Evaluating Chemoradiation Resistance using 18F-FDG PET/CT in Murine Head and Neck Squamous Cell Carcinoma

Abstract

Purpose: There is an urgent need for enhanced prognostic tools and insights into the biology andbiomarkers of chemoradiation resistance. The purpose of this research is to identify prognostic radiomic features on 18F-FDG micro-PET/CT images for the response to chemoradiation in mouse models of head and neck squamous cell carcinoma (HNSCC). Methods: Two orthotopic murine human papillomavirus (HPV)-negative (MOC1, MOC2) models and one HPV-positive HNSCC model (MLM1) were utilized. Oral cavity tumors were induced by injecting HNSCC cells into the buccal mucosa of C57BL/6J mice. Bidirectional caliper tumor measurements were conducted thrice weekly with chemoradiation initiated once tumors exceeded 50mm3: cisplatin (5 mg/kg, intraperitoneal) and image-guided radiation therapy (8 Gy) on days 0 and 7. On day 14, 18F-FDG PET/CT imaging was performed. Mice were euthanized when they reached humane endpoint (tumor >12mm, any dimension). Tumors were segmented on PET/CT, and volume, SUVmean, and SUVmax were extracted. Liver regions of interest were segmented for normalization of tumor SUVmax to liver SUVmean. Treatment response was evaluated using tumor size on day 10 relative to day 0. Tumor growth and survival were compared across models (Kruskal-Wallis with Tukey’s post hoc test) and based on image feature parameters (Mann-Whitney U test). The associations between survival, SUVmax, and tumor volumes were analyzed by Cox proportional hazards model and Kaplan-Meier curves with log-rank test. Results: 121 mice underwent treatment and imaging. Univariate analysis showed that median tumor volume and SUVmax were significantly associated with survival and treatment response (p<0.05). The Cox model indicated a significant difference in survival probability based on risk score values derived from the model's coefficients estimating their relative risk of time-to-event (p<0.0001). Conclusion: These results suggest that image features on 18F-PET/CT can provide prognostic insight into treatment response and survival in preclinical HNSCC models, providing a platform for further studies to improve understanding of the biological underpinnings of radiomic expression associated with chemoradiation resistance.