Purpose: Repeat radiation therapy (re-RT) is an increasingly utilized therapy for the recurrence of Glioblastoma, but there is uncertainty about the optimal dosing regimen. We report the results with conventionally fractionated radiation, intending to maximize concurrent daily temozolomide and safe treatment of larger volumes.
Methodology: Patients with high-grade gliomas treated with conventional fractionated re-RT at a single institution from 2016-2022 were retrospectively reviewed. All patients received conventionally fractionated radiation therapy initially. Patients diagnosed initially with low-grade glioma were included if there was a confirmed transition to high-grade glioma on pathology. Outcome metrics included overall survival (OS), prognostic factors for survival, and treatment-related toxicity. Radiation necrosis was defined by imaging or pathology. Univariate and multivariate Cox proportional hazard models for OS were constructed and survival was estimated using the Kaplan-Meier analysis. Associations between treatment parameters and radiation necrosis were assessed using chi-squared tests.
Results: 129 patients (median age: 53 years, median Karnofsky performance status: 80) were treated with conventionally fractionated re-RT for recurrent high-grade glioma with a median follow-up of 7.5 months. 70.5% of patients were treated with surgical resection before re-RT. The median time between initial RT and re-RT was 24 months (2-267 months). The median dose at initial RT was 6000 cGy (5040-7500 cGy), with 89.9% receiving concurrent temozolomide, while median dose at re-RT was 4500 cGy (180-6000 cGy) to a median planning target volume (PTV) of 204.7 cc (15.9-824.9 cc). 72.7% received concurrent temozolomide, 0.8% received bevacizumab, 0.8% received temozolomide plus bevacizumab, and 25.8% received no concurrent systemic therapy with re-RT. Planned re-RT was completed by 92.3% of patients. Median OS from completion of re-RT was 11.2 (95% confidence interval [CI], 8.3-13.5) for all patients. By initial glioma grade, median OS from the end of re-RT end was 13.5, 13.6, and 8.2 months for grades 2, 3, and 4, respectively. On univariate analysis, time between initial RT and re-RT ≤24 months (HR 0.45, CI 0.29-0.70, p< 0.001), re-RT dose received ≤4140 cGy (HR 0.60, CI 0.38-0.92, p=0.02), lymphopenia (HR 1.37, CI 1.11-1.69, p=0.003) and thrombocytopenia (HR 2.46, CI 1.59-3.81, p< 0.001) during or within one month after re-RT were associated with shorter OS. On multivariate analysis, re-RT dose received ≤4140 cGy (HR 0.47, CI 0.28-0.78, p=0.004) and thrombocytopenia (HR 2.47, CI 1.50-4.07, p< 0.001) remained associated with shorter OS. 11.63% of patients experienced radiation necrosis. Received re-RT dose > 4140 cGy (p=0.62) and re-RT PTV >200 cc (p=0.47) were not significantly associated with radiation necrosis.
Conclusions: Treatment of high-grade glioma with conventionally fractionated reirradiation doses> 4140 cGy appears to be a safe salvage option and may offer these patients a survival benefit. These data also support the safety of re-RT of large treatment volumes, >200 cc, and repeat use of concurrent temozolomide.
