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J. Matsubayashi



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    MO26 - Anatomical Pathology II (ID 129)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
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      MO26.11 - Proposal on incorporating Blood Vessel Invasion into the T classification parts as a practical staging system for stage I Non-small cell Lung Cancer (ID 842)

      11:30 - 11:35  |  Author(s): J. Matsubayashi

      • Abstract
      • Presentation
      • Slides

      Background
      We investigated blood vessel invasion (BVI) as a possible negative prognostic factor in patients with stage I non-small cell lung cancer (NSCLC) according to the 7[th] Edition of the TNM classification.

      Methods
      Between 1999 and 2007, a total of 694 consecutive patients with pathological stage I NSCLC underwent complete resection with systematic lymph node dissection at Tokyo Medical University Hospital. All sections of the specimens were stained by Elastica van Gieson to visualize elastic fibers and were examined to determine the prognostic symptoms of BVI. We statistically analyzed the association between BVI and clinicopathologic factors, as well as clinical outcomes.

      Results
      BVI was detected in 201 patients with stage I NSCLC (29.0%). The 5-year overall survival (OS) rates of the non-BVI and BVI patients were 90.5% and 66.0%, respectively (p < 0.0001). BVI was found to be a significant independent prognostic factor by multivariate survival analysis in stage IA and stage IB NSCLC (HR 2.591, p < 0.001; HR 2.347, p = 0.009, respectively). The 5-year OS rate of patients with BVI was significantly worse than that of patients without BVI in the T1a (94.5% vs 87.5%, p < 0.0001), T1b (82.7% vs 65.9%, p = 0.034), and T2a (90.9% vs 61.8%, p < 0.0001) subgroups.

      Conclusion
      We identified the presence of BVI as an independent poor prognostic factor in patients with stage I NSCLC. In the future revision of the TNM staging system, the routine use of elastic fiber stains in pathological evaluations of lung cancer for BVI determination might be recommended, and tumors with BVI should be upstaged to the higher current T staging.

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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-010 - Analytical Performance of the cobas EGFR Mutation Assay for Japanese Non-Small Cell Lung Cancer (ID 1101)

      09:30 - 09:30  |  Author(s): J. Matsubayashi

      • Abstract

      Background
      Patients’ EGFR mutation status prior to treatment impacts outcomes and, EGFR testing has been developed as a companion diagnostic; this relationship between therapeutic and diagnostic agents is known as personalized healthcare. Recently, it was reported that about half of patients may acquire resistance to EGFR-TKIs following therapy, mainly by appearance of EGFR mutations, such as T790M. Thus, it is important to assess EGFR mutation status before and during treatment to determine the most appropriate treatment regimens for patients. A number of PCR-based techniques are used in the assessment of EGFR mutations. In Japan, the “Scorpion-ARMS” therascreen® EGFR Rotor-Gene Q PCR Kitis (therascreen EGFR assay) the only available in vitro diagnostic (IVD) test. The cobas® EGFR Mutation Test (cobas EGFR assay) is the only FDA-approved kit for IVD testing in the US.In this study, we compared the performance of the cobas EGFR assay and the therascreen® EGFR assay using FFPE tissue specimens from NSCLC patients.

      Methods
      We extracted DNA from 149 FFPE tissues of NSCLC, according to the manufacturer’s instructions and performed a comparative study of cobas EGFR and therascreen EGFR methods.

      Results
      EGFR mutations were identified in 63 NSCLC specimens (42.3%) using the cobas EGFR assay and 61 samples (41.2%) using the therascreen EGFR assay. The concordance rate between the cobas EGFR assay and therascreen EGFR assays was 145/149 (97.3%). Only three discordants between these EGFR assays were observed. One T790M mutation in combination with an L858R mutation was identified by the cobas EGFR assay. No invalid assay results occurred with the cobas EGFR assay.

      Conclusion
      The cobas EGFR assay has two advantages. One is that the process is easily performed by stable methods. It takes only 8 hours, from tumor specimen to results generated using the semi-automated system. Thus, patients assessed using the cobas EGFR assay can begin the most appropriate treatment quickly. The other advantage is that only a very small amount of DNA (150 ng) is required to detect mutation status using the cobas EGFR assay. Our results show a high concordance rate (97.3%) of cobas EGFR with an existing IVD product, the therascreen EGFR assay. In this study, one double mutant, T790M in combination with L858R, was only identified by the cobas EGFR assay. The cobas EGFR assay appears to give the most accurate and appropriate results for NSCLC patients.

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    P3.19 - Poster Session 3 - Imaging (ID 181)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 2
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      P3.19-001 - Correlation between whole tumor size and solid component size on high-resolution computed tomography in the prediction of the degree of pathologic malignancy and the prognostic outcome in primary lung adenocarcinoma (ID 138)

      09:30 - 09:30  |  Author(s): J. Matsubayashi

      • Abstract

      Background
      It is known that in lung adenocarcinoma, ground glass nodule (GGN) tumors have a better prognosis than solid tumors. The aim of this study is to determine whether it is more useful to evaluate the whole tumor size or only the solid component size to predict the pathologic malignancy and the prognostic outcome in lung adenocarcinoma.

      Methods
      Using high-resolution computed tomography (HRCT) data of 232 patients with adenocarcinoma 7 cm or less who underwent curative resection, we retrospectively measured the whole tumor and solid component sizes with lung window setting (WTLW and SCLW) and whole tumor sizes with a mediastinal window setting (WTMW).

      Results
      There was significant correlation between the WTLW and the measurements of pathological specimens (r=0.792, P<0.0001). The SCLW and WTMW values significantly correlated with the area of pathologically confirmed invasion (r=0.762, P<0.0001 and r=0.771, P<0.0001, respectively). The receiver operating characteristics area under the curve for WTLW, SCLW and WTMW used to identify lymph node metastasis or lymphatic or vascular invasion were 0.693, 0.817 and 0.824, respectively. Kaplan-Meier curves of DFS and OS were better divided according to SCLW and WTMW, compared with WTLW. Multivariate analysis of DFS and OS revealed that WTMW was an independent prognostic factor (HR=0.72, 95%CI=0.58-0.90, P=0.004 and HR=0.74, 95%CI=0.57-0.96, P=0.022, respectively).

      Conclusion
      The predictive values of the solid tumor size visualized on HRCT especially in the mediastinal window for pathologic high-grade malignancy and prognosis in lung adenocarcinoma less than 7 cm were greater than those of whole tumor size.

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      P3.19-020 - Multivariable analysis of the high resolution-CT findings of the presence or absence of epidermal growth factor receptor mutation for 476 primary lung adenocarcinomas (ID 1589)

      09:30 - 09:30  |  Author(s): J. Matsubayashi

      • Abstract

      Background
      The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor make very important role in chemotherapy for primary lung adenocarcinoma. It is necessary to examine EGFR mutation before medication, but it is difficult to examine for all patients. Our purpose is to determine EGFR mutation presence by HRCT findings of primary lung adenocarcinoma.

      Methods
      This study consists of 476 primary lung adenocarcinomas which were examined EGFR mutation (exon 18, 19 and 21) by a genetic analysis. EGFR mutation-positive group (EGFR-P) were 223 cases (resected =178, non-resected =45), and EGFR wild-type group (EGFR-W) were 253 cases (resected =161, non-resected =92). At first, presence of findings, such as much pleural effusion, atelectasis, or secondary pneumonia, that come to have difficulty in evaluation of size and the character of tumor, was determined. Then, all evaluable parameters were analyzed. The high resolution-CT (HRCT) findings that were analyzed independently by 2 radiologists with special attention were 21 parameters (tumor size, well-defined margin, irregular margin, spiculation, lobulation, pure ground-glass opacity (GGO), part-solid, solid, air bronchogram, cavity, calcification, broncho-vascular convergence, pleural indentation, pleural concave, pleural thickness, lymphangitis carcinomatosis, emphysema, interstitial pneumonia, pulmonary metastasis, pleural effusion, and lymph node enlargement). The age, gender and smoking history were additionally reviewed. These parameters were evaluated with Chi square test and multivariate analysis. A p-value less than 0.01 were considered to indicate a statistically significant difference.

      Results
      The cases that were hard to analyze a tumor into by such as atelectasis were two (EGFR-P) and 26 (EGFR-W), respectively. A statistical significant difference was present (p=3.4E-05). Chi square test showed a statistically significant difference about "part-solid (p=5.5E-06)", "air bronchogram (p=0.0036)" and "pleural indentation (p=0.0002)" more frequently in EGFR-P than in EGFR-W. Similarly “woman (p=1.3E-09)” and “non-smoker (p=2.7E-13)” were observed more frequently in EGFR-P than in EGFR-W. On the other hand, “solid (p=2.1E-07)”, “cavity (p=0.0004)”, “emphysema (p=5.1E-14)”, “interstitial pneumonia (p=3.1E-8)” and “lymph node enlargement (p=0.0008)” were observed more frequently in EGFR-W than in EGFR-P. And Multivariable analysis showed that “cavity (p=0.003)”, “emphysema (p=0.001)” and “interstitial pneumonia (p=0.001)” were observed more frequently in EGFR-W than in EGFR-P. On the other hand, there was no parameter that became statistically significantly more frequently in EGFR-P than EGFR-W. By the multivariable analysis, there was no significant statistical difference about gender and smoking history.

      Conclusion
      The cases that were hard to analyze a tumor into by such as atelectasis were significant in EGFR-W. Some HRCT findings (part-solid, solid, air bronchogram, cavity, pleural indentation, emphysema and interstitial pneumonia) indicated more statistically significant usefulness for a diagnosis of the EGFR mutation. Especially multivariable analysis showed that HRCT findings (cavity, emphysema and interstitial pneumonia) were more statistically significant about EGFR mutation than gender and smoking history.