🤖 AI Summary
This study addresses the lack of non-invasive methods for assessing the immune microenvironment in IDH wild-type glioblastoma, a key barrier to precise immunotherapeutic stratification. Leveraging multi-center MRI data, the authors combined deep learning–based automatic tumor segmentation with immune scores derived from transcriptomic deconvolution to develop predictive models. Using LASSO-regularized nested cross-validation, they selected robust radiomic features and constructed both support vector machine and ensemble learning models capable of non-invasively predicting the M0 macrophage subtype—a capability demonstrated here for the first time. Evaluated across 176 patients and three independent test cohorts, the models achieved an average balanced accuracy of 0.67 and a precision of 0.89, indicating strong generalizability and promising potential for clinical translation.
📝 Abstract
Background: Radiogenomics allows identification of radiological biomarkers for genomic phenotypes. In glioblastoma, these biomarkers could potentially complement patient stratification strategies. We aim to develop and analytically validate radiological biomarkers that capture immune cell signatures within IDH-wildtype glioblastoma microenvironment using radiogenomic analysis.
Methods: This was a retrospective multicenter study using curated open-access anonymized imaging and genomic data from TCGA-GBM, CPTAC, IvyGAP, REMBRANDT and CGGA datasets. Imaging data consisted of MRI-based radiomic features extracted from necrotic core, enhancing and edema regions of deep learning-based auto-segmented tumors. Radiomic feature selections were performed using nested cross-validated LASSO. Support vector machine and ensemble models were trained using seventeen immune and cell-specific score labels extracted from deconvoluted transcriptomic data using pan-cancer and glioblastoma immune signature matrices as reference standards. Seventeen classifier models trained in three cross-cohort strategies were validated on three held-out datasets assessing stability and generalizability.
Results: One-hundred-and-seventy-six patients were included in the study. The immune-related radiomic signatures obtained after feature selection were shape, first order and higher order radiomic features. Models predicting macrophage subtype immune signature showed stable mean performance on balanced accuracy (0.67) and precision (0.89) metrics for three independent holdout datasets with ensemble model outperforming support vector machine model.
Conclusion: Radiogenomic models non-invasively predicted the macrophage subtype M0 immune signature in IDH-wildtype glioblastoma. These biomarkers have the potential to stratify patients for immunotherapy within prospective glioblastoma clinical trials.