Yoshitaka Zenke1, Masahiro Tsuboi2, Yasutaka Chiba3, Kayoko Tsujino4, Miyako Satouchi5, Kenji Sawa6, Junichi Shimizu7, Haruko Daga8, Daichi Fujimoto9, Masahide Mori10, Takuya Aoki11, Toshiyuki Sawa12, Shota Omori13, Hideo Saka14, Yasuo Iwamoto15, Motoyasu Okuno16, Tomonori Hirashima17, Kosuke Kashiwabara18, Motoko Tachihara19, Nobuyuki Ymamoto20, Kazuhiko Nakagawa21. 1. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 2. Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan. 3. Clinical Research Center, Kindai University Hospital, Osaka, Japan. 4. Department of Radiation Oncology, Hyogo Cancer Center, Akashi, Hyogo, Japan. 5. Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Hyogo, Japan. 6. Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. 7. Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan. 8. Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan. 9. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. 10. Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, Osaka, Japan. 11. Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan. 12. Division of Respiratory Medicine and Oncology, Gifu Municipal Hospital, Gifu, Japan. 13. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 14. Department of Respiratory Medicine and Medical Oncology, National Hospital Organization Nagoya Medical Center, Aichi, Japan. 15. Department of Respiratory Medicine, Hiroshima City Hospital, Hiroshima, Japan. 16. Department of Respiratory Medicine, Okazaki City Hospital, Okazaki, Japan. 17. Department of Thoracic Oncology, Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, Osaka, Japan. 18. Department of Respiratory Medicine, Kumamoto Regional Medical Center, Kumamoto, Japan. 19. Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. 20. Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. 21. Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
Abstract
IMPORTANCE: Insufficient data are available regarding the long-term outcomes and cumulative incidences of toxic effects that are associated with chemoradiotherapy (CRT) for patients with stage III non-small-cell lung cancer. OBJECTIVE: To evaluate survival and late toxic effects 10 years after patients were treated with curative CRT. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3 West Japan Thoracic Oncology Group (WJTOG) 0105 randomized clinical trial was conducted between September 2001 and September 2005 in Japan. Patients with histologically or cytologically confirmed non-small-cell lung cancer with unresectable stage III disease were assessed for eligibility. Additional data were analyzed from January 2018 to December 2019. INTERVENTIONS: A total of 440 eligible patients were randomly assigned to groups as follows: A (control), 4 cycles of mitomycin/vindesine/cisplatin plus thoracic radiotherapy (TRT) of 60 Gy; B, weekly irinotecan/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of irinotecan/carboplatin consolidation; or C, weekly paclitaxel/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of paclitaxel/carboplatin consolidation. MAIN OUTCOMES AND MEASURES: The primary outcome was 10-year survival probability after CRT. The secondary outcome was late toxic effects that occurred more than 90 days after initiating CRT. RESULTS: From September 2001 to September 2005, 440 patients (group A, n = 146 [33.2%; median (range) age, 63 (31-74) years; 18 women (12.3%)]; group B, n = 147 [33.4%; median (range) age, 63 (30-75) years; 22 women (15.0%)]; group C, n = 147 [33.4%; median (range) age, 63 (38-74) years; 19 women (12.9%)]) were enrolled. The median (range) follow-up was 11.9 (7.6-13.3) years. In groups A, B, and C, median (range) overall survival times were 20.5 (17.5-26.0), 19.8 (16.7-23.5), and 22.0 (18.7-26.2) months, respectively, and 10-year survival probabilities were 13.6%, 7.5%, and 15.2%, respectively. There were no significant differences in overall survival among treatment groups. The 10-year progression-free survival probabilities were 8.5%, 6.5%, and 11.1% in groups A, B, and C, respectively. Grade 3 or 4 late toxic effect rates were 3.4% (heart, 0.7%; lung, 2.7%) in group A, and those only affecting the lung represented 3.4% and 4.1% in groups B and C, respectively. No other cases of late toxic effects (grades 3/4) were observed since the initial report. CONCLUSION AND RELEVANCE: In this 10-year follow-up of a phase 3 randomized clinical trial, group C achieved similar efficacy and toxic effect profiles as group A 10 years after initiating treatment. These results serve as a historical control for the long-term comparisons of outcomes of future clinical trials of CRT. TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000030811.
IMPORTANCE: Insufficient data are available regarding the long-term outcomes and cumulative incidences of toxic effects that are associated with chemoradiotherapy (CRT) for patients with stage III non-small-cell lung cancer. OBJECTIVE: To evaluate survival and late toxic effects 10 years after patients were treated with curative CRT. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3 West Japan Thoracic Oncology Group (WJTOG) 0105 randomized clinical trial was conducted between September 2001 and September 2005 in Japan. Patients with histologically or cytologically confirmed non-small-cell lung cancer with unresectable stage III disease were assessed for eligibility. Additional data were analyzed from January 2018 to December 2019. INTERVENTIONS: A total of 440 eligible patients were randomly assigned to groups as follows: A (control), 4 cycles of mitomycin/vindesine/cisplatin plus thoracic radiotherapy (TRT) of 60 Gy; B, weekly irinotecan/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of irinotecan/carboplatin consolidation; or C, weekly paclitaxel/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of paclitaxel/carboplatin consolidation. MAIN OUTCOMES AND MEASURES: The primary outcome was 10-year survival probability after CRT. The secondary outcome was late toxic effects that occurred more than 90 days after initiating CRT. RESULTS: From September 2001 to September 2005, 440 patients (group A, n = 146 [33.2%; median (range) age, 63 (31-74) years; 18 women (12.3%)]; group B, n = 147 [33.4%; median (range) age, 63 (30-75) years; 22 women (15.0%)]; group C, n = 147 [33.4%; median (range) age, 63 (38-74) years; 19 women (12.9%)]) were enrolled. The median (range) follow-up was 11.9 (7.6-13.3) years. In groups A, B, and C, median (range) overall survival times were 20.5 (17.5-26.0), 19.8 (16.7-23.5), and 22.0 (18.7-26.2) months, respectively, and 10-year survival probabilities were 13.6%, 7.5%, and 15.2%, respectively. There were no significant differences in overall survival among treatment groups. The 10-year progression-free survival probabilities were 8.5%, 6.5%, and 11.1% in groups A, B, and C, respectively. Grade 3 or 4 late toxic effect rates were 3.4% (heart, 0.7%; lung, 2.7%) in group A, and those only affecting the lung represented 3.4% and 4.1% in groups B and C, respectively. No other cases of late toxic effects (grades 3/4) were observed since the initial report. CONCLUSION AND RELEVANCE: In this 10-year follow-up of a phase 3 randomized clinical trial, group C achieved similar efficacy and toxic effect profiles as group A 10 years after initiating treatment. These results serve as a historical control for the long-term comparisons of outcomes of future clinical trials of CRT. TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000030811.