Technical Note: On the development of an outcome-driven frequency filter for improving Radiomics-based modeling of Human Papilloma Virus (HPV) in patients with oropharyngeal squamous cell carcinomas.

Abstract

PURPOSE\nTo implement an outcome-driven frequency filter for improving radiomics-based modeling of human papilloma virus (HPV) for patients with oropharyngeal squamous cell carcinoma (OPSCC).\n\n\nMETHODS AND MATERIALS\nOne hundred twenty-eight OPSCC patients with known HPV status (60-HPV+ and 68-HPV-, confirmed by immunohistochemistry-P16 protein testing) were retrospectively studied. A 3D Discrete Fourier Transform was applied on contrast-enhanced CT images of patient gross tumor volumes (GTV s) to transform intensity distributions to the frequency domain and estimate frequency power spectrums of HPV- and HPV+ patient cohorts. Statistical analyses were performed to rank frequency bands contributing towards prediction of HPV status. An outcome-driven frequency filter was designed accordingly and applied to GTV frequency information. 3D Inverse-Discrete-Fourier-Transform was applied to reconstruct HPV-related frequency-filtered images. Radiomics features (11 feature-categories) were extracted from pre- and post- frequency filtered images using our previously published ROdiomiX software. Least-Absolute-Shrinkage-and-Selection-Operation (Lasso) combined with a Generalized-Linear-Model (Lasso-GLM) was developed to identify and rank feature subsets with optimal information for prediction of HPV+/-. Radiomics-based Lasso-GLM classifiers (pre- and post-frequency filtered) were constructed and validated using a random permutation sampling and nested cross-validation techniques. Average Area Under Receiver Operating Characteristic (AUC), and Positive and Negative Predictive values (PPV, NPV) were computed to estimate generalization error and prediction performance.\n\n\nRESULTS\nAmong 192 radiomic features, 15 features were found to be statistically significant discriminators between HPV+/- cohorts on post-frequency filtered CE-CT images; 14 such radiomic features were observed on pre-frequency filtered datasets. Discriminant features included tumor morphology and intensity contrast. Performances for prediction of HPV for the pre- and post-frequency filtered Lasso-GLM classifiers were: AUC/PPV/NPV = 0.789/0.755/0.805 and 0.850/0.808/0.877 respectively. Nested-CV performances for prediction of HPV for the pre- and post-frequency filtered Lasso-GLM classifiers were: AUC/PPV/NPV = 0.814/0.725/0.877 and 0.890/0.820/0.911 respectively.\n\n\nCONCLUSION\nAlbeit subject to confirmation in a larger cohort, this pilot study presents encouraging results on the importance of frequency analysis prior to radiomic feature extraction toward enhancement of model performance for characterizing HPV in patients with OPSCC. This article is protected by copyright. All rights reserved.