Comparative Outcomes of Standard Radiation Therapy and 5-Fraction Adaptive Stereotactic Radiation Therapy in Newly Diagnosed Glioblastoma: A Propensity Score-Matched Analysis

Abstract

Purpose: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, with poor survival despite advancements in treatment. Adaptive stereotactic radiation therapy (RT) using a magnetic resonance imaging linear accelerator is an emerging approach for patients with newly diagnosed GBM eligible for conventional fractionation. We hypothesize that adaptive stereotactic RT can provide comparable outcomes with conventional fractionation while reducing treatment burden.

Methods and materials: We retrospectively reviewed 96 adults with newly diagnosed GBM treated at our institution between 2018 and 2024. Inclusion criteria included the age of 18 years, confirmed GBM diagnosis, and completed treatment. Patients with prior brain irradiation or incomplete treatment were excluded. Propensity score matching was performed to balance demographics, tumor characteristics, and treatment protocols across 5-fraction, 15-fraction, and 30-fraction groups. Statistical analyses included the Fisher exact test, Mann-Whitney U test, Cox proportional hazards models, and Kaplan-Meier survival curves.

Results: After propensity score matching, 17 pairs were matched for 5 versus 30 fractions and 14 pairs for 5 versus 15 fractions. Median overall survival was 21.1 versus 18.2 months (5 vs 15 fractions, P = .77) and 11.7 versus 14.6 months (5 vs 30 fractions, P = .5). Median progression-free survival was 9.0 versus 7.9 months (5 vs 15 fractions, P = .89) and 8.9 versus 9.7 months (5 vs 30 fractions, P = .97). Local failure and grade 3 toxicity rates were similar across groups. O6-methylguanine-DNA-methyltransferase unmethylated status, higher Eastern Cooperative Oncology Group scores, and age 60 years were associated with worse progression-free survival and overall survival. Median travel distances were lower in the 5-fraction group, with a median of 220 miles compared with 877.5 (15 fractions) and 1638 miles (30 fractions). Adaptive RT allowed for real-time tumor monitoring but volumetric changes did not correlate with clinical outcomes.

Conclusions: Adaptive 5-fraction RT demonstrates comparable survival outcomes with conventional fractionation while reducing treatment-related travel burden. Further prospective studies are needed to validate its role in GBM management.

Figure 1

Kaplan-Meier survival curves for (A) overall survival for 15 versus 5 fractions, (B) progression-free survival for 15 versus 5 fractions, (C) overall survival for 30 versus 5 fractions, and (D) progression-free survival for 30 versus 5 fractions.

Figure 2

Cumulative incidence of local failure in the (A) 5-fraction versus 15-fraction and (B) 5-fraction versus 30-fraction groups.

Figure 3

Cumulative incidence of grade 3+ cerebral edema (A) and bone marrow toxicity (B) in the 5-fraction versus 15-fraction groups, and grade 3+ cerebral edema (C) and bone marrow toxicity (D) in the 5-fraction versus 30-fraction groups.