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A Personalized Approach to Adjuvant Therapy: Cytoplasmic HuR Status Predicts Disease Free Survival After Resection for Pancreatic Ductal Adenocarcinoma
Talar Tatarian^*1, Amanda Grigoli¹, Benjamin E. Leiby², Masaya Jimbo¹, Nooreen Dabbish², Wei Jiang³, John P. Neoptolemos⁴, William Greenhalf ⁴, Eithne Costello ⁴, Paula Ghaneh⁴, Daniel Palmer⁴, Markus Buchler⁵, Charles J. Yeo¹, Jordan M. Winter¹, Jonathan R. Brody^1
1Jefferson Pancreas, Biliary, and Related Cancer Center, Department of Surgery, Sidney Kimmel Medical College, Philadelphia, PA; ²Department of Pharmacology & Experimental Therapeutics, Sidney Kimmel Medical College, Philadelphia, PA; ³Department of Pathology, Anatomy, & Cell Biology,, Sidney Kimmel Medical College, Philadelphia, PA; ⁴Institute of Translational Medicine, Cancer Research, UK Liverpool Cancer Trials Unit, Liverpool, United Kingdom; ⁵Department of Surgery, University of Heidelberg, Heidelberg, Germany

Objective: Previous studies have validated the RNA binding protein, HuR, as a predictive marker for pancreatic ductal adenocarcinoma (PDA) in the adjuvant setting. These studies, however, were based on small cohorts of patients outside of a clinical trial, where patients received combination therapies. To better evaluate cytoplasmic HuR (cHuR) as a predictive marker, we examined tumor samples from an international, randomized trial (ESPAC-3) in which resected PDA patients received either gemcitabine [GEM] vs. 5-fluoruracil [5-FU] adjuvant monotherapy.
Methods: Tissue samples from 379 PDA patients enrolled in the ESPAC-3 trial were stained with an anti-HuR antibody. cHuR expression was dichotomized to high versus low histological scores.
Results: Median disease free survival (DFS; shown in figure) for patients treated with GEM with tumors exhibiting low cHuR was 12.9 months (95% CI=11.2-15.4), vs. 10.9 months (95% CI=7.5-14.2) for high cHuR. The median DFS for patients treated with 5-FU with tumors with low cHuR was 12.8 months (95% CI=10.6-14.6) vs. 20.1 months (95% CI=8.3-36.4) for high cHuR. Unadjusted Cox regression of DFS supports high cHuR as a predictive marker for patients receiving 5-FU treatment (p=0.012).
Conclusion: High cHuR is a positive predictive marker for patients who receive 5-FU adjuvant therapy. If validated, this personalized approach may improve outcomes after resection. Future studies will determine if cHuR is also predictive for FOLFIRINOX therapy in the adjuvant setting.

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