, Squamous carcinoma(SCC) 31%, Adenosquamous CC 10%, Large CC 5% and Large Neuroendocrine 11%. Metastasis: Liver 79%, Bones: 72%, Adrenal: 37%, Lung: 35%, Brain: 23% of pts. Cbs included: hypertension, diabetes,heart disease, dyslipidemia, COPD, hypothyroidism, osteoporosis, Parkinson and dementia in 81, 68, 56, 56, 52, 42, 14 and 6% of pts .In Group B had ≥3 comorbidities more often (59% vs 42%), p<0.05).

      Symptoms at presentation No of pts (%) N=208 Group A% N= 106 Group B N = 102 p
      Haemoptysis 163 (78%) 78(74%) 85(83%) 0.05
      Cough 69(33%) 35(33%) 34(33%) NS
      Dyspnoea 60(29%) 22(21%) 38(37%) x<0.01
      Chest discomfort 46(22%) 17(16%) 29(28%) 0.01
      Cervical lymphadenopathy 38(18%) 18(17%) 20(19%) NS
      SVCS 27(13%) 12(11%) 15(15%) NS
      Pancoast tumors 9(4%) 4(4%) 5(5%) NS


      Results:
      Four pts(4.5%) mutated received TKI ± chemo(CT) (Paclitaxel,Carboplatin,Bevacizumab) and are still in PR for 12+, 14+, 14+, 32+, 12+ mo respectively. In 40 selected pts (≥ 80y, PS=3, ± brain metastases ± ≥5 cbs ± weight loss ≥7%) single agent was given. RR in 44% with mPFS 7(3-12)mo, mOS 11(5-16)mo. The rest received 3 cycles least of chemo ± brain RT + GCSF support: ORR: 56% in A and 49% in B. mPFS: 9(3+ - 18)mo and mOS 18(3+ - 56+)mo, 17(3+ - 56+) in A and 16 (3+ - 44+) in B. RR was 64% and 34% for pts PS 0-1 vs 2-3, p<0.001. In 720 cycles (410 and 310 in A and B),toxicity grade ≥ III: Febrile neutropenia in 11 vs 19% cycles, p <0.01, Anemia in 23 vs 27%, p=NS, Thrombocytopenia in 25 vs 30%, p=NS, Mucositis in 11 vs 15%, p=NS.

      Conclusion:
      1. When indicative CT should be given, without reduction. 2. Haemoptysis and chest discomfort are common in older pts. 3. Febrile neutropenia was the main serious side effect. 4. GCSF prophylaxis is necessary. 5. In selective patients >80y single agent seems beneficial in second line .

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      P1.06-030 - Extended Lymph Node Dissection through Median Sternotomy in N3 Left NSCLC Surgical Results and Anatomical Findings (ID 5553)

      14:30 - 14:30  |  Author(s): S. Ikeda, T. Yokota, T. Hoshino, T. Sakai

      • Abstract

      Background:
      The role of surgical approach to stage IIIA or IIIB disease surgery has been considered not appropriate. Patients with mediastinal lymph node metastasis have a poor prognosis, especially for N3 (contra lateral lymph node metastases) diseases, and lung operation is not typically indicated. We performed bilateral mediastinal lymph node dissection by median sternotomy to resect lung cancer and dissect the bilateral mediastinal lymph nodes.

      Methods:
      An extended surgical approach to bilateral neck and mediastinal nodal dissection based on the knowledge about the pathways of lymph drainage,’ systematic neck and bilateral mediastinal nodal dissection through a median sternotomy,’ beyond the anatomical difficulties would bring some improvement on the survival of the patients with N3 left NSCLC without any preoperative treatments routinely.

      Results:
      Patients with p- N3α and N3γ (neck lymph node metastases case) cases have poor prognosis, and lung operation is not normally indicated. We have performed neck and bilateral mediastinal lymph node dissection by median sternotomy to resect lung cancer and dissect the bilateral mediastinal lymph nodes. We have performed this operation in 289 patients with primary left lung cancer excluding small cell carcinoma and stageIV since 1987. 42 patients had p-N3 lymph node metastases. We will report the investigation of the prognoses of left NSCLC patients who underwent initially our extended neck and bilateral mediastinal dissection, focused on the patients with N3 disease. According to the macroscopic dissection procedure, dissection of the lymphatics from the lungs to the supraclavicular lymph nodes was performed by sequential removal of the related organs. We systematically compared and reviewed the route of lymphatic communications to the neck and contra lateral side with the anatomical significance of left-to-right lymphatic communications in the bilateral mediastinal lymph nodes. The 5-year survival rate (Kaplan-Meier method), including operative deaths and deaths due to unrelated diseases, was 48.8% in p-N3α、35.8% in N3γ.

      Conclusion:
      We found various lymphatic metastases pattern such as between neck and mediastinal lymph nodes and around the trachea in terms of clinical and anatomical status. Our surgical approach suggest the importance of the extend dissection by median sternotomy.

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      P1.06-031 - A North Malaysia Pulmonology Center Experience in Management of Advanced Non-Small Cell Lung Cancer (ID 3798)

      14:30 - 14:30  |  Author(s): S.S. Sirol Aflah, R.M.N. Md Kassim, N.M. Pathi

      • Abstract

      Background:
      Pulmonologist plays an important role not just in getting tissue sampling for diagnosis and molecular testing and staging but also administer the treatment when there is no medical oncologist available on site in some centers in some part of the world. Hence, the treatment needed to be delivered promptly to the patient under the care of pulmonologist.

      Methods:
      We retrospectively included patients who undergone palliative chemotherapy and radiotherapy with non-small cell lung cancer histology. Data were collected from clinical notes and statistical analysis was done using SPSS statistic software. The aim of the study is to look at the outcome of advanced NSCLC patients treated with palliative chemotherapy and radiotherapy with the prognostic factors.

      Results:
      In total, 86 patients were analyzed (56 male, 30 female, median age 59.36 ±12.08 with 53% of them were former and current smoker). Tissue diagnosis were obtained by endobronchial biopsy(34%), pleural biopsy (36%), CT guided (26%) and ultrasound guided transthoracic biopsy (4%).Majority tissue histology were adenocarcinoma (77.9%), squamous cell carcinoma (16.3%) and remaining was non-small cell carcinoma. Performance status of patients range from 0 to 2 (based on Eastern Cooperative Oncology Group). Among all adenocarcinoma cases,27 patients with epidermal growth factor receptor(EGFR) positive and 16 patient received oral tyrosine kinase inhibitor(TKI). The systemic chemotherapy used were Vinorelbin with Cisplatin/Carboplatin, Premetrexed, Docetaxel and Bevacizumab. All patients received first line chemotherapy(13 patients received oral TKI for first line), 24 patients received 2nd line, 6 patients on 3rd line and 3 patients on 4th line chemotherapy. 16 patients undergone concomitant radiotherapy. The median overall survival (OS) of all patients received chemotherapy was 5.16 months. The median OS were significantly longer in patients who received 2nd and 3rd line chemotherapy (12.88 month, p < 0.01 and 20.84 months, p <0.013) than 4th line chemotherapy (20.84 months, p< 0.89). Former and current smoker patient who undergone chemotherapy is 2.3 times higher risk (HR: 2.30; 95%CI: 1.35, 3.92) to die compare to non­smoker. Patients who had increase in one unit of number of chemotherapy, will reduce 47% risk to die from advanced non-small cell lung cancer (HR: 0.53; 95%CI: 0.36, 0.76). Patient who undergo radiotherapy treatment is 66% less risk(HR:0.34,95% CI:0.17,0.69) to die compared to those who did not go for radiotherapy.

      Conclusion:
      There were clinical benefits for patients received more than first line chemotherapy and radiotherapy, smoking during treatment has negative impact on survival in our cohort of patients.

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      P1.06-032 - The Humanistic Burden of Advanced Non-Small Cell Lung Cancer Patients in Europe - A Real World Survey (ID 5654)

      14:30 - 14:30  |  Author(s): G.J. Taylor-Stokes, R. Wood, B. Malcolm, M. Lees, O. Chirita

      • Abstract
      • Slides

      Background:
      Previous publications have demonstrated that advanced Non-Small Cell Lung Cancer (aNSCLC) patients have worse HRQoL compared to the general population. Few publications have focused on the impact of aNSCLC on activities of daily living and the humanistic burden incurred by different groups of aNSCLC patients in the real world setting.

      Methods:
      Data were taken from a multi-center, cross-sectional study of aNSCLC patients conducted in France, Germany and Italy. The study consisted of three components: medical chart review, patient questionnaire and caregiver questionnaire. Overall, 683 consulting patients were recruited via treating physicians. Patients’ health state was quantified using the EuroQoL-5D (EQ-5D-3L - comprising of five domains: mobility, self-care, ability to perform usual activities, pain, anxiety and depression) and the burden on HRQoL quantified using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), a 30 item questionnaire yielding five functional scales, three symptom scales, a global health status/QoL scale, and six single items. Analysis was stratified by patients’ line of therapy. Statistical significance was assessed using Mann-Whitney U tests.

      Results:
      Patients’ mean (SD) age was 65.2 (9.7), 68.8% were male and 89.0% had stage IV NSCLC. Over two-thirds (71%) of patients were receiving 1st line advanced therapy, whilst 29% were receiving later lines of therapy. Regarding histology, 74% of patients were non-squamous compared to 26% squamous. The mean EQ-5D-3L index for 2[nd] line or later patients was significantly lower compared to patients on 1[st] line treatment (0.57 vs 0.65; p=0.002). Three domains showed significant decreases: mobility, self-care and ability to perform usual activities. In terms of EORTC scores, patients on later lines of treatment experienced a lower overall global health status (QL2) compared to 1[st] line patients (43.8 vs 50.7; p<0.001). Significant differences were also observed in all other EORTC scales except for diarrhoea.

      Conclusion:
      1[st] line aNSCLC patients have a diminished health state in comparison to the general population (EQ-5D scores 0.65 v 0.78). In addition compared to other cancer sufferers, aNSCLC patients have a worse QoL (QLQ-C-30 QL2 score 48.8 v 61.5 for stage IIIB/IV cancer patients). The real world study shows that both health status and QoL significantly worsen with advancement to later lines of treatment. The results show a high unmet need for more effective 1[st]–line treatments to prevent disease progression while maintaining patient quality of life.

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      P1.06-033 - Non-Small Cell Lung Cancer in Young Patients; Clinico-Pathologic Criteria and Prognostic Factors (ID 3809)

      14:30 - 14:30  |  Author(s): M. Rahouma, H. Aziz, F. Abou Elkassem, I. Loay, G. Ghaly, M. Kamel, A.M. Abdelrahman

      • Abstract
      • Slides

      Background:
      A cancer registry was analyzed to determine the clinicopathologic characteristics and prognosis of non-small cell lung cancer (NSCLC) in patients < 45 years old at diagnosis as they were not thoroughly investigated

      Methods:
      Among enrolled NSCLC cases attending National Cancer Institute –Cairo (NCI) between 2007-2012, we retrospectively reviewed those who were 45 years old or younger. Data regarding demographics, ECCOG-performance status(PS), histology, grade, stage, chemotherapy type, number of cycles, overall and progression free survival (OS, PFS) were obtained. Pearson’s (X[2]) test , Cox regression and Kaplan-Meier survival curves were used for statistical analysis.

      Results:
      Among 99 NSCLC cases, we identified 22cases ≤ 45years. Lower stages were more prevalent among young (77.3%) versus old group(54.5%) p=0.05 Median OS in young versus old group was 18 versus 15 months(p=0.773), while PFS was 4 versus 6 months respectively (p=0.322) In our subgroup analysis(n=22); median age was 42years(30-45years), Nearly three-quarters were males, 40.9% were PS >1. The majority of cases in young group were stage IIIB(77.3.%). Pathology was squamous(40.9%), adenocarcinoma(22.7%), undifferentiated(22.7%) and adenosquamous carcinoma in 4.5% of our cases. Median OS and PFS was 18 and 4 months respectively. Significant difference in OS and PFS was observed among responder versus non responders in multivariate analysis (Figure)

      Conclusion:
      Good response to chemotherapy is the best way to prolong survival among young NSCLC cases irrespective of PS, gender, stage or pathology. Figure 1



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      P1.06-034 - Outcomes after Pulmonary Metastasectomy for Metastatic Cancer (ID 5789)

      14:30 - 14:30  |  Author(s): P. Balakrishnan, Y. Al-Sheibani, S. Galvin, B. Mahon, J. Riordan, J. McGiven

      • Abstract

      Background:
      In most malignant diseases , the ability to constantly metastasize remains a truly challenging obstacle in cancer patients . Historically in the past , any local surgical treatment in patients with systemic malignant disease is considered without any prognostic benefit , this has since evolved with many studies confering huge success rates with excellent prognostic benefits . We hereby report our experience over the last 10 years at Wellington Regional Hospital , Cardiothoracic unit .

      Methods:
      A retrospective study was undertaken in series of patients with colorectal , melanoma , breast , sarcoma & renal metastatic disease undergoing pulmonary metastasectomy , from year 2000 to 2010 . These data was identified & stratified into groups using hospital patient database & ORSOS theatre database with the aid of Excel spreadsheet .

      Results:
      All these patients were operated on either – unilateral versus bilateral , VATS or thoracotomies with or without lymph node dssection as well as repeat surgeries . The role of metastatectomy in their treatment options & the prognostic factors with impact on survival discussed .

      Conclusion:
      In carefully selected surgical patients , pulmonary metastasectomy for metastatic diseases confers continual prognostic & survival advantage for these patients .

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      P1.06-035 - Frequency and Clinical Relevance of EGFR-Mutations and EML4-ALK-Translocations in Octagenarians with NSCLC (ID 5923)

      14:30 - 14:30  |  Author(s): A. Tufman, S. Reu, S. Hasmann, D. Kauffmann-Guerrero, K. Milger, Z. Syunyaeva, K. Kahnert, R. Huber

      • Abstract

      Background:
      Novel therapies targeting genetic alterations have improved response rates and overall survival for some patients with NSCLC; however, only a minority of caucasian patients with lung cancer benefit from these treatments. Testing for EGFR mutation and ALK translocation is recommended for all patients with advanced adenocarcinoma, but the highest occurance of these driver mutations has been described in younger patients, females, and those with little or no smoking history. The frequency of driver mutations in elderly and very elderly patients has not been described.

      Methods:
      We reviewed the charts of all patients over age 70 treated at our centre in 2015 and assessed the frequency of EGFR and ALK testing. We report the frequency of EGFR and ALK alterations in patients aged 70-74 , 75-79 and >80 years.

      Results:
      Out of 179 patients diagnosed at our centre in 2015, 15 were 80 years or older at the time of first diagnosis and 7 of 15 had non-squamous histology. Among these very elderly patients, 3 patients were found to have EML4-ALK translocations and 2 patients were found to have EGFR mutation (1 Del19, 1 L858R). This represents a 71% frequency of treatable driver mutations in octagenarians with non-squamous NSCLC. Rates of genetic drivers were somewhat lower, but still clinically relevant, in non-squamous NSCLC patients aged 70-74 (27.0%) and 75-79 (26.7%).

      Conclusion:
      Very elderly patients (>80 years of age) with non-squamous NSCLC were found to have high rates of the driver alterations EGFR mutation and ALK translocation. This is clinically relevant, as this often frail and comorbid population may not be suitable for treatment with cytotoxic chemotherapy and may benefit from first line treatment with a targeted tyrosine kinase inhibitor. Testing for these genetic alterations should not be restricted to younger patients. The biology of lung cancer in the very elderly may differ from that of moderately elderly patients, as the longevity of these patients may select for individuals more resistant to, or with little exposure to, environmental carcinogens.

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      P1.06-036 - Post-Recurrence Survival Analysis of Stage I Non-Small Cell Lung Cancer: Prognostic Significance of Local Treatment (ID 5805)

      14:30 - 14:30  |  Author(s): K. Lee, H.R. Kim, D.K. Kim, Y. Kim, S. Park, S.H. Choi, S.K. Hwang, J.S. Bok, H.P. Lee, B.K. Chong

      • Abstract
      • Slides

      Background:
      The aim of this retrospective study was to review recurrence patterns of stage I non-small cell lung cancer(NSCLC), and to identify prognostic factors for post-recurrence survival(PRS).

      Methods:
      Among 940 patients with pathological stage I NSCLC who had undergone curative resection between 2001 and 2009, total 261 patients who had experienced recurrence were included in this study. Number of patients with adenocarcinoma(ADC) were 188, squamous cell carcinoma(SCC) were 62. Oligo-recurrence was defined as 1-3 loco-regional or distant recurrent lesions restricted to a single organ. Potentially-curative local treatment(PCLT) included surgery, stereotactic radiotherapy(SRT), and photodynamic therapy(PDT).

      Results:
      Median follow-up duration was 65 months(range, 4-186 months) and median disease-free interval(DFI) was 23 months(range, 2-95 months). Number of patients with oligo-recurrence was 154, and the most common sites of oligo-recurrence were lung in 84 patients, followed by brain in 18 patients, bronchial stump in 18, and single-station of mediastinal lymph nodes in 12. Local treatment for recurrent tumor included surgery in 59 patients, SRT in 50, PDT in 2, and other radiotherapy in 53. Seventy-four patients received chemotherapy only, and 36 patients took conservative treatment. Among 125 patients who were evaluated for EGFR gene mutation study, positive results was detected in 62 patients, and 31 patients were treated with TKI. The 3- and 5-year post-recurrence survival rates were 49.1% and 33.8%, respectively. Age at recurrence, adenocarcinoma cell-type, DFI, TKI and PCLT were independent prognostic factors in multivariate analysis. Figure 1



      Conclusion:
      Local treatment of oligo-recurrence should be considered in selected candidates, and use of TKI is reasonable if EGFR mutation is detected.

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      P1.06-037 - Non-Small Cell Lung Cancer Invading the Diaphragm: Outcome and Prognostic Factors (ID 6240)

      14:30 - 14:30  |  Author(s): D. Galetta, L. Spaggiari

      • Abstract

      Background:
      Diaphragmatic infiltration by non-small cell lung cancer (NSCLC) is a rare occurrence and surgical results are unclear. We assessed our experience with en bloc resection of lung cancer invading the diaphragm analyzing prognostic factors and long-term outcomes.

      Methods:
      We analyzed a prospective database of patients with NSCLC infiltrating the diaphragm who underwent en bloc resection. Univariate and multivariate analysis was performed to identify prognostic factors. Survival was calculated by the Kaplan-Meier method.

      Results:
      Nineteen patients (14 men, mean age 64 years) were identified. Surgery included nine pneumonectomies, eight lobectomies, and two segmentectomies. A partial diaphragmatic infiltration was observed in 10 patients (52.6%), and full-depth invasion in nine (47.4%). Diaphragmatic reconstruction was done primarily in 13 patients (68.4%), and by prosthetic material in six (31.6%). Pathological nodal status included nine N0, four N1, and six N2. Median hospital stay was seven days (range, 4-36 days). Postoperative mortality was 5.2% (1/19). Two patients (10.5%) had major complications (acute respiratory distress syndrome and bleeding), and 10 minor complications, arrhythmia in seven (36.8%), and pneumonia in three (15.8%). Five-year survival was 29.8%. Mean survival and disease-free survival were 30 months (range, 1-164 months) and 20 months (range, 1-83 months), respectively. Factors adversely affecting survival were diaphragmatic infiltration (50% superficial vs 0% full-depth infiltration; log-rank test, P=0.04), and nodal involvement (43% N0 vs 20% N1-2; log-rank test, P=0.03).

      Conclusion:
      Resection of NSCLC invading the diaphragm is technically feasible and could be a valid therapeutic option with acceptable morbidity and mortality and long-term survival in highly selected patients.

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      P1.06-038 - Survival and Prognostic Factors of Oligometastatic Non-Small Cell Lung Carcinoma: A Single Center Experience (ID 5283)

      14:30 - 14:30  |  Author(s): D. Kızılgöz, P. Akın Kabalak, U. Yılmaz, T. İnal Cengiz, M. Karaca, E. Tunç, S.Ş.E. Gülhan, K. Wang

      • Abstract

      Background:
      In patients without targeted mutations platinum-based chemotherapy is still current treatment method with a median survival rates of 8-11 months. Patients with single side oligo-metastatic disease should be consider for curative aggressive therapies for both primary and metastatic sides for better survival (NCCN 2016).

      Methods:
      Totally 19 oligo-metastatic NSCLC patients was evaluated retrospectively by using hospital database. All patients had single metastatic side.

      Results:
      Among 19 eligible patents there was male predominance (n= 16, 84.2%). Eight patients had co-morbidities requiring regular medication. Histopathological, there were 13 (68.4%) adenocarcinoma and 6 (31.6%) non-adenocarcinoma. While brain was the most common site for metastasis 10 (52.6%), it was followed by bone (n=6, 31.6%). Treatments for primary tumour side were surgery (n=6, 31.7%), concurrent CRT (n=5, 26.3%) and sequential CRT (n=1, 5.3%). Median follow-up for whole cases were 59.1 weeks. Median overall survival (OS) and progression free survival (PFS) were 140 (±33.7) and 76 (±24.2) weeks respectively. Progressions were observed mostly in 45.4. week. Univariate cox regression analyses for OS and PFS is indicated in Table 1. Clinical T and N staging had significant relation with OS (p=0.02 and 0.03 respectively). There was no relation between bone or brain metastasis and histopathology, gender, clinical T and N staging. Median survival after first progression (SAFP) was 63 weeks (±SS 29.05). Among study parameters only clinical T staging had significant relation with SAFP (p=0.026). Median SFAP was better in patients with progression of primary tumour however median OS was better in patients with progression of distant metastasis (p>0.05).

      Factor OS PFS
      Hazard Ratio p Hazard Ratio p
      Age (cut-off=65) 1.034 (0.18-5.1) 0.96 0.4 (0.1-2.2) 0.3
      Co-morbidity 2.3 (0.54-9.8) 0.24 3.4 (0.8-14) 0.07
      Brain Metastasis 0.88 (0.21-3.6) 0.86 1.5 (0.42-5.45) 0.52
      Histopathology (adeno vs non-adeno) 0.22 (0.03-1.4) 0.10 0.67 (0.16-2.8) 0.6
      Bone Metastasis 1.78 (0.43-7.31) 0.42 1.7 (0.47-6.6) 0.4
      pN Staging (n0 and N1-2) 0.12 (0-173) 0.21 0.94 (0.22-4.02) 0.94
      cT Staging 2.17 (1-4.7) 0.02 1.11 (0.73-1.81) 0.54
      cN Staging (n0 and N1-2) 2.3 (0.86-6.6) 0.03 1.77 (0.79-3.97) 0.1
      Non-surgical curative treatment 1.88 (0.41-8.52) 0.42 1.9 (0.50-7.38) 0.34
      Surgery 0.31 (0.06-1.65) 0.14 0.21 (0.02-1.78) 0.09


      Conclusion:
      Even oligo-metastatic NSCLC means stage 4 of disease, curative treatment approaches for both primary and metastasis sides can increase patients’ prognosis than other stage 4 cases. Similar to the existed retrospective studies we had OS more than 2 years and PFS more than 1 year.

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      P1.06-039 - Retrospective Study of the Incidence and Outcomes from Lung Cancer That Developed Following a Solid Organ Transplant (ID 5136)

      14:30 - 14:30  |  Author(s): K. Young, M. Marquez, J. Yeung, F. Shepherd, S. Keshavjee, E. Renner, J. Kim, H. Ross, T. Aliev, G. Liu, N.B. Leighl, R. Feld, P.A. Bradbury

      • Abstract
      • Slides

      Background:
      Organ transplant recipients (OTR) have an increased risk of developing post-transplant malignancies with lung cancer being one of the most common. We investigated incidence and outcomes of lung cancer in OTR managed at the University Health Network.

      Methods:
      The study population, patient characteristics, treatments and outcomes were summarized from solid OTR databases, our cancer registry and patient charts from January 1, 1980 to December 31, 2015. Univariate Kaplan-Meyer curves estimated overall survival (OS) by histology, stage and chemotherapy.

      Results:
      Amongst 7994 OTR (heart [N=765], lung [n=1668], liver [n=238], kidney [n=3273]), 123 developed lung cancer (1.54%) of which (55) 44.7% occurred in lung OTR; 108 (1.35%) patients had sufficient data for subsequent analyses. Median age: 62 years (29 - 85); male: 66%; smoking status at time of transplant - former/current/never/unknown: 62%/10%/15%/8%. Histologies included non-small cell lung cancer (NSCLC): 81%; small cell lung cancer (SCLC): 10%; neuro-endocrine tumours: 9%. NSCLC: Adjuvant chemotherapy, after it became standard of care (SOC), was given to 16% of eligible NSCLC patients. At recurrence, 28% received chemotherapy while 28% received a TKI. In patients initially presenting with stage IV NSCLC, 18% received chemotherapy and 3% received a TKI. SCLC: For limited and extensive stage SCLC patients, 83% and 60% received SOC chemotherapy, respectively. All: Where chemotherapy dosing was known (n=23), 42% of patients received initial dose reductions. For early stage patients, 22% required dose reduction and 11% had chemotherapy discontinuation due to toxicity. For stage IV patients, 42% required dose reductions and 50% required discontinuations.

      Median OS by Subgroup
      Patients by Histology, Stage at Diagnosis & Systemic Treatment n median OS (months) 95% C.I.
      NSCLC: Stage I/II Systemic Treatment No treatment 48 11 37 24.9 25.7 24.9 (17.3-36.6) (14-51.6) (16.2-72.9)
      NSCLC: Stage III Systemic Treatment No treatment 7 1 6 24.6 84.0 24.6 (4.5-NA) NA (4.5-NA)
      NSCLC: Stage IV Systemic Treatment No treatment 33 7 26 3.2 8.7 2.3 (2-4) (4.7-52.4) (1.5-3.5)
      SCLC: Limited Stage Systemic Treatment No treatment 6 5 1 9.6 14.3 2.0 (2-NA) (8.4-NA) NA
      SCLC: Extensive Stage Systemic Treatment No treatment 5 3 2 1.7 5.5 0.2 (0.2-NA) (1.7-NA) (0.2-NA)


      Conclusion:
      Survival was poor in our OTR population compared to historical norms in non-transplant patients. A minority of NSCLC patients received adjuvant or palliative chemotherapy, while most SCLC patients were treated. Both often had sub-standard dosing. Chemotherapy appeared better tolerated in early stage disease.

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      P1.06-040 - Home-Based Pulmonary Rehabilitation in Advanced Non Small Cell Lung Cancer Patients Treated by Oral Targeted Therapy: A Feasibility Study (ID 4453)

      14:30 - 14:30  |  Author(s): C. Pagniez, C. Olivier, A. Olislagers, S. Peres, E. Wasielewski, A. Baranzelli, M. Willemin, X. Dhalluin, A.B. Cortot, A. Hoorelbeke, A. Scherpereel

      • Abstract
      • Slides

      Background:
      Pulmonary rehabilitation (PR) is valuable in the peri-operative setting of non small cell lung cancer (NSCLC) patients, but not established for stage IIIB-IV disease. Previously, we showed that home-based PR is feasible and may significantly improve quality of life (QoL) and functional status of NSCLC patients treated by chemotherapy (submitted). The goal of this study was to assess the feasibility and value of home-based PR in advanced NSCLC patients treated by oral targeted therapies.

      Methods:
      Advanced NSCLC patients with oral targeted therapy were recruited in a prospective study in 2015-2016 in Lille University Hospital, France. After written informed consent, they benefited from 8 weeks home-based PR including functional exercises, psychological and nutrition support, therapeutic education. Exclusion criteria were cardiovascular contraindication to PR, symptomatic brain metastasis, bone metastasis with high fracture risk, or severe cognitive disorder. Main endpoints were adherence, inclusion rate, and cause of refusal. Secondary endpoints were PR benefits assessed by QoL scales (EORTC QLQ C 30, FACT-L, HAD); functional capacity: 6min walk test, 6 min stepper test, spirometry, respiratory muscle strength; and global condition: nutrition, treatment tolerance. This study was approved by local Ethical Committee

      Results:
      Among 36 screened patients, the adhesion rate was 55.6% with 20 patients joining the study. Other patients refused mostly because (a) of “lack of interest for PR and they don’t want to be disturbed” (40% of cases), or (b) they considered “their physical activity already sufficient” (12%), or (c) “family constraints” (12%). Only 15 patients (41.6%) started PR (3 early deaths, 1 exclusion for intraventricular thrombosis, 1 consent withdrawal). No serious adverse event was reported but only grade 1 asthenia or musculoskeletal pain. Significant increases of FACT-L score from 84.7 to 100.2 (p=0.02) and 6 min stepper test from 140 to 195.7 steps (p=0.01) were found after PR, and preservation of patients’ autonomy reflected by stability of 6WT data. Most of other parameters exhibited a positive but not significant trend, likely due to the limited number of participants.

      Conclusion:
      Home-based PR is feasible and well-tolerated in patients with advanced NSCLC treated by oral targeted therapies. Significant improvements were obtained with PR based on 6ST and QoL FACT-L data. Moreover, PR was highly appreciated by patients, their relatives, and all medical teams raising our will to be able to propose PR to all our stage III-IV NSCLC patients. Currently, this study is still ongoing and multicentric, aiming at recruiting 50 extra patients.

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      P1.06-041 - Overall Survival and Intermediate Outcomes among Scandinavian Non-Small Cell Lung Cancer Patients: The SCAN-LEAF Study (ID 5141)

      14:30 - 14:30  |  Author(s): S. Ekman, J.B. Sørensen, J. Rockberg, M. Sandelin, M.M. Daumont, P. Sobocki, P. Klint, H. Huang, J. Svärd, O. Chirita, L. Jørgensen, M. Planck

      • Abstract
      • Slides

      Background:
      The past decade has seen several advances in the field of non-small cell lung cancer (NSCLC), with improved tools for tumor characterization as well as novel targeted and immune therapies. It is important to understand the current treatment landscape including treatment outcomes, in order to maximize patient benefits from these advances. SCAN-LEAF is a Scandinavian retrospective cohort study with prospective annual data cuts, providing a unique opportunity for insights into real-world clinical NSCLC practice over more than a decade. It includes clinical practice patterns of tissue biopsy, pathological diagnosis and tumor biomarker status testing, and their relationship to treatment choices and outcomes. Here, we present intermediate and survival outcomes by disease stage and histology subtype, and factors associated with survival.

      Methods:
      SCAN-LEAF consists of a registry-based cohort including all diagnosed NSCLC patients in Denmark, Norway and Sweden (Cohort 1), and a Swedish sub-cohort (Cohort 2) supplemented with data from electronic medical records (EMRs). Based on the first data collection including data from NSCLC patients diagnosed 2005-2013, overall survival (OS; Cohort 1 & 2) and progression-free survival (PFS; Cohort 2) will be estimated using Kaplan-Meier analysis and reported as cumulative incidences (with 95% CI) by disease stage at diagnosis, histological subtype, biomarker status, presence of metastases, age and gender. Response rates (Cohort 2) will be described by treatment line in addition to stage and histology subtype. Association of stage with survival (Cohort 1 & 2) and treatment response (Cohort 2) will be analyzed by Cox regression with time to event (death or response) as outcome variable and disease stage category at diagnosis, follow-up time, and therapy line as stratification variables. In addition, the relationship between OS and intermediate outcomes, as well as predictors of OS (e.g. smoking and biomarker status, lesion location, metastasis at diagnosis), will be explored by Cox regression (Cohort 2).

      Results:
      Intermediate and survival outcomes for Scandinavian NSCLC patients diagnosed between 2005 and 2013, as well as any association between overall survival and factors such as patient characteristics and treatment patterns, will be presented.

      Conclusion:
      The SCAN-LEAF study, expected to include >115,000 Scandinavian NSCLC patients and >2,000 sub-cohort patients diagnosed between 2005 and 2018 during the full duration of the study, will give valuable insights into current care, changing treatment patterns and patient outcomes in a real-world setting. A better understanding of factors associated with survival and intermediate outcomes among NSCLC patients will inform clinical decision-making.

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      P1.06-042 - The Importance of Medication Related Osteonecrosis of the Jaws (MRONJ) (ID 4309)

      14:30 - 14:30  |  Author(s): M. Krasnik, H.A. Mahedi, M. Schiodt

      • Abstract

      Background:
      Medication related osteonecrosis of the jaws (MRONJ) is an increasing problem globally, which may lead to loss of teeth and jaw bone and has a significant impact on qualtity of life. MRONJ is known since 2003, reported after antiresorptive treatment with bisphosphonate, and since 2010 also from Denosumab for skeletal metastases from breast cancer, prostate cancer and multiple myeloma, Recently, MRONJ has also been related to chemotherapy, including Tyrosine Kinase Inhibitors for lung cancer, kidney cancer and gastrointestinal cancer without skeletal metastases. The onset of MRONJ is often precipitated by of one of the above medication types in combination with a tooth extraction. Therefore it is recommended that all patients have a dental screening and relevant dental treatment before the start of medication with antiresorptives (bisphosphobnates/denosumab) or Tyrosine Kinase Inhibitors The purpose of this pstudy is to raise awareness that MRONJ can be prevented and that MRONJ also occurs among patients receiving chemotherapy without bisphosphonates or denosumab. .

      Methods:
      Rigshospitalet established the Copenhagen ONJ Cohort of consecutive patients with MRONJ since 2004, and have performed systematic prospective data collection since 2010.

      Results:
      Among 247 patients enrolled in the Copenhagen ONJ Cohort 163 had cancer and received treatment with bishosphonates in 109 cases and denosumab in 54 cases. In addition, since 2013 we have received 7 patients with MRONJ from Tyrosine Kinase inhibitors. In 85 out of 163 cancer patients (52%) the onset of MRONJ was related to tooth extraction.

      Conclusion:
      More than 50% of the MRONJ cases could potentially be avoided.If all patients had dental examination and had repaired or extracted bad teeth before start of antiresorptive medication, Thus all cancer patients should have dental examination before start of medical treatment.

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      P1.06-043 - A Study to Select Rational Therapeutics in Subjects with Advanced Malignancies (WINTHER) - The Sheba Experience in Lung Cancer Patients (ID 6414)

      14:30 - 14:30  |  Author(s): A. Onn, J. Bar, T. Sela, A. Ackerstein, S. Halperin, G. Hout-Siloni, S. Lieberman, H. Nechushatan, R. Berger

      • Abstract

      Background:
      Patient-tailored therapy based on tumor genomics is a promising tool in cancer therapy. However, in current practice it is limited to 30-40% of the patients whose tumor harbor actionable DNA mutations or amplifications

      Methods:
      : WINTHER is an open label non-randomized clinical trial developed by the WIN consortium to provide a rational personalized therapeutic choice to all (100 %) enrolled patients, irrespective of the type of genomic events. The study includes patients with metastatic cancer who progressed on at least one line of therapy. Matched tumor and normal tissue biopsies are collected from each patient and analyzed by next-generation-sequencing for known oncogenic driver aberrations (Foundation Medicine) or by functional genomics utilizing a prediction model of efficacy developed at Ben Gurion University. Based on these results study leaders from all centers make therapy decisions. The study aim is to compare progression free survival rates between the previous treatment line and the study drug/s. Patient accrual began in 2013 in four international cancer centers. The following is a description of the experience at Sheba Medical Center., specifically focusing on a large sub-population of lung cancer patients.

      Results:
      Fifty six patients were screened and biopsied for the study. The majority of patients were diagnosed with lung cancers (52%), with a diverse representation of other malignancies including breast (16%), renal (9%), colon (9%), sarcoma, bladder and head and neck. Successful biopsies yielding sufficient material for genomic analyses were achieved in 35 subjects (63%). Lung biopsy success rates were 75% and 60% respectively for normal and tumor specimens. To date, 11 lung cancer patients were treated with a variety of chemotherapy (1) or biologic agents (11) based on study recommendations while 3 have yet to progress on previous therapy. Targeted genomic alterations included EGFR (3), RET (2), KRAS (2), ALK (1), ErbB2 (1), ErbB3 (1), BRAF (1). We observed a clinical benefit rate (CBR) of 55% (6/11) with 1 subject achieving compete response (CR), 2 partial responses (PR) and 3 stable disease (SD). Subjects recruited during the second year of the study, compared to the first year had a reduced biopsy failure rate, were more likely to receive treatment and achieved an increased clinical benefit.

      Conclusion:
      The proposed strategy for tumor genomic analysis based on the comparison of matched tumor and normal biopsies is acceptable and feasible. The experience of the multidisciplinary team is an important contributor to the program’s success.

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      P1.06-044 - Costs of Adverse Events (AE) Associated with Cancer Therapies in Non-Small Cell Lung Cancer (NSCLC) in France (ID 5970)

      14:30 - 14:30  |  Author(s): C. Chouaid, D. Loirat, C. Godard, E. Clay, L. Lévy-Bachelot, A. Millier, E. Angevin

      • Abstract

      Background:
      AE associated with existing and future treatments in NSCLC are frequent and should be accounted for in health economic models. In addition to utility decrements, appropriate costing of AE management is needed. In the case of NSCLC which affects 45 200 patients per year in France, published data are scarce and not always complete. It was therefore thought of importance to assess resource use and costs associated with AEs.

      Methods:
      When looking at the grade 3 or 4 AEs appearing for at least 1% of patients in the clinical trials for erlotinib (TITAN, LUX-LUNG 8), ramucirumab plus docetaxel (REVEL), docetaxel and pembrolizumab (KEYNOTE 010), a list of 20 grade 3 and 4 AE was identified as relevant for Health Economic analysis. Among them, 7 did not have cost data available in the literature. Three French oncology experts were consulted. A questionnaire was sent before the meeting with the experts, asking for, according to the grade, insight on resource use (hospitalisation, follow-up visits, diagnosis exams, treatments). Results were discussed during the meeting in order to reach a consensus. Direct medical cost per AE, expressed in 2016 Euros, was then calculated from a national health insurance perspective based on public and private weighted tariffs and 2014 PMSI database.

      Results:
      The mean AE cost was €206 for thrombocytopenia, €263 for ocular toxic effect, €2,332 for arthralgia, €3,282 for venous thromboembolism, €3,732 for pulmonary bleeding, €5,176 for dehydration, €5,751 for pneumonia, infiltration or pneumonitis. Hospitalization costs corresponded to 46% to 100% of total AE cost. These AE costs were consistent with the costs of other grade ¾ AEs previously published for NSCLC therapies.

      Conclusion:
      Among seven grade 3 and 4 AEs seen, four appear to have an important economic impact, with a management cost of at least €3,000 per event.

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      P1.06-045 - Multiple Neoplasms Consist of Lung Cancer and Hematological Malignancies (ID 5737)

      14:30 - 14:30  |  Author(s): K. Natori, D. Nagase, S. Ishihara, Y. Mitsui, A. Sakai, Y. Kuraishi, H. Izumi

      • Abstract

      Background:
      The lung cancer is a cancer of the most in Japan and first place in cause of death. Lung cancer (LC)is still poor prognosis disease that cure only in early clinical stage. We report that we reviewed 55 cases of multiple neoplasms with lung cancer and the hematological malignancies.

      Methods:
      We intended for multiple neoplasms 339 cases including hematological malignancy. We reviewed 55 multiple neoplasms including the lung cancer. All patients were followed up until death or untile August 2016. Survival was measured from the diagnosis of multiple cancer to time of death or last contact. Definition of the multiple neoplasms in compliance with Warren & Gates. Also we determined the synchronous type and metachronous type in accordance with the definition of Moertel, so within less than 6 months was synchronous type, more than 6 months was metachronous type.

      Results:
      All cases are 55 cases, consist of male 44 cases, female 11 cases, type of multiple neoplasms, synchronous type 14 cases, metachronous type 41 cases. Number of multiple neoplasms, double neoplasms 38 cases, triple neoplasms 14 cases, quadple neoplasms 3 cases. The median age was 71years (range,47-86years) The counterpart of malignancies, MHL 26 cases, MDS 7 cases, AML 7 cases, HL 2 cases, MG 1 case, CLL 2 cases, CML 2 case, ALL 1 case, MGUS 3 cases. In double neoplasms, the median age of first diagnosis, 69years, the second cancer were 71years, About interval between lung cancer and hematological malignancies, lung cancer precedence case was 40M, hematological malignancy precedence case was 54M. The median overall survival was 24M.

      Conclusion:
      Diagnosis of LC within 5 years were 26 cases out of 41 cases. The important point is that 5 years are required for careful observation at the time of hematological malignancy diagnosis. We think that a prognosis is improved.

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      P1.06-046 - Can We Better Manage Advanced NSCLC in the Elderly with the New Therapeutic Agents? Preliminary Analysis of a Real-Life Multicenter Study (ID 5814)

      14:30 - 14:30  |  Author(s): T. Franchina, S. Novello, A. Russo, M. Gianetta, E. Capelletto, D. Galetta, A. Catino, M.R. Migliorino, S. Ricciardi, F. Morgillo, C.M. Della Corte, D. Rocco, H.J. Soto Parra, A. Russo, F. Ambrosio, V. Franchina, V. Adamo

      • Abstract
      • Slides

      Background:
      Systemic treatment of NSCLC has profoundly changed over the past years with novel therapeutic strategies recently implemented in clinical practice. Benefit of these novel agents in elderly patients (pts) is uncertain, given the paucity of prospective data in this population. Moreover, elderly pts are often undertreated, due to comorbidities and toxicity concerns. Therefore, we aimed to evaluate the access, safety and outcome with novel therapeutic agents in pts ≥ 70 years (yrs).

      Methods:
      We planned an observational study to retrospectively evaluate consecutive elderly patients (≥ 70 yrs) with metastatic NSCLC treated at 9 Italian Centers between January 2014 and December 2015. Data collected include clinical and pathological characteristics, treatment types, safety and outcome report.

      Results:
      220 patients with stage IV NSCLC were included in this preliminary analysis (53% IVa, 47% IVb). Median age was 74,5 (range 70-85) and 69% were male. 15% of pts aged 80 years or older. ECOG PS was 0, 1, 2 in 37%, 51% and 12% of pts, respectively. According to comprehensive geriatric assessment, 59% of pts were fit, 28% vulnerable and 13% frail. Histology was 23% squamous cell carcinoma, 72% non-squamous cell carcinoma and 5% NOS. EGFR mutation was diagnosed in 24% of cases; 1,4% and 1% of pts had ALK and ROS-1 translocations, respectively. 90% of pts received a systemic therapy: 48% a platinum doublet chemotherapy (CHT), 27% a mono-CHT, 25% an EGFR tyrosine kinase inhibitor (TKI). Only 1% of pts were treated with antiangiogenic drugs. Immunotherapy (IT) was administered in 16% of all treated pts. 7% of pts received only BSC. Second- and third-line treatment were given to 44% and 8% of pts, respectively. 51% of pts who received second line treatment and 60% of pts treated with a third line therapy had a novel therapeutic agent (II line TKI 20%, IT 31%; III line TKI 33%, IT 27%). 31% of pts were included in clinical trials. A dose reduction was reported in 41% of therapies and the discontinuation rate was 9%. Survival data are not mature at this time.

      Conclusion:
      Our data, albeit preliminary, suggest an evolution in the management of NSCLC in the elderly. The interesting activity and the good safety profile encourage the use of novel agents also in this setting of NSCLC. Adequate selection of elderly pts and personalized approach are still matters of debate. Use of adapted schedule and dose reduction could warrant a good compromise between safety and efficacy.

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      P1.06-047 - Management of Patients Aged over 70 Years with Newly Diagnosed Lung Cancer (ID 4159)

      14:30 - 14:30  |  Author(s): H. Abbas, M. Jafri, A. Williams, M. Jones, J. Thompson

      • Abstract

      Background:
      Lung cancer is an important cause of mortality and morbidity worldwide. It is the third most common cancer in the UK. Due to an increase in life expectancy there is an increase in the proportion of patients greater than 70 years being diagnosed with lung cancer. We looked at the management of patients diagnosed with newly diagnosed lung cancer over a period of 12 months in a large UK Teaching hospital. The main aim of this study was to compare the outcome of various treatment options offered to elderly patients diagnosed with lung cancer.

      Methods:
      All individuals diagnosed with lung cancer discussed at specialist thoracic multidisciplinary meeting aged over 70 between September 2014 and September 2015 were identified and retrospectively reviewed. Demographic data, histology, treatment and survival were evaluated

      Results:
      123 patients were included in the study, 37% were between 70-74yrs, 39% were between 75-79yrs and 48% were >= 80yrs. The commonest histology was adenocarcinoma which constituted 36.2% followed by squamous cell about 19.3%. Majority of patients were referred from hospital (57%), about 30% were referred from A&E and 12% were referred from GP. In terms of treatment; 52% received best supportive care (BSC), 30% surgery and 17% chemotherapy. Common reasons for patients receiving BSC were: poor performance status (65%), and co-morbidities (21%). Patients who had chemotherapy had improved survival compared to BSC; 5 v.s. 10 months. Node positivity was poor prognostic sign; median survival for N0, N1, N2 and N3 were 17, 10, 5 and 3 months respectively

      Conclusion:
      Treating elderly patients with lung cancer is challenging because at the time of diagnosis the tumor is often advanced and furthermore elderly patients often suffer with multiple comorbidites which makes treatment more difficult. In our cohort, patients who received active oncological treatment had improved overall survival. Majority of the patients didnt receive active oncological treatment due to poor perfomance status or co morbidites and hence not fit for treatment. Our data suggests that age should not be considered as a limiting factor for chemotherapy and there is a need for prospective studies to further evaluate active oncological management of older patients, since with careful selection this group can benefit from active treatment.

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    P1.07 - Poster Session with Presenters Present (ID 459)

    • Type: Poster Presenters Present
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 55
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      P1.07-001 - A Phase II Study of Etirinotecan Pegol (NKTR-102), a Topoisomerase-l lnhibitor Polymer Conjugate, in Small Cell Lung Cancer (ID 4349)

      14:30 - 14:30  |  Author(s): H. Chen, G.K. Dy, A. Groman, W. Brady, S. Jamshed, P. Bushunow, N. Brunsing, A. Adjei

      • Abstract
      • Slides

      Background:
      Small cell lung cancer (SCLC) has poor prognosis and systemic chemotherapy is the standard treatment. Irinotecan is a topoisomerase-I inhibitor that has been used in treating SCLC. Etirinotecan pegol (NKTR-102) is a polyethylene glycol conjugate of irinotecan. It is a next generation topoisomerase-I inhibitor uniquely designed for prolonged tumor cell exposure by using the polymer conjugate technology. This is a single arm phase II study to evaluate single agent etirinotecan pegol in patients with relapsed SCLC (NCT01876446).

      Methods:
      A total of 38 patients who have received only one prior systemic therapy for SCLC are being accrued over 3 years. There are 2 patient cohorts: those progressing on first-line chemotherapy <3 months after completion of treatment (Group A: chemotherapy-resistant, N=20) and those progressing on first-line chemotherapy ≥3 months after completion of treatment (Group B: chemotherapy-sensitive, N=18). Etirinotecan pegol was administered at 145 mg/m[2] IV once every 3 weeks. Cycles were repeated every 21 days until disease progression, unacceptable toxicity, or withdrawal from study. The primary endpoint is the 18-week progression free survival (PFS) rate. The secondary endpoints are objective response rate (ORR), duration of response (DOR), overall survival (OS) and toxicity. A single-stage design is used to assess the primary endpoint separately for each patient group.

      Results:
      Accrual of Group A is ongoing. Group B has completed targeted enrollment of 18 patients and the results are presented here. Median age was 61.6 (50-76.5) years, with 50% male. Prior chemotherapy included cisplatin/etoposide (41.2%) and carboplatin/etoposide (58.8%). Patients received a median of 6 (1-30) cycles of etirinotecan pegol, with dose reduction in 22.2%. PFS rate at week 18 was 72.2% (13/18, 95% Confidence Interval (CI): 47-90%). ORR was 44.5% (8/18), including one complete response. Another one-third (6/18) of patients had stable disease. Median DOR was 4 (1.4-14.5) months. Median PFS was 21.9 (95% CI: 11.7, 29.3) weeks, and OS was 7.1 (95% CI: 4.8, 14.7) months. The most common treatment-related adverse events (AEs) of any grade were diarrhea (66.7%), nausea (55.6%), fatigue (38.9%), and vomiting (27.8%). Neutropenia occurred in 2 cases, both grade 2, without neutropenic fever. The most common AEs ≥grade 3 were lymphopenia, hyponatremia and muscular weakness (2 cases each, all grade 3).

      Conclusion:
      Etirinotecan pegol has shown promising activity with acceptable toxicity profile in treatment of chemotherapy-sensitive patients with relapsed SCLC. Accrual of chemotherapy-resistant patients is expected to be completed soon.

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      P1.07-002 - G1T28, a Cyclin Dependent Kinase 4/6 Inhibitor, in Combination with Topotecan for Previously Treated Small Cell Lung Cancer: Preliminary Results (ID 5213)

      14:30 - 14:30  |  Author(s): L.L. Hart, P.J. Roberts, R. Ferrarotto, R. Bordoni, P. Conkling, T. Patil, C.M.S. Rocha Lima, T.K. Owonikoko, S.R. Schuster, R. Jotte, R. Hoyer, K. Stabler, K.M. Makhuli, R. Aljumaily, W.J. Edenfield, A. Spira, R.K. Malik, G.I. Shapiro

      • Abstract

      Background:
      Chemotherapy-induced bone marrow and immune system toxicity causes significant acute and long-term consequences. G1T28 is a potent and selective CDK4/6 inhibitor (CDK4/6i) in development to reduce chemotherapy-induced myelosuppression and preserve immune system function in small cell lung cancer (SCLC) patients. Hematopoietic stem and progenitor cells (HSPC) are dependent upon CDK4/6 for proliferation, and preclinical models demonstrated that transient G1T28-induced G~1~ cell cycle arrest renders them resistant to chemotherapy cytotoxicity, allowing faster hematopoietic recovery, preservation of long-term stem cell and immune system function, and enhancement of chemotherapy anti-tumor activity.

      Methods:
      Objectives of this ongoing multicenter Phase 1b/2a study are to assess the dose limiting toxicities (DLTs), safety, hematological profile, PK, and anti-tumor activity of G1T28 in combination with topotecan (NCT02514447). The study consists of a limited open-label, dose-finding portion (Part 1; up to 40 patients), and an open‑label, single-arm expansion portion (Part 2; 28 patients). Eligible patients had histologically/cytologically confirmed SCLC, adequate organ function, ECOG performance status 0-2, 1-2 prior lines of chemotherapy, and no symptomatic brain metastases. G1T28, at a starting dose of 200 mg/m[2] (derived from the Phase 1a healthy volunteer study and expected to maintain HSPC G1 arrest beyond topotecan exposure), was administered IV prior to IV topotecan on days 1-5 every 21-days.

      Results:
      21 patients (median age 68, 5 females, 20 white and 1 African-American) have been enrolled across 5 cohorts. DLTs due to Grade 3/4 myelotoxicity occurred in the first two cohorts and were associated with supra-therapeutic topotecan exposures due to decreased topotecan clearance by G1T28. Reducing the topotecan dose achieved exposures in the therapeutic range and was well tolerated. No episodes of febrile neutropenia or bleeding have occurred to date. For the 17 evaluable patients, there were 5 PR, 8 SD, and 4 PD. In the 6 platinum refractory patients there were 1 PR, 3 SD, and 2 PD.

      Conclusion:
      G1T28, a novel CDK4/6i, combined with topotecan for previously treated SCLC patients has been well tolerated, without any episodes of febrile neutropenia or bleeding. There are encouraging early signs of anti-tumor activity, with a response rate of 29% overall (36%, 4/11 in sensitive and 17%, 1/6 in refractory) and a clinical benefit rate (CR+PR+SD) of 76% overall (82%, 9/11 in sensitive and 67%, 4/6 in refractory). This novel approach, allowing the administration of chemotherapy with preservation of hematopoietic function and cellular immunity, could potentially improve treatment outcomes of patients with CDK4/6-independent tumors. Updated data will be presented.

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      P1.07-003 - A Phase II Study Evaluating the Combination of Everolimus with Carboplatin/Paclitaxel as 1st Line Treatment in Patients with Advanced LCNEC (ID 4370)

      14:30 - 14:30  |  Author(s): C. Grohé, W. Engel-Riedel, C. Kropf-Sanchen, V.P. Joachim, S. Gütz, J. Kollmeier, W. Eberhardt, P. Christopoulos, I. Nimmrich, C. Sieder, V. Baum, M. Serke, M. Thomas

      • Abstract
      • Slides

      Background:
      Approximately 3% of all lung cancers are made up of large cell neuroendocrine carcinoma of the lung (LCNEC). These tumors in general have a bad prognosis and currently there are only very limited treatment options, including platinum derivatives and etoposide. The PI3/AKT/mTOR pathway is known to be dysregulated in neuroendocrine tumors (NETs). Since the mTOR inhibitor RAD001 (everolimus) already has proven effectiveness in different types of NETs, we tested whether everolimus might be also an effective treatment option in advanced LCNEC patients.

      Methods:
      In this multi-center, open-label, phase II study, everolimus was combined with platin-based chemotherapy in patients with histologically confirmed stage IV LCNEC according to WHO criteria. Further inclusion criteria were measurable disease according to RECIST 1.1 and adequate bone marrow, renal, and liver function. Main exclusion criteria were symptomatic CNS metastases and prior treatment for advanced LCNEC. Enrolled patients received everolimus once a day in combination with 4 cycles of carboplatin and paclitaxel, followed by daily everolimus maintenance therapy. The primary objective was to evaluate the efficacy by assessing the proportion of progression-free patients after three months of treatment.

      Results:
      Ten German trial sites enrolled altogether 49 patients (mean age: 62 ± 9 years; 71% men). The primary endpoint (proportion of pts progression-free at month 3) was achieved by 24 patients (49%), assessed by an independent central imaging reviewer. Further efficacy evaluation showed an overall response rate (ORR) until month 3 of 45%, a disease control rate (DCR) until month 3 of 73.5%, a median progression-free survival (PFS) of 4.3 months, and a median overall survival (OS) of 9.8 months. At least one toxicity occurred in 86% of all enrolled patients with grade 3/4 toxicities in 51%. Most frequent toxicities were diarrhea, fatigue, anemia, and neutropenia.

      Conclusion:
      The results show that a combined therapy of carboplatin and paclitaxel with the mTOR inhibitor everolimus is an alternative treatment option for LCNEC patients. When comparing to other trials, the effectiveness is comparable to a treatment regimen of cisplatin and etoposide.

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      P1.07-004 - Updated Analysis of Phase II Study of HA-Irinotecan, a CD44-Targeting Formulation of Hyaluronic Acid and Irinotecan, in Small Cell Lung Cancer (ID 5868)

      14:30 - 14:30  |  Author(s): M. Alamgeer, P. Briggs, B. Markman, P. Midolo, N. Watkins, B. Kumar, V. Ganju

      • Abstract

      Background:
      Preclinical studies in small cell lung cancer cell (SCLC) have shown that hyaluronic acid (HA) can be effectively used to deliver irinotecan and selectively decrease CD44 expressing (stem cell-like) tumour cells. The current “proof of principle” study was aimed to replicate these findings by investigating the effect on clinical outcome according to CD44 expression. Final efficacy and bio-marker data on the study is presented.

      Methods:
      Patients with ESLC, having measurable disease, suitable for safe biopsy and able to give informed consent were screened for this study. First 5 patients were treated with HA-irinotecan (150mg/m[2]) and carboplatin (AUC 5), every 3 weeks to evaluate safety data. Subsequent patients were stratified as first line or second line. All second line patients receive open label HA-irinotecan, while first line patients are randomized to receive either HA-irinotecan/carboplatin or irinotecan/carboplatin. The response was measured by CT/PET at baseline, after 1 cycle and every 2 cycles subsequently. Baseline tumour samples were stained for CD44s (standard) and CD44v6 (variant 6). Blood samples for circulating tumour cells (CTCs) were also obtained at the baseline and before each treatment cycle till progression of disease.

      Results:
      Forty (40) patients, median age 66 (range 39-83) were enrolled treated on this study. Seven (7) patients either died or progressed before the first evaluation scan. Of 34 evaluable patients, the overall response rate was 50%, with 4 (12%) complete and 13 (38%) partial responses. Four patients (12%) achieved stable disease while 7 patients (20%) progressed during the treatment. There was no PFS difference in the two first line treatment arms (median 28 weeks in experimental vs 42 week in standard arm) (P = 0.892 HR=0.93, 95% CI 0.36-2042). Median PFS was 14.4 weeks in the second line cohort. The toxicity profile was similar to standard irinotecan, with the incidence of grade III/IV diarrhea seen in the experimental arm of 11% compared with 25% in the standard arm. Biomarker data was available in case of 24 patients, which suggested that there was no difference in response rates or survival according to baseline CD44s or CD44v6 expression. A possible correlation between the number of CTCs and tumour response and relapse was noticed.

      Conclusion:
      HA-irinotecan is well tolerated and has shown activity in the treatment of extensive stage small cell lung cancer. However, no improvement in efficacy was seen in CD44s+ or CD44v6+ SCLC treated with HA-irinotecan. Further strategies to combine HA with other chemotherapeutic agents may be warranted.

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      P1.07-005 - A Retrospective Study of Sequential Chemoradiotherapy for LD-SCLC Patients in Whom Concurrent Therapy is Not Indicated (ID 4066)

      14:30 - 14:30  |  Author(s): S. Ohara, S. Kanda, K. Goto, H. Shiraishi, H. Okuma, K. Itahashi, Y. Goto, H. Horinouchi, Y. Fujiwara, H. Nokihara, Y. Ito, N. Yamamoto, K. Usui, Y. Ohe

      • Abstract
      • Slides

      Background:
      The standard treatment for limited-disease small-cell lung cancer (LD-SCLC) is a combination of cisplatin-doublet chemotherapy and concurrent thoracic radiotherapy. However, sequential radiotherapy, rather than concurrent radiotherapy, is selected for some cases because of concerns regarding the irradiation field, patient age, comorbidities, or performance status. Nevertheless, the efficacy of sequential chemoradiotherapy in patients in whom concurrent chemoradiotherapy is contraindicated is not well known.

      Methods:
      We retrospectively analyzed 286 patients with LD-SCLC at the National Cancer Center Hospital and the NTT Medical Center in Japan between 2000 and 2014. We then compared the clinical characteristics and treatment outcomes of patients undergoing sequential radiotherapy with those undergoing concurrent radiotherapy.

      Results:
      One hundred and eighty-three patients received concurrent chemoradiotherapy and 30 received sequential chemoradiotherapy. The median age of the patients was 64 years (range, 18-81 years) for the concurrent group and 71.5 years (50-83 years) for the sequential group. The concurrent group contained 43 women (23%), while the sequential group contained 9 women (30%). The major reasons for the selection of sequential radiotherapy were patient age (13 patients), a large irradiation field (8 patients), and comorbidities (5 patients). In the sequential group, 23 (77%) received conventional radiotherapy, whereas 7 (23%) received accelerated hyperfractionated radiotherapy. The median overall survival period was 34.5 months for the concurrent group and 27.6 months for the sequential group (P = 0.39). The 2-, 3-, and 5-year survival rates were 71%, 50%, and 40% for the concurrent group and 56%, 56%, and 35% for the sequential group. Recurrence was seen in 149 patients (81%) in the concurrent group and 19 patients (63%) in the sequential group.

      Conclusion:
      We obtained treatment outcomes for patients who could not receive concurrent radiotherapy but could complete sequential radiotherapy that were comparable with the outcomes for those who received concurrent radiotherapy. For patients in whom concurrent chemoradiotherapy is not indicated, sequential chemoradiotherapy should be considered.

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      P1.07-006 - Preclinical Support for Evaluation of Irinotecan Liposome Injection (nal-IRI, MM-398) in Small Cell Lung Cancer (ID 4937)

      14:30 - 14:30  |  Author(s): S.C. Leonard, H. Lee, S. Klinz, N. Paz, J. Fitzgerald, B. Hendriks

      • Abstract
      • Slides

      Background:
      Nal-IRI (irinotecan liposome injection, MM-398, ONIVYDE[®]), in combination with 5-fluorouracil and leucovorin, is currently approved by the FDA for treatment of patients with advanced pancreatic cancer who have progressed on gemcitabine-based therapies. Nal-IRI is designed for extended circulation relative to non-liposomal irinotecan and to exploit leaky tumor vasculature for enhanced drug delivery to tumors. Following tumor deposition, nal-IRI is taken up by phagocytic cells followed by irinotecan release and conversion to its active metabolite SN-38 in the tumors. Sustained inhibition of topoisomerase 1 (TOP1) by extended SN-38 delivery is hypothesized to enable superior anti-tumor activity compared to traditional TOP1 inhibitors. Topotecan, a TOP1 inhibitor, is currently a standard of care for second-line treatment of small cell lung cancer (SCLC). Here, we evaluate nal-IRI compared to topotecan in preclinical models of SCLC.

      Methods:
      Anti-tumor activity of nal-IRI as a monotherapy was evaluated in DMS-53 and NCI-H1048 xenograft models. Cells were implanted subcutaneously into right flanks of NOD-SCID mice; treatments were initiated when tumors had reached approximately 280 mm[3]. Nal-IRI was dosed at 16 mg/kg salt, q1w, which is equivalent to a proposed clinical dose of 90 mg/m[2] free base, q2w. Topotecan was dosed at 0.83 mg/kg/week, Day 1-2 every 7 days, which approximates a clinical dose intensity of 1.5 mg/m[2] (Day 1-5 every 21 days). Tumor metabolite levels were compared in mice treated with nal-IRI or non-liposomal irinotecan at 24 hours post-injection, using previously established high performance liquid chromatography methods.

      Results:
      Carboxylesterase activity and sensitivity to SN-38 in mouse SCLC models were comparable to those measured in tumor types where either nal-IRI or irinotecan HCl has proven to be efficacious clinically (e.g. pancreatic cancer, colorectal cancer). Nal-IRI delivered irinotecan to SCLC tumors to a similar or greater extent than other tumor types including pancreatic tumors. The tumor irinotecan and SN-38 levels of nal-IRI (16 mg/kg salt) were 12 to 57-fold and 5 to 20-fold higher than non-liposomal irinotecan (30 mg/kg salt), respectively. Nal-IRI demonstrated anti-tumor activity in both xenograft models of SCLC at clinically relevant dose levels, and resulted in complete or partial responses after 4 cycles in NCI-H1048 or DMS-53 models, respectively, compared with topotecan which had limited tumor growth control.

      Conclusion:
      This study demonstrated that nal-IRI is more active than topotecan at clinically relevant doses in SCLC preclinical models, and thus support further clinical development of nal-IRI versus topotecan in patients with SCLC that have progressed on prior platinum-based therapy.

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      P1.07-007 - Clinical Outcomes of Patients with LS-SCLC Treated with Chemoradiotherapy. Can We Find Candidates for Salvage Surgery? (ID 5288)

      14:30 - 14:30  |  Author(s): J. Shimizu, Y. Oya, K. Tanaka, C. Kondo, H. Furuta, T. Yoshida, Y. Horio, Y. Sakao, Y. Yatabe, T. Hida

      • Abstract

      Background:
      Although small cell lung cancer (SCLC) is generally considered a systemic disease even in patients with limited stage (LS). Selected recurrent LS-SCLC patients after chemoradiation treatment have been reported long survival with receiving salvage surgery. Purpose of this study was to find candidates for salvage surgery.

      Methods:
      We retrospectively reviewed the charts of 43 consecutive patients who were treated with chemoradiotherapy for LS-SCLC at our hospital from January 2011 to December 2015 to search for the patients with locoregional progression without mediastinal lymph node involvement.

      Results:
      Of the 43 patients, the median age was 69 (38-83), 91% were male and all of them had ECOG PS 0 or 1. Clinical stage: IIA (12%), IIIA (53%), IIIB (35%). 35 (81%) received hyperfractionated RT (45Gy/30fr/3w). Objective response rate was 95%. One patient died of pneumonia. The median survival time was 1584 days and the median progression free survival was 280 days. 33 (77%) demonstrated disease progression. The first progression site was distant (include pulmonary metastasis and malignant pleural effusion) in 17, locoregional in 11, lymph node metastasis out of the radiation field in 2 and both distant and locoregional in 3. In the locoregional progression patients, 6 developed mediastinal lymph node progression in their clinical courses. Finally, 5 in 33 progressive patients had locoregional progression without mediastinal lymph node progression, and were thought possible candidates for salvage surgery.

      Conclusion:
      Most of the patients experienced distant metastasis and/or mediastinal lymph node progression. About 15% of patients who presented with apparently localized disease at the primary pulmonary site after chemoradiation might become possible candidates for salvage surgery.

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      P1.07-008 - Lomustine Endoxan VP16 as Second or Further Line for Recurrent or Progressive Brain Metastases from SCLC (ID 6153)

      14:30 - 14:30  |  Author(s): C. Naltet, A. Dugué, C. Dubos, P. Dô, S. Danhier, D. Lerouge, C. Chouaid, R. Gervais

      • Abstract

      Background:
      Up to fifty percent of patients with small-cell lung cancer (SCLC) will experience brain metastases (BM) during the whole course of their disease. The oral regimen Lomustine Cyclophosphamide Etoposide (LCE) has been tested in SCLC as second line treatment and was shown to be equivalent to the intravenous regimen Cyclophosphamide Adriamycin Vincristine (Gervais R et al. Clin Lung Cancer 2015;16:100-5). This retrospective study evaluates the cerebral response rate (CRR) of this oral chemotherapy on brain metastases (BM) from SCLC relapsing after platinum-based chemotherapy.

      Methods:
      Patients with disease progression after one or more prior chemotherapy regimens for SCLC were included if they had at least one measurable BM according to RECIST 1.1, with PS<2. Patients with symptomatic BM were eligible. They were excluded if they had received previous whole brain irradiation before LCE or were receiving concomitant brain irradiation. Patients received the chemotherapy according to modalities described in the GFPC-0501 study (1). The doses were determined by a therapeutic risk level: lomustine, 80 to 120 mg on day 1, cyclophosphamide 100 mg/d, and etoposide 75 mg/d, for 6 to 14 days, every 28 days, until progression or major toxicity. Primary prophylactic granulocyte colony-stimulating factor was recommended. The primary objective was the cerebral response rate (CRR) using RECIST 1.1 .Secondary objectives included the extra-cerebral response rate (ECRR), the overall survival and the safety.

      Results:
      From 2008 to 2014 in Baclesse comprehensive cancer center, 24 patients fulfilled the inclusion criteria. The median age was 57.5 years (interquartile range [IR] 51.5–64.5). CCR was 50% while ECRR was 26% (NS, p=0.135). Interestingly, 8 of the 9 patients with neurological symptoms had symptomatic improvement. Previous treatment (chemotherapy and/or radiotherapy) for BM did not appear to have any effect on CRR (p=1.000). The hematologic toxicities were the most common side effects with neutropenia (grade ¾ : 26%) and thrombocytopenia (grade ¾ : 21%). Median overall survival was 6.3 months.

      Conclusion:
      In our study, Lomustine Cyclophosphamide Endoxan has a high activity on BM from SCLC, with a comparable extra cerebral response rate than others regimen currently used in second line setting. It has a manageable toxicity profile and the oral route allows patients with a short expectancy of life to benefit from a home-delivered treatment. We suggest that this combination should be tested in a prospective study.

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      P1.07-009 - Outcomes of Patients with Relapsed Small-Cell Lung Cancer Treated with Paclitaxel plus Gemcitabine. 10 Year-Analysis (ID 6403)

      14:30 - 14:30  |  Author(s): A.L. Ortega Granados, N. Luque Caro, J.F. Marín Pozo, N. Cárdenas Quesada, F.J. García Verdejo, D. Fernández Garay, C. De La Torre Cabrera, M. Ruiz Sanjuan, M. Fernández Navarro, C. Rosa Garrido, M.Á. Moreno Jiménez, P. Sánchez Rovira

      • Abstract