LAUSR

HPV status, or treatmentwithRTalone, concurrent chemotherapy, or upfront laryngectomy. We defined radiation-resistance as persistent or recurrent diseasewithin 3 years of receiving treatment. Early-stage LSCCwas defined as stage I or II tumors without lymph node involvement. Candidate genes associated with the radiation resistance included NFE2L2, KEAP1, CUL3, HRAS, NRAS, NOTCH2, NOTCH3, KRAS, RAF1, BCL-2, and BIRC5. Results: Twenty LSCC tumors were categorized as either radiation sensitive (RS, NZ9) or radiation resistant (RR, NZ11). Six were early-stage tumors (RR: NZ3 and RS: NZ3). Basic demographic factors were balanced between the 2 groups. Among all 20 samples, we found increased somatic mutations in the NOTCH pathway in RR patients (NOTCH 2: 44% vs. 0%, PZ .04; NOTCH 3 44% vs. 11%, PZ.19). In the 6 early-stage LSCC patients, we found all 3 RR tumors to have mutations in the KEAP1/ NFE2L2 pathway, while none of the RS tumors had mutations (PZ.014). Conclusion: In RR patients, there was a higher somatic mutational burden involving the NOTCH family. Interestingly, all early-stage LSCC patients with RR (NZ3) had mutations in the KEAP1/NRF2 oxidative stress pathway. In LSCC patients, downregulation of the KEAP1/NRF2 oxidative stress pathway may result in RT resistance. Further validation in a larger population is warranted. Alterations in both the NOTCH and KEAP1/ NRF2 oxidative stress pathway may serve as genomic determinants to predict radiation resistance in LSCC. Author Disclosure: D. Farquhar: None. S. Sheth: None. A. Mazul: None. P. Little: None. D.N. Hayes: None. J.P. Zevallos: None.