5589 Background: We sought, in a large, long-term follow-up cohort, to determine benchmark cross-sectional analysis of HNC patient (pt) symptom profiles as a function of chemotherapy (CT)/RT strategy. Methods: Pts treated with RT with or without CT in remission > 18 mos. were surveyed with the MD Anderson Symptom Inventory–Head and Neck Module (MDASI-HN). Clinical data were extracted. Data were tabulated, and group comparison performed using non-parametric analyses. Results: 250 pts participated; 81% were male. Median age at RT was 54 years. 87% had oropharynx HNC. Most were T1/X (41%), 37% T2 and, 22% T3/4. For N-category, most were N2 (55%), <5% N3, and 40% NX-1. 18% had induction CT, 26% concurrent, 5% both, and 50% had none. At a median follow-up time of 5.9 years (range 2-15), 11% of pts were entirely symptom free, 31% reported ≤mild symptom severity, 20% ≤moderate, and 38% reported ≥1 symptom as severe. 16% of pts receiving RT alone and 11% sequential CT followed by RT were symptom free, vs. 1% of those receiving concurrent CT (chi-square p<0.01), and the symptom distribution profile was distinct (p<0.03). The proportion of pts who received concurrent CT reporting any severe symptom item was 44%, vs. 36% of those not receiving concurrent CT (p=n.s.). No difference was seen in the moderate to severe (M/S) symptom report by treatment group. For all MDASI-HN items, most pts rated “0” or “not present”, except dry mouth and difficulty swallowing items, where mild symptoms were most likely (36% and 33%). The most common symptoms rated M/S were dry mouth, swallowing, choking, fatigue, and mouth and throat mucus reported by 42%, 23%, 18%, 16%, and 16%. MVA demonstrated T-stage and primary site, but not CT cohort correlated with M/S symptom report. Conclusions: Cumulatively, most pts had no more that mild symptom severity, but a substantial group of pts experience M/S levels. The symptom severity profile was highest with concurrent CT, though this effect appears mediated by disease specific factors. The addition of sequential CT to RT did not to appear to alter M/S symptom report substantially; however, concurrent pts were almost never symptom free, in contrast to induction and no CT cohorts.