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Makoto Suzuki



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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: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.16-59 - A Phase II Study of Adjuvant Chemotherapy with Tegafur-Uracil for Vessel Invasion Positive Stage IA Non-Small Cell Lung Cancer (LOGIK0602) (ID 12111)

      16:45 - 18:00  |  Author(s): Makoto Suzuki

      • Abstract

      Background

      Vessel invasion, which includes vascular or lymphatic invasions, is a representative prognostic factor in lung cancer therapy. Even in the patients with resected stage IA non-small cell lung cancer (NSCLC), vessel invasion is a significant poor prognostic factor. The pathological analysis of 322 cases of resected stage IA NSCLC in Oita Prefectural Hospital revealed that the 5-yr overall survival rate was 71.8% in the vessel invasion-positive group and significantly worse than the 89.6% in the vessel invasion-negative group. Interestingly, the 5-yr overall survival rate of the oral tegafur-uracil adjuvant chemotherapy group was 93.3% and significantly better than the 66.6% of the untreated group. Tegafur-uracil is known to affect vascular endothelial growth factor overexpressing tumours. Therefore, to estimate the positive effect of adjuvant tegafur-uracil in patients with vessel invasion-positive stage IA NSCLC, we conducted a multi-center single-arm phase II study (LOGIK0602).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The patients with completely resected vessel invasion-positive stage IA NSCLC were registered at the Lung Oncology Group in Kyushu (LOGIK). Vessel invasion was diagnosed by two of the three pathologists. Adjuvant chemotherapy consisted of 2 years of oral tegafur-uracil at 250 mg/m2/day. Fifty-five patients from 7 institutions were enrolled from June 2007 to September 2012. The primary endpoint was the 5-yr overall survival rate. Secondary endpoints were the rate of accomplishment of scheduled adjuvant chemotherapy, incidence and grade of adverse reactions, 3-yr overall and relapse-free survival rates, and 5-yr relapse-free survival rate.

      4c3880bb027f159e801041b1021e88e8 Result

      Among the 52 eligible patients, 16 (30.8%) discontinued tegafur-uracil administration and 36 (69.2%) completed the treatment course. The observation period was calculated as 562 to 3107 days and median observation period as 1947 days using the reverse Kaplan-Meier method. There were 39 male and 13 female patients. The 3-yr and 5-yr overall survival rates were 96.2% and 94.2% respectively, which were obviously better than the historical data of 28% to 78.7% in 8 reports. The 3-yr and 5-yr relapse-free survival rates were 92.3% and 88.5%, respectively. Eighteen adverse reactions were observed including 4 cases of grade 3 hepatic function disorder (7.7%) and 5 cases of grade 2 anorexia (9.6%). No grade 4 adverse effect was encountered. Five recurrences were observed including 1 distant metastasis (adrenal) and 4 local recurrences (lung: 2, lymph node: 2).

      8eea62084ca7e541d918e823422bd82e Conclusion

      A 2-year course of oral tegafur-uracil administration is feasible and might have a significant benefit in the adjuvant treatment of vessel invasion-positive stage IA NSCLC.

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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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      P3.09-14 - Pathobiology of Notch2 in Lung Cancer (ID 13789)

      12:00 - 13:30  |  Author(s): Makoto Suzuki

      • Abstract
      • Slides

      Background

      Notch signaling is known to be involved in the initiation, progression, and suppression of various types of cancers. The pathological significance of Notch1 has been well studied in lung cancer, but that of Notch2 is still unclear.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Immunohistochemical study was performed to measure the expression of NOTCH2 in non-neoplastic lung tissues and lung cancers in comparison with the Clara (Club) cell 10 kD protein (CC10), and Western blotting analysis was performed to detect NOTCH2 in human cancer cell lines. Notch2 gene knockdown experiment and transient transfection of the intracellular domain of the Notch2 (N2ICD) gene were conducted to reveal the function of Notch2. In addition, we studied the relationships between the expressions of Notch1, 2, and 3.

      4c3880bb027f159e801041b1021e88e8 Result

      Immunohistochemical study of lung tissues revealed that NOTCH2 was detected in bronchiolar epithelial cells and was often colocalized with CC10, and that adenocarcinoma tissues were more positively stained than those of squamous cell carcinoma and small cell carcinoma tissues. In human lung cancer cell lines the expression of NOTCH2 was similar to that of NOTCH1 and preferentially detected in non-small cell lung carcinoma (NSCLC) cell lines. Knockdown experiments of the Notch2 gene in NSCLC cell lines showed no significant changes in the expression of molecules associated with cell differentiation, proliferation, apoptosis, and motility. The effects of Notch2 gene knockdown could have be masked by concomitant Notch1 activation, as indicated by an increase in the intracellular domain of NOTCH1. Additionally, the transient transfection of the N2ICD gene induced CC10 expression in an adenocarcinoma cell line.

      8eea62084ca7e541d918e823422bd82e Conclusion

      notch2 iaslc-1.tif
      The present study revealed that Notch2 is important in Club cell differentiation in normal lungs and in adenocarcinoma. We also determined that Notch1 and Notch2 are covariant, and the balance of the expression of Notch receptors could determine the biological behaviors of lung cancer cells.

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