Conventional Chemoradiotherapy Versus hypofractionated Chemoradiotherapy in Glioblastoma Multiforme Patients: Are We Ready to Change a Paradigm?

Background/Objectives: Hypofractionated radiation therapy (Hypo-RT) schedules may offer radiobiological, patient convenience, and healthcare resource advantages over standard fractionated radiation therapy (S-RT) for glioblastoma (GBM). Additionally, simulated integrated boost (SIB) Hypo-RT is proven to be an effective and safe treatment. We report on our experience regarding progression-free survival (PFS), overall survival (OS), and RT-related toxicities in GBM patients treated with Hypo-RT and S-RT. Methods: Patients with IDH-wildtype GBM received either Hypo-RT (40.05-52.5 Gy/15 fractions) or S-RT (60-70 Gy/30 fractions). Volumetric modulated arc therapy was performed for all patients. Concomitant temozolomide (75 mg/m²/day) and adjuvant chemotherapy (TMZ 150-200 mg/m² for 5 days every 28 days) were administered. OS and PFS were estimated using the Kaplan-Meier method. Results: Ninety-five patients were treated (Hypo-RT: 52, S-RT: 43). With a median follow-up of 25 months (range 9-63), the median age was 65 and 54 years for the Hypo-RT and S-RT groups, respectively. All patients tolerated the treatment well; no significant adverse effects were observed in either group. No acute or late neurological side effects of grade ≥ 2 were reported during RT. Grade 3-4 hematologic toxicity occurred in five cases, all of which interrupted concomitant TMZ (all occurring in the S-RT arm). The time to progression for the S-RT and Hypo-RT groups was 13.7 and 11.1 months, respectively (p=0.243). Regarding OS, the S-RT group had a median OS of 28.8 months compared to 17.5 months in the Hypo-RT group (p=0.007). Conclusions: Although further investigations are ongoing, a statistically significant difference exists in OS between Hypo-RT and S-RT. Hypo-RT could potentially become the standard of care not only for elderly patients but also for those with poor prognosis. Additional investigation with more data is necessary in this context to determine the best standard approach.