Modified Target Delineation and Moderately Hypofractionated Radiotherapy for High-Grade Glioma

Importance: Optimizing irradiation volumes and evaluating the effect of dose escalation on total and fractionated doses are critical for improving outcomes in high-grade glioma (HGG). Objective: To assess the efficacy of modified target delineation guided by multimodal magnetic resonance imaging and white matter tracts combined with moderately hypofractionated simultaneous boost intensity-modulated radiotherapy (HSIB-IMRT) in patients with newly diagnosed HGG. Design, Setting, and Participants: This single-center, 2-arm, open-label randomized clinical trial enrolled 154 patients aged 18 to 70 years with histologically confirmed, newly diagnosed HGG at a Chinese medical center from January 1, 2018, to August 31, 2022. Follow-up was completed in June 2024. Interventions: Patients were randomized to receive modified target delineation guided by multimodal magnetic resonance imaging and white matter tracts combined with HSIB-IMRT (experimental arm) or standard IMRT per guideline recommendations (standard arm). Both arms received concurrent and adjuvant temozolomide chemotherapy. Main Outcomes and Measures: The primary end point was progression-free survival (PFS). The secondary end point was overall survival (OS). Results: Among 154 enrolled patients (76 in the experimental arm and 78 in the standard arm; 85 55.2% male; median range age, 51.5 23.0-70.0 years), the median (range) follow-up duration was 22 (4-76) months, with 96 deaths by June 2024. The median PFS was 15.5 months (95% CI, 11.7-19.3 months) in the experimental arm and 13.5 months (95% CI, 8.7-18.3 months) in the standard arm (P = .89). The median OS was 27.0 months (95% CI, 13.9-40.1 months) in the experimental arm and 21.0 months (95% CI, 18.0-24.0 months) in the standard arm (P = .24). The clinical target volume in the experimental arm (CTV1: median range, 116.7 20.2-370.7 cm3; CTV2: median range, 174.4 34.5-463.2 cm3) was significantly smaller than the clinical target volume in the standard arm (median range, 225.0 70.2-542.1 cm3; P < .001). Recurrence rates within, outside, and multicentric to the target volume were comparable between arms. Grade 3 or 4 adverse events occurred in 4 patients (5.3%) in the experimental arm and 3 (3.8%) in the standard arm (P = .72). Conclusions and Relevance: In this randomized clinical trial, modified target delineation with HSIB-IMRT demonstrated comparable PFS and OS to standard IMRT in patients with newly diagnosed HGG, while significantly reducing the irradiation target volume without increasing the recurrence rates outside the target volume. These results suggest valuable insights for future research aimed at personalized, reduced volume strategies to optimize outcomes and minimize neurotoxicity in HGG. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR1800014396.