Role of Dose on Survival in Adjuvant Chemoradiation Pancreatic Cancer

Purpose/Objective(s): ACEi and ARB are commonly prescribed medications in the management of hypertension and diabetes. Pre-clinical and clinical data has suggested mitigating effects of these drugs on radiationinduced lung injury, which has implications for thoracic radiation therapy (RT). Whether ACEi/ARBs have a negative effect on tumor response still needs to be elucidated. In this study, we examined the correlation between ACEi/ARB and incidence of pCR as a surrogate for anti-tumor effect in patients receiving trimodality therapy for esophageal cancer. Materials/Methods: Between March 2000 and July 2012 135 patients with esophageal cancer were treated with NA-CRT followed by esophagectomy at our institution. The median age at diagnosis was 59 years (range, 26-82). The cohort was dominated by male patients (86%), distal esophageal primary (89%) and adenocarcinoma histology (76%). Predominant stage distribution was stage III (47%) and stage II (36%). Median radiation dose was 50.4 Gy (range 45.0-56.4Gy). Most common concurrent chemotherapy regimen was Cisplatin/5-Fu (59%). Primary endpoint was pCR rates with secondary endpoints of overall survival (OS) and progression free survival (PFS). Chi-square analysis along with univariate and multivariate Kaplan-Meier and Cox Regression analysis were performed. Results: With a median follow-up of 2.1 years, estimated median OS and PFS for the entire cohort were 2.7 years (95% CI: 2.0-3.4) and 2.8 years (95% CI: 1.9-3.7). 45 patients (33%) were taking ACEi/ARB at the time of radiation oncology consultation compared to 90 (67%) patients not taking ARBs. There were no significant differences in the distribution of key baseline variables between the two groups. The pCR rates with and without ACEi/ARB use were 36% and 43%, respectively (pZ0.39). Median OS and PFS in this group were 2.4 and 1.7 years, respectively. 3-year OS with and without ACEi/ARB use was 38.1% and 47.2% respectively, pZ0.2. Similarly, 3-year PFS was 42.9% and 47.6% respectively, pZ0.94. On multivariate analysis including use of ACEi/ARB in the model, none of the baseline characteristics impacted OS (borderline significance for N-stage, p < 0.1) and only advanced nodal status was associated with worse PFS (HRZ1.9, 95% CI 1.1-3.3, pZ0.03) with borderline significance of anatomical location and gender (p < 0.1). Conclusion: In our study, the use of ACEi/ARB was not associated with inferior pCR rates, OS or PFS. Validation in larger prospective databases with longer follow up is necessary to assess confounding effect of associated medical comorbidities on survival. If validated, then this absence of a negative impact supports their development as mitigators of radiation induced lung injury. Author Disclosure: J. Hyder: None. H. Boggs: None. M.D. Chuong: None. M. Suntharalingam: None. W. Burrows: None. N. Horiba: None. D.P. Zandberg: None. T.N. Tyer: None. E.P. Cohen: Research Grant; Department of Veterans Affairs. review of policy, planning meeting; Cancer and Kidney International Network. Z. Vujaskovic: None. P. Mohindra: None.