Akira Ono1, Mitsuhiro Isaka2, Masakuni Serizawa3, Katsuhiro Omae4, Hideaki Kojima5, Kazuhisa Nakashima6, Shota Omori6, Kazushige Wakuda6, Hirotsugu Kenmotsu6, Tateaki Naito6, Haruyasu Murakami6, Kenichi Urakami7, Takeshi Nagashima8, Takashi Sugino9, Masatoshi Kusuhara10, Toshiaki Takahashi6, Ken Yamaguchi11, Yasuhisa Ohde5. 1. Division of Thoracic Oncology, Shizuoka Cancer Center, Japan. Electronic address: a.ono@scchr.jp. 2. Division of Thoracic Surgery, Shizuoka Cancer Center, Japan. Electronic address: mi.isaka@scchr.jp. 3. Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Japan. Electronic address: m.serizawa@scchr.jp. 4. School of Public Health, Graduate School of Medicine, Kyoto University, Japan. 5. Division of Thoracic Surgery, Shizuoka Cancer Center, Japan. 6. Division of Thoracic Oncology, Shizuoka Cancer Center, Japan. 7. Cancer Diagnostics Division, Shizuoka Cancer Center Research Institute, Japan. 8. SRL Inc, Tokyo, Japan. 9. Division of Diagnostic Pathology, Shizuoka Cancer Center, Japan. 10. Region Resources Division, Shizuoka Cancer Center Research Institute, Japan. 11. Shizuoka Cancer Center, Japan.
Abstract
OBJECTIVES: This study assessed the associations between the molecular signatures and clinical information in non-small cell lung cancer (NSCLC) patients with postoperative disease-free survival (p-dfs) to identify novel prognostic factors, focusing on associations with driver gene alterations. MATERIALS AND METHODS: Between February 2014 and September 2015, 242 patients with NSCLC, including 192 patients with adenocarcinoma (Ad) and 50 patients with squamous cell carcinoma (Sq), underwent surgery and were enrolled in this study. Surgically resected tissues were subjected to whole exome sequencing. Mt detected in 138 cancer-related genes were evaluated as driver mutations. A multivariate analysis using the multi-state model was used to establish the associations between co-variables and p-dfs. RESULTS: Postoperative recurrence (p-rec) was observed in 49 (20.2%) and 19 (7.9%) patients with Ad and Sq, respectively. The median (range) follow-up period for all the censored cases was 2.5 (2.0-3.5) years. The characteristics of the patients with postoperative recurrence were as follows: median age (range), 71 (50-87) years; male, 38 (56%); smoker, 51 (75%); p-stage (I/II/III), 30 (44%)/19 (28%)/19 (28%); histological type (Ad/Sq), 49 (72%)/19 (28%); adjuvant chemotherapy (yes/no), 30 (44%)/38 (56%); and driver gene alteration (presence/absence), 65 (96%)/3 (4%). In univariate analyses, age (<70/≧70 years), smoking history (yes/no), p-stage (I, II/III), histological type (Ad/Sq), and driver mutation (presence/absence) were favorable prognostic factors (P = .017, P = .048, P = .0002, P = .006, P = .029, respectively). A multivariate analysis also revealed a significant association between the driver mutation status and p-dfs (P = .046; odds ratio [OR], 2.86; 95% confidence interval [CI], 1.02-8.08), when adjusted according to histological type (P = .10), smoking status (P = .09), gender (P = .51), age (P = .008) and p-stage (P = .00003). CONCLUSION: The driver mutation status may be an independent prognostic factor of p-dfs in NSCLC.
OBJECTIVES: This study assessed the associations between the molecular signatures and clinical information in non-small cell lung cancer (NSCLC) patients with postoperative disease-free survival (p-dfs) to identify novel prognostic factors, focusing on associations with driver gene alterations. MATERIALS AND METHODS: Between February 2014 and September 2015, 242 patients with NSCLC, including 192 patients with adenocarcinoma (Ad) and 50 patients with squamous cell carcinoma (Sq), underwent surgery and were enrolled in this study. Surgically resected tissues were subjected to whole exome sequencing. Mt detected in 138 cancer-related genes were evaluated as driver mutations. A multivariate analysis using the multi-state model was used to establish the associations between co-variables and p-dfs. RESULTS: Postoperative recurrence (p-rec) was observed in 49 (20.2%) and 19 (7.9%) patients with Ad and Sq, respectively. The median (range) follow-up period for all the censored cases was 2.5 (2.0-3.5) years. The characteristics of the patients with postoperative recurrence were as follows: median age (range), 71 (50-87) years; male, 38 (56%); smoker, 51 (75%); p-stage (I/II/III), 30 (44%)/19 (28%)/19 (28%); histological type (Ad/Sq), 49 (72%)/19 (28%); adjuvant chemotherapy (yes/no), 30 (44%)/38 (56%); and driver gene alteration (presence/absence), 65 (96%)/3 (4%). In univariate analyses, age (<70/≧70 years), smoking history (yes/no), p-stage (I, II/III), histological type (Ad/Sq), and driver mutation (presence/absence) were favorable prognostic factors (P = .017, P = .048, P = .0002, P = .006, P = .029, respectively). A multivariate analysis also revealed a significant association between the driver mutation status and p-dfs (P = .046; odds ratio [OR], 2.86; 95% confidence interval [CI], 1.02-8.08), when adjusted according to histological type (P = .10), smoking status (P = .09), gender (P = .51), age (P = .008) and p-stage (P = .00003). CONCLUSION: The driver mutation status may be an independent prognostic factor of p-dfs in NSCLC.