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setting have yet to be examined. The purpose of our study is to determine whether NAC followed by CCRT provides an overall survival (OS) benefit, particularly among high-risk patients. Materials/Methods: We queried the national cancer database for patients with NPC and limited the initial 13,929 patients to those treated with either NAC followed by CCRT or CCRT alone; defining NAC followed by CCRT as chemotherapy initiation 21 days prior to RT initiation and CCRT as initiation 20 days prior to and 36 days after RT initiation. After excluding patients with metastatic disease, those treated with surgery or palliative therapy, and without clinical staging, we arrived at a total of 5274 patients. We performed survival analyses using univariate (UVA) and multivariate (MVA) cox proportional analysis to determine if an association between NAC and OS exists. Results: The median survival of the entire patient cohort was 8.9 years, with a median follow up of 3.3 years. Median survival for the NAC plus CCRT group was 9.4 years and 8.8 years in the CCRT alone group. NAC plus CCRT did not affect OS on UVA (HR 1.01; 95% CI [0.90,1.14)]; P Z .870) and MVA (HR 0.89; 95% CI [0.79,1.00]; P Z .053) though trending towards significance. We also stratified patients into risk categories. High-risk included patients with clinical stage IV or keratinizing histology and low all others. NAC plus CCRT improved OS in the highrisk population on MVA (HR 0.86; 95% CI [0.75, 0.98]; P Z.023) but not in the low risk (HR 1.06; 95% CI [0.80, 1.39]; P Z .692). Conclusion: Patients with nonmetastatic NPC treated with NAC plus CCRT trended towards a statistically significant OS benefit on multivariate analysis. However, higher risk patients, who we defined as having clinical stage IV disease or keratinizing histology, benefitted with an improved OS compared to those with low risk disease. Therefore, we conclude that a subset of patients presenting with locally advanced disease who are at a higher risk of distant micrometastases and those with unfavorable histology who are most resistant to radiation therapy may benefit from treatment with NAC plus CCRT, underscoring the necessity of additional future phase 3 trials to confirm these results.

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Materials/Methods: We identified cases of treatment-naïve p16(-) LA-HNSCC (stage III-IVB) of the oropharynx (31%), larynx (55%), and hypopharynx (13%) who received definitive (70 Gy) CTX-bioRT (n Z 35), CB-CRT (n Z 43), or CP-CRT (n Z 67) at our institution from 2009 to 2015. Variables with P < .05 on log-rank/Kaplan-Meier analysis were included as covariates in Cox proportional hazards modeling to adjust for potential confounders; variables included: concurrent systemic agent, sex, age, smoking history, T stage, N stage, performance status, and primary tumor site. Results: We identified 145 cases: 107 men (73.7%), median age 60 years (range, 41-87), T3 (63.4%), and N2b (56.6%). There were no statistical differences in sex, age, smoking history, T stage, N stage, performance status, or frequency of primary site among the groups. The most common reasons for CP ineligibility were hearing loss (41.0%), medical comorbidities (35.9%), and renal disease (9%). Median follow up was 3 years. Locoregional control (LRC), distant metastasis-free survival (DMFS), recurrence-free survival (RFS), and overall survival (OS) at 3 years were not statistically different between those treated with CB or CP-CRT. When compared to CTX-bioRT, CB-CRT improved 3-year LRC (81.5 vs 40.0%; P Z .001), RFS (76.9 vs 38.3%; P Z .009), and OS (60.0 vs 55.2%; P Z .05), with a trend toward improved distant metastasis free survival (89.5% vs 65.8%; P Z .06). On MVA CB-CRT remained associated with improved LRC (HR 0.25, 95% CI 0.10-0.67; P Z .006), RFS (HR 0.30, 95% CI 0.12-0.76; P Z 0.01), and OS (HR 0.44, 95% CI 0.20-0.96; P Z .04) compared to CTX-bioRT. On subset analysis of non-oropharynx primary tumors, concurrent platinum agents (CP or CB) were associated with improved 3-year larynx preservation compared to CTX-bioRT (83.6 vs 47.1%; P Z .02). Conclusion: When patients cannot receive CP, CB-CRT is an effective alternative in p16(-) LA-HNSCC. Furthermore, CB-CRT markedly improved LRC, RFS, and OS compared to CTX-bioRT and should be a preferred substitute for CP in this population. Prospective validation of these results is needed.