Comparing the Recurrence Patterns of Reduced-Margins vs. RTOG-Protocol in Adjuvant Chemoradiation of High-Grade Gliomas: A Multicenter, Open-Label, Randomized Controlled Trial

Anvari, Kazem; Javadinia, Sseyed Alireza; Fazilatpanah, Danial; Esmaily, Habibollah; Aledavood, Seyed Amir; Shahidsales, Soudabe; Ganjeifar, Babak; Dayani, Mahdiye; Rabiei, Parisa

doi:10.31557/APJCP.2026.27.6.2005

Comparing the Recurrence Patterns of Reduced-Margins vs. RTOG-Protocol in Adjuvant Chemoradiation of High-Grade Gliomas: A Multicenter, Open-Label, Randomized Controlled Trial

Document Type : Research Articles

Authors

¹ Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

² Non-Communicable Diseases Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.

³ Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

⁴ Department of Public Health & Epidemiology, Mashhad University of Medical Sciences, Mashhad, Iran.

⁵ Department of Neurological Surgery, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

⁶ Reza Radiotherapy and Oncology Center, Mashhad, Iran.

10.31557/APJCP.2026.27.6.2005

Abstract

Background: Radiotherapy following maximal-safe resection is a cornerstone of treatment for high-grade gliomas (HGGs). However, the optimal clinical target volume (CTV) margin remains controversial. This study aimed to evaluate the safety, efficacy, and recurrence patterns associated with a reduced CTV margin in patients with HGGs, compared to standard RTOG-based planning. Methods: In this multicenter, phase III randomized clinical trial, patients aged 18–75 years with newly diagnosed WHO-grade 3 or 4 gliomas were randomly assigned to receive adjuvant radiotherapy with either a standard 2-cm clinical target volume (CTV) margin (control group) or a reduced 1-cm margin (intervention group). The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS) and patterns of recurrence. Results: A total of 258 patients were enrolled, of whom 75.6% had grade 4 gliomas. After a median follow-up of 14.5 months, median PFS was 15 ± 1.25 months in the intervention group but it was 19 ± 2.71 months in the control group (hazard ratio [HR] = 1.32; 95% CI, 0.93–1.87; p = 0.121). Median OS was 22.0 ± 2.98 months in the intervention group, while it was not reached in the control group (HR = 1.52; 95% CI, 0.99–2.33; p = 0.057). Imaging progression occurred in 35% of patients in the intervention group and 32.2% in the control group (p = 0.637). In-field recurrence was the predominant pattern in both groups (84% vs. 83.8%; p = 0.829), with no significant increase in marginal or out-of-field failures associated with margin reduction. Conclusion: Reducing the clinical target volume (CTV) margin from 2 cm to 1 cm in the adjuvant radiotherapy of high-grade gliomas did not significantly affect progression-free survival (PFS), overall survival (OS), or recurrence patterns. These findings support the feasibility and safety of margin reduction, even in settings where three-dimensional conformal radiotherapy (3D-CRT) is the primary technique.

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