Site-Specific Variation in Radiomic Features of Head and Neck Squamous Cell Carcinoma and Its Impact on Machine Learning Models

SIMPLE SUMMARY: Head and neck squamous cell carcinoma (HNSCC) is the most common mucosal malignancy of the head and neck and a leading cause of cancer death. HNSCC arises from different primary anatomical locations that are typically combined during radiomic analyses assuming that the radiomic features, i.e., quantitative image-based features, are similar based on histopathologic characteristics. However, whether these quantitative features are comparable across tumor sites remains unknown. The aim of our retrospective study was to assess if systematic differences exist between radiomic features based on different tumor sites in HNSCC and how they might affect machine learning model performance in endpoint prediction. Using a population of 605 HNSCC patients, we observed significant differences in radiomic features of tumors from different locations and showed that these differences can impact machine learning model performance. This suggests that tumor site should be considered when developing and evaluating radiomics-based models. ABSTRACT: Current radiomic studies of head and neck squamous cell carcinomas (HNSCC) are typically based on datasets combining tumors from different locations, assuming that the radiomic features are similar based on histopathologic characteristics. However, molecular pathogenesis and treatment in HNSCC substantially vary across different tumor sites. It is not known if a statistical difference exists between radiomic features from different tumor sites and how they affect machine learning model performance in endpoint prediction. To answer these questions, we extracted radiomic features from contrast-enhanced neck computed tomography scans (CTs) of 605 patients with HNSCC originating from the oral cavity, oropharynx, and hypopharynx/larynx. The difference in radiomic features of tumors from these sites was assessed using statistical analyses and Random Forest classifiers on the radiomic features with 10-fold cross-validation to predict tumor sites, nodal metastasis, and HPV status. We found statistically significant differences (p-value ≤ 0.05) between the radiomic features of HNSCC depending on tumor location. We also observed that differences in quantitative features among HNSCC from different locations impact the performance of machine learning models. This suggests that radiomic features may reveal biologic heterogeneity complementary to current gold standard histopathologic evaluation. We recommend considering tumor site in radiomic studies of HNSCC.