NeuroRAD-FM: A Foundation Model for Neuro-Oncology with Distributionally Robust Training

Neuro-oncology poses unique challenges for machine learning due to heterogeneous data and tumor complexity, limiting the ability of foundation models (FMs) to generalize across cohorts. Existing FMs also perform poorly in predicting uncommon molecular markers, which are essential for treatment response and risk stratification. To address these gaps, we developed a neuro-oncology specific FM with a distributionally robust loss function, enabling accurate estimation of tumor phenotypes while maintaining cross-institution generalization. We pretrained self-supervised backbones (BYOL, DINO, MAE, MoCo) on multi-institutional brain tumor MRI and applied distributionally robust optimization (DRO) to mitigate site and class imbalance. Downstream tasks included molecular classification of common markers (MGMT, IDH1, 1p/19q, EGFR), uncommon alterations (ATRX, TP53, CDKN2A/2B, TERT), continuous markers (Ki-67, TP53), and overall survival prediction in IDH1 wild-type glioblastoma at UCSF, UPenn, and CUIMC. Our method improved molecular prediction and reduced site-specific embedding differences. At CUIMC, mean balanced accuracy rose from 0.744 to 0.785 and AUC from 0.656 to 0.676, with the largest gains for underrepresented endpoints (CDKN2A/2B accuracy 0.86 to 0.92, AUC 0.73 to 0.92; ATRX AUC 0.69 to 0.82; Ki-67 accuracy 0.60 to 0.69). For survival, c-index improved at all sites: CUIMC 0.592 to 0.597, UPenn 0.647 to 0.672, UCSF 0.600 to 0.627. Grad-CAM highlighted tumor and peri-tumoral regions, confirming interpretability. Overall, coupling FMs with DRO yields more site-invariant representations, improves prediction of common and uncommon markers, and enhances survival discrimination, underscoring the need for prospective validation and integration of longitudinal and interventional signals to advance precision neuro-oncology.