Eva Versteijne1, Mustafa Suker2, Karin Groothuis3, Janine M Akkermans-Vogelaar3, Marc G Besselink4, Bert A Bonsing5, Jeroen Buijsen6, Olivier R Busch4, Geert-Jan M Creemers7, Ronald M van Dam8, Ferry A L M Eskens9, Sebastiaan Festen10, Jan Willem B de Groot11, Bas Groot Koerkamp2, Ignace H de Hingh12, Marjolein Y V Homs9, Jeanin E van Hooft13, Emile D Kerver14, Saskia A C Luelmo15, Karen J Neelis16, Joost Nuyttens17, Gabriel M R M Paardekooper18, Gijs A Patijn19, Maurice J C van der Sangen20, Judith de Vos-Geelen21, Johanna W Wilmink22, Aeilko H Zwinderman22, Cornelis J Punt22, Casper H van Eijck2, Geertjan van Tienhoven1. 1. Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. 2. Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 3. Clinical Research Department, Comprehensive Cancer Organisation the Netherlands (IKNL), Nijmegen, the Netherlands. 4. Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. 5. Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. 6. Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands. 7. Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands. 8. Department of Surgery, Division of Hepato-Pancreato-Biliary & Oncology, European Surgery Center Aachen Maastricht, Maastricht UMC+, Maastricht, the Netherlands. 9. Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 10. Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands. 11. Department of Medical Oncology, Isala Oncology Centre, Zwolle, the Netherlands. 12. Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands. 13. Department of Gastroenterology and Hepatology, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. 14. Department of Medical Oncology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands. 15. Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands. 16. Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands. 17. Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 18. Department of Radiation Oncology, Isala Oncology Center, Zwolle, the Netherlands. 19. Department of Surgery, Isala Oncology Center, Zwolle, the Netherlands. 20. Department of Radiation Oncology, Catharina Hospital, Eindhoven, the Netherlands. 21. Department of Internal Medicine, Division of Medical Oncology, GROW School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, the Netherlands. 22. Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Abstract
PURPOSE:Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven. PATIENTS AND METHODS: In this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 × 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat. RESULTS:Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned topreoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = .096). The resection rate was 61% and 72% (P = .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery (P < .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2 v 19.8 months; P = .029). The proportion of patients who suffered serious adverse events was 52% versus 41% (P = .096). CONCLUSION:Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.
RCT Entities:
PURPOSE: Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven. PATIENTS AND METHODS: In this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 × 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat. RESULTS: Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = .096). The resection rate was 61% and 72% (P = .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery (P < .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2 v 19.8 months; P = .029). The proportion of patients who suffered serious adverse events was 52% versus 41% (P = .096). CONCLUSION: Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.
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