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H. Asamura

Moderator of

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    IA05 - The Practical Use of the TNM Classifications for Thoracic Cancers (ID 291)

    • Event: WCLC 2016
    • Type: Interactive Session
    • Track: Radiology/Staging/Screening
    • Presentations: 4
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      IA05.01 - Lung Cancer Cases (ID 6524)

      11:00 - 12:30  |  Author(s): G. Lyons

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The definition of staging in Lung Cancer is the determination of the anatomic extent of three tumor components: the primary tumor (T), the lymph nodes (N), and the metastases (M). Their accurate evaluation allows grouping patients in stages that is one, and perhaps the single most important, of several prognostic factors that guide the appropriate treatment option(s) to offer the patient. The clinical classification cTNM (Pre-treatment clinical classification), is based on evidence acquired before treatment The pathological classification pTNM (Post-surgical histopathological classification), is based on the evidence acquired before treatment, supplemented or modified by the additional evidence acquired from surgery and from pathological examination. A minimum number of tests is not required to define the extent of the disease, but it’s very clear that as more exhaustive the explorations more accurate and precise the staging will be. This may be strongly affected by the availability of physical and human resources, multidisciplinary work and adherence to clinical practice guidelines. After the changes proposed by the new IASLC-ATS-ERS lung adenocarcinoma classification and the IASLC proposals for revision of the T, N and M descriptors and stage groupings in the forthcoming (Eighth) edition of the TNM Classification for Lung Cancer, we must incorporate this new information into our clinical practice. (1, 2) The changes that The IASLC Staging Committee recommends for the T, N and M components and the resulting new stage grouping and their survival are summarized in table 1 and figure 1. The main changes in T components are the relevance of the size of the tumor for each cm, grouping of the involvement of the main bronchus or partial and total atelectasis or pneumonitis as a T2 descriptor and the reclassification of diaphragm invasion as T4. (3) N component remains without changes. (4) In M component a new M1b category includes patients with a single metastatic lesion in a single organ site and a new M1c category was introduce for patients with multiple lesions in a single organ or multiple lesions in multiple organs. (5) Some new stage groupings are proposed. The new size cut points of T1-N0-M0 tumors has been assigned to stage IA1, IA2, and IA3. The new stage IIIC (T3 and T4-N3-M0) reflects their worse outcome. Finally, stage IV disease has been divided into IVA (M1a, M1b) and IVB (M1c). The new IVA stage grouping should be used in trials analyzing patients with oligo-metastasis or pleural or pericardial disease. (2) For the newly described types of adenocarcinoma of the lung, The IASLC recommends incorporating the coding of AIS as Tis (AIS) and of MIA as T1mi into the traditional TNM classification. For part-solid tumors, the size of the invasive component should be used to assign a T category, but the whole tumor size should also be recorded. However, the measurements will be influenced by a number of observer-dependent and technical factors. It is important to perform the measurements for clinical staging on contiguous thin CT sections reconstructed with a high-resolution algorithm with multiplanar reconstruction. (6) For pathologic staging, attention should be given to the assessment of invasive and lepidic components. It can be helpful to correlate microscopic findings with measurements made on gross examination, particularly in inflated specimens or with CT findings. Patients who present with more than one pulmonary site of lung cancer may represent different patterns of disease as synchronous primary lung cancers, those with a separate solid tumor nodule(s) (intrapulmonary metastases), multifocal lung cancer presenting as multiple nodules with ground glass/lepidic features, and diffuse pneumonic-type adenocarcinoma. It is proposed that the T category of patients presenting ground glass/lepidic (GG/L) tumors be classified using the T category of the highest T lesion and in parentheses either the number of GG/L tumors or simply m for multiple (#/m). A single N and M category is assigned for all GG/L tumors combined. (7) Both clinical information (the presence of additional lesions identified by imaging) and the pathologic information (from resected lesions) should be used to determine the TNM classification. Lesions smaller than 5 mm or AAH are not counted. The pneumonic type of adenocarcinoma should be classified according to the size of the area of lung involved, or as T4 or M1a in the case of involvement of more than one lobe (i.e., either ipsilateral or contralateral). A single N and M category is assigned. In patients with separate tumor nodules (intrapulmonary metastases), it is proposed that the seventh edition classification of same-lobe nodules as T3, same side (different lobe) nodules as T4, and other-side nodules as M1a be carried forward. (8) It is easier to establish that two pulmonary foci of cancer are separate primary tumors than that they are metastatic from one another. Few features are sufficiently reliable by themselves, such as different histologic type and differences by a comprehensive histologic assessment of resected specimens or by matching breakpoints by DNA sequencing. Most criteria can be suggestive, but are associated with potential misclassification. These include biomarker patterns, imaging characteristics, and the presence or absence of nodal involvement. The fact that generally only biopsy specimens are available at the time of clinical decision making further adds to the uncertainty and difficulty of the assessment. A constellation of factors is better than any single factor; it is best to make a determination of separate primary versus metastatic lesions through a collective judgment of a multidisciplinary tumor board after taking into account all of the available information. (9) Synchronous primary cancers are classified with a T, N, and M category for each tumor; separate tumor nodules result in a T3, T4, or M1a category depending on the separate nodule’s location relative to the primary tumor. (10) Despite these proposals of staging, there will always be areas of difficulty and tumors that are challenging to classify. The prognostic value of clinical and pathological TNM staging in patients with SCLC was also confirmed, and the continued usage is recommended for SCLC in relation to proposed changes to T, N, and M descriptors for NSCLC in the eighth edition. (11) Table 1 Descriptors and T and M categories in the seventh edition and as proposed for the eighth edition. Figure 1 *Where there is a change, the resultant stage groupings proposed for the eighth edition are in bold, and the stage in the seventh edition is given in parenthesis. Figure 1 Overall survival by clinical and pathological stage according to the proposed eighth edition groupings using the entire database available for the eighth edition. Figure 2References: 1. Travis WD, et al. The New IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. J Thorac Oncol. 2011;6: 244–285. 2. Goldstraw P et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer Journal of Thoracic Oncology, Vol. 11, Issue 1, p39–51 3. Rami-Porta R et al. The IASLC Lung Cancer Staging Project: Proposals for the Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. Journal of Thoracic Oncology, Vol. 10, Issue 7, p990–1003 4. Asamura H et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the N Descriptors in the Forthcoming 8th Edition of the TNM Classification for Lung Cancer. Journal of Thoracic Oncology, Vol. 10, Issue 12, p1675–1684 5. Eberhardt W E.et al. The IASLC Lung Cancer Staging Project: Proposals for the Revision of the M Descriptors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. Journal of Thoracic Oncology, Vol. 10, Issue 11, p1515–1522 6. Travis WD, et al. The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. Journal of Thoracic Oncology, Vol. 11, Issue 8, p1204–1223 7. Detterbeck FC et al. The IASLC Lung Cancer Staging Project: Background Data and Proposals for the Application of TNM Staging Rules to Lung Cancer Presenting as Multiple Nodules with Ground Glass or Lepidic Features or a Pneumonic Type of Involvement in the Forthcoming Eighth Edition of the TNM Classification. Journal of Thoracic Oncology, Vol. 11, Issue 5, p666–680 8. Detterbeck FC et al. The IASLC Lung Cancer Staging Project: Background Data and Proposals for the Classification of Lung Cancer with Separate Tumor Nodules in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. Journal of Thoracic Oncology, Vol. 11, Issue 5, p681–692 9. Detterbeck FC et al. The IASLC Lung Cancer Staging Project: Background Data and Proposed Criteria to Distinguish Separate Primary Lung Cancers from Metastatic Foci in Patients with Two Lung Tumors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. Journal of Thoracic Oncology, Vol. 11, Issue 5, p651–665 10. Detterbeck FC et al. The IASLC Lung Cancer Staging Project: Summary of Proposals for Revisions of the Classification of Lung Cancers with Multiple Pulmonary Sites of Involvement in the Forthcoming Eighth Edition of the TNM Classification. Journal of Thoracic Oncology, Vol. 11, Issue 5, p639–650 11. Nicholson AG et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the Clinical and Pathologic Staging of Small Cell Lung Cancer in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. Journal of Thoracic Oncology, Vol. 11, Issue 3, p300–311





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      IA05.02 - Mesothelioma Cases (ID 6525)

      11:00 - 12:30  |  Author(s): M.A. Hoda

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Malignant pleural mesothelioma (MPM) is a highly lethal malignancy arising from the serosal lining of the pleural cavity [1]. In up to 80% of patients, asbestos is considered to contribute to the development of this tumor within about 20 to 40 years of exposure time [2]. The incidence of MPM is expected to increase dramatically over the next few decades. It has been estimated that 250 000 people will die of MPM in Europe in the next three decades, and 2500–3000 new cases are diagnosed each year in the USA [3]. The macroscopic appearance of MPM depends on disease stage. In early stage MPM, the cancer presents as multiple small nodules on the surface of both pleural linings. In advanced stages, the multiple small nodules form a tumor plate which surrounds the lung like a cage and in most cases invades the lung parenchyma, diaphragm and pericardium [4]. The establishment of the pathological diagnosis of MPM and the classification in three main histological subtypes (namely epitheloid, biphasic and sarcomatoid) is important and has an impact on therapy and prognosis. Epitheloid MPM is more therapy responsive and associated with better outcome compared to biphasic and sarcomatoid histotypes. Other very important simple prognostic factors for MPM are disease stage and lymph node involvement. Therefore an adequate staging of MPM patients is crucial for therapy decision-making. The currently widely used staging system is the one according to International Mesothelioma Interest Group (IMIG) established in 1996 [5]. Based on the TNM (tumor-node-metastasis) system for malignant tumors, this staging system describes: the extent and size of the primary tumor, lymph node involvement and distant metastases. By the different TNM descriptors, MPM can be classified and summarized in four different tumor stages (IMIG I-IV). Patients suffering from stage I-III are considered for surgery within multimodality protocols, while palliative systemic or local treatment is indicated for stage IV in accordance with the current classification. Butchart et al. [6]proposed in 1976 an alternative staging system, referred to as the Butchart Staging. Contrary to the IMIG system (based on lung cancer staging) the Butchart system is particularly set up for MPM. Therefore, several differences between both staging systems exist. However, the IMIG in collaboration with the International Association for the Study of Lung Cancer (IASLC) have proposed a new T, N and M descriptors for in the forthcoming 8[th] edition of the TNM classification for MPM with significant changes to the 7[th] TNM edition and proposals have been very recently published [7-9]. With regard to the T descriptor, a fusion of both, clinical and pathological T1a and T1b into a T1 was recommended [7]. Regarding the N descriptor, a summary of the clinical and pathological N1 and N2 categories into a single category with the classification into ipsilateral, intrathoracic nodal metastases (N1) was proposed [8]. No changes have been recommended for the M descriptor in the 8[th] edition of the TNM [9]. In this presentation, 4 patient cases of different stages of MPM patients will be presented and the newly proposed TNM descriptors and IMIG staging will be applied. Cases and changes in the staging system will be discussed together with the attending audience in an interactive manner. After the presentation, the participants will be able to understand and practically apply the forthcoming changes in the TNM system for staging of MPM patients. 1. Whitaker, D., J.M. Papadimitriou, and M.N. Walters, The mesothelium and its reactions: a review. Crit Rev Toxicol, 1982. 10(2): p. 81-144. 2. Lanphear, B.P. and C.R. Buncher, Latent period for malignant mesothelioma of occupational origin. J Occup Med, 1992. 34(7): p. 718-21. 3. Peto, J., et al., The European mesothelioma epidemic. Br J Cancer, 1999. 79(3-4): p. 666-72. 4. Rudd, R.M., Malignant mesothelioma. Br Med Bull, 2010. 93: p. 105-23. 5. Rusch, V.W., A proposed new international TNM staging system for malignant pleural mesothelioma from the International Mesothelioma Interest Group. Lung Cancer, 1996. 14(1): p. 1-12. 6. Butchart, E.G., et al., Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax, 1976. 31(1): p. 15-24. 7. Nowak, A.K., et al., The IASLC Mesothelioma Staging Project: Proposals for Revisions of the T descriptors in the forthcoming Eighth edition of the TNM classification for pleural mesothelioma. J Thorac Oncol, 2016. 8. Rice, D., et al., The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma. J Thorac Oncol, 2016. 9. Rusch, V.W., et al., The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Mesothelioma. J Thorac Oncol, 2016.

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      IA05.03 - Thymic Carcinoma Cases (ID 6526)

      11:00 - 12:30  |  Author(s): F. Detterbeck

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      IA05.04 - Esophageal Carcinoma Cases (ID 6527)

      11:00 - 12:30  |  Author(s): T. Rice

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    ED05 - The 8th Edition of the TNM Staging System (ID 268)

    • Event: WCLC 2016
    • Type: Education Session
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      ED05.01 - What’s New in Lung Cancer Staging? (ID 6443)

      16:00 - 17:30  |  Author(s): H. Asamura

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The tumor, node and metastasis (TNM) classification for malignant tumors has been periodically revised in the International Union for Cancer Control (UICC) and American Joint Committee on Cancer (AJCC). As for lung cancer, the process of revision is quite unique compared with malignancies of other organs in that the corresponding professional society, the International Association for the Study of Lung Cancer (IASLC), has been playing a principal role in database construction, making revision agenda, simulation, and validation as a proposal to UICC and AJCC. The agenda articles have been already published for T, N, M, and stage grouping in the official journal of IASLC. In brief, the IASLC database included 77,156 evaluable patients diagnosed with lung cancer from 1999 to 2010, originating from 35 different databases in 16 countries of 5 continents. Among these, the data of 3905 patients were given by electric data capturing. In the T descriptors, new tumor-size groups were created: T1a 1-2 cm; T1c >2-3cm; T2a >3-4cm; T2b >4-5cm; T3 >5-7cm; and T4 >7cm. Endobronchial l ocation <2cm from the carina has better prognosis than any other T3 descriptor and will be classified as T2. Total atelectasis/pneumonitis will be classified as T2 because it has a T2 prognosis. Diaphramatic invasion will be T4. Visceral pleural invasion remains the same, and mediastinal pleura invasion, seldom used, disappears as a T descriptor. The N component remains the same, but the number of involved nodal stations has prognostic impact. Therefore, it was proposed to divide N1 into N1a (single station N1) and N1b (multiple station N1), N2 into N2a1 (single station N2 without pN1 involvement), N2a2 (single station N2 with pN1 involvement) and N2b (multiple station N2) for testing. For the M component, M1a (intrathoracic metastases) remains the same, but extrathoracic metastases are divided into single extrathoracic metastasis (new M1b) and multiple extrathoracic metastases in a single or multiple organs (M1c). Regarding stages, stage IA is divided into IA1, IA2 and IA3 to accommodate T1a, T1b and T1cN0M0 tumors; all N1 disease are stage IIB except for T3-T4N1M0 that are IIIA; a new stage IIIC is created for T3-T4N3M0 tumors; and stage IV is divided into IVA (M1a and M1b) and IVB (M1c). The 8[th] edition of the TNM classification of lung cancer defines new tumor-size groups, confirms the prognostic relevance of quantifying nodal disease, establishes a new category for single extrathoracic metastasis, and creates new stage groupings. Looking at these, the importance of the accurate measurement of tumor diameter and accurate counting of the swollen nodes and lesions of distant disease has been raised. In this way it improves our understanding of the anatomic extent of the tumor, enhances ,our capacity to indicate prognosis at clinical and pathologic staging, and increases the possibilities of research by facilitating tumor stratification for future clinical trials.

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    OA10 - EGFR Mutations (ID 382)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
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      OA10.05 - EGFR Gene Mutations Affect Tumor-Infiltrating Stromal Cell Components in Early-Stage Lung Adenocarcinoma (ID 6305)

      11:00 - 12:30  |  Author(s): H. Asamura

      • Abstract
      • Presentation
      • Slides

      Background:
      Tumors are complex structures consisting of cancer cells surrounded by a tumor stroma that is now recognized to be critical for cancer progression. Although epidermal growth factor receptor (EGFR) mutations are frequently observed in non-small cell lung carcinoma, it remains poorly understood whether EGFR mutations in cancer cells affect the tumor stroma. In this study, we studied the status of EGFR mutations in early-stage lung adenocarcinoma and analyzed the relations of EGFR mutations to tumor-infiltrating stromal cell components.

      Methods:
      A total of 152 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete tumor resection in Keio University Hospital between 2010 and 2014 were studied. Genomic DNA was isolated from formalin-fixed, paraffin-embedded tumor sections and mutational analyses of EGFR gene exons 19, 20 and 21 were performed by a polymerase chain reaction-based method. Paraffin sections were also subjected to immunohistochemistry for CD3, FOXP3, CD163 or CD204. Numbers of CD3-, FOXP3-, CD163- or CD204-immunostained cells were counted by observing 5 different fields at x200 magnification.

      Results:
      EGFR mutations were detected in 71 (47%) of the 152 patients with clinical stage IA lung adenocarcinoma and were found more frequently in women and non-smokers. These contained 38 patients with missense mutations in exon 21 (L858R) and 30 patients with deletions in exon 19. By immunohistochemistry, the number of stromal macrophages positive for CD163 or CD204, markers for tumor-associated macrophages (TAMs), was significantly decreased within tumors with EGFR mutations compared to within those with wild-type EGFR, whereas the number of CD3[+] T cells or FOXP3[+] regulatory T cells was comparable between these groups. Both tumors with missense mutations in exon 21 and deletions in exon 19 had a similar trend toward decreased TAMs in the tumor stroma.

      Conclusion:
      Our data suggest that EGFR mutations in early-stage lung adenocarcinoma are associated with decreased TAMs in the tumor stroma. EGFR mutation status might act on not only cancer cell behavior but tumor microenvironment.

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    OA12 - SBRT and Other Issues in Early Stage NSCLC (ID 383)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Early Stage NSCLC
    • Presentations: 1
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      OA12.03 - Percutaneous Cryoablation for Lung Cancer Patients for Whom Surgery or Radiotherapy is Contraindicated Due to Idiopathic Pulmonary Fibrosis (ID 3830)

      11:00 - 12:30  |  Author(s): H. Asamura

      • Abstract
      • Presentation
      • Slides

      Background:
      Interstitial lung disease, such as idiopathic pulmonary fibrosis (IPF), have been widely known to be associated with lung cancer. Lung cancer patients concomitant with IPF sometimes develop a life-threatening acute exacerbation after surgery or radiotherapy. Percutaneous cryoablation is evolving as a potentially less invasive local treatment for lung cancer. The purpose of this study is to retrospectively analyze the outcomes of cryoablation for clinical T1N0M0 non-small cell lung cancer (NSCLC) patients for whom surgery or radiotherapy is contraindicated because of IPF.

      Methods:
      Between December 2003 to March 2016, 210 patients underwent computer tomography guided percutaneous cryoablation for lung tumors at our institution. Of these, 11 histologically proven clinical T1N0M0 NSCLC patients, for whom surgery or radiotherapy was considered contraindicated because of severe IPF, were retrospectively reviewed. Complications, local progression-free survival and clinicopathological factors were evaluated.

      Results:
      The cohort was composed of 11 men with a mean age of 74 years (range: 68 to 82). The median follow-up time was 20 months (range: 6 to 55 months). The mean Krebs von den Lungen-6 (KL-6) level was 1608 ±1025 U/mL. The mean tumor size was 24 ± 7mm. The mean percentage of predicted diffusing capacity for carbon monoxide (DLCO) was 37±27%. Thirty and 90-day mortality was 0 and 18%, respectively. Two patients required chest tube drainage because of severe pneumothorax. Acute exacerbation of IPF occurred in two patients (18%). The use of oral steroids and need for chest tube drainage were predictors of higher mortality (p < 0.05) and higher incidence of acute exacerbation of IPF (p < 0.05). However, higher level of KL-6 and low percentage of DLCO were not significant risk factors of mortality or acute exacerbation of IPF. Local progression-free survival at 1, 2 and 3 year was 51, 41 and 31%, respectively.

      Conclusion:
      Percutaneous cryoablation for lung cancer patients with IPF provoked acute exacerbation of IPF in 18% of patients. The use of oral steroids and need for chest tube drainage were predictors of higher mortality and higher incidence of acute exacerbation of IPF.

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

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 1
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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 - 15:45  |  Author(s): 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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    P2.04 - Poster Session with Presenters Present (ID 466)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      P2.04-016 - Is FDG-PET Useful for Distinguishing between Thymic Epithelial Tumors and Malignant Lymphoma? (ID 5234)

      14:30 - 15:45  |  Author(s): H. Asamura

      • Abstract

      Background:
      It is difficult to diagnose the tumor in the anterior mediastinum by computed tomography. Distinguishing between thymic epithelial tumors and malignant lymphoma is important, because therapeutic strategy is difficult in each disease. The objective of this study was to clarify the usefulness of positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) for distinguishing thymic epithelial tumors and malignant lymphoma.

      Methods:
      We retrospectively reviewed FDG PET-CT scans of 42 patients pathologically diagnosed by surgery or biopsy as thymic epithelial tumors or malignant lymphoma. FDG uptake was measured as the maximum standard uptake value (SUVmax). Student t tests were used to assess association between SUVmax and pathological diagnosis.

      Results:
      Among the 42 patients, 26 patients had a pathological diagnosis of thymoma: WHO classification type A in 3 patients (11%), type AB in 5 patients (19%), type B1 in 10 patients (19%), type B2 in 11 patients (42%), and type B3 in 2 patients (7%). Eight patients had the thymic carcinoma. Eight patients had the malignant lymphoma. The SUVmax in malignant lymphoma (13.4±6.3) was significantly higher than that in the thymic epithelial tumors (4.9±2.4) (p<0.001). The SUVmax in thymic carcinoma (7.9±3.0) was higher than that in the thymoma (4.5±1.3) (p=0.002) . The ROC curve of SUVmax for predicting malignant lymphoma indicated that the optimal cutoff value was 7.3. This value had a sensitivity of 0.88 and a specificity of 0.99 (area under curve, 0.93).

      Conclusion:
      FDG PET-CT is helpful for distinguishing malignant lymphoma from thymic epithelial tumors with cut off value of 7.3.

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    P3.01 - Poster Session with Presenters Present (ID 469)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 2
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      P3.01-006 - Prognostic Impact of Tumor Spread through Air Spaces in Limited Resection for pStage I Lung Cancer (ID 4377)

      14:30 - 15:45  |  Author(s): H. Asamura

      • Abstract

      Background:
      Tumor spread through air space (STAS) is proposed as a new factor of lung cancer invasion, according to the new World Health Organization (WHO) classification. The aim of this study is to elucidate the prognostic impact and conduct a histopathological evaluation of STAS in primary lung cancer patients who underwent limited resection.

      Methods:
      We retrospectively collected 508 samples from p-Stage I primary lung cancer patients who underwent limited resection between 2004 and 2013. Hematoxylin and eosin stained tumor slides were reviewed to evaluate pathological features, including the presence or absence of STAS, and the morphological pattern in cases with STAS. We defined the pattern of STAS as single cell (SG), small cluster (SM), or large cluster (LG). Clinicopathological characteristics and patient outcome data were collected from medical records. SPSS statistical software (IBM Corporation, Somers, NY, USA) was used for statistical analysis.

      Results:
      Histological diagnoses were 440 adenocarcinomas (Ad) (including 107 Adenocarcinoma in situ and 144 Minimally invasive adenocarcinoma), 44 squamous cell carcinomas (Sq), and 24 other types of cancer. Seventy-six cases (15.0%: 60 Ad, 9 Sq, and 7 other types of cancer) were positive for STAS. The morphological STAS patterns were 12 SG, 45 SM, and 19 LG, respectively. There was no significant relationship between recurrence rate and morphological STAS pattern. The STAS-positive group was associated with the presence of micropapillary and/or solid components in Ad, and with lymphovascular and pleural invasion, compared to the STAS-negative group (p < 0.01). The median follow-up was 51 months. Eight local recurrences (1.6%), 16 locoregional (lung parenchyma, hilum, mediastinum) recurrences (3.1%), and 10 distant recurrences (2.0%) were recorded. In multivariate analysis, the risk of local (hazard ratio [HR]: 12.75; p < 0.01) and locoregional (HR: 4.12; p = 0.01) recurrence was significantly higher in the STAS-positive group than in the STAS-negative group. However, in a multivariate Cox model the presence of STAS was not associated with distant recurrence (p = 0.58).

      Conclusion:
      Our results indicated that the presence of STAS is a significant risk factor for local and locoregional recurrence, but not distant recurrence, in p-Stage I lung cancer following limited resection.

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      P3.01-015 - Prognostic Impact of Histologic Invasion Factors in Pulmonary Adenocarcinoma, with Particular Focus on the Pattern of Architectural Remodeling (ID 4975)

      14:30 - 15:45  |  Author(s): H. Asamura

      • Abstract
      • Slides

      Background:
      In the 2015 WHO classification, histologic factors that are associated with invasion in primary lung adenocarcinoma (AdCa) include the presence of non-lepidic histologic subtypes (invasive subtypes) and the presence of cancer-associated myofibroblasts (CAFs). The prognostic significance of CAFs in combination with each invasive subtype has not been well assessed. We conducted this study to clarify the prognostic impact of CAFs in the absence of architectural remodeling.

      Methods:
      We retrospectively collected data and re-evaluated samples from 1052 patients with pathological stage 0 or IA pulmonary AdCa who underwent complete resection at our hospital between 2007 and 2012. HE and elastica van Gieson stains were used for histological evaluation. We defined two invasive subtypes: those with (INV-1) and without (INV-2) architectural remodeling of lung parenchyma. The postoperative recurrence of tumor was analyzed in each group.

      Results:
      Our reviewed diagnoses were 172 Stage 0 and 880 Stage IA AdCa. Of the 880 stage IA cases, 706 (80.2%) and 174 (19.8%) were categorized as INV-1 and INV-2, respectively. CAFs were observed in all cases in the INV-2 group, but were not always present in the INV-1 group. In the INV-2 group, the median diameter of the invasive component was 6 mm (range: 1-16), the median postoperative follow-up period was 60 months (range: 2-105), and none of the cases developed recurrence. In the INV-1 group, the median postoperative follow-up period was 55 months (range: 1-104) and the estimated 5-year recurrence-free probability by the Kaplan-Meier method was 93.0%. All cases with postoperative recurrence were categorized in the INV-1 group.

      Conclusion:
      The INV-2 group AdCa had a low risk of recurrence. These findings suggest that certain subtypes of invasive AdCa, which are classifiable based on the architectural remodeling pattern and the presence of CAF, can be considered to have a good prognosis.

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    PL05 - Closing Plenary Session: A Life in Thoracic Oncology - Reflections from Giants on Milestones in the Treatment Advances in Lung Cancer (ID 433)

    • Event: WCLC 2016
    • Type: Plenary
    • Track:
    • Presentations: 1
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      PL05.08 - Welcome to Yokohama for WCLC 2017 (ID 6920)

      16:00 - 18:00  |  Author(s): H. Asamura

      • Abstract
      • Presentation

      Abstract not provided

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