Benedikt Wiestler

Background The diffuse growth pattern of glioblastoma is one of the main challenges for accurate treatment. Computational tumor growth modeling has emerged as a promising tool to guide personalized therapy. Here, we performed clinical and biological validation of a novel growth model, aiming to close the gap between the experimental state and clinical implementation. Methods One hundred and twenty-four patients from The Cancer Genome Archive (TCGA) and 397 patients from the UCSF Glioma Dataset were assessed for significant correlations between clinical data, genetic pathway activation maps (generated with PARADIGM; TCGA only), and infiltration (Dw) as well as proliferation (ρ) parameters stemming from a Fisher–Kolmogorov growth model. To further evaluate clinical potential, we performed the same growth modeling on preoperative magnetic resonance imaging data from 30 patients of our institution and compared model-derived tumor volume and recurrence coverage with standard radiotherapy plans. Results The parameter ratio Dw/ρ (P < .05 in TCGA) as well as the simulated tumor volume (P < .05 in TCGA/UCSF) were significantly inversely correlated with overall survival. Interestingly, we found a significant correlation between 11 proliferation pathways and the estimated proliferation parameter. Depending on the cutoff value for tumor cell density, we observed a significant improvement in recurrence coverage without significantly increased radiation volume utilizing model-derived target volumes instead of standard radiation plans. Conclusions Identifying a significant correlation between computed growth parameters and clinical and biological data, we highlight the potential of tumor growth modeling for individualized therapy of glioblastoma. This might improve the accuracy of radiation planning in the near future.