Reduced Clinical Target Volume Margins in Glioblastoma: Exploratory Evidence Supporting Further Margin Reduction Independent of MGMT Status

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Background: Clinical target volume (CTV) delineation in glioblastoma remains debated, particularly in the era of modern chemoradiation and image-guided radiotherapy. Whether reduced CTV margins can preserve oncological outcomes without increasing marginal or out-of-field failures remains uncertain. We evaluated the association of GTV-to-CTV margin with survival, patterns of failure, and its interaction with MGMT promoter methylation status. Materials and Methods: We retrospectively analyzed a single-center cohort of patients with glioblastoma treated with conventionally fractionated chemoradiation (58–60 Gy in 29–33 fractions). Patients were categorized into two predefined margin groups: < 1.5 cm and equal to 1.5 cm. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and patterns of failure. Survival was assessed using Kaplan–Meier estimates and Cox regression, including an interaction term with MGMT status. Results: Among 102 eligible patients, 95 were included in the margin-based OS analysis. Reduced margins (< 1.5 cm) were not associated with worse OS, either overall or within MGMT subgroups. No significant differences were observed in PFS or patterns of failure, with overlapping recurrence distributions and no increase in marginal or out-of-field recurrences. MGMT methylation and gross total resection were independently associated with improved survival, while no interaction between margin and MGMT status was detected. Conclusions: Reduction of the GTV-to-CTV margin to ≤1.2 cm was not associated with worse survival or unfavorable recurrence patterns, consistently across MGMT subgroups. These findings support the oncological adequacy of margins of approximately 15 mm and provide a rationale for exploring further margin reduction, potentially independent of MGMT status. Prospective validation is warranted.

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