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T. Tsuchiya



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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. Tsuchiya

      • 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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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-038 - A phase II trial of the combination of gemcitabine and carboplatin as adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. (Kenbyo 0601) (ID 2185)

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

      • Abstract

      Background
      Background: Adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC) is recommended with survival benefit, however low compliance in recent clinical trials. Objectives: We conducted a phase II trial of gemcitabine(G) and carboplatin(C) regimen for patients with completely resected NSCLC and carboplatin is administrated on day 8 to reduce hematological toxicity especially thrombocytopenia.

      Methods
      Eligibility criteria included: PS(ECOG) 0-1, ageā‰¦75 years, p-stage IB-IIIA NSCLC is complexly resected (R0), adequate hematological liver renal and cardiac function. Regimen: G (1000mg/m2) d1 +8 and C (AUC 5, d8) q.3wks. Primary end point of this study is feasibility and secondary end points are toxicity, overall and disease-free survival.

      Results
      44 patients (20 male, 24 female) were included, median age 63 (40-71) years. Adenocarcinoma in 39, squamous cell ca. in 4, pleomorphic ca. in 1, and pathological stage IB in 25, IIA in 8, IIB in 5, and IIIA in 6 patients. Thirty-three patients (75%) completed the planned 4 cycles of GC therapy and 28 (64%) received the planned doses. Thirty-four percent of the patients had grade 3/4 neutropenia, 2 (6%) had thrombocytopenia, and the other 2 (6%) had anemia. Non-hematological adverse effects were infrequent and no treatment-related death was noted in this study.

      Conclusion
      Hematological toxicity, especially thrombocytopenia in this study is less than that in the standard administration of CG (C day1) regimen. We conclude that this regimen is feasible with sufficient compliance as adjuvant chemotherapy for completely resected stage IB-IIIA NSCLC patients.

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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. Tsuchiya

      • 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.

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    P2.07 - Poster Session 2 - Surgery (ID 190)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P2.07-021 - Results of surgical treatment for lung cancer in patients aged 80 years or over - Single institution over 20 year experience (ID 1781)

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

      • Abstract

      Background
      The average age of the general population is increasing in the worldwide. Therefore, there is also an increasing number of elderly patients presenting with potentially-resectable lung cancer. We retrospectively reviewed the outcomes of octogenarians or over who underwent pulmonary resection for primary non-small cell lung cancer (NSCLC) to identify the independent factor of overall survival.

      Methods
      We conducted a retrospective single-institution review of patients aged 80 years or over who underwent pulmonary resection for primary NSCLC from 1990 to 2012 at Nagasaki university hospital. The various clinicopathological data, including gender, histological type, body mass index, comorbidity, clinical stage, surgical procedure, extent of lymph node dissection, and pathological stage were analyzed.

      Results
      119 octogenarians or over underwent pulmonary resection. The median age was 82 years (range 80-92 years). Of the total patient number, 56 (47.1%) had respiratory and 44 (33.6%) had cardiovascular comorbidity diagnosed preoperatively. The clinical stage was I in 97 (81.5%) patients, II in 13, III in 6, IV in 3. Operations included 82 (68.9%) lobectomies, 2 (1.7%) bilobectomies, 15 (12.6%) segmentectomies, and 19 (16.0%) partial resections. Only 31 (26.1%) were performed mediastinal lymph node dissection. The pathological stage was I in 79 (81.5 down to 66.4 %) patients, II in 16 (13.4%), III in 21 (17.7%), IV in 3 (2.5%). 26 (21.8%) patients presented with postoperative respiratory complications, and 11 (9.2%) were cardiovascular, and the operative mortality was 1 (0.8%). The 5-year survival rates were 46.0% for all patients, 60.8% for stage I patients. The disease specific 5-year survival rates were 60.1% for all patients, 79.5% for stage I patients, respectively. In univariate analysis, female (p<0.04), clinical stage (p<0.002), and pathological stage (p<0.000) was independent and cardiovascular comorbidity was marginally (p<0.05) factor for overall survival. In multivariate analysis, only advanced pathologic stage (stage II, more) was independent predictor of overall survival [p<0.0001, Hazard ratio: 3.17, 95% confidence interval 1.76-5.73]. Figure 1

      Conclusion
      Surgical treatment for selected patients aged 80 years or over or with primary NSCLC can be performed safely with low morbidity and mortality in this study. We recommend that limited operation might be the best surgical treatment, especially for stage I NSCLC. In the future, establishment of accurate clinical staging as well as early detection for lung cancer, and the appropriate treatment for advanced stage NSCLC for aged people should be studied for the upcoming aged society.