Radiosensensitivity index prognostic for survival with adjuvant radiation in resectable pancreatic cancer.

Abstract

398 Background: Adjuvant radiation therapy (RT) for resectable pancreatic cancer remains controversial. We evaluated whether a previously validated molecular signature of tumor radiosensitivity (RSI) is prognostic for survival in pancreatic cancer. Methods: We identified patients treated with upfront surgery between 2006 and 2012. Briefly, RSI score is derived from the expression of 10 specific genes and a linear regression algorithm modeled on SF2 of 48 cancer cells (RSI, high index = radioresistant). We assessed the relative radiosensitivity of pancreatic cancers compared with other common cancers and then tested the association of RSI with overall survival (OS). Results: Compared with other common cancers such as lung, breast, and prostate, pancreatic cancers were more radioresistant as a group (p<0.0001). We identified 80 patients who underwent upfront surgery with both RSI and clinical outcome available (49 RT, 31 no RT). Median follow-up among surviving patients was 4.1 years. Median OS for radiosensitive tumors (RS), defined by lower ½ RSI, was 2.7 years compared with 1.5 years for radioresistant (RR) tumors (p=0.35). Among the high-risk pancreatic cohort, (positive margins, positive lymph nodes, or a post-operative CA 19-9 >90), irradiated patients with RS tumors had a trend toward improved OS (3y OS: 38% vs. 8%; p=0.07), while there was no difference in OS between RS and RR patients who weren’t treated with RT (p=0.79). When RSI was integrated, high-risk-RS patients had similar OS compared with low-risk-RR patients (3y OS: 38% vs. 50%; p=0.29). When low-risk-RR and high-risk-RS were combined into a single intermediate-risk group, RSI score added substantial prognostic value to OS outcomes on univariate (3 y OS: 78%, 42%, and 8%, for low-risk-RS, intermediate-risk group, and high-risk-RR, respectively; p=0.001) and multivariate analysis (intermediate-risk HR: 4.3, 1.0-18.6; p=0.053; high-risk HR: 9.9, 2.2-45.1; p=0.003). Conclusions: Patients with pancreatic tumors have relatively radioresistant tumors. Integrating RSI with standard prognostic variables refines the classification of resected pancreatic cancer patients.