Development and validation of radiomic signatures of head and neck squamous cell carcinoma molecular features and subtypes

Background: Radiomics-based non-invasive biomarkers are promising to facilitate the translation of therapeutically related molecular subtypes for treatment allocation of patients with head and neck squamous cell carcinoma (HNSCC). Methods: We included 113 HNSCC patients from The Cancer Genome Atlas (TCGA-HNSCC) project. Molecular phenotypes analyzed were RNA-defined HPV status, five DNA methylation subtypes, four gene expression subtypes and five somatic gene mutations. A total of 540 quantitative image features were extracted from pretreatment CT scans. Features were selected and used in a regularized logistic regression model to build binary classifiers for each molecular subtype. Models were evaluated using the average area under the Receiver Operator Characteristic curve (AUC) of a stratified 10-fold cross-validation procedure repeated 10 times. Next, an HPV model was trained with the TCGA-HNSCC, and tested on a Stanford cohort (N = 53). Findings: Our results show that quantitative image features are capable of distinguishing several molecular phenotypes. We obtained significant predictive performance for RNA-defined HPV+ (AUC = 0.73), DNA methylation subtypes MethylMix HPV+ (AUC = 0.79), non-CIMP-atypical (AUC = 0.77) and Stem-like-Smoking (AUC = 0.71), and mutation of NSD1 (AUC = 0.73). We externally validated the HPV prediction model (AUC = 0.76) on the Stanford cohort. When compared to clinical models, radiomic models were superior to subtypes such as NOTCH1 mutation and DNA methylation subtype non-CIMP-atypical while were inferior for DNA methylation subtype CIMP-atypical and NSD1 mutation. Interpretation: Our study demonstrates that radiomics can potentially serve as a non-invasive tool to identify treatment-relevant subtypes of HNSCC, opening up the possibility for patient stratification, treatment allocation and inclusion in clinical trials. (C) 2019 Published by Elsevier B.V.