Department of Thoracic and Visceral Surgery,Gunma University Graduate School of Medicine, Maebashi, Japan
Jun Atsumi , Kimihiro Shimizu , Kyoichi Kaira , Toshiteru Nagashima , Yoichi Ohtaki , Kai Obayashi , Seiichi Kakegawa , Osamu Kawashima , Mitsuhiro Kamiyoshihara , Masayuki Sugano , Izumi Takeyoshi
Background: A deletion polymorphism of the Bim gene is observed in the Asian population; this polymorphism has been reported to be a prognostic factor for non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy. We investigated the impact of the Bim deletion polymorphism on the survival of patients with completely resected NSCLC. Methods: Distribution of the Bim polymorphism was detected using polymerase chain reaction analysis from peripheral neutrophils in samples from 412 NSCLC patients who underwent complete resection. We measured overall survival (OS) and disease free survival (DFS) in all eligible patients, and post-recurrence survival (PRS) in 98 patients who developed recurrences and received anti-cancer therapy. Results: The Bim deletion polymorphism was detected in 63 (14.0%) patients. OS and DFS rates were significantly lower for patients with the Bim deletion polymorphism than those with wild type (OS, P < .001; DFS, P = .006). On multivariable analysis, Bim deletion polymorphism was identified as an independent prognostic factor for OS (hazard ratio [HR] = 1.99; 95% confidential interval [CI], 1.18 to 3.38; P = .010), but not for DFS (HR = 1.19; 95% CI, 0.78 to 1.98; P = .367). Among the 98 patients who developed recurrences and were treated with anticancer therapy, patients with the Bim deletion polymorphism had a significantly worse PRS than those with wild type (median 11.4 months vs 26.9 months, respectively, P < .001). This trend was consistent with subgroup analysis stratified by EGFR mutation status (P = .001 for EGFR mutant group; P = .002 for EGFR wild type group) or histology (P = .012 for adenocarcinomas; P = .013 for non-adenocarcinomas). A multivariate analysis suggested that the Bim deletion polymorphism is an independent predictor of PRS (HR = 2.99; 95% CI, 1.58 to 5.50; P = .001). Conclusions: The Bim deletion polymorphism is a novel indicator of shorter PRS among patients with recurrent NSCLC treated with anticancer therapy in the Asian population.
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