Journal Article

The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study

Pessaux, Patrick, Kleeff, Jorg, Mazzotta, Alessandro, Besselink, Marc G., Suarez Muñoz, Miguel Angel, Wilmink, Johanna W., Mazzola, Michele, Koek, Sharnice, Dalla Valle, Raffaele, Salvia, Roberto, Cabús, Santiago Sánchez, Hilal, Mohammed Abu, Serradilla, Mario, Ghidini, Michele, Kent, Tara S., Berger, Adam C., Koerkamp, Bas Groot, Korkolis, Dimitris, Fusai, Giuseppe Kito, Luyer, Misha, Kazemier, Geert, Zaniboni, Alberto, Ghorbani, Poya, White, Steven, Zerbi, Alessandro, Fisher, William E., Ielpo, Benedetto, Boggi, Ugo, Roberts, Keith J., Jamieson, Nigel, Bolm, Louisa, Lemmers, Daniël H., Goh, Brian K. P., Alseidi, Adnan, Uijterwijk, Bas A., Ball, Chad G., Vladimirov, Miljana, Mavroeidis, Vasileios K., Soonawalla, Zahir, Ferarri, Clarissa, Björnsson, Bergthor, House, Michael G.

2024

Overview

Background Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. Patients and methods Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). Results The study included a total of 2866 patients with DAC ( n  = 330), AmpIT ( n  = 765), AmpPB ( n  = 819), and dCCA ( n  = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB ( P  = 0.004) and dCCA ( P  < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine ( P  = 0.004) and gemcitabine – cisplatin ( P  = 0.001). For patients with AmpPB, no superior ACT regime was found ( P  > 0.226). ACT was not associated with improved OS for DAC and AmpIT ( P  = 0.113 and P  = 0.445, respectively). Discussion Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/4028/546 / 692/4028/67/1059/99 / Adenocarcinoma / Adenocarcinoma - drug therapy / Adenocarcinoma - pathology / Aged / Ampulla of Vater - pathology / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Bile Duct Neoplasms - drug therapy / Bile Duct Neoplasms - pathology / Bile Duct Neoplasms - surgery / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Capecitabine - administration & dosage / Capecitabine - therapeutic use / Chemotherapy / Chemotherapy, Adjuvant / Cholangiocarcinoma / Cholangiocarcinoma - drug therapy / Cholangiocarcinoma - pathology / Cholangiocarcinoma - surgery / Cisplatin / Cohort Studies / Common Bile Duct Neoplasms - drug therapy / Common Bile Duct Neoplasms - mortality / Common Bile Duct Neoplasms - pathology / Common Bile Duct Neoplasms - surgery / Drug Resistance / Duodenal Neoplasms - drug therapy / Duodenal Neoplasms - pathology / Duodenal Neoplasms - surgery / Epidemiology / Female / Gemcitabine / Humans / Male / Medical prognosis / Middle Aged / Molecular Medicine / Oncology / Pancreas / Pancreaticoduodenectomy / Retrospective Studies / Tumors