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T. Miyazaki



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-007 - Relationship between 5FU related enzymes and EGFR mutation status in non-small cell lung cancer treated with S-1 adjuvant therapy (ID 890)

      09:30 - 09:30  |  Author(s): T. Miyazaki

      • Abstract

      Background
      Anti-cancer effect of 5-fluorouracil (5FU) is affected by the expressions of 5FU related enzymes, such as dihydropyrimidine dehydrogenase (DPD) and thymidine synthase (TS) and orotate phosphoribosyltransferase (OPRT), in each tumor. On the other hand, anti-cancer effect of epidermal growth factor receptor tyrosine kinase (EGFR-TKI) is affected by EGFR mutation status in each tumor. In 2007, Suehisa and colleagues reported that adjuvant chemotherapy with uracil-tegafur, a fluorouracil prodrug, significantly prolonged survival rates among patients with EGFR wild-type adenocarcinoma but not among patients with EGFR mutant tumors. In this study, the correlation between 5FU related enzymes and EGFR mutation status was analyzed.

      Methods
      We analyzed 49 patients with primary NSCLC who were postoperatively treated with S-1, an oral fluorouracil anticancer prodrug composed of tegafur, CDHP, and potassium oxonate in the molar ratio 1:0.4:1. We then evaluated the relation between the EGFR mutation status, each of the 5FU related enzymes and various clinicopathological factors. In vitro, DPD mRNA and protein expression was investigated in various cell lines.

      Results
      Among the 49 cases (thirty adenocarcinoma (ADC), sixteen squamous cell carcinoma (SQCC), two adenosquamous carcinoma, and one carcinoid), EGFR mutation was observed only in ADC (12 patients; 24.5%). In immunohistochemical examination, 10 patients were DPD immune-positive (20.4%), 31 patients were OPRT immune-positive (63.3%), and 16 patients were TS immune-positive (32.7%). Three year disease free survival rate of single S-1 adjuvant therapy was 77.6%, and three year overall survival rate was 89.7%. DPD immune-positive cases were significantly correlated with EGFR mutation status (p = 0.003). In vitro, EGFR mutated cell lines showed high DPD mRNA and protein expression.Figure 1

      Conclusion
      High DPD expression was shown to be correlated with EGFR mutation in adenocarcinoma cells and tissues. This result indicates that 5FU might be effective for EGFR wild type tumors than mutant type tumor, and EGFR mutation status might be a potential poor predictive marker for treatment with 5FU drugs.

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    P1.24 - Poster Session 1 - Clinical Care (ID 146)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P1.24-021 - Bronchoplasty and bronchoangioplasty for primary non-small cell lung cancer (ID 1595)

      09:30 - 09:30  |  Author(s): T. Miyazaki

      • Abstract

      Background
      The objective of this study was to evaluate the operative mortality, morbidity, and survival of bronchoplasty and bronchoangioplasty for non-small cell lung cancer. Multivariate analysis was done to determine potential prognostic factors for both procedures based on our 27-year single-center experience.

      Methods
      Between January 1985 and March 2012, 204 bronchoplastic procedures were done in 1978 patients who underwent lung resections for non-small cell lung cancer at Nagasaki University Hospital. After excluding 18 carino-plasty patients and 13 wedge angioplasty of pulmonary artery, 173 patients (141 bronchoplasty and 32 broncho-angioplasty) were included.

      Results
      In the bronchoplasty group, the postoperative morbidity was 29% (41/141) and the 90-day postoperative mortality was 5.7% (8/141), while in the broncho-angioplasty group the postoperative morbidity was 28% (9/32) and the postoperative mortality was 15.6% (5/32). Eleven patients (6.4%) experienced bronchopleural fistulas. Multivariate analysis demonstrated that induction therapy (p=0.047) and combined multiple organ resection (p=0.012) were risk factors for postoperative anastomotic complication. The 5-year survival rate for all patients was 46.3%. The 5-year survival rate was 69.5% in patients with pathological stage I disease. In patients with stage II disease, the 5-year survival rate was 34.7%. In patients with stage III-IV disease, the 5-year survival rate was 33.2%. The survival rate in stage I disease was significantly better compared with other stage disease (p<0.0003). Multivariate analysis indicated that the type of operation (bronchoplasty versus bronchoangioplasty), postoperative complications, histologic type (squamous cell carcinoma versus non squamous cell carcinoma), and pN status (N0-1 versus N2-3) were significant factors affecting survival.

      Conclusion
      Both bronchoplasty and broncho-angioplasty are useful for the treatment of patients with non-small cell lung cancer and should be performed in stage I. However, careful patient selection is mandatory in patients with advanced tumor stages and in those with nonsquamous cell carcinoma, especially if broncho-angioplasty is being considered.