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T. Sutedja

Moderator of

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    MS23 - Treatment of the Small Malignant Nodule (ID 40)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 7
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      Case Part 2 (ID 5670)

      14:00 - 15:30  |  Author(s): H. Jo

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS23.1 - Case Part 1 (ID 567)

      14:00 - 15:30  |  Author(s): H. Jo

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS23.2 - Is Tissue Diagnosis Necessary? (ID 568)

      14:00 - 15:30  |  Author(s): D.P. Steinfort

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS23.3 - SABR for Early Stage Lung Cancer and Pulmonary Oligometastases (ID 569)

      14:00 - 15:30  |  Author(s): H. Onishi

      • Abstract
      • Presentation
      • Slides

      Abstract
      With the recent popularization of computed tomography (CT) screening, small malignant nodules are increasingly detected. In Japanese cases of lung cancer surgery, tumors in more than 60% of lung cancer patients were under 3cm in diameter. Stereotactic ablative radiotherapy (SABR) is a new treatment modality where narrow beams from several directions focus on the target while sparing the adjacent normal tissues with high accuracy. By SABR, the biological effect of radiation on tumors was increased and the overall treatment time was shortened. SABR has emerged as one of the radical treatment options for stage I non-small cell lung cancer (NSCLC), mainly in medically inoperable patients. First of all, Uematsu et al reported in 2001, that 3-year local control and overall survival rates of SABR (50-60Gy in 10 fractions) were 94% and 66%, respectively. Then Nagata et al reported in 2005, that 3-year overall survival rate of SABR (48Gy in 4 fractions) was 83% in stage IA and 72% in stage IB. In Japanese multi-centers large database of more than 2000 patients treated with SABR for stage I NSCLC, overall survival rate at three year (OS-3y) and disease-specific survival rate at three year of total patients was 72% and 85%, respectively. Locally progression free rate at three year of T1 and T2 tumors were 87% and 72%, respectively. In USA, Timmerman et al reported in 2010, that 3-year overall survival rate of SABR (54Gy in 3 fractions) was 55.8%. In Europe, Bauman et al reported in 2009, that 3-year overall survival rate of SABR (45Gy in 3 fractions) was 60%. According to a lot of previous studies demonstrating better results of SABR compared with conventional radiotherapy, a consensus that SABR is a standard radical treatment for inoperable patients with stage I NSCLC has been generally accepted. The overall survival rate for subgroup of medically operable patients who rejected surgery in retrospective and prospective studies was almost comparative to that of surgical series considering the same age range though its evidence level is not high. Onishi et al reported five-year overall survival of 87 patients with stage I NSCLC was 69% according to the multicenter retrospective study,. In the phase II trial of SABR with 48Gy in 4 fractions for stage IA (JCOG0403), Nagata et al reported three-year overall of 65 operable patients was 76%. For patients with stage I NSCLC, resection of full lobe and systemic lymph nodes represents standard treatment but can be associated with significant morbidity and even mortality, particularly because patients suffering from lung cancer are often elderly with high comorbidity rates. For such high-risk operable patients, SABR is considered as an alternative option of radical treatment. According to American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, SABR and surgical wedge resection are suggested over no therapy for patients with clinical stage I NSCLC who cannot tolerate a lobectomy or segmentectomy (Grade 2C), but surgical resection has the potential benefit of definitive histologic analysis and pathologic nodal information. In compromised patients for whom such information would not change management and also in patients for whom an adequate margin in unlikely with a surgical wedge resection, SABR is a preferred option. According to good results of these retrospective or prospective studies, some phase III prospective trials comparing SABR versus surgery (lobar resection) have been started, but the patient accrual seems to be difficult. Patient accrual of a trial exploring the efficacy and safety of sublobar resection for patients with smaller tumors has been completed by surgeon recently. SABR is a just local therapy, therefore it essentially should be compared with sublobar resection in high-risk operable patients for lobar resection with such small peripheral tumors. In the meantime, SABR represents a recent trend in radiation oncology also for oligometastases. Local aggressive therapy for oligometastases may improve outcomes, including survival in some cases. SABR has emerged as one option for local therapy against oligometastases in various body sites, most commonly in the lungs and liver. According to published papers of SABR for lung metastases, local control with SABR distributed from 70 to 90% with very low rates of serious toxicities. Although further investigation should be undertaken to clarify the benefits of SABR for the treatment of oligometastases, SABR may be worthwhile for patients who hope for treatment to acquire better local control and possible longer survival. Concerning toxicities, SABR for peripheral tumors is an almost safe and comfortable treatment. Rib fracture is a common adverse effect after SABR but the symptom is generally mild. But severe radiation-related pneumonitis occurs occasionally in the patients having pulmonary fibrosis. As the clear dose-constraint for mediastinal organs has not been demonstrated, the safety of SABR for cases with a central lesion has not been assured. When the tumor recurred only locally after SABR in operable patients, salvage radical surgery was mostly operated safely. Primary radiation therapy remains the primary curative intent approach generally for patients who refuse surgical resection or are determined by a multidisciplinary team to be inoperable or high-risk operable. However, good tumor control, less toxicity, and fewer treatment courses of SABR decrease the indirect costs of cancer care, including lost time and economic productivity secondary to treatment-related and cancer-related illness and death. On the other hand of promising results and advantages of SABR, it is imperative to assess its cost-effectiveness as well as its efficacy because SABR is becoming used in more clinical situations. SABR employing image guidance, high-precision dose delivery, more accurate target definition with better anatomical and biological imaging, and the possibility of dose verification during treatment via dose-adaptive radiation therapy permits a higher probability of tumor control. Such major technological progress certainly comes at a higher cost, and there are many concerns regarding the value of that progress. In the symposium, we will discuss what the benefits and disadvantages of SABR compared to surgical treatment in high or low risk surgical patients with early-stage NSCLC or pulmonary oligometastases are, and how we can decide best to proceed with treatment.

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      MS23.4 - Surgery for Early Stage Lung Cancer and Oligometastases (ID 570)

      14:00 - 15:30  |  Author(s): H. Asamura

      • Abstract
      • Presentation
      • Slides

      Abstract
      Very recently, the revised international multidisciplinary classification of lung adenocarcinoma was published by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society, and European Respiratory Society.[1,2] This new classification is characterized by the creation/abandonment of some terminology for early and advanced adenocarcinomas and by a multidisciplinary approach for the application of the new classification in a clinical setting. In particular, the term "bronchioloalveolar carcinoma (BAC)" is no longer used and, instead, new concepts are introduced, such as “adenocarcinoma in situ (AIS)” and “minimally invasive adenocarcinoma (MIA)”. Invasive adenocarcinomas are classified according to the predominant pattern after comprehensive histologic subtyping with lepidic, acinar, papillary, micropapillary, and solid patterns. The term of mixed subtype adenocarcinoma is no longer used. The gold standard surgery for documented lung cancer has been lobectomy with lymph node sampling/dissection. The randomized, prospective study was performed between lobectomy and sublobar, limited resection in 1980’s by North American Lung Cancer Study Group (LCSG) and the results of this study justified the lobectomy as the standard surgical mode.[ 3] However, looking back this study from the present view point, it is obvious that the earlier forms of lung cancer, as mentioned above as adenocarcinomas of AIS or MIA, were not involved in the LCSG study, and its conclusion could not be applied for these tumors. The present-day issue of lung cancer surgery is to define the role of lobectomy or limited, sublobar resection in relation to newly defined pathological entities. The Japan Clinical Oncology Group (JCOG) has been focusing upon defining the most appropriate surgical approach for tumors of relatively early stages in recent series of clinical trials. JCOG 0201 was intended to define the radiological non-invasive lung cancer on the high-resolution CT image, and it has shown that a consolidation/tumor ratio (C/T ratio) on thin-section computed tomography (TSCT) ≤0.25 in cT1a (≤2.0 cm) could be used as a radiological criterion for a noninvasive pathology.[4] Further prognostic analyses have also indicated that according to this radiological definition of non-invasive lung cancer the 5-year overall survival rate at 97.1% could be achieved.[5] JCOG 0804 is a prospective phase II trial, targeting the radiological non-invasive lung cancers of a diameter of 2.0 cm.[6] Again, the radiological criteria of non-invasive lung cancer were defined as those with a consolidation/tumor ratio (C/T ratio) on thin-section computed tomography (TSCT) ≤0.25. For these tumors, the wide wedge resection or segmentectomy was performed. Targeted number of accrual is 340 patients, and accrual has been already over, awaiting the data maturation. JCOG 0802 is a prospective, randomized phase III trial between lobectomy and segmentectomy for peripheral lung cancers with a diameter of 2 cm or less in a non-inferiority setting.[6] The endpoints are overall survival (primary) and postoperative pulmonary function (secondary), and the targeted accrual is 1,100 patients. As of June, 2013, more than 800 patients were registered. In case that the prognosis of patients undergoing segmentectomy was not significantly inferior to that of those undergoing lobectomy and that the postoperative pulmonary function is significantly better for those undergoing segmentectomy, it can be definitively concluded that standard surgical mode for these early tumors are segmentectomy. The similar randomized trial is also underway in US (CALGB), and the sooner launch of these data is expected to change the daily practice of lung cancer surgery. Oligometastases are the state in which the patients show distant relapse in only a limited number of organs/sites. These distant, metastatic lesions are found both before and immediately after surgery, and obviously these indicate the systemic spread of the cancer cells as stage IV disease. The gold standard treatment for systemic disease has been systemic therapy (chemotherapy). However, it has been anecdotally reported that local treatment modality such as surgery for both primary and metastatic sites cure the patients. The present-day issue for patients with oligometastatic disease is the proper selection of surgical candidate who might benefit from such aggressive treatment in lung cancer. REFERENCES 1. Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011;6:144-85. 2.Van Schil P, Asamura H, Rusch VW, et al. Surgical implications of the new IASLC/ATS/ERS adenocarcinoma classification. Eur Respir J 2012;39:478-86. 3. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995;60:615-22. 4. Suzuki K, Koike T, Asakawa T, et al. A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol 2011;6:751-6. 5. Asamura H, Hishida T, Suzuki K, Japan Clinical Oncology Group Lung Cancer Surgical Study Group. Radiographically determined noninvasive adenocarcinoma of the lung: Survival outcomes of Japan Clinical Oncology Group 0201. J Thorac Cardiovasc Surg. 2013 [Epub ahead of print]. 6. Nakamura K, Saji H, Nakajima R, Okada M, Asamura H, Shibata T, et al. A phase III randomized trial of lobectomy versus limited resection for small-sized peripheral non-small cell lung cancer (JCOG0802/WJOG4607L). Jpn J Clin Oncol 2010;40:271-4. 7. Niibe Y, Hayakawa K. Oligometastases and oligorecurrence: the new era of cancer therapy. Jpn J Clin Oncol 2010;40:107-11.

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      MS23.5 - Thermal Ablation for Early Stage Lung Cancer and Oligometastases (ID 571)

      14:00 - 15:30  |  Author(s): K. Steinke

      • Abstract
      • Presentation
      • Slides

      Abstract
      Lung cancer is the number one cancer killer worldwide accounting for more cancer deaths than colorectal cancer, breast cancer and prostate cancer combined. While the outlook is dismal in advanced lung cancer, when patients are diagnosed once they have become symptomatic, the prognosis is more favourable in early stage node-negative disease. Small lung cancers are increasingly diagnosed as incidental findings on cross-sectional imaging such as CT-coronary angiogram (CTCA), CT-pulmonary angiogram (CTPA), CT angiograms for vascular conditions or CT -intravenous pyelogram (CT-IVP). As many as 15% of patients with early stage NSCLC are not eligible for surgery due to comorbidities, usually poor cardio-respiratory reserve. This number doubles in the patient population 75y and older. Approximately 30% of patients dying of malignancy have pulmonary metastases at autopsy with some primary cancers metastasising exclusively to the lungs. In the setting of primary cancer site being under control, reasonably long disease free interval (DFI) and oligometastatic lung disease with metastases of reasonable size and in amenable positions, data shows a survival benefit for metastasectomy in a selected patient population. Metastasectomies, even if performed as sub-lobar or wedge resections, often carry a substantial morbidity and have a major impact on quality of life. Thermal ablations can be performed in an outpatient setting, they spare healthy tissue, are repeatable and are extremely well tolerated. Thermal ablation has been applied to lung tumours for over a decade and has managed to become an established minimally invasive therapy option for a selected patient population. It is used as a therapeutic means in primary and secondary lung cancer, both with a curative and palliative intent. Combination of thermal ablation with radiotherapy for NSCLC should be a viable consideration in the therapy planning pathway, with available radiofrequency ablation (RFA)/external radiation therapy (XRT) data showing convincing 5y cumulative survival rates of 39% at no additional toxicity. Microwave ablation (MWA) represents the most recent addition to the growing armamentarium of minimally invasive thermal ablation therapies. Advantages of microwave over RF energy are perceived to be many. RF heating requires an electrical conduction path and is therefore less effective in areas of low electrical conductivity and high baseline impedance such as lung parenchyma. Unlike RF and laser, microwaves can even penetrate through the charred or desiccated tissues that build up around all hyperthermic ablation applicators, resulting in limited power delivery for non-microwave energy systems. Further advantages of MWA over RFA are that the system does not require grounding pads, thus avoiding pad site burns, that implanted cardiac devices are less prone to malfunction during MWA than during RFA and that heating occurs faster with is less susceptibility to heat sink, allowing for larger and more homogenous ablation volumes. Multiple microwave antennas can be powered simultaneously to maximise the ablation volume when placed in close proximity to each other, or when widely spaced, to ablate several tumours simultaneously, particularly helpful in the case of multiple metastatic ablations. This presentation will focus on the indications for pulmonary thermal ablation, the limitations of the procedure and the advantages of MWA over RFA.

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      MS23.6 - Panel Discussion (ID 572)

      14:00 - 15:30  |  Author(s): N. n/a

      • Abstract

      Abstract not provided



Author of

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    O28 - Endoscopy (ID 124)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      O28.08 - DISCUSSANT (ID 3979)

      10:30 - 12:00  |  Author(s): T. Sutedja

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    P1.17 - Poster Session 1 - Bronchoscopy, Endoscopy (ID 182)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 3
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      P1.17-006 - Early Bronchoscopic Interventional Strategy in Highly at Risk Morbid Ageing Cohort (ID 2322)

      09:30 - 16:30  |  Author(s): T. Sutedja

      • Abstract

      Background
      We retrospectively reviewed our longitudinal data (1992 - 2012) with regard to early interventional techniques using advancements of non- and minimally invasive techniques (NiMiT) as alternatives for early intervention in squamous carcinogenesis in highly at risk -including frail elderly individuals. >50% lung cancer develops in >70 years age cohort and cancer and ageing are becoming an important health care issue in our society.

      Methods
      So far, 159 surgically non-resectable candidates with various comorbidities (Previous LC/ENT primaries, COPD, etc.) have been closely monitored using autofluorescence bronchoscopy for suspicious endobronchial lesions (e.g. dysplasia, carcinoma in situ and microinvasive squamous cancer). End points were the development of squamous cancer and its outcome with the use NiMiT (Chest 2001;120:1327; Respiration 2004;71:391

      Results
      Patient characteristics and outcome are shown in the table. Cohort analyses of age ≤70 years versus over, showed a significant longer time of survival in the elderly cohort (35.9 vs 18.5 months; p = 0.01). Lung cancer specific mortality was low ,respectively 15% and 22%. Table: Longitudinal carcinogenesis study in cohorts highly at risk to develop (subsequent) squamous cancer primaries and its outcome.

      Age cohort (years) n patients <70 112 >70 47 p-value
      Gender - Male - Female 93 (83%) 19 (17%) 39 (83%) 8 (17%) NS
      Mean age years (range) 60(42-70) 74(70-83)
      Indication for close surveillance: - Previous LC /ENT cancer - Suspicion occult lung cancer 55 (49%) 57 (51%) 19 (40%) 28 (60%) NS
      Mean pack-years smoked (range) 44(4-120) 49(20-137) NS
      COPD Non-COPD Unknown 72 (64%) 32 (29%) 8 (7%) 29 (62%) 10 (21%) 8 (17%) NS
      Interval to (subsequent) primaries (months) 69(0-198) 54(1-184) NS
      Acquiring (subsequent) squamous ca. Recurrences of previous primaries 41 (37%) 4 (4%) 12 (26%) 2 (4%) NS NS
      Death due to lung cancer Other causes 25 (22%) 31 (28%) 7 (15%) 17 (36%) NS NS
      Survival after curative treatment (months) 19 (0-110) 36 (0-106) 0,01

      Conclusion
      In contrast to the undocumented belief about less aggressive cancer, the need for less aggressive treatment, potential toxicities in the co-morbid elderly and their expected shorter life span, the outcome shows that early interventional strategy is warranted. LC mortality is relatively low despite the highly negative selection bias, especially in the frail – ageing – subcohort. This warrants further studies to increase the cost-effectiveness of NiMiT in our ageing population.

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      P1.17-007 - A proposal for a new clinical strategy and follow-up in patients with bronchial carcinoids initially treated bronchoscopically. (ID 2468)

      09:30 - 16:30  |  Author(s): T. Sutedja

      • Abstract

      Background
      Bronchial carcinoids (BC) belong to the wide spectrum of neuroendocrine tumors; ranging from tumorlets, typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), to highly malignant large cell neuroendocrine and small cell carcinoma. The Travis classification (Am J SurgPathol 1998; 22:934) seems essential for choosing the best treatment strategy based on retrospective analyses of surgically resected specimens. We implemented an initial bronchoscopic treatment (IBT) strategy and its long term outcome have been reported with update of the final analysis (J Thorac Cardiovasc Surg. 2007 Apr;133(4):973; Abstract IASLC Sydney submitted). The long-term outcome seems to justify IBT and the histological differentiation between typical versus atypical seems to matter much less, while conservation of normal lung parenchyma is optimal. We question how optimal the close surveillance strategy of IBT protocol should be, i.e. in performing regular high resolution CT (HRCT) and/or bronchoscopy after the initial success of bronchoscopic treatment.

      Methods
      In the IBT protocol, HRCT and bronchoscopy were performed 6-monthly in the first two years and annually until the fifth year. Thereafter a yearly check-up was advised to the referring pulmonologists. We analyzed retrospectively the value of HRCT and/or bronchoscopy in this IBT cohort for early detection of local recurrences, that require surgical salvage.

      Results
      So far, IBT was successful in 57 of the 133 patients (43%). Sixty-seven patients (50%) could be immediately identified to be surgical candidates without further delay due to obvious extraluminal tumor growth. Four patients (3%) developed extraluminal tumor recurrence and surgical salvage was performed at 47, 104, 115, 192 months. In all four cases follow-up HRCT suggested local extraluminal tumor growth, which were confirmed by bronchoscopy. The surgical outcome was radical and did not lead to more extensive resections than initially anticipated. Detailed treatment results are shown in table 1. Table 1. Initial bronchoscopic treatment strategy in patients with bronchial carcinoids

      BT Completion Surgery Remark
      Number of patients 62 71
      Histology TC AC 56 (90%) 6 (10%) 43 (61%) 28 (39%)
      Follow up (median) in months 87.5 (2-223) 87 (12-264)
      Completely resected 57 (92%) 64 (90%)
      Residual after CT/recurrences Additional treatment bronchoscopy Additional treatment surgery 3 4 0 0 Interval in months: 10,13,63 47,104,115,192
      Alive with disease 5 0 2 unfit for surgery 3 refused surgery
      Alive with metastatic disease 0 1 40 months
      Carcinoid related mortalities 0 2 Pulmonary metastases
      Treatment related mortalities 0 1
      Non-carcinoid related mortalities 8 3

      Conclusion
      Initial bronchoscopic treatment strategy in patients with bronchial carcinoids is justifiable. Local regrowth after successful bronchoscopic removal was infrequent (3%) and was timely detected by HRCT. HRCT can be performed much less frequent and regular bronchoscopy was redundant if IBT attempt was successful. The significance of an iceberg phenomenon is questionable.

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      P1.17-008 - Results of a close surveillance strategy for subjects with pre-invasive endobronchial squamous lesions (ID 2678)

      09:30 - 16:30  |  Author(s): T. Sutedja

      • Abstract

      Background
      The dismal overall 5-year survival of non-small cell lung cancer (NSCLC) patients is mainly due to advanced stage of disease at time of initial diagnosis in most and the inability to cure metastatic disease in all patients. In contrast, the prognoses of in situ mucosal and small parenchymal lesions are excellent. Early detection strategies might result in the identification of early-stage, (pre-)invasive lesions that are still eligible for curative treatment. The present study was set out to characterize the risk of lung cancer development in a cohort of high-risk subjects harboring pre-invasive endobronchial lesions and to assess the results of surveillance using autofluorescence bronchoscopy (AFB) and computed tomography (CT) scan.

      Methods
      Between November 1995 and December 2012, one hundred and sixty-four at risk individuals with pre-invasive endobronchial lesions were monitored by repeated AFB and CT. During the course of surveillance, progression of lesions to cancer (in situ), recurrences and second primary cancers were treated with different modalities (e.g. endobronchial techniques, surgery, radiotherapy), depending on tumor stage and location. Log-rank tests were performed to examine the relation between baseline characteristics and progression-free and overall survival (PFS and OS, respectively). Cox regression was used for multivariate survival analysis.

      Results
      Demographical and clinical variables of the cohort are shown (Table). At inclusion, 80 individuals were identified with one or more high-grade pre-invasive lesions (severe dysplasia or CIS; HGD), whereas 84 subjects were identified solely with lower grade pre-invasive lesions (LGD). During close surveillance (median follow-up (FU) of 30 months, range 4-152), sixty-one lung cancers were detected (26 CT-detected, 35 AFB-detected cancers) in 55 individuals within a median time to event of 16.5 months. Mean PFS was similar between individuals with radiographically occult lesions vs. FU after surgery for early-stage NSCLC/ENT ca (122.3 vs. 126.9 months, p=0.237) and COPD vs. non-COPD (118.8 vs. 136.8 months, p=0.162). There was a relatively large difference in PFS between LGD and HGD groups (142.6 vs. 93.7 months, p=0.057). Independent risk determinants for OS were indication for surveillance (FU after surgery for early-stage NSCLC/ENT ca vs. radiographically occult lesions, p=0.008) and COPD-status (COPD vs. non-COPD, p<0.001).

      Referral for radiographically occult lesion Follow-up after surgery for early-stage NSCLC / ENT ca
      total
      individuals, n 164 92 72
      Gender
      male 134 72 62
      female 30 20 10
      Age at baseline
      years, mean (range) 64.2 (42-83) 64.8 (42-81) 64.0 (43-82)
      Smoking status
      current smoker 75 44 31
      former smoker 74 36 38
      unknown 15 12 3
      Smoking history
      Pack-years, mean (range) 45 (4-137) 45 (4-120) 40 (15-137)
      COPD-status
      COPD 100 56 44
      non-COPD 45 22 23
      unknown 19 14 5
      AF Bronchoscopies
      Number, mean (range) 7 (1-27) 5 (2-27) 6 (1-18)
      CT-scans
      Number, mean (range) 3 (0-20) 2 (0-20) 3 (0-18)
      No. of detected lung cancers
      During surveillance period 61 29 32
      Parenchymal cancer 21 12 9
      Site-specific lesion progression 24 13 11
      Interval cancer 10 4 6
      Recurrences previous primaries 6 0 6
      Patient outcome
      alive 80 56 24
      died of lung cancer 33 13 20
      died of other/unknown cause 51 23 28

      Conclusion
      Our findings demonstrate that individuals with pre-invasive endobronchial lesions are at high risk of developing (second primary) lung cancers. Combined surveillance using AFB in addition to CT screening facilitated early detection and early (endobronchial) intervention in most patients. Future clinical trials are warranted to determine whether the current approach improves patient outcome.

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    P2.17 - Poster Session 2 - Bronchoscopy, Endoscopy (ID 183)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      P2.17-006 - Long term outcome of initial bronchoscopic treatment strategy in patients with bronchial carcinoids (ID 2447)

      09:30 - 16:30  |  Author(s): T. Sutedja

      • Abstract

      Background
      Bronchial carcinoids are considered low-grade malignancies and, traditionally, are treated surgically. Tumor biology and advances in diagnostic and therapeutic techniques, however, enable a less invasive approach such as surgical bronchoplasty can preserve normal lung parenchyma. We previously reported favourable outcome for initial bronchoscopic treatment (BT) strategy in patients with intraluminally located bronchial carcinoids. We now present our long term results.

      Methods
      In patients presenting with a bronchial carcinoid, an initial diagnostic therapeutic bronchoscopy is attempted for complete tumor eradication for sampling sufficient tissue for the proper differentiation between typical (TC) and atypical (AC) histologic type apart from to optimally improve pre-surgical condition. A high resolution computed tomography is performed six weeks later, to determine intra- versus extraluminal tumor growth. In case of intraluminal growth of TC bronchoscopic removal attempt can be repeated. We perform surgical resection in case of extraluminal disease, or failure to bronchoscopic radical resection (i.e. recurrence or persistent residual tumor). Complete bronchoscopic resection of AC histological type is currently not followed by surgical resection.

      Results
      So far, 133 patients have been treated; 76 females, 67 males, median age 46 (range 16 – 85 years). Median follow up was 87 (range 2 – 264) months. Ninety-nine patients (84%) had TC, and 34 (26%) had AC. Bronchoscopic eradication was successful in 57 (43%) patients (51 TC, 6 AC). Detailed treatment results are shown in table 1. Table 1. Initial bronchoscopic treatment strategy in patients with bronchial carcinoids

      BT Completion Surgery Remark
      Number of patients 62 71
      Histology TC AC 56 (90%) 6 (10%) 43 (61%) 28 (39%)
      Follow up (median) in months 87.5 (2-223) 87 (12-264)
      Completely resected 57 (92%) 64 (90%)
      Residual after CT/recurrences Additional treatment bronchoscopy Additional treatment surgery 3 4 0 0 Interval in months: 10,13,63 47,104,115,192
      Alive with disease 5 0 2 unfit for surgery 3 refused surgery
      Alive with metastatic disease 0 1 40 months
      Carcinoid related mortalities 0 2 Pulmonary metastases
      Treatment related mortalities 0 1
      Non-carcinoid related mortalities 8 3

      Conclusion
      Initial bronchoscopic treatment strategy in patients with bronchial carcinoids is justifiable with excellent long term outcome. It should be implemented in the standard algorithm for patients with bronchial carcinoids.

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    P2.20 - Poster Session 2 - Early Detection and Screening (ID 173)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P2.20-004 - DNA copy number aberrations in endobronchial lesions: a validated predictor for cancer (ID 1166)

      09:30 - 16:30  |  Author(s): T. Sutedja

      • Abstract

      Background
      Individuals who present with squamous metaplastic and dysplastic lesions are considered at high risk of lung cancer. However, these lesions behave erratically and only a minority progresses towards lung cancer. Therefore, biomarkers need to be discovered that can aid in assessing an individual’s risk for subsequent cancer. We recently identified a DNA copy number aberration (CNA)-classifier, including changes at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3, as a risk predictor for cancer in individuals presenting with endobronchial squamous metaplasia (van Boerdonk et al, AJRCCM, 2011). The current study was set out to validate this classifier in an independent series of endobronchial squamous metaplastic and dysplastic lesions.

      Methods
      DNA copy number profiles (i.e., chromosomal gains and losses) were determined in a set of endobronchial lesions (8 squamous metaplasia (SqM), and 28 dysplasias (Dys) of various grades), identified and biopsied during autofluorescence bronchoscopy, of 36 high-risk subjects using a nested case-control design. Of the 36 patients, 12 cases had a carcinoma in situ or invasive carcinoma at the same site at follow-up (median 11 months, range 4-24), while 24 controls remained cancer-free (median 78 months, range 21-142). DNA copy number profiles were related to lesion outcome. The prediction accuracy of the predefined CNA-based classifier to predict endobronchial carcinoma (in situ) in this series was determined.

      Results
      All SqM and Dys lesions of controls showed no or a relatively low number of CNAs (i.e., quiescent profile with on average 0.2% altered probe features, range 0.0 – 2.4%), while the majority of lesions of cases showed multiple CNAs (i.e. highly aberrant profile with on average 38.8% altered probe features, range 0.0 – 76.7%). The previously defined CNA-classifier demonstrated 92% accuracy for cancer (in situ) prediction in the current series. All nine subjects with CNA-classifier-positive endobronchial lesions at baseline had cancer as final outcome (i.e., a positive predictive value of 100%). The negative predictive value of the classifier was 89%, i.e., all 24 controls and 3 cases were classified as being low-risk.

      Conclusion
      CNAs are a highly accurate biomarker for assessing the progression risk of endobronchial squamous metaplastic and dysplastic lesions. This classifier could assist in selecting subjects with endobronchial lesions who might benefit from more aggressive therapeutic interventions.