Developing a Histology-Based Artificial Intelligence Biomarker to Predict Adjuvant Chemotherapy Benefit in Pancreatic Cancer

作者：Audrey Beaufils, Julien de Martino, X Y Jiang, Théau Blanchard, Nicolas Fraunhoffer, Diana Mendes, Camille Pignolet, Taib Bourega, Asier Rabasco Meneghetti, Srividhya Sainath, Miguel Albuquerque, Nathalie Colnot, Matthieu Tihy, Anthony Turpin, Méher Ben Abdelghani, Alice C. Wei, Emmanuel Mitry, Thierry Lecomte, James Biagi, Pascal Artru, Ludovic Evesque, Aurélien Lambert, Daniel J. Renouf, Marjorie Mauduit, Nelson Dusetti, Pascal Hammel, Thierry Conroy, Jean‐Baptiste Bachet, Louis de Mestier, Vinciane Rebours, Jérôme Cros, Jakob Nikolas Kather, Rémy Nicolle · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco-26-00327 · 研究领域：Pancreatic and Hepatic Oncology Research、AI in cancer detection、Radiomics and Machine Learning in Medical Imaging

PURPOSE The choice of adjuvant chemotherapy in pancreatic ductal adenocarcinoma (PDAC) is mainly guided by patients' general condition. We hypothesized that tumor morphology may predict differential treatment benefit and tested whether deep learning applied to histology images could derive a biomarker of relative benefit from gemcitabine (GEM) versus modified FOLFIRINOX (mFOLFIRINOX) in resected PDAC. PATIENTS AND METHODS Standard whole-slide images from a retrospective multicentric series of 231 patients who underwent curative-intent pancreatectomy and received adjuvant mFOLFIRINOX (n = 54) or GEM (n = 177) were used to train regimen-specific histology models on disease-free survival (DFS), which were then combined into PANCprAId, a biomarker estimating personalized relative benefit from adjuvant GEM versus mFOLFIRINOX. External validation was performed in the randomized PRODIGE-24/CCTG PA6 trial (n = 313). RESULTS In PRODIGE-24/CCTG PA6, the treatment-specific histology scores used to construct PANCprAId stratified outcomes among patients treated with GEM (hazard ratio [HR], 1.69 [95% CI, 1.04 to 2.73]; P = .03) and mFOLFIRINOX (HR, 2.02 [95% CI, 1.4 to 3.0]; P < .001). When combined into PANCprAId, the biomarker identified subgroups with differential relative benefit from adjuvant GEM versus mFOLFIRINOX, with significant treatment interactions for DFS (interaction P = .003) and cancer-specific survival (interaction P = .001). Predicted sensitivity to each regimen was as...