Shinichiro Takahashi1,2, Izumi Ohno3, Masafumi Ikeda3, Masaru Konishi1, Tatsushi Kobayashi4, Tetsuo Akimoto5, Motohiro Kojima6, Soichiro Morinaga7, Hirochika Toyama8, Yasuhiro Shimizu9, Atsushi Miyamoto10, Moriaki Tomikawa11, Norihisa Takakura12, Wataru Takayama13, Satoshi Hirano14, Takehito Otsubo15, Masato Nagino16, Wataru Kimura17, Keishi Sugimachi18, Katsuhiko Uesaka19. 1. Department of Hepato-biliary Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan. 2. Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan. 3. Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 4. Department of Diagnostic Radiology, National Cancer Center Hospital East, Kashiwa, Japan. 5. Department of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 6. Division of Pathology, National Cancer Center Hospital East, Kashiwa, Japan. 7. Department of Hepato-Biliary-Pancreatic Surgery, Kanagawa Cancer Center, Yokohama, Japan. 8. Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. 9. Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. 10. Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan. 11. Department of Hepato-Biliary-Pancreatic Surgery, Tochigi Cancer Center, Utsunomiya, Japan. 12. Department of Surgery, Fukuyama City Hospital, Fukuyama, Japan. 13. Department of Hepato-Biliary-Pancreatic Surgery, Chiba Cancer Center, Chiba, Japan. 14. Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan. 15. Department of Gastroenterological Surgery, St. Marianna University School of Medicine Hospital, Kawasaki, Japan. 16. Gastroenterological Surgery 1, Nagoya University Hospital, Nagoya, Japan. 17. Department of Surgery 1, Yamagata University Hospital, Yamagata, Japan. 18. Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization Kyusyu Cancer Center, Fukuoka, Japan. 19. Department of Hepato-biliary Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Abstract
OBJECTIVE: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in BRPC. SUMMARY OF BACKGROUND DATA: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established. METHODS: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m 2 bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a 1-sided α = 0.05 and β = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively. RESULTS: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively. CONCLUSIONS: S-1 and concurrent radiotherapy seem to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC. TRIAL REGISTRATION: UMIN000009172.
OBJECTIVE: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in BRPC. SUMMARY OF BACKGROUND DATA: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established. METHODS: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m 2 bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a 1-sided α = 0.05 and β = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively. RESULTS: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively. CONCLUSIONS: S-1 and concurrent radiotherapy seem to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC. TRIAL REGISTRATION: UMIN000009172.