Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial. / Jones, Robert P; Psarelli, Eftychia-Eirini; Jackson, Richard; Ghaneh, Paula; Halloran, Christopher M; Palmer, Daniel H; Campbell, Fiona; Valle, Juan W; Faluyi, Olusola; O'Reilly, Derek A; 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; Büchler, Markus W; Neoptolemos, John P; European Study Group for Pancreatic Cancer.
In: JAMA SURG, Vol. 154, No. 11, 01.11.2019, p. 1038–1048.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
AU - Jones, Robert P
AU - Psarelli, Eftychia-Eirini
AU - Jackson, Richard
AU - Ghaneh, Paula
AU - Halloran, Christopher M
AU - Palmer, Daniel H
AU - Campbell, Fiona
AU - Valle, Juan W
AU - Faluyi, Olusola
AU - O'Reilly, Derek A
AU - Cunningham, David
AU - Wadsley, Jonathan
AU - Darby, Suzanne
AU - Meyer, Tim
AU - Gillmore, Roopinder
AU - Anthoney, Alan
AU - Lind, Pehr
AU - Glimelius, Bengt
AU - Falk, Stephen
AU - Izbicki, Jakob R
AU - Middleton, Gary William
AU - Cummins, Sebastian
AU - Ross, Paul J
AU - Wasan, Harpreet
AU - McDonald, Alec
AU - Crosby, Tom
AU - Ting, Yuk
AU - Patel, Kinnari
AU - Sherriff, David
AU - Soomal, Rubin
AU - Borg, David
AU - Sothi, Sharmila
AU - Hammel, Pascal
AU - Lerch, Markus M
AU - Mayerle, Julia
AU - Tjaden, Christine
AU - Strobel, Oliver
AU - Hackert, Thilo
AU - Büchler, Markus W
AU - Neoptolemos, John P
AU - European Study Group for Pancreatic Cancer
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: 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.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: 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).Conclusions and Relevance: 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.Trial Registration: Clinicaltrials.gov Identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434.
AB - Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: 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.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: 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).Conclusions and Relevance: 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.Trial Registration: Clinicaltrials.gov Identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434.
U2 - 10.1001/jamasurg.2019.3337
DO - 10.1001/jamasurg.2019.3337
M3 - SCORING: Journal article
C2 - 31483448
VL - 154
SP - 1038
EP - 1048
JO - JAMA SURG
JF - JAMA SURG
SN - 2168-6254
IS - 11
ER -
