Author: Rico Castillo, Katherine Gonzalez, Casey C. Heirman, Kyle J. Lafata, Xiang Li, Yvonne M Mowery, Yvonne M Mowery, Allison Pittman, Ashlyn G. Rickard, Breylon Riley ๐จโ๐ฌ
Affiliation: Duke University, Department of Radiation Oncology, Duke University, University of Pittsburgh ๐
Purpose: To evaluate the relationships between quantitative imaging biomarkers and chemoradiation resistance in head and neck squamous cell carcinoma (HNSCC) using preclinical mouse models.
Methods: Oral cavity tumors were generated in mice using three models with varied immunological profiles: (i) MOC1 (HPV-negative), (ii) MOC2 (HPV-negative), and (iii) MLM1 (HPV-positive) transplant tumors. Tumor dimensions were recorded three times per week, and chemoradiation therapy was initiated once tumors reached a volume of 50 mmยณ. Treatment included cisplatin (5 mg/kg, intraperitoneally) and image-guided radiation therapy (8 Gy) administered on days 0 and 7. Tumor volume and SUVmax, normalized to mean liver uptake, were assessed on day 14 using 18F-FDG ฮผPET/CT imaging. Radiomic features were derived from segmented tumor regions to assess metabolic texture, while pathomic features were extracted from digital pathology of necropsy specimens stained with H&E. Correlations between radiomic features, pathomic features, tumor immunological profiles, and overall survival (OS) were analyzed.
Results: MOC1 tumors displayed the highest radiosensitivity, with a median survival of 45 days, while MOC2 tumors (30 days) were the most resistant, and MLM1 tumors had a mixed response (39 days). Early response differences were significant (p < 0.0001), with 26% of mice demonstrating tumor volume reduction by day 10. Multivariate Cox proportional hazard models with Bonferroni correction identified 31 significant radiomic features after adjusting for SUVmax. For instance, increased homogeneity in regions with low SUV uptake, characterized by Long Run Low Gray Level Emphasis, was associated with lower risk, suggesting connections to hypoxic or necrotic tumor regions. The mean k-core, a pathomic feature assessing cellular connectivity within 40 ยตm, was higher in organized tissue, indicating stronger connections, while disorganized tissue showed lower values, reflecting fragmentation.
Conclusion: Preclinical mouse models are valuable for exploring chemoradiation resistance mechanisms and uncovering radiomic and pathomic patterns that reflect critical aspects of tumor biology.