Abstract
BACKGROUND: Microsatellite instability (MSI) status is a strong predictor of response to immunotherapy of colorectal cancer. Radiogenomic approaches promise the ability to gain insight into the underlying tumor biology using non-invasive routine clinical images. This study investigates the association between tumor morphology and the status of MSI versus microsatellite stability (MSS), validating a novel radiomic signature on an external multicenter cohort. METHODS: Preoperative computed tomography scans with matched MSI status were retrospectively collected for 243 colorectal cancer patients from three hospitals: Seoul National University Hospital (SNUH); Netherlands Cancer Institute (NKI); and Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy (INT). Radiologists delineated primary tumors in each scan, from which radiomic features were extracted. Machine learning models trained on SNUH data to identify MSI tumors underwent external validation using NKI and INT images. Performances were compared in terms of area under the receiving operating curve (AUROC). RESULTS: We identified a radiomic signature comprising seven radiomic features that were predictive of tumors with MSS or MSI (AUROC 0.69, 95% confidence interval [CI] 0.54-0.84, p = 0.018). Integrating radiomic and clinical data into an algorithm improved predictive performance to an AUROC of 0.78 (95% CI 0.60-0.91, p = 0.002) and enhanced the reliability of the predictions. CONCLUSION: Differences in the radiomic morphological phenotype between tumors MSS or MSI could be detected using radiogenomic approaches. Future research involving large-scale multicenter prospective studies that combine various diagnostic data is necessary to refine and validate more robust, potentially tumor-agnostic MSI radiogenomic models. RELEVANCE STATEMENT: Noninvasive radiomic signatures derived from computed tomography scans can predict MSI in colorectal cancer, potentially augmenting traditional biopsy-based methods and enhancing personalized treatment strategies. KEY POINTS: Noninvasive CT-based radiomics predicted MSI in colorectal cancer, enhancing stratification. A seven-feature radiomic signature differentiated tumors with MSI from those with MSS in multicenter cohorts. Integrating radiomic and clinical data improved the algorithm's predictive performance.