Preclinical Evaluation of Chemoradiation Resistance Using 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma

Heirman, C. C.; Rickard, A. G.; Castillo, R.; Gonzalez, K.; Pittman, A.; Smith, J.; Kelly, K. E.; Stevens, J. B.; Watts, T.; Mowery, Y. M.; Lafata, K. J.

doi:10.64898/2026.08.03.742521

bioRxiv · 10.64898/2026.08.03.742521

Preclinical Evaluation of Chemoradiation Resistance Using 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma

Heirman, C. C.·Rickard, A. G.·Castillo, R.·Gonzalez, K.·Pittman, A.·Smith, J.·Kelly, K. E.·Stevens, J. B.·Watts, T.·Mowery, Y. M.·Lafata, K. J.

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Abstract

PurposeThere is an urgent need for improved prognostic tools and biological understanding of chemoradiation resistance in head and neck squamous cell carcinoma (HNSCC). This study established a preclinical imaging dataset aimed at identifying prognostic imaging features from 18F-FDG micro-PET/CT scans in HNSCC mouse models. MethodsThree orthotopic murine models were utilized: two human papillomavirus (HPV)-negative (MOC1, MOC2) and one HPV-positive (MLM1). When tumor volume exceeded 50 mm3, chemoradiation was initiated using cisplatin (5 mg/kg) and image-guided radiation therapy (8 Gy) on days 0 and 7. 18F-FDG micro-PET/CT imaging was performed on day 14. Tumors were manually segmented on PET/CT, and quantitative image features including tumor volume, SUVmean, and SUVmax were extracted. Treatment response was evaluated by relative tumor size on day 11 compared to day 0. Tumor growth and survival were compared across models using multiple-effects model and log-rank. Imaging feature associations were evaluated by Mann-Whitney U tests. Associations between survival, SUVmax, and tumor volume were assessed using Cox proportional hazards modeling and Kaplan-Meier analysis with log-rank testing. ResultsA total of 121 mice were treated and imaged. Significant differences in tumor growth and survival were observed among the three models (p < 0.01 for pairwise growth comparisons; p < 0.0001 for survival). Day 11 treatment response groups demonstrated significantly different growth trajectories following chemoradiation (p < 0.0001). SUVmax was significantly associated with survival (p = 0.0009), whereas SUVmean was not significant (p = 0.13). PET tumor volume demonstrated the strongest association with survival (p < 0.0001). A multivariate Cox proportional hazards model incorporating SUVmax and tumor volume significantly stratified survival risk (p < 0.0001). ConclusionOverall, these findings demonstrate that 18F-FDG PET/CT-derived metrics, particularly SUVmax and tumor volume, are robust predictors of chemoradiation response in orthotopic murine models of HNSCC.

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Heirman, C. C., Rickard, A. G., Castillo, R., Gonzalez, K., Pittman, A., Smith, J., Kelly, K. E., Stevens, J. B., Watts, T., Mowery, Y. M., Lafata, K. J.. 2026-08-04. Preclinical Evaluation of Chemoradiation Resistance Using 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma. https://doi.org/10.64898/2026.08.03.742521

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