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Peer-reviewedCC BY-NC 4.0Asian Pacific Journal of Cancer Prevention : APJCP

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

  • Kazem Anvari1
  • Seyed Alireza Javadinia2
  • Danial Fazilat-Panah3
  • Habibollah Esmaily4
  • Seyed Amir Aledavood1
  • Sudabeh Shahidsales1
  • Babak Ganjeifar5
  • Mahdieh Dayyani6
  • Parisa Rabiei1
6 affiliations
  1. 1Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
  2. 2Non-Communicable Diseases Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.
  3. 3Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
  4. 4Department of Public Health & Epidemiology, Mashhad University of Medical Sciences, Mashhad, Iran.
  5. 5Department of Neurological Surgery, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  6. 6Reza Radiotherapy and Oncology Center, Mashhad, Iran.
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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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Cite

BibTeXRIS
BibTeX
@article{anvari2026comparing,
  title = {{Comparing the Recurrence Patterns of Reduced-Margins vs. RTOG-Protocol in Adjuvant Chemoradiation of High-Grade Gliomas: A Multicenter, Open-Label, Randomized Controlled Trial}},
  author = {Kazem Anvari and Seyed Alireza Javadinia and Danial Fazilat-Panah and Habibollah Esmaily and Seyed Amir Aledavood and Sudabeh Shahidsales and Babak Ganjeifar and Mahdieh Dayyani and Parisa Rabiei},
  journal = {Asian Pacific Journal of Cancer Prevention : APJCP},
  year = {2026},
  month = jun,
  doi = {10.31557/apjcp.2026.27.6.2005},
  url = {https://doi.org/10.31557/apjcp.2026.27.6.2005},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Comparing the Recurrence Patterns of Reduced-Margins vs. RTOG-Protocol in Adjuvant Chemoradiation of High-Grade Gliomas: A Multicenter, Open-Label, Randomized Controlled Trial
AU  - Kazem Anvari
AU  - Seyed Alireza Javadinia
AU  - Danial Fazilat-Panah
AU  - Habibollah Esmaily
AU  - Seyed Amir Aledavood
AU  - Sudabeh Shahidsales
AU  - Babak Ganjeifar
AU  - Mahdieh Dayyani
AU  - Parisa Rabiei
PY  - 2026
DA  - 2026/06/18
JO  - Asian Pacific Journal of Cancer Prevention : APJCP
DO  - 10.31557/apjcp.2026.27.6.2005
UR  - https://doi.org/10.31557/apjcp.2026.27.6.2005
AB  - 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.
SN  - 1513-7368
SN  - 2476-762X
ER  -