Purpose: We investigate the feasibility of using a biophysically guided approach for delineating the Clinical Target Volume (CTV) in Glioblastoma Multiforme (GBM) by evaluating its impact on the treatment outcomes, specifically Overall Survival (OS) time.

Methods: An established reaction–diffusion model was employed to simulate the spatiotemporal evolution of cancerous regions in T1-MRI images of GBM patients. The effects of the parameters of this model on the simulated tumor borders were quantified and the optimal values were used to estimate the distribution of infiltrative cells (CTVmodel). Radiomics and deep learning models were examined to predict the OS time by analyzing the GTV, clinical CTV, and CTVmodel.

Results: The study involves 126 subjects for model development and 62 independent subjects for testing. Evaluation of the proposed approach demonstrates comparable predictive power for OS time that is achieved with the clinically defined CTV. Specifically, for the binary survival prediction, short vs. long time, the proposed CTVmodel resulted in improvements of prognostic power, in terms of AUROC, both for the validation (0.77 from 0.75) and the testing (0.73 from 0.71) set. Quantitative comparisons for three-class prediction and survival regression models exhibited a similar trend of comparable performance.

Conclusion: The findings highlight the potential of biophysical modeling for estimating and incorporating the spread of infiltrating cells into CTV delineation. Further clinical investigations are required to validate the clinical efficacy.