Sequential curative surgery and outcome in a multicenter randomized phase III trial comparing conversion chemotherapy followed by chemoradiotherapy vs continuous chemotherapy in patients with unresectable pancreatic cancer (CONKO-007 trial).
Abstract
e16458 Background: Secondary surgery is increasingly used in patients with unresectable pancreatic cancer. Objections have been raised about the potential harmful effect of preoperative radiotherapy on the surgical complication rate and a discussion on the benefits of major arterial and venous resection is being held. Methods: Within the CONKO-007 Trial an observational analysis of patients (pts.) with secondary surgery (S) was performed. The trial randomly assigned (1:1) pts with pancreatic cancer regarded as anatomically unresectable after initial chemotherapy (FOLFIRINOX or Gemcitabine, physicians’ choice) to Radiochemotherapy (RCT,50.4Gy+Gemcitabine) or further chemotherapy (CT) followed by second evaluation of resectability and surgical intervention at the discretion of the treatment center. The analysis consisted of a per-protocol approach. The endpoints of the present analyses were the rate of postoperative complications (non-hematological CTC-AE and Clavien-Dindo-CD), in-house mortality and survival. Results: This analysis included surgically treated 122 pts.; 60/167 following CT, 62/169 RCT of 336 randomized and previously 525 registered pts. 96/525 (18.2%) received curative intended surgery and 26 (4,9%) a surgical exploration. 11/122 pts. died closely to surgery (9.0%); 6 following RCT+S (d2-37, median d15), and 5 following CT+S (d 2-11, median d4). Cause of death after CT were related to impaired perfusion of the liver, lungs, colon; after RCT 3/6 had leakage or hemorrhage. CD-Grade 3/4: 10% (CT) vs. 11% (RCT; p = 1) and CTC-AE Grade 3/4: 10% vs. 6% (p = 0.52) did not differ. Median Overall Survival after resection did not differ by randomized treatment (p = 0.40), however by the extend of pancreatic resection (Pancreatoduodenectomy/distal pancreatectomy/central pancreatectomy vs. total pancreatectomy (23.0 vs. 13.0 mo., univariate, p = 0.01), the extend of resection of arterial vessels (TC, AMS, AH) vs. venous (VP; VMS) or no major vessel resection (10.0 vs. 23.0 mo.) multivariate, p = 0.002, HR: 1.42) and reaching R0 vs. R1/R2: (24.0 vs. 14.0 mo.) multivariate, p = 0.012; HR:1.97). Conclusions: Surgery was feasible in initial unresectable pancreatic cancer following RCT or CT in a multicenter approach with specific challenges in postoperative management. Survival was determined by extend of vessel resection and reaching R0. Clinical trial information: EudraCT Number: 2009-014476-21 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Sabine Semrau
Robert Grützmann
Michael Ghadimi
From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...
Uwe Wittel
Kliniken Nordoberpfalz AG, Klinik für Allgemein- und Visceralchirurgie, Weiden, Germany
Lutz Jacobasch
11Praxis of Haematology and Oncology, Dresden, Germany
Waldemar Uhl
Department of General and Visceral Surgery, St. Josef Hospital, Ruhr University, Bochum, Germany
Roland Croner
Universitätsklinikum Magdeburg; Universitätsklinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie, Magdeburg, Germany
Wolf Otto Bechstein
Dirk Thomas Waldschmidt
Uniklinik Koeln, Köln, Germany
Stefan Hubert Boeck
Department of Hematology and Oncology, München Klinik Neuperlach and Department of Medicine III and Comprehensive Cancer Center, University Hospital, LMU Munich and German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
Nicolas Moosmann
Anke C. Reinacher-Schick
COLOPREDICT Platform and Department of Hematology, Oncology and Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
Henriette Golcher
Werner Adler
Rainer Fietkau, MD, Sabine Semrau, MD, and Annett Kallies, PhD, Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany, National Center for Tumor Diseases (NCT), NCT WERA, a Partnership Between DKFZ, and the Universities and University Hospitals in Wurzburg, Erlangen, Germany; Werner Adler, PhD, Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen-Nurnberg, Erlangen, Germany, Helmut Oettle, MD, Department of Hematology, Oncology, and Tumor Immunology, Charité—Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
Annett Kallies
Rainer Fietkau, MD, Sabine Semrau, MD, and Annett Kallies, PhD, Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany, National Center for Tumor Diseases (NCT), NCT WERA, a Partnership Between DKFZ, and the Universities and University Hospitals in Wurzburg, Erlangen, Germany; Werner Adler, PhD, Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen-Nurnberg, Erlangen, Germany, Helmut Oettle, MD, Department of Hematology, Oncology, and Tumor Immunology, Charité—Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
Markus Hecht
Institute of Organic Chemistry
Andrea Tannapfel
COLOPREDICT Platform and Institute of Pathology, Ruhr-University, Bochum, Germany
Benjamin Frey
Helmut Oettle
Rainer Fietkau, MD, Sabine Semrau, MD, and Annett Kallies, PhD, Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany, National Center for Tumor Diseases (NCT), NCT WERA, a Partnership Between DKFZ, and the Universities and University Hospitals in Wurzburg, Erlangen, Germany; Werner Adler, PhD, Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen-Nurnberg, Erlangen, Germany, Helmut Oettle, MD, Department of Hematology, Oncology, and Tumor Immunology, Charité—Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
Rainer Fietkau