Tsuyoshi Hayashi1, Toru Nakamura2, Yasutoshi Kimura3, Makoto Yoshida4, Masanori Someya5, Hiroshi Kawakami6, Yusuke Sakuhara7, Norio Katoh8, Kuniyuki Takahashi9, Yoshiyasu Ambo10, Katsutoshi Miura11, Masayo Motoya12, Eiichi Tanaka13, Katsuhiko Murakawa14, Takumi Yamabuki15, Hajime Yamazaki16, Akio Katanuma4, Satoshi Hirano2. 1. Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan; Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. Electronic address: thayashi244@gmail.com. 2. Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan. 3. Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. 4. Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. 5. Department of Radiology Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. 6. Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan. 7. Department of Diagnostic and Interventional Radiology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. 8. Department of Radiation Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. 9. Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan. 10. Department of Surgery, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan. 11. Department of Radiology, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan. 12. Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. 13. Department of Surgery, Hokkaido Gastroenterology Hospital, Sapporo, Japan. 14. Department of Surgery, Obihiro Kosei General Hospital, Obihiro, Japan. 15. Department of Surgery, National Hospital Organization, Hakodate National Hospital, Hakodate, Japan. 16. Department of Healthcare Epidemiology, School of Public Health, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Abstract
PURPOSE: Preoperative treatment is recommended for borderline resectable pancreatic ductal adenocarcinoma. However, the standard treatment has not yet been determined. We conducted a multicenter phase 2 study to investigate the efficacy of neoadjuvant treatment of sequential chemoradiation followed by chemotherapy. METHODS AND MATERIALS: All enrolled patients were treated by preoperative chemoradiation (a total dose of 50.4 Gy in 28 fractions and orally administered S-1 at 80 mg/m2 on the day of irradiation) followed by chemotherapy (administration of gemcitabine at 1000 mg/m2/dose on days 1, 8, and 15 in 3 cycles of 4 weeks) and attempted curative resection. The primary outcome was an R0 resection rate among patients who completed preoperative treatment and pancreatectomy. The threshold of the R0 resection rate was defined as 74% based on a previous study of up-front surgery. RESULTS: Forty-five patients were included. Twenty-one patients could not undergo pancreatectomy because of progressive diseases (n = 14), adverse events (n = 5), or consent withdrawal (n = 2), and 4 patients underwent additional resection after dropping out. The resection rates were 53.3% and 62.2% in the per-protocol set (PPS) and full analysis set (FAS) populations, respectively. The R0 resection rates were 95.8% (95% confidence interval, 78.9%-99.9%) and 96.4% (81.7%-99.9%) in the PPS and FAS populations, respectively. The median overall survival and progression-free survival of all the included patients were 17.3 and 10.5 months, respectively. The median survival time of the patients with pancreatectomy was significantly longer than that of the patients without pancreatectomy in the PPS (27.9 vs 12.3 months; P = .001) and FAS populations (32.2 vs 11.8 months; P < .001). CONCLUSIONS: This study revealed that a long duration of preoperative treatment of sequential chemoradiation followed by systemic chemotherapy provides a high rate of R0 resection and sufficient survival time in patients undergoing pancreatectomy.
PURPOSE: Preoperative treatment is recommended for borderline resectable pancreatic ductal adenocarcinoma. However, the standard treatment has not yet been determined. We conducted a multicenter phase 2 study to investigate the efficacy of neoadjuvant treatment of sequential chemoradiation followed by chemotherapy. METHODS AND MATERIALS: All enrolled patients were treated by preoperative chemoradiation (a total dose of 50.4 Gy in 28 fractions and orally administered S-1 at 80 mg/m2 on the day of irradiation) followed by chemotherapy (administration of gemcitabine at 1000 mg/m2/dose on days 1, 8, and 15 in 3 cycles of 4 weeks) and attempted curative resection. The primary outcome was an R0 resection rate among patients who completed preoperative treatment and pancreatectomy. The threshold of the R0 resection rate was defined as 74% based on a previous study of up-front surgery. RESULTS: Forty-five patients were included. Twenty-one patients could not undergo pancreatectomy because of progressive diseases (n = 14), adverse events (n = 5), or consent withdrawal (n = 2), and 4 patients underwent additional resection after dropping out. The resection rates were 53.3% and 62.2% in the per-protocol set (PPS) and full analysis set (FAS) populations, respectively. The R0 resection rates were 95.8% (95% confidence interval, 78.9%-99.9%) and 96.4% (81.7%-99.9%) in the PPS and FAS populations, respectively. The median overall survival and progression-free survival of all the included patients were 17.3 and 10.5 months, respectively. The median survival time of the patients with pancreatectomy was significantly longer than that of the patients without pancreatectomy in the PPS (27.9 vs 12.3 months; P = .001) and FAS populations (32.2 vs 11.8 months; P < .001). CONCLUSIONS: This study revealed that a long duration of preoperative treatment of sequential chemoradiation followed by systemic chemotherapy provides a high rate of R0 resection and sufficient survival time in patients undergoing pancreatectomy.
Authors: Ottavia De Simoni; Marco Scarpa; Caterina Soldà; Francesca Bergamo; Sara Lonardi; Alberto Fantin; Pierluigi Pilati; Mario Gruppo Journal: J Clin Med Date: 2022-02-03 Impact factor: 4.241