Abstract Background: The standard of care for T4 laryngeal cancer patients (pts) includes surgical resection followed by adjuvant radiation (RT) with or without chemotherapy (CRT). Our institution has experience with organ preservation (OP) for this population. This study assessed racial differences in survival outcomes of T4 larynx cancer pts pursuing OP.Method: T4 larynx pts at our institution who received definitive CRT were identified from January 1990 to December 2019. Race was self-reported. CRT consisted of 4-6 alternating weekly cycles of paclitaxel (100mg/m2 on d1), infusion 5-fluorouracil (600mg/m2/d on d1-5), hydroxyurea (500mg PO BID), and either 2 Gy daily or 1.5 Gy twice-daily RT (TFHX). Clinicodemographic characteristics: age at diagnosis, sex, diagnosis period (10-year), nodal stage, tracheostomy or g-tube use, chemotherapy, RT dose or fractionation, and clinical trial enrollment were compared using Student’s t, X2, or Fisher’s exact tests. The Kaplan-Meier method was used to estimate 2- and 5-year distant metastasis-free survival (DMFS), overall survival (OS), and laryngectomy free-survival (LFFS), overall and by race. Multivariable Cox proportional hazards were modeled for survival outcomes between Black and White pts to report adjusted hazard ratios (aHR) and 95% confidence intervals (CI).Results: Of 104 pts, 45% were Black, 55% were White, mean age at diagnosis was 60 (SD 10) years, 66% were male, and median follow-up time was 52 (IQR: 24-99) months. The rate of Black pts decreased from 71% (1990-1999), 54% (2000-2009) to 28% (2010-2019). 64% of Black pts enrolled in a clinical trial compared to 51% of White pts. A higher rate of Black pts required tracheostomy before treatment than White pts (87% vs. 47%, p<0.001). In 2010-2019, 36% of Black pts were tracheostomy-free at 1 year compared to 81% of White pts (p=0.02). No differences were observed in rates of upfront g-tube use between races (29% vs. 45%, p=0.11; 39% overall), but a lower rate of Black pts were g-tube-free at 1 year than White pts (36% vs 94%, p<0.001). No differences in clinicodemographic characteristics were detected between Black and White pts. Only 4 (4%) Black and 1 (1%) White pts diagnosed from 1990-2009, and no pts diagnosed after 2009 required a salvage laryngectomy for dysfunctional larynx. 2-year OS, LFFS and DMFS were 78%, 95%, and 81% for Black pts, and 82%, 88%, and 88% for White pts, respectively. 5-year OS, LFFS, and DMFS were 52%, 92%, and 77% for Black pts, and 70%, 88%, and 86% for White pts. After covariate adjustment, no differences in survival outcomes were detected between Black and White pts for OS (aHR 1.1, 95% CI: 0.6-1.9), LFFS (aHR 0.8, 95% CI: 0.3-2.7), or DMFS (aHR 2.0, 95% CI: 0.8-5.3).Conclusion: Promising LFFS is seen with TFHX CRT for T4 laryngeal cancer in the largest single institutional experience of OP. Black pts had increased tracheostomy and g-tube rates at 1 year, but there were no differences in survival outcomes between races. T4 disease had outcomes similar to pts with less advanced disease treated on RTOG 91-11. Citation Format: Jared H. Hara, Jason Q. Freeman, Sara E. Kochanny, Naomi S. Ecanow, Ari J. Rosenberg, Alexander T. Pearson, Zhen Gooi, Brandon J. Baird, Elizabeth A. Blair, Nishant Agrawal, Everett E. Vokes, Daniel J. Haraf, Aditya Juloori. Racial differences in organ preservation with definitive chemoradiotherapy among patients with T4 laryngeal squamous cell carcinoma [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A085.