Comparative Outcomes of Conventional Fractionation and 5-Fraction Adaptive Focal Stereotactic Radiation Therapy (FSRT) in Newly Diagnosed Glioblastoma: A Propensity Score-Matched Analysis

Summary: Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain tumor in adults, with poor survival despite treatment advancements. Focal stereotactic radiation therapy (FSRT) is an emerging adjuvant treatment for newly diagnosed GBM, traditionally delivered using static radiotherapy plans. Our approach utilizes adaptive FSRT with an MRI-linear accelerator (MRI-Linac) for patients eligible for conventional fractionation. We hypothesize that adaptive FSRT yields outcomes comparable to conventional fractionation, potentially reducing treatment burden for patients and families. We retrospectively reviewed 110 adults with newly diagnosed GBM treated at our institution (2018–2024). Inclusion criteria included age >18, confirmed GBM diagnosis, and completed treatment, excluding prior brain irradiation, other malignancies, or incomplete follow-up. Data on demographics, tumor characteristics, and treatment protocols were collected. Propensity-score matching (PSM) enhanced comparability between patients receiving 5-fraction adaptive FSRT, 15-fraction hypofractionation, and 30-fraction treatments, based on age, tumor volume, performance status, resection type, MGMT, and IDH status, using one-to-one nearest neighbor matching with a 0.1 caliper. Fisher’s exact test and Mann-Whitney U test compared categorical and continuous variables. Competing risk regression analyzed local control and grade 3+ toxicity (cerebral edema, blood toxicity), with Gray’s test for significance. Cox proportional hazards models evaluated time to local failure and grade 3+ vasogenic edema. Kaplan-Meier curves with log-rank tests compared OS and PFS. Analyses used SPSS 28.0.0.0 and R 4.3.3. We identified 19 patients in the 5-fraction group, 20 in the 15-fraction group, and 69 in the 30-fraction group. After exclusions and PSM, there were 17 pairs for 5 vs. 30-fraction and 14 pairs for 5 vs. 15-fraction comparisons. MGMT unmethylated status predicted worse PFS and local failure (5 vs. 15), while higher ECOG, MGMT unmethylated status, T2 FLAIR, and age ≥60 predicted worse PFS and OS (5 vs. 30). Median OS was 21.1 vs. 18.15 months (5 vs. 15) and 11.7 vs. 14.59 months (5 vs. 30), with PFS at 7.03 vs. 7.89 months (5 vs. 15) and 8.28 vs. 7.56 months (5 vs. 30), showing no significant differences. Local failure at 1 year was higher in the 30-fraction group (65% vs. 25%, p = 0.036). Grade 3+ toxicity (blood and cerebral edema) rates were similar. Median travel distances were 220 vs. 1,638 miles (5 vs. 30) and 254 vs. 877.5 miles (5 vs. 15). For newly diagnosed GBM patients, 5-fraction therapy with MR-LINAC emerges as a promising alternative, demonstrating similar survival outcomes compared to traditional 15- and 30-fraction treatments, with potential benefits in reducing treatment burden even in younger patients. Prospective studies are warranted to validate these findings and advance the understanding of FSRT in the management of newly diagnosed GBM in patients who traditionally would be eligible for conventional fractionation only. Luiza Giuliani Schmitt, MD (Presenting Author) - UT Southwestern Medical Center; Soummitra Anand, BS (Co-Author) - UT Southwestern Medical Center; Michael Youssef, MD (Co-Author) - UT Southwestern Medical Center; Nawal Shaikh, MD (Co-Author) - UT Southwestern Medical Center; Toral Patel, MD (Co-Author) - UT Southwestern Medical Center; Ankur Patel, MD (Co-Author) - UT Southwestern Medical Center; Sam Barnett, MD (Co-Author) - UT Southwestern Medical Center; MinJae Lee, PhD (Co-Author) - UT Southwestern Medical Center; Jill De Vis, MD, PhD (Co-Author) - UT Southwestern Medical Center; Xin Cai, MD, PhD (Co-Author) - UT Southwestern Medical Center; Robert Timmerman, MD (Co-Author) - UT Southwestern Medical Center; Tu Dan, MD (Co-Author) - UT Southwestern Medical Center; Zabihullah Wardak, MD (Co-Author) - UT Southwestern Medical Center; Michael Dohopolski, MD (Co-Author) - UT Southwestern Medical Center