Eva Versteijne1, Jacob L van Dam2, Mustafa Suker2, Quisette P Janssen2, Karin Groothuis3, Janine M Akkermans-Vogelaar3, Marc G Besselink4, Bert A Bonsing5, Jeroen Buijsen6, Olivier R Busch4, Geert-Jan M Creemers7, Ronald M van Dam8,9,10, Ferry A L M Eskens11, Sebastiaan Festen12, Jan Willem B de Groot13, Bas Groot Koerkamp2, Ignace H de Hingh14, Marjolein Y V Homs11, Jeanin E van Hooft15,16, Emile D Kerver17, Saskia A C Luelmo18, Karen J Neelis19, Joost Nuyttens20, Gabriel M R M Paardekooper21, Gijs A Patijn22, Maurice J C van der Sangen23, Judith de Vos-Geelen24, Johanna W Wilmink25, Aeilko H Zwinderman26, Cornelis J Punt27, Geertjan van Tienhoven1, Casper H J van Eijck2. 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 Center, Maastricht, the Netherlands. 7. Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands. 8. Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands. 9. Department of General, Visceral and Transplant Surgery, University Hospital Aachen, Aachen, Germany. 10. GROW - School for Oncology and Developmental Biology, Maastricht University, the Netherlands. 11. Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 12. Department of Surgery, OLVG, Amsterdam, the Netherlands. 13. Department of Medical Oncology, Isala Oncology Center, Zwolle, the Netherlands. 14. Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands. 15. Department of Gastroenterology and Hepatology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. 16. Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands. 17. Department of Medical Oncology, OLVG, Amsterdam, the Netherlands. 18. Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands. 19. Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands. 20. Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 21. Department of Radiation Oncology, Isala Oncology Center, Zwolle, the Netherlands. 22. Department of Surgery, Isala Oncology Center, Zwolle, the Netherlands. 23. Department of Radiation Oncology, Catharina Hospital, Eindhoven, the Netherlands. 24. Department of Internal Medicine, Division of Medical Oncology, GROW-School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, the Netherlands. 25. Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. 26. Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. 27. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Centre, Utrecht University, the Netherlands.
Abstract
PURPOSE: The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported. METHODS: In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial. RESULTS: Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96; P = .025). Although the difference in median survival was only 1.4 months (15.7 months v 14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer. CONCLUSION: Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer.
PURPOSE: The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported. METHODS: In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial. RESULTS: Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96; P = .025). Although the difference in median survival was only 1.4 months (15.7 months v 14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer. CONCLUSION: Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer.
Authors: William L Hwang; Karthik A Jagadeesh; Jimmy A Guo; Hannah I Hoffman; Payman Yadollahpour; Jason W Reeves; Rahul Mohan; Eugene Drokhlyansky; Nicholas Van Wittenberghe; Orr Ashenberg; Samouil L Farhi; Denis Schapiro; Prajan Divakar; Eric Miller; Daniel R Zollinger; George Eng; Jason M Schenkel; Jennifer Su; Carina Shiau; Patrick Yu; William A Freed-Pastor; Domenic Abbondanza; Arnav Mehta; Joshua Gould; Conner Lambden; Caroline B M Porter; Alexander Tsankov; Danielle Dionne; Julia Waldman; Michael S Cuoco; Lan Nguyen; Toni Delorey; Devan Phillips; Jaimie L Barth; Marina Kem; Clifton Rodrigues; Debora Ciprani; Jorge Roldan; Piotr Zelga; Vjola Jorgji; Jonathan H Chen; Zackery Ely; Daniel Zhao; Kit Fuhrman; Robin Fropf; Joseph M Beechem; Jay S Loeffler; David P Ryan; Colin D Weekes; Cristina R Ferrone; Motaz Qadan; Martin J Aryee; Rakesh K Jain; Donna S Neuberg; Jennifer Y Wo; Theodore S Hong; Ramnik Xavier; Andrew J Aguirre; Orit Rozenblatt-Rosen; Mari Mino-Kenudson; Carlos Fernandez-Del Castillo; Andrew S Liss; David T Ting; Tyler Jacks; Aviv Regev Journal: Nat Genet Date: 2022-07-28 Impact factor: 41.307
Authors: Timothy P DiPeri; Timothy E Newhook; Laura R Prakash; Naruhiko Ikoma; Jessica E Maxwell; Michael P Kim; Jeffrey E Lee; Matthew H G Katz; Ching-Wei D Tzeng Journal: J Surg Oncol Date: 2022-06-20 Impact factor: 2.885
Authors: Samer AlMasri; Mazen Zenati; Abdulrahman Hammad; Ibrahim Nassour; Hao Liu; Melissa E Hogg; Herbert J Zeh; Brian Boone; Nathan Bahary; Aatur D Singhi; Kenneth K Lee; Alessandro Paniccia; Amer H Zureikat Journal: JAMA Netw Open Date: 2022-06-01
Authors: Anne Jacobsen; Mirianna Hobbs; Susanne Merkel; Anke Mittelstädt; Franziska Czubayko; Christian Krautz; Georg F Weber; Robert Grützmann; Maximilian Brunner Journal: J Clin Med Date: 2022-07-29 Impact factor: 4.964