Background: This research aims to improve glioblastoma survival prediction by integrating MR images, clinical and molecular-pathologic data in a transformer-based deep learning model, addressing data heterogeneity and performance generalizability. Method: We propose and evaluate a transformer-based non-linear and non-proportional survival prediction model. The model employs self-supervised learning techniques to effectively encode the high-dimensional MRI input for integration with non-imaging data using cross-attention. To demonstrate model generalizability, the model is assessed with the time-dependent concordance index (Cdt) in two training setups using three independent public test sets: UPenn-GBM, UCSF-PDGM, and RHUH-GBM, each comprising 378, 366, and 36 cases, respectively. Results: The proposed transformer model achieved promising performance for imaging as well as non-imaging data, effectively integrating both modalities for enhanced performance (UPenn-GBM test-set, imaging Cdt 0.645, multimodal Cdt 0.707) while outperforming state-of-the-art late-fusion 3D-CNN-based models. Consistent performance was observed across the three independent multicenter test sets with Cdt values of 0.707 (UPenn-GBM, internal test set), 0.672 (UCSF-PDGM, first external test set) and 0.618 (RHUH-GBM, second external test set). The model achieved significant discrimination between patients with favorable and unfavorable survival for all three datasets (logrank p 1.9\times{10}^{-8}, 9.7\times{10}^{-3}, and 1.2\times{10}^{-2}). Conclusions: The proposed transformer-based survival prediction model integrates complementary information from diverse input modalities, contributing to improved glioblastoma survival prediction compared to state-of-the-art methods. Consistent performance was observed across institutions supporting model generalizability.
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