High γ‐ H2AX Predicts Clinical Benefit From Platinum‐Based Chemotherapy ( mFOLFIRINOX ) at Recurrence After Pancreatic Cancer Resection

Background Postoperative regimen selection between mFOLFIRINOX and GnP for recurrent pancreatic ductal adenocarcinoma (PDAC) lacks evidence, highlighting the need for a simple biomarker. This study explores the impact of γ‐H2AX overexpression, a DNA damage marker, in resected PDAC for predicting platinum‐based treatment response in recurrences. Methods In this study, we assessed γ‐H2AX and ABCB1 expressions in resected PDAC tissues from 198 patients to evaluate their impact on prognosis after surgery and response to chemotherapy in 109 recurrent cases. Results High γ‐H2AX expression was linked to shorter recurrence‐free survival and overall survival (OS) compared to low expression ( p = 0.024 and 0.0013). It was an independent poor prognostic factor post‐surgery. In recurrent cases with high γ‐H2AX expression, mFOLFIRINOX significantly improved OS compared to GnP ( p = 0.013), while low γ‐H2AX cases showed no significant OS difference between regimens ( p = 0.576). Conclusions γ‐H2AX overexpression in PDAC tissue is an independent negative prognostic factor. In recurrent cases, high γ‐H2AX expression suggests better OS and treatment response with mFOLFIRINOX, indicating its potential as a chemosensitivity marker for personalized therapy in PDAC recurrence.