Adjuvant chemoradiation in pancreatic cancer: impact of radiotherapy dose on survival
Alessio G. Morganti,
Francesco Cellini,
Milly Buwenge,
Alessandra Arcelli,
Sergio Alfieri,
Felipe A. Calvo,
Riccardo Casadei,
Savino Cilla,
Francesco Deodato,
Giancarmine Di Gioia,
Mariacristina Di Marco,
Lorenzo Fuccio,
Federica Bertini,
Alessandra Guido,
Joseph M. Herman,
Gabriella Macchia,
Bert W. Maidment,
Robert C. Miller,
Francesco Minni,
Paolo Passoni,
Chiara Valentini,
Alessia Re,
William F. Regine,
Michele Reni,
Massimo Falconi,
Vincenzo Valentini,
Gian Carlo Mattiucci
Affiliations
Alessio G. Morganti
Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital
Francesco Cellini
UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore
Milly Buwenge
Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital
Alessandra Arcelli
Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital
Sergio Alfieri
Istituto di Clinica Chirurgica, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore
Felipe A. Calvo
Department of Oncology, Hospital General Universitario Gregorio Marañón, Complutense University
Riccardo Casadei
Department of Medical and Surgical Sciences – DIMEC, University of Bologna
Savino Cilla
Unit of Medical Physics, Fondazione Giovanni Paolo II
Francesco Deodato
Radiotherapy Unit, Fondazione Giovanni Paolo II
Giancarmine Di Gioia
Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital
Mariacristina Di Marco
Department of Experimental, Diagnostic, and Specialty Medicine - DIMES, Sant’Orsola-Malpighi Hospital, University of Bologna
Lorenzo Fuccio
Department of Medical and Surgical Sciences – DIMEC, University of Bologna
Federica Bertini
Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital
Alessandra Guido
Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital
Joseph M. Herman
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine
Gabriella Macchia
Radiotherapy Unit, Fondazione Giovanni Paolo II
Bert W. Maidment
Department of Radiation Oncology, University of Virginia
Robert C. Miller
Department of Radiation Oncology, Mayo Clinic
Francesco Minni
Department of Medical and Surgical Sciences – DIMEC, University of Bologna
Paolo Passoni
IRCCS, Ospedale S. Raffaele
Chiara Valentini
Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden
Alessia Re
UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore
William F. Regine
Department of Radiation Oncology, University of Maryland Medical Center
Michele Reni
IRCCS, Ospedale S. Raffaele
Massimo Falconi
Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Hospital, University “Vita e Salute”
Vincenzo Valentini
UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore
Gian Carlo Mattiucci
UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore
Abstract Background To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). Methods A multicenter retrospective analysis on 514 patients with PDAC (T1–4; N0–1; M0) treated with surgical resection with macroscopically negative margins (R0–1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: < 45 Gy, group 2: ≥ 45 and < 50 Gy, group 3: ≥ 50 and < 55 Gy, group 4: ≥ 55 Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test. Results Median follow-up was 35 months (range: 3–120 months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (≥ 90 U/ml; p < 0.001), higher tumor grade (G3–4, p = 0.004), R1 resection (p = 0.004), higher pT stage (pT3–4, p = 0.002) and positive nodes (p < 0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0 months, 21.0 months, 22.0 months, and 28.0 months, respectively (p = 0.004). The significant impact of higher dose was confirmed by multivariate analysis. Conclusions Increasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to < 45 Gy dose generally used.
