A comprehensive retrospective study conducted at Johns Hopkins University has demonstrated the safety and efficacy of fractionated reirradiation for patients with recurrent high-grade glioma, potentially expanding treatment options for this challenging condition.
The study, published in Neuro-Oncology Advances, analyzed data from 230 patients treated between 2007 and 2022, revealing a median overall survival of 10.2 months from the start of reirradiation. For patients with IDH wildtype glioblastoma, the median survival was 8.7 months.
Treatment Protocol and Dosing
Patients received a median reirradiation dose of 41.4 Gy, with 80.4% receiving concurrent systemic therapy. The majority (93%) underwent conventionally fractionated reirradiation with 1.8 to 2 Gy fractions. Common treatment regimens included 45 Gy in 25 fractions (38.3%) and 36 Gy in 20 fractions (22.6%).
When systemic therapy was administered, Temodar (temozolomide) was given at 75 mg/m² daily, while Avastin (bevacizumab) was administered at 10 mg/kg biweekly. The median cumulative maximum doses to brainstem and optic structures were 77.9 Gy and 55.1 Gy, respectively.
Safety Profile and Toxicity
The study revealed encouraging safety data, with minimal neurotoxicity observed. Key findings include:
- Acute grade 3 or higher toxicity occurred in 9.6% of patients
- Late grade 3 or higher toxicity was observed in 6.5% of cases
- Radiation necrosis occurred in 7.8% of all patients
- No brainstem radiation necrosis was reported
- No injuries to optic structures were identified
Factors Influencing Survival Outcomes
Multivariate analysis identified several factors associated with improved overall survival:
- Better Karnofsky performance status
- Longer interval between radiotherapy sessions
- Reirradiation at first recurrence
- Reirradiation dose ≥41.4 Gy
For patients with IDH wildtype tumors specifically, improved survival was linked to longer intervals between radiotherapy sessions and higher reirradiation doses.
Clinical Implications
"These data support the safety and efficacy of fractionated reirradiation for recurrent high-grade glioma," stated Dr. Michael C. LeCompte, the study's lead author from Johns Hopkins University's Department of Radiation Oncology and Molecular Radiation Sciences.
The findings are particularly significant given the current lack of standard-of-care treatment for recurrent high-grade glioma. The study suggests that higher reirradiation doses may be feasible, even for large treatment volumes and tumors near critical brain structures.
Patient Population and Treatment Characteristics
Of the study cohort, 82.2% had grade 3 or 4 glioma at diagnosis. Among patients with available molecular data, 65.5% were IDH wildtype, and 49.4% showed MGMT promoter methylation. Sixty percent underwent surgery before reirradiation, with 20.4% achieving gross total resection.
The median interval between initial treatment and reirradiation was 25.9 months, with 58.2% of patients receiving reirradiation at first recurrence. This timing proved to be a significant factor in treatment outcomes.
The study's findings establish fractionated reirradiation as a viable salvage therapy option for recurrent high-grade glioma, particularly when administered at doses of 41.4 to 45 Gy alongside concurrent daily Temodar. These results provide a foundation for future clinical trials and the development of novel concurrent treatments.
