Dominique L Birrer1, Henriette Golcher2, Riccardo Casadei3,4, Sarah R Haile5, Ralph Fritsch6, Saskia Hussung6, Thomas B Brunner7, Rainer Fietkau8, Thomas Meyer9, Robert Grützmann2, Susanne Merkel2, Claudio Ricci3,4, Carlo Ingaldi3,4, Mariacristina Di Marco10,11, Alessandra Guido3, Carla Serra3, Francesco Minni3,4, Bernhard Pestalozzi6, Henrik Petrowsky1, Michelle DeOliveira1, Wolf O Bechstein12, Christiane J Bruns13, Christian E Oberkofler1, Milo Puhan5, Mickaël Lesurtel14, Stefan Heinrich15, Pierre-Alain Clavien1. 1. Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland. 2. Department of Surgery, University Hospital Erlangen, Erlangen, Germany. 3. Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy. 4. Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy. 5. Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland. 6. Department of Oncology, University Hospital Zurich, Zurich, Switzerland. 7. Department of Radiation Oncology, University Hospital Magdeburg, Magdeburg, Germany. 8. Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany. 9. Department of Surgery, Hospital Ansbach, Ansbach, Germany. 10. Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy. 11. Medical Oncology, IRCCS Azienda Ospedaliero, University of Bologna, Bologna, Italy. 12. Department of General, Visceral- and Transplantation Surgery, University Hospital Frankfurt am Main, Frankfurt, Germany. 13. Department of General and Transplantation Surgery, University Hospital Cologne, Köln, Germany. 14. Department of Digestive Surgery and Liver Transplantation, Croix Rousse University Hospital, University Lyon I, Lyon, France. 15. Department of General, Visceral and Transplantation Surgery, University Hospital of Mainz, Mainz, Germany.
Abstract
OBJECTIVE: The aim of this study was to pool data from randomized controlled trials (RCT) limited to resectable pancreatic ductal adenocarcinoma (PDAC) to determine whether a neoadjuvant therapy impacts on disease-free survival (DFS) and surgical outcome. SUMMARY BACKGROUND DATA: Few underpowered studies have suggested benefits from neoadjuvant chemo (± radiation) for strictly resectable PDAC without offering conclusive recommendations. METHODS: Three RCTs were identified comparing neoadjuvant chemo (± radio) therapy vs. upfront surgery followed by adjuvant therapy in all cases. Data were pooled targeting DFS as primary endpoint, whereas overall survival (OS), postoperative morbidity, and mortality were investigated as secondary endpoints. Survival endpoints DFS and OS were compared using Cox proportional hazards regression with study-specific baseline hazards. RESULTS: A total of 130 patients were randomized (56 in the neoadjuvant and 74 in the control group). DFS was significantly longer in the neoadjuvant treatment group compared to surgery only [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.4-0.9] (P = 0.01). Furthermore, DFS for the subgroup of R0 resections was similarly longer in the neoadjuvant treated group (HR 0.6, 95% CI 0.35-0.9, P = 0.045). Although postoperative complications (Comprehensive Complication Index, CCI®) occurred less frequently (P = 0.008), patients after neoadjuvant therapy experienced a higher toxicity, but without negative impact on oncological or surgical outcome parameters. CONCLUSION: Neoadjuvant therapy can be offered as an acceptable standard of care for patients with purely resectable PDAC. Future research with the advances of precision oncology should now focus on the definition of the optimal regimen.
OBJECTIVE: The aim of this study was to pool data from randomized controlled trials (RCT) limited to resectable pancreatic ductal adenocarcinoma (PDAC) to determine whether a neoadjuvant therapy impacts on disease-free survival (DFS) and surgical outcome. SUMMARY BACKGROUND DATA: Few underpowered studies have suggested benefits from neoadjuvant chemo (± radiation) for strictly resectable PDAC without offering conclusive recommendations. METHODS: Three RCTs were identified comparing neoadjuvant chemo (± radio) therapy vs. upfront surgery followed by adjuvant therapy in all cases. Data were pooled targeting DFS as primary endpoint, whereas overall survival (OS), postoperative morbidity, and mortality were investigated as secondary endpoints. Survival endpoints DFS and OS were compared using Cox proportional hazards regression with study-specific baseline hazards. RESULTS: A total of 130 patients were randomized (56 in the neoadjuvant and 74 in the control group). DFS was significantly longer in the neoadjuvant treatment group compared to surgery only [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.4-0.9] (P = 0.01). Furthermore, DFS for the subgroup of R0 resections was similarly longer in the neoadjuvant treated group (HR 0.6, 95% CI 0.35-0.9, P = 0.045). Although postoperative complications (Comprehensive Complication Index, CCI®) occurred less frequently (P = 0.008), patients after neoadjuvant therapy experienced a higher toxicity, but without negative impact on oncological or surgical outcome parameters. CONCLUSION: Neoadjuvant therapy can be offered as an acceptable standard of care for patients with purely resectable PDAC. Future research with the advances of precision oncology should now focus on the definition of the optimal regimen.
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: I Ghanem; D Lora; N Herradón; G de Velasco; A Carretero-González; M Á Jiménez-Varas; P Vázquez de Parga; J Feliu Journal: ESMO Open Date: 2022-05-14
Authors: Eva Versteijne; Ignace H J T de Hingh; Marjolein Y V Homs; Martijn P W Intven; Joost M Klaase; Hjalmar C van Santvoort; Judith de Vos-Geelen; Johanna W Wilmink; Geertjan van Tienhoven Journal: Front Oncol Date: 2022-02-14 Impact factor: 6.244
Authors: Eric Pion; Julia Karnosky; Sofie Boscheck; Benedikt J Wagner; Katharina M Schmidt; Stefan M Brunner; Hans J Schlitt; Thiha Aung; Christina Hackl; Silke Haerteis Journal: Cancers (Basel) Date: 2022-07-31 Impact factor: 6.575