Optimizing Cardiac Medications in Patients with Locally Advanced Non–Small Cell Lung Cancer Undergoing Definitive Radiation

Abstract

Lung cancer accounts for one in four cancer-related deaths in United States. Despite the use of concurrent chemoradiation (CRT) for locally-advanced non-small cell lung cancer (LA-NSCLC), local failure rates are high and two year overall survival is only 50%. Efforts to improve outcomes through RT dose-escalation have been similarly disappointing due increased toxicity and decreased survival. Recent multi-institutional evidence suggests that higher rates of cardiac events (CE) are contributing to this high mortality. The aim of this study was to evaluate the association between pre-CRT cardiac medical optimization and grade 2 or higher CE-free survival (CEFS). Between 2004 and 2013, 191 patients with lung cancer were enrolled on one of four prospective CRT dose-escalation trials at an academic institution or its affiliated VA hospital. For this study, we excluded patients who had small cell histology, stage I disease, stereotactic body radiation (SBRT), or incomplete medication records (n = 112). Baseline demographics were analyzed to determine which patients had indications for statin, renin-angiotension-aldosterone blockers, beta-blockers, or antiplatelet therapy according to American Heart Association/American College of Cardiology (AHA/ACC) guidelines. Patients were considered to be optimized if they were on all of the appropriate medications. Fisher’s exact test was used to evaluate differences between the optimized, non-optimized, and “medication not necessary” cohorts. CEFS was estimated with the Kaplan Meier method and a log rank test was used to compare curves. A Cox Proportional Hazard model was used to identify predictors of CEFS. Men (n = 84) were significantly more likely than women (n = 28) to need medical therapy (89% vs. 36%, p < 0.0001), as were current and former smokers compared to never-smokers (77% vs. 83% vs. 0%, respectively, p < 0.02) and patients treated at the VA compared to academic institution (89% vs. 57%, p < 0.0001). Of the 85 patients who had indications for medical therapy, only 42 (49%) were optimized. Patients who required medical therapy had worse CEFS compared to the remaining cohort (p = 0.0149). There were no significant differences in the RT dose delivered (p > 0.05) or CEFS between the non-optimized vs. optimized groups (HR = 0.90, 0.30 - 2.73). This study has identified a cohort of patients who are at increased risk for CE during CRT, however less than half of these are medically optimized according to AHA/ACC guidelines. Further investigation is warranted to determine whether increasing pretreatment cardiac optimization rates may allow for tumor dose escalation and improved outcomes in LA-NSCLC.