Prognostic Value of Weekly Delta-Radiomics during MR-Linac Radiotherapy of Glioblastoma

Abstract

MRI after chemoradiotherapy (chemoRT) shows areas of presumed tumor growth in ≤ 50% of glioblastoma (GBM) patients, which can be true progression (TP) - tumor growth with poor treatment response, or pseudoprogression (PP) - edema and tumor necrosis with favorable treatment response. Patients with TP have median overall survival (OS) of only 7 months, while patients with PP have median OS of 36 months. However, on imaging, TP and PP are usually not discernible during treatment, making it difficult to adapt radiation for poor responders. The purpose of this study was to investigate the prognostic value of delta radiomic features from MR-Linac for GBM. Using an IRB-approved prospective cohort of GBM patients undergoing 30 fractions of chemoRT to 60 Gy on a 0.35T MR-Linac, 2 regions of interest (ROI) were contoured on daily T2-weighted treatment set-up scans: 1) tumor/edema (lesion) and 2) post-surgical resection cavity (RC). The lesion ROI were used to calculate texture features: second order radiomics features based on the gray-level co-occurrence matrix (GLCM), gray-level size zone matrix (GLSZM), gray-level run length matrix (GLRLM), and neighborhood gray-tone difference matrix (NGTDM). Each of these describe the probability of spatial relationships of gray levels occurring within the ROI. Features from fraction 1 (pre-radiation) were subtracted from fractions 5, 10, 15, 25, and 30 to create delta features at 5 timepoints (D5-D30). Patient response was retrospectively defined as no progression (NP), TP, or PP. Supervised machine learning was utilized using a 500-tree random forest (RF) classification model with TP or PP as the outcome. Variable importance analysis was conducted by calculating the out-of-bag errors with multiple bootstrapped data sets. The most prognostic features were selected using the RF importance scores. Thirty-six patients were screened for inclusion: 9 were excluded due to no T2 lesion (RC ROI only). Of the remaining 27 patients: 10 had NP, 11 had TP, and 6 had PP. Thirty-nine texture features, plus lesion volume and mean lesion intensity (for a total of 41 variables per time point) were calculated and included in the model. Of the 10 most prognostic features, 6 were from D10, suggesting that prognostic changes in the underlying lesion microenvironment are occurring within the first 10 fractions of treatment. The model selected GLSZM high gray-level zone emphasis (HGZE) D10, IBSI code 5GN9, as the most prognostic feature. The receiver operator characteristic (ROC) area under the curve (AUC) for GLSZM HGZE D10 was 0.94 (95% CI = 0.81-1.00). Delta radiomic features extracted from MR-Linac imaging may predict between PP and TP in GBM patients during treatment, which is earlier than current methods. This could allow physicians to adapt/intensify treatment in real time for poorly responding patients. Future directions include analysis with a larger patient cohort and with additional MRI contrasts (MR-Linac multiparametric MRI).