Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial

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Jones, Robert P ORCID: 0000-0001-5608-001X, Psarelli, Eftychia-Eirini ORCID: 0000-0002-3102-0288, Jackson, Richard, Ghaneh, Paula, Halloran, Christopher M ORCID: 0000-0002-5471-4178, Palmer, Daniel H ORCID: 0000-0002-7147-5703, Campbell, Fiona, Valle, Juan W, Faluyi, Olusola, O'Reilly, Derek A et al (show 92 more authors) , Cunningham, David, Wadsley, Jonathan, Darby, Suzanne, Meyer, Tim, Gillmore, Roopinder, Anthoney, Alan, Lind, Pehr, Glimelius, Bengt, Falk, Stephen, Izbicki, Jakob R, Middleton, Gary William, Cummins, Sebastian, Ross, Paul J, Wasan, Harpreet, McDonald, Alec, Crosby, Tom, Ting, Yuk, Patel, Kinnari, Sherriff, David, Soomal, Rubin, Borg, David, Sothi, Sharmila, Hammel, Pascal, Lerch, Markus M, Mayerle, Julia, Tjaden, Christine, Strobel, Oliver, Hackert, Thilo, Buchler, Markus W, Neoptolemos, John P, Hill, Mark, Corrie, Pippa, Hickish, Tamas, Napier, Mark, Slater, Sarah, Valle, Juan, Shablak, Alaaeldin, Cunnell, Michelle, Guimbaud, Rosine, Roques, Tom, Iveson, Tim, Jamil, Arshad, Robinson, Angus, Garcia-Alonso, Angel, Chang, David, Tsang, David, Wadd, Nick, Wall, Lucy, Nielsen, Niels Hilmer, Lerch, Markus, Mehta, Ajay, Sivaramalingam, Muthiah, Fyfe, David, Osborne, Richard, Blesing, Claire, Bulusu, Venkata Ramesh, Rathbone, Emma, Seitz, Jean-Francois, Beaumont, Erica, Dernedde, Ulrike, McAdam, Karen, Dimopoulos, Prokopios, Cominos, Mathilda, Askill, Colin, Piwowar, Andrzej, Bachet, Jean-Baptiste, Sumpter, Kate, Raouf, Sherif, Nicoll, Jonathan, Rees, Charlotte, Dhinakaran, Kathirvelu, Haux, Johan, Bengrine-Lefevre, Leila, Terrebonne, Eric, Shankland, Catherine, Palmer, Cheryl, Medley, Louise, Toy, Elizabeth, Kaur, Jasvinder, Gupta, Kamalnayan, Cheeseman, Sue, Patterson, Daniel, Candish, Charles, Thompson, Joyce, Coxon, Fareeda, Connolly, Caroline, McPhail, Neil, Williams, Rachel, Flygare, Petra, Elmlund, Mattias, Artru, Pascal and Millat, Bertrand (2019) Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial. JAMA SURGERY, 154 (11). pp. 1038-1048.

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Abstract

<h4>Importance</h4>The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.<h4>Objective</h4>To define patterns of recurrence after adjuvant chemotherapy and the association with survival.<h4>Design, setting, and participants</h4>Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.<h4>Interventions</h4>Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.<h4>Main outcomes and measures</h4>Overall survival, recurrence, and sites of recurrence.<h4>Results</h4>Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P = .03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P = .04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P = .27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P = .85 and P = .35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .03).<h4>Conclusions and relevance</h4>There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.<h4>Trial registration</h4>ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434.

Item Type:	Article
Uncontrolled Keywords:	European Study Group for Pancreatic Cancer, Humans, Carcinoma, Pancreatic Ductal, Pancreatic Neoplasms, Neoplasm Recurrence, Local, Deoxycytidine, Antineoplastic Combined Chemotherapy Protocols, Disease-Free Survival, Treatment Outcome, Chemotherapy, Adjuvant, Prospective Studies, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Capecitabine, Gemcitabine
Depositing User:	Symplectic Admin
Date Deposited:	23 Sep 2019 13:13
Last Modified:	08 Feb 2023 13:10
DOI:	10.1001/jamasurg.2019.3337
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3055637