Treatment Outcomes after Dose-Escalated Moderately Hypofractionated Radiotherapy for Frail Patients with High-Grade Glioma

Simple Summary Historically, frail patients who were older and showed poor performance status have been treated with a total dose of 40-45 Gy in 15 fractions, 34 Gy in 10 fractions, or 25 Gy in 5 fractions. We analyzed the oncologic outcomes after dose-escalated fractionated radiotherapy with a total dose of 56 Gy in 20 fractions for high-grade glioma in frail patients who were older than 70 years or showed poor performance status. This dose-escalated regimen with a total dose of 56 Gy in 20 fractions were comparable equivalent dose to conventional radiotherapy with a total dose 60 Gy in 30 fractions for non-frail patients. We observed survival outcomes outperforming historical data. The median overall survival was 12 months. Also, none of these patients experienced severe treatment-related toxicities. Furthermore, salvage treatment (either systemic therapy or local therapy) after progressive disease significantly improved survival outcomes after recurrence compared to supportive care even in frail patients.Abstract For high-grade glioma (HGG) patients with old age or poor performance status, hypofractionated radiotherapy (hypoRT) in 10-15 fractions is recommended. Also, limited data exist on the impact of salvage treatment after progression in frail patients. We retrospectively analyzed the outcomes of dose-escalated hypoRT in 40 frail HGG patients who were treated with hypoRT between 2013 and 2021. With a median biologically effective dose of 71.7 Gy, a total dose of 56 Gy in 20 fractions was the most frequently used regimen (53.7%). The median age and Karnofsky Performance Status of patients were 74 years and 70, respectively. Most patients (n = 31, 77.5%) were diagnosed with glioblastoma, IDH-wildtype, CNS WHO grade 4. Only 10 (25.0%) patients underwent surgical resection, and 28 (70.0%) patients received concurrent temozolomide during hypoRT. With a median follow-up of 9.7 months, the median overall survival (OS) was 12.2 months. Of the 30 (75.0%) patients with disease progression, only 12 patients received salvage treatment. The OS after progression differed significantly depending on salvage treatment (median OS, 9.6 vs. 4.6 months, p = 0.032). Dose-escalated hypoRT in 20 fractions produced survival outcomes outperforming historical data for frail patients.