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Norihiko Ikeda



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    P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.16-15 - Evaluation of Emphysema Severity by 3D-CT for Predicting Postoperative Respiratory Complications and Prognosis of Lung Cancer (ID 12953)

      16:45 - 18:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      Emphysema is one of the main causes of respiratory complications and perioperative mortality and morbidity in lung cancer patients. We have used 3D-CT for depicting emphysematous areas as low attenuation areas (LAAs) and visual scores based on Goddard classification (Goddard score: GS). This study aimed to investigate the effectiveness of the 3D-CT function analysis of emphysema severity and its association with respiratory complications and prognostic outcomes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The study included 504 patients who underwent preoperative 3D-CT for surgical simulation followed by resection for lung cancer from October 2010 to March 2015. GS and LAA% (LAA / total lung volume) were measured using 3D-CT data. We studied the relationship between the development of postoperative respiratory complications/ overall survival (OS) and independent variables including age, sex, forced expiratory volume in 1 second as percent forced vital capacity (FEV1%), histology, smoking status, surgical procedure, GS, and LAA%.

      4c3880bb027f159e801041b1021e88e8 Result

      Postoperative respiratory complications were observed in 69 patients (13.6%). These included prolonged air leakage > 7 days (n = 22), pneumonia (n = 13), bronchial fistula (n = 4), atelectasis (n = 5), pulmonary fibrosis (n = 3), empyema (n = 5), recurrent nerve paralysis (n = 2), chylothorax (n = 5), pleural effusion (n = 3) and other respiratory-related adverse events (n = 7). The ROC curves for respiratory complications determined using the GS and LAA% dichotomized at each cut-off level (1 and 0.7%, respectively) showed that the events were observed in 32% of the patients with GS ≥ 1 and in 25% of the patients with LAA% ≥ 0.7. On multivariate analyses, the GS or LAA% was significantly correlated with postoperative respiratory complications (p < 0.001 and p = 0.016, respectively). Univariate and multivariate analysis using the Cox regression model for prognosis also showed GS was significantly associated with unfavorable OS among 362 patients with pathological Stage I NSCLC patients (p = 0.039). Five-year OS rates in these patients with or without emphysema were 84.0% and 94.1%, respectively (p < 0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Preoperative measurement of GS and LAA% using 3D-CT in patients with lung cancer, particularly with the coexistence of emphysema, was beneficial for predicting postoperative respiratory complications and prognosis in lung cancer patients.

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      P1.16-17 - The Role of Quantitative Metabolic Metrics on FDG-PET/CT in Predicting Pathological Invasive Factors in cN0 Lung Adenocarcinoma (ID 13195)

      16:45 - 18:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      Growing evidence suggests that FDG-PET/CT has greatly contributed the preoperative investigation of early-stage lung cancer. The maximum standardized uptake values (SUVmax) of the primary lesion is widely reported to be associated with prognosis in NSCLC while other metabolic metrics, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been explored as a measure of metabolic tumor burden in recent years. The purpose of this study is to investigate the role of quantitative metabolic metrics in predicting the incidence of pathological invasive factors including microscopic vascular invasion, pleural invasion, and lymph node metastasis in cN0 lung adenocarcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We examined 265 patients with clinical stage 0-II(cN0) adenocarcinoma. Pre-operative PET/CT and subsequent complete resection was performed for all the patients during the period from August 2012 to July 2017. The maximum tumor and solid-part diameter on HRCT and the three metabolic metrics on PET/CT measured by the SYNAPSE VINCENT (Fujifilm Medical, Tokyo, Japan) as the volume viewer softwarewere observed. In the current study, MTV was defined as the total tumor volume with an SUV > 2.5 while TLG was calculated as meanSUV x MTV. We assessed the relationship between these parameters and the incidence of pathological invasive factors.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 265 patients, 18 (7%) patients were clinically staged as 0, 205 (77%) as IA, 32 (12%) as IB, and 10 (4%) as II, respectively. Pathological vascular invasion, pleural invasion, and lymph node metastasis were found in 100 (38%), 53 (20%), and 45 (17%) patients, respectively. SUVmax, MTV, and TLG were dichotomized at cut-off level by the receiver operating characteristic (ROC) curves for pathological invasive factors (SUVmax of 4.4, MTV of 0.75mm3, and TLG of 2.6, respectively). ROC curve yielded area under the curve values of 0.812, 0.915, and 0.882 for SUVmax, MTV, and TLG, respectively. Univariate analysis showed that SUVmax (Hazard Ratio (HR), 27.185; p<0.001), MTV (HR, 24.580; p<0.001), TLG (HR, 24.580; p<0.001), maximum tumor size (HR, 2.495; p<0.001), solid-tumor size (HR, 7.830; p<0.001), c-stage (HR, 14.418; p<0.001), and sex (HR, 1.882; p=0.013) were significantly associated with the incidence of pathological invasive factors. Multivariate analysis showed that SUVmax was the independent predictor (HR, 7.006; p=0.001). The frequency of pathological invasive factors of patients with SUVmax > 4.4, MTV > 0.75mm3, and TLG > 2.6 were 82%, 84%, and 84%, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In cN0 early-stage lung adenocarcinoma, the measurement of SUVmax, MTV, and TLG on FDG-PET/CT was beneficial for the prediction of pathological invasive factors.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.11 - Screening and Early Detection (Not CME Accredited Session) (ID 960)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.11-12 - Metabolomic Analysis in Lung Cancer for Screening and Early Detection (ID 12131)

      16:45 - 18:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      Metabolomics, a simultaneous measurment technique for hundsleds of low weight molecules, generally called metabolites, is an effective technique to understand how metabolism is changed by various factors, including environment and diseases, particularly malignant diseases. Body fluids, such as urine or saliva, harvested non-invasively have been used in this analytical technology, which yielded a potential of precise diagnosis of various cancers. Metabolomic analysis has begun to be reported based on the pattern information of metabolites. It can be used for practical clinical early detection of carcinoma of various organs. However, practical metabolomic analysis regarding lung cancer has not been repored yet. We used surgically resected specimen of lung cancer to analyze and clarify metabolomic profiles as an aspect of lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We obtained blood and saliva from 110 patients with lung cancer after obtaining informed consent for this study and compared the metabolomic profiles of both blood and saliva in 83 who has neither pulmonary disease nor past history of any cancer in terms of various clinical aspects. Metabolomic analysis was performed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) of metabolites of the blood and saliva, then analysed ionized sample which contained the most metabolites in primary pathways.

      4c3880bb027f159e801041b1021e88e8 Result

      Analysis of serum and metabolite organization by CE-TOFMS revealed that the intermediate metabolite levels of several pathways changed markedly in lung cancer blood and saliva. We identified characteristic metabolomic patterns in advanced lung cancer with metabolomic clinical information by analysing the association with the overall metabolism profile.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We identified metabolomic biomarkers which were characteristic of lung cancer using blood and saliva in this study. At present, we are analysing various body fluids for analysis of lung cancer cases including prognostic implications. Applications to non-invasive, simple, easy and low-cost cancer screening are expected in the future.

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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-24 - The Importance to Switch from EGFR-TKI to Cytotoxic Chemotherapy for EGFR Mutation-Positive Adenocarcinoma (ID 12819)

      12:00 - 13:30  |  Author(s): Norihiko Ikeda

      • Abstract

      Background

      Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become the first-line treatment for EGFR-positive non-small cell lung cancer (NSCLC) patients all over the world. Furthermore, EGFR-positive patients who received not only EGFR-TKI but also chemotherapy have good prognosis. However, transition rate from first-line EGFR-TKI to chemotherapy is low.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 229 consecutive patients with adenocarcinoma were treated with EGFR-TKI from January 2010 to December 2016 at Tokyo Medical University Hospital. Among these, 159 patients were analyzed in the present study. After excluding 70 patients (45 patients undergone first-line treatment, 7 received chemoradiotherapy,and 18 received osimertinib). The prognosis according to treatment sequence and the reasons patients could not switch from first-line EGFR-TKIs to chemotherapy were analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      The median follow-up period was 22.5 months. Of the total 159 patients, 113 (71%) were female, 114 (72%) were <75 years old, and 86 (54%) showed postoperative recurrence. The most frequent subtypes of EGFR were exon 19 deletion in 84 patients (53%) followed by exon 21 L858R in 54 patients (34%). EGFR-TKIs were administered as a first-line therapy in 93 (58%) patients, and chemotherapy was administered in 66 (42%) patients. The most common first administered EGFR-TKI as a first-line was gefitinib in 133 (84%) of 159 patients. Among the 93 patients who were administered EGFR-TKIs as a first-line treatment, 32 (34%) patients transitioned to chemotherapy. The median survival times (MST) of EGFR-TKIs combined with chemotherapy group and EGFR-TKIs alone group were 59.8 months and 22.5 months, respectively (p < 0.001), and MST of patients who received EGFR-TKIs first and chemotherapy first were 38.8 months and 66.4 months, respectively (p = 0.016). The main reasons patients could not transition to chemotherapy was worsening of performance status followed by the patient’s preference.

      8eea62084ca7e541d918e823422bd82e Conclusion

      EGFR-TKIs and chemotherapy led to good prognosis in EGFR mutation-positive adenocarcinoma patients. It is necessary to consider the timing to switch the treatment strategy before PS becomes worse.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P3.01-78 - The Cytology Samples and Plasma Specimens were Feasible for the EGFR Molecular Testing. (ID 12991)

      12:00 - 13:30  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      EGFR mutation detection with real-time PCR is standard method to identify eligible patients for EGFR-TKI treatments in daily routine practice. Surgically resected tissues or biopsy specimens are mainly used as the sample materials for testing. However, the biopsy samples sometimes have a certain limitation in their volume and so the cytology specimens are chosen for EGFR testing instead. Plasma has also become an option especially in EGFR-TKI resistant cases in which often have difficulties to obtain the adequate tumor yield. In this study, we evaluated the feasibilities of using cytology samples and plasma specimens for the EGFR molecular testing.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      atients provided written informed consent for use of the samples were participated in this prospective research. Cytology samples were obtained from biopsy and cells were suspended into liquid-based cytology (LBC) media. Tumor contents in the samples were confirmed with Papanicolaou stained slides. Plasma samples were also collected from patients shortly before the tissue biopsy. EGFR mutations in these samples were analyzed by cobas EGFR Mutation Test v2. Also, EGFR testing result of tissue specimens of the patients corresponded were collected from the medical records measured by cobas EGFR Mutation Test v2 as reference.
      The feasibilities of both cytology and plasma specimen were evaluated comparing with the tissue samples.

      4c3880bb027f159e801041b1021e88e8 Result

      One-hundred fifty-eight patients were registered to this study. Among those patients, 77 patients with matched set of samples were enrolled to this study. EGFR mutation rates in tissue, cytology, and plasma were 37.7, 29.9 and 16.9 %, respectively. Overall agreement rate of the cytology specimens and the plasma specimens against the tissue samples were 87.0 and 75.3%, respectively. All eightT790M mutation positive cases were perfectly matched between tissue and cytology specimens.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The results suggested that tissue specimen is the most suitable sample for detecting mutations. Since high specificities were confirmed in both cytology and plasma specimens, the results are reliable as long as the call is positive. Choosing cytology or plasma specimens for EGFR testing can be the considerations for the patients who have difficulties in collecting tissue samples in the real world setting.

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    P3.08 - Oligometastatic NSCLC (Not CME Accredited Session) (ID 974)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.08-08 - Outcomes of Pulmonary Metastasectomy in Breast Cancer: Prognosis Based on the Metastatic Lung Tumor Study Group of Japan (ID 12242)

      12:00 - 13:30  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      Although pulmonary metastasectomy is a common treatment in other primary cancers, its role in patients with primary breast cancer is still controversial. The purpose of this study was to analyze a Japanese multi-center database to assess the prognostic factors and indications of metastasectomy in breast cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Data of 387 patients with histologically proven pulmonary metastases from breast cancer have been prospectively enrolled in the Metastatic Lung Tumor Study Group of Japan between December 1982 and March 2017. Those with inadequate information about perioperative data, surgery for biopsy, male or non–epithelial malignancies were excluded. A total of 253 female with invasive breast carcinoma between 1982 and 2017 constituted the study population, and their clinical and prognostic data were retrospectively analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      The median follow-up period was 5.4 (range, 0–24) years. The mean age of patients was 56 (range, 32–82) years, the median disease-free interval was 4.8 (range, 0–31) years, pulmonary metastasis (215 solitary, 38 multiple) was treated with surgeries, namely, wedge resection (n = 113, 45%), segmentectomy (n = 22, 9%), lobectomy (n = 116, 45%), and pneumonectomy (n = 2, 1%). Nodal metastases were found in 56 (22%) patients. There were 24 (9%) patients with incomplete resection. Additional treatments after metastasectomy were performed in 141 patients (56%). Recurrence after pulmonary metastasectomy developed in 98 of 229 (43%) patients without incomplete resection, namely, intrathoracic lesion (n = 21, 23%), distant metastasis (n = 47, 51%), and unknown (n = 25, 27%). The 5-year and 10-year survival rates after pulmonary metastasectomy were 66% and 52%, respectively, and the median survival period was 10 years. In the univariate analysis, early treatment period (<2001; p = 0.02), short disease-free interval (<3 years; p < 0.01), large tumor size (>2 cm; p < 0.01), surgical procedure (lobectomy and pneumonectomy; p = 0.01), intrathoracic nodal metastasis (p < 0.01), and incomplete resection (p = 0.05) were shown to be associated with poor survival. Multivariate analysis revealed that only short disease-free interval (<3 years; p < 0.01) was significantly worse prognostic factor in 253 patients.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The main poor prognostic factor was disease-free interval (<3 years). However, complete resection of metastases was not a significant prognostic factor. The efficacy of pulmonary metastasectomy in breast cancer is still controversy. For pulmonary metastais from breast cancer, pulmonary metastasectomy is considered to be optional treatment.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.09 - Pathology (Not CME Accredited Session) (ID 975)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.09-23 - Accuracy and Reproducibility of Touch Imprint Cytology in Resected Lung Cancer (ID 13092)

      12:00 - 13:30  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      With the development of high-resolution computed tomography (CT), small-sized tumors showing ground-glass opacity (GGO) on chest CT images has been more frequently encountered. However, methods such as the transbronchial biopsy and the computed tomography-guided fine-needle aspiration cytology are limited in their ability to diagnose such small lung tumors. We evaluated about the association of the cytological features with the histological examination using the surgically resected specimen.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      169 patients, age between 31–87 years old, who showed radiological signs of peripheral lung tumors less than 3.0cm in diameter on CT images, underwent surgical resection at our institution between 2015 and 2016. The histological examination was performed on surgical specimen, fixed with 10% formalin and stain with Hematoxylin–Eosin. The cytological examination was performed on stamps from surgical material by Papanicolaou staining. The morphological features were compared both histopathogical diagnosis and cytological diagnosis of imprint cyotology derived from the resected specimen. Interobserver reproducibility was assessed by Kappa coefficient providing a measure for agreement beyond chance.

      4c3880bb027f159e801041b1021e88e8 Result

      By histological examination (in the 169 cases), the diagnostic of lung cancer was given with the establishing of the histological type. In 139 cases (82.2%) of the cases diagnosed as adenocarcinoma, in 25 cases (14.8%) squamous cell carcinoma, in 3cases (1.7%) was neuroendocrine tumors, and one case each of adenosquamous carcinoma and pleomorphic carcinoma. There was 86.3% (146 of 169 cases) agreement with a k statisticvalue of 0.65. Obtained kappa values from imprint cytology showed good (from 0.60 to 0.8) for detection of epithelial cell abnormalities indicating high observer diagnostic reproducibility.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This kappa statistic method allows assessment of the diagnostic quality of a respiratory cytology. Imprint cytology for small peripheral lung cancer is a useful method for evaluating tumors. Our data indicate the fact that the cytological examination on stamps from surgical material offers a very high percentage of positive results, close to the histological one. But in the tumor size less than 1.0cm, the establishing of the histological type of lung cancer is more difficult by cytological examination. Despite this, the cytology may be extremely useful in diagnose of the small peripheral tumors. The cytological characteristics of small peripheral adenocarcinoma were little reference to the differentiation at the cellular level. Our findings indicated that the presence of several nucleoli and granular chromatin densely are the factors of adenocarcinoma.

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    P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.16-27 - Clinical Outcome of Preoperative Intervention Bronchoscopy Followed by Surgery (ID 13111)

      12:00 - 13:30  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      The report of patients with respiratory disease who could receive surgery after bronchial intervention (IVB) is relatively rare. We still experience patients with advanced lung cancer that develops with severe dysplasia and bleeding. To assess the usefulness intervention bronchoscopy combined with surgery.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We experienced a total of 5 lung cancer patients treated by surgery after IVB at Tokyo Medical University Ibaraki Medical Center. Chief complain were severe dysplasia in 4 cases and bronchial bleeding in one case. The lesions were located at central bronchus in 4 cases. Histological types were 2 squamous cell carcinomas, 1 adenocarcinoma, 1 large cell carcinoma, and 1 pleomorphic carcinoma. Endobronchial snare & argon plasma coagulation (APC) were firstly performed in 2 cases, airway stentings using Dumon stent or Dumon-Y stent in 2 cases, and endobronchial Watanabe spigot (EWS) in 1 case. We evaluated the clinical outcome retrospectively.

      4c3880bb027f159e801041b1021e88e8 Result

      4 cases with obstructive lesions were treated by endobronchial snare and APC, and the other 2 cases were used bronchial stent. EWS was used to occlude the bronchi in the purpose of stopping blood aspiration in advanced adenocarcinoma case. After reducing the massive bleeding using EWS, we could perform salvage surgery. Performance status improved from 2 and 3 to 1 in all patients. All cases showed their symptom improvements after IVB, and were examined full staging (cT4N0M0) and checked operative risk. Thereafter, we could undergo salvage surgery (lobectomy: 2, bi-lobectomy: 1, pneumonectomy: 1, tracheoplasty: 1, carinoplasty: 1). Mean time of IVB followed by surgery was 115.7 days. Overall survival was 22.5 months (1-107.2 months), 5 years survival was 50%, and recurrent rate was 40% (2/5), respectively.

      .

      8eea62084ca7e541d918e823422bd82e Conclusion

      IVB followed by surgery is useful modality, and we should realize that there are some patients who can be treated by surgery after IVB because of improvements of their conditions. Also, IVB can be effective for reducing performance status.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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