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



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) (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.

[thumbnail of ESPAC 4 patterns of recurrence 5 Feb 2019 - ch.docx] Text
ESPAC 4 patterns of recurrence 5 Feb 2019 - ch.docx - Author Accepted Manuscript

Download (251kB)

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:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3055637