330 - Tumor Hypoxia on 18F-Fluoromisonidazole Positive Emission Tomography as a Predictor of Distant Metastasis-Free Survival after Chemoradiation for Head and Neck Squamous Cell Carcinoma: A Pooled Analysi

C. Gui¹, R. Wray², H. Schoder², M. Grkovski³, J. Humm², R. J. Wong⁴, E. Sherman⁵, N. Riaz¹, and N. Y. Lee¹; ¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, ³Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, ⁴Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, ⁵Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): High rates of locoregional control are observed after chemoradiation (CRT) for head and neck squamous cell carcinoma (HNSCC), but distant metastasis (DM) remains a major cause of morbidity and mortality. Improved prediction of adverse oncologic outcomes would facilitate patient selection for escalated therapy. Prior studies have shown that tumor hypoxia on FMISO PET predicts for local failure after CRT, but data showing an association with DM are limited. We combined data from two clinical trials to evaluate whether tumor hypoxia on FMISO PET predicts DM-free survival (DMFS) and overall survival (OS) after CRT for HNSCC. Materials/

Methods: From 2004 to 2020, patients undergoing CRT for nonmetastatic HNSCC who enrolled on two clinical trials investigating the role of FMISO PET (NCT00606294, NCT03323463) were included in this analysis. FMISO PET before and = 7 days after starting CRT were evaluated for tumor hypoxia. Pre- and intra-treatment hypoxia were hypothesized to predict worse DMFS and OS, measured from the end of CRT. DMFS was defined using a composite endpoint, consisting of biopsy-proven HNSCC outside the head and neck or death. Predictors of DMFS and OS were modeled with Cox regression.

Results: Among 295 patients, 86% had oropharyngeal primaries, and 89% had HPV+ disease. Per AJCC 7th edition staging, 15% had T = 3, and 18% had N = 2c. De-escalated 30 Gy CRT was delivered to 49% of patients; all others received 70 Gy CRT. Pre- and intra-treatment hypoxia on FMISO PET were identified in 218 (74%) and 69 (23%) patients, respectively. Median follow-up among survivors was 4.4 years. DMFS and OS at 4 years were 89% and 94%, respectively. Among 17 patients with DM, 4 had prior locoregional recurrence. Among 69 patients negative for pre-treatment hypoxia, none experienced DM. In univariable models, worse DMFS was associated with pre-treatment hypoxia (HR 3.37, 95% CI 1.03-11.1, p = 0.04) and intra-treatment hypoxia (HR 2.57, 95% CI 1.28-5.15, p = 0.008). In a multivariable model, intra-treatment hypoxia independently predicted worse DMFS (HR 2.94, 95% CI 1.40-6.21, p = 0.005), alongside T = 3 disease. In univariable models, trends toward worse OS were seen with pre-treatment hypoxia (HR 2.76, 95% CI 0.84-9.08, p = 0.09) and intra-treatment hypoxia (HR 1.76, 95% CI 0.85-3.61, p = 0.13).

Conclusion: We report the largest clinical series evaluating tumor hypoxia on FMISO PET as a predictor for DMFS and OS after CRT for HNSCC. Pre- and intra-treatment hypoxia on FMISO PET significantly predicted worse DMFS. Intra-treatment hypoxia predicted worse DMFS independent of tumor stage. No patients who were negative for hypoxia on pre-treatment FMISO PET experienced DM. Tumor hypoxia on FMISO PET may aid in selecting patients for escalated treatment strategies aimed at preventing DM.