Abstract
BACKGROUND
The purpose of this study was to assess the feasibility and effectiveness of AI-guided personalized precision radiation therapy (PPRT) with targeted dose escalation in enhancing outcomes for patients with newly diagnosed glioblastoma.
METHODS
An open-label trial was conducted at the University of Pennsylvania (NCT03477513) from August 2018 to April 2023, enrolling 20 patients with IDH-wildtype glioblastoma who underwent maximal safe resection. They were matched with a contemporaneous cohort of glioblastoma patients based on age, sex, extent of resection (EOR), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation status, and IDH status. Propensity score matching (PSM) was employed to select the control group, utilizing one-to-four nearest neighbor matching. One patient was excluded due to concurrent treatment with tumor treating fields (TTFields). The PPRT group received personalized radiation dose escalation to 75 Gy in 30 fractions guided by AI-based predictive modeling of recurrence, along with temozolomide chemotherapy. The control group received standard-of-care chemoradiotherapy, 60 Gy in 30 fractions. A previously published and evaluated (retrospectively and prospectively) predictive AI model, which has demonstrated high predictive value for neoplastic cell infiltration and future tumor recurrence using preoperative, multi-parametric MRIs, was utilized.
RESULTS
Median overall survival was 24.3 months in the PPRT-temozolomide group compared to 17.5 months in the standard-of-care treatment group (hazard ratio [HR]=0.30; 95% CI: 0.16-0.57; p<0.001). Excluding two patients with leptomeningeal disease and bone marrow metastasis, the median survival was 35.4 months (HR=0.25; 95% CI: 0.12-0.51; p<0.001).
CONCLUSION
AI-guided PPRT for newly diagnosed glioblastoma patients demonstrated feasibility in routine clinical practice and significantly improved overall survival compared to matched controls receiving standard-of-care treatment. These findings underscore the potential of personalized precision radiation therapy, with focused dose escalation, in improving outcomes for glioblastoma patients and emphasize the need for prospective validation in a randomized controlled clinical trial.