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Kawaguchi T.,Kinki chuo Chest Medical Center | Tamiya A.,Kinki chuo Chest Medical Center | Tamura A.,NHO Tokyo Hospital | Arao M.,University of Fukui | And 4 more authors.
Clinical Lung Cancer | Year: 2012

Background: It remains to be determined in elderly patients with advanced non-small-cell lung cancers (NSCLCs) if there is a benefit of chemotherapy in patients aged 80 or older. Methods: Using a database from the Japan National Hospital Organization Study Group for Lung Cancer from 1990 to 2005, 3 cohorts based on the age of diagnosis were examined in patients with stage IIIB and IV NSCLC. Cohort 1 was for 70- to 74-year-old patients, cohort 2 for 75- to 79-year old, and cohort 3 for 80 years and older (80+). Multivariate analysis of survival for each cohort was performed using the Cox regression method using the following covariates: age, PS, histology, stage, smoking status, and chemotherapy. Results: There were 1617 patients in cohort 1, 1349 in cohort 2, and 1010 in cohort 3. The number of patients treated with chemotherapy were 991 (61%) in cohort 1, 648 (48%) in cohort 2, and 286 (28%) in cohort 3. Multivariate analysis for overall survival (OS) showed that chemotherapy was a significant prognostic factor among cohort 1 (hazard ratio [HR], 0.540; 95% confidence interval [CI], 0.481-0.607; P <.0001) and cohort 2 (HR, 0.715; 95% CI, 0.632-0.810; P <.0001) and showed a benefit trend among cohort 3 (HR, 0.869; 95% CI, 0.742-1.018; P =.0940). Conclusions: After adjustment for PS, a trend of survival benefit of chemotherapy remained in patients aged 80 or older. © 2012 Elsevier Inc. All Rights Reserved. Source


Maeda H.,National Hospital Organization Toneyama Hospital | Matsumura A.,Kinki chuo Chest Medical Center | Kawabata T.,NHO Okinawa Hospital | Suito T.,NHO Ibaraki Higashi Hospital | And 4 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2012

OBJECTIVES: An adenosquamous carcinoma (ASC) of the lung is a relatively rare tumor. In this multi-institutional cohort study, we tested the hypothesis that an ASC exhibits more aggressive clinical behavior as compared to adenocarcinoma (AC) and squamous cell carcinoma (SC). METHODS: This retrospective cohort study used a prospective database produced by the Japan National Hospital Organization Study Group for Lung Cancer over a 7-year period (operations from 1997 to 2003, follow-up data until March 2010). During that period, 4668 cases underwent an operation for various types of primary malignant lung tumors. When a sample from a tumor comprised at least 20% each of SC and AC, the case was classified as ASC. Pathologic staging was done according to the seventh edition of the International Union against Cancer (UICC) Tumor Node Matastasis (TNM) classification of malignant tumors. RESULTS: We identified 114 patients with ASC (2.4%), 2993 withAC (64.2%), and 1369 with SC (29.3%). Kaplan-Meier survival curves for all stage cases, p-stage IA, IB, and IIIA tumors indicated that ASC cases had the least favorable survival. The 5-year survival rates for all stage cases were 23.3% for ASC, 58.0% for AC (p < 0.0001), and 40.8% for SC (p < 0.0001). The 5-year survival rates for p-stage IA were 42.0%for ASC, 81.8% for AC (p = 0.0005), and 63.4% for SC not significant (NS), while those for p-stage IB were 19.3%, 65.3% (p = 0.0024), and 46.8% (NS), respectively, and those for p-stage IIIA were 17.8%, 24.8% (p = 0.0154), and 18.8% (NS), respectively. There was a tendency for greater survival differences between ASC and AC in earlier tumor stages. A step-wise multivariable model demonstrated that sex, age, performance status, histology, tumor size, p-stage, operative method,and neoadjuvant/adjuvant therapy were independent prognostic factors. CONCLUSION: ASC of the lung is more aggressive than AC and SC. The decreased survival of patients with ASC as compared with either of those single histology tumors suggests the need for a clinical trial of adjuvant chemotherapy that includes early-stage patients. © The Author 2011. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Source


Shimizu K.,Gunma University | Kaira K.,Gunma University | Tomizawa Y.,NHO Nishi Gunma Hospital | Sunaga N.,Gunma University | And 8 more authors.
British journal of cancer | Year: 2014

ASC amino-acid transporter 2 (ASCT2) is a major glutamine transporter that has an essential role in tumour growth and progression. Although ASCT2 is highly expressed in various cancer cells, the clinicopathological significance of its expression in non-small cell lung cancer (NSCLC) remains unclear. One hundred and four patients with surgically resected NSCLC were evaluated as one institutional cohort. Tumour sections were stained by immunohistochemistry (IHC) for ASCT2, Ki-67, phospho-mTOR (mammalian target of rapamycin), and CD34 to assess the microvessel density. Two hundred and four patients with NSCLC were also validated by IHC from an independent cohort. ASC amino-acid transporter 2 was expressed in 66% of patients, and was closely correlated with disease stage, lymphatic permeation, vascular invasion, CD98, cell proliferation, angiogenesis, and mTOR phosphorylation, particularly in patients with adenocarcinoma (AC). Moreover, two independent cohorts confirmed that ASCT2 was an independent marker for poor outcome in AC patients. ASC amino-acid transporter 2 expression has a crucial role in the metastasis of pulmonary AC, and is a potential molecular marker for predicting poor prognosis after surgery. Source


Kawaguchi T.,Kinki chuo Chest Medical Center | Takada M.,Kinki University | Ando M.,Kyoto University | Okishio K.,Kinki chuo Chest Medical Center | And 9 more authors.
European Journal of Cancer | Year: 2012

Aim: To evaluate the efficacy and feasibility of the consolidation therapy of the oral fluoropyrimidine agent S-1 after concurrent chemoradiotherapy for unresectable stage III non-small cell lung cancer (NSCLC). Methods: Eligible patients had unresectable stage III NSCLC with performance status of 0 or 1. Chemoradiotherapy at a total dose of 60 Gy consisted of cisplatin (80 mg/m 2) on days 1 and 29, vinorelbine (20 mg/m 2) on days 1, 8, 29 and 36. Sequential consolidation S-1 therapy was commenced at a dose of 80-120 mg twice daily on day 57 with two cycles of 4 weeks administration and 2 weeks withdrawal. Results: Of the 66 patients, 65 were evaluated. Chemoradiotherapy was completed in 57 (87.7%) patients, and S-1 consolidation therapy was administered in 45 (69.2%) and completed in 31 (47.6%). Grade 3 pneumonitis developed in three patients with one dying of it. The response rate was 61.5% (95% confidence interval [CI], 48.6-73.3%). The median progression-free survival was 10.2 (95% CI, 8.6-13.7) months and median survival time 21.8 (95% CI, 15.6-27.6) months. The 1- and 3-year survival rates were 73.9% and 34.0%, respectively. Conclusions: Chemoradiotherapy with cisplatin and vinorelbine followed by S-1 consolidation demonstrated a reasonable overall survival in patients with stage III NSCLC. However, less than half of the patients completed this regimen, and the additional effect of S-1 was marginal compared with historical control. We concluded that chemoradiotherapy alone is still the recommended standard treatment for patients. © 2011 Elsevier Ltd. All rights reserved. Source


Kaira K.,Gunma University | Tomizawa Y.,NHO Nishi Gunma Hospital | Yoshino R.,NHO Nishi Gunma Hospital | Miura Y.,NHO Nishi Gunma Hospital | And 14 more authors.
Lung Cancer | Year: 2013

Background: We conducted a phase II study to evaluate the efficacy and safety of S-1 plus cisplatin with bevacizumab followed by maintenance bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Patients and methods: Chemotherapy-naïve patients received S-1 plus cisplatin with bevacizumab. S-1 (80mg/m2) was administered orally twice daily for 14 days, cisplatin (60mg/m2) on day 1, and bevacizumab (15mg/kg) on day 1 and every 3 weeks for 4-6 cycles. Patients with an objective response or stable disease received maintenance bevacizumab every 3 weeks until disease progression. Results: Thirty patients were enrolled in this study. The median number of chemotherapy was four (range, 1-6 cycles), and the median number of bevacizumab alone was three (range, 1-31 cycles). The grade 3/4 toxicities were neutropaenia (23%), thrombocytopaenia (10%), febrile neutropaenia (3%), hypertension (17%), pneumonia (7%), and bowel perforation (3%). The objective response rate was 71% (95% CI, 55-88%) for a disease control rate of 100%. The median progression-free and overall survival times were 7.0 months and 20.0 months, respectively. Conclusions: S-1 plus cisplatin with bevacizumab is an active and well-tolerated regimen in patients with chemotherapy-naïve non-squamous NSCLC. © 2013 Elsevier Ireland Ltd. Source

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