Background: Using PROs from our previously completed clinical trial (NCT00410826), we conducted an exploratory analysis to identify PRO associations with clinical factors and oncologic outcomes. Methods: From 12/2006 to 10/2011, 204 patients(pts) were randomized to cisplatin 100mg/m² on radiation (XRT) days(d)1, 22, and 43 concurrent with 70Gy XRT (Arm A) or the same treatment with erlotinib 150mg daily starting XRT d-7 until XRT completion (Arm B). Using the validated University of Washington QOL form, PROs were measured on XRT d-7 (Arm B only), d0, d30, and d180. PRO associations with clinical factors and oncologic outcomes were explored using linear mixed, logistic and cox models, while adjusting for potential confounders. Results: One hundred eighty nine (93%) [Arm A (N = 97); Arm B (N = 92)] pts consented to PRO collection. PRO scores were available in Arm A: 55 (56%) pts at d0, 65 (67%) at d30, and 45 (46%) at d180 and Arm B: 82 (89%) pts at d-7, 58 (63%) at d0, 69 (75%) at d30, and 41 (44%) at d180. Demographic and tumor characteristics were well-balanced apart from more females in Arm A [20 (19%) vs 8 (8%); p = 0.03]. There were 7 (16%) black pts in Arm A and 13 (13%) in Arm B (p = 0.28). There was no change in mean PRO scores from d-7 on d0 (p = 0.83). Scores were significantly lower in both arms at d30 (estimated difference from baseline -13.21 (CI -18.32, -8.1), with no significant difference by Arm (p = 0.71). D180 remained lower than d-7 for Arm A (estimated difference from baseline -6.56 (CI -12.30, -0.82) p = 0.03), however were not significantly different from d-7 (baseline) in Arm B (p = 0.68). After adjusting for potential confounders on multivariable analysis, black race was an independent predictor for inferior PRO scores [OR -15.87; 95% CI (-21.11, -10.63); p < 0.0001] at all timepoints, complete response rates [OR 0.23; 95% CI (0.1, 0.53); p < 0.001] and overall survival [OR 3.94; 95% CI (1.89, 8.24); p < 0.001]. Conclusions: PRO worsened during chemoradiation, but returned to baseline in pts on Arm B. Black pts had inferior PRO and overall survival, meriting further investigation.