2552 - Conventionally Fractionated Reirradiation of Recurrent High Grade Gliomas: A Look at Dose Escalation and Safety

M. C. LeCompte¹, N. K. Vuppala², J. M. Reyes³, B. R. Page¹, V. J. Croog¹, C. Kut¹, E. Huang¹, K. J. Redmond¹, and L. R. Kleinberg¹; ¹Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, ²Alabama College of Osteopathic Medicine, Dothan, AL, ³Johns Hopkins University, Baltimore, MD

Purpose/Objective(s): Repeat radiotherapy (re-RT) is being increasingly utilized for recurrent Glioblastoma, but the optimal fractionation schedule remains unclear. The current study evaluates outcomes and toxicity after conventionally fractionated re-RT for recurrent high grade glioma (HGG), along with the impact of dose escalation. Materials/

Methods: Patients with HGG treated with conventionally fractionated re-RT at a single institution from 2007-2022 were retrospectively reviewed. All patients initially received conventionally fractionated RT. Patients with initial low grade gliomas were included if pathology confirmed transition to HGG. Cumulative maximum dose (Dmax) to optic apparatus and brainstem was determined by composite co-registered plans, when available. Outcome metrics included overall survival (OS), prognostic factors for survival, and treatment-related toxicity. Radiation necrosis (RN) was determined by imaging or pathology. Survival was estimated using Kaplan-Meier methodology. Univariate and multivariate Cox proportional hazard models for OS were constructed. Bivariable associations with RN were estimated using chi squared tests.
Results: 236 patients (median age: 50.5 yrs, median Karnofsky performance status: 80) were treated with re-RT for recurrent HGG with median followup of 7.3 mo. 58% of patients were treated with surgical resection prior to re-RT (20% GTR, 28% STR, 10% unknown). Median time between initial RT and re-RT was 26 mo (range 2-214 mo). Median dose at initial RT was 6000 cGy (5040-7500cGy) with 83.9% receiving concurrent temozolomide (TMZ), while median received dose at re-RT was 4140 cGy (180-6000 cGy) to a median planning target volume (PTV) of 200.5 cc (15.9-900.6 cc). Median cumulative Dmax to the optics and brainstem were 5483 cGy (338-10315 cGy) and 7806 cGy (491-11081 cGy), respectively. 63.1% received concurrent TMZ, 7.6% received TMZ + bevacizumab (BEV), 8.9% received BEV alone, and 19.5% received no concurrent systemic therapy with re-RT. 46.6% were confirmed IDH-WT, and 24.6% were IDH-mutant. Median OS from completion of re-RT was 9.1 mo (95% CI 7.8-10.5 mo). On univariate analysis, time between initial RT and re-RT <24 mo (HR 0.42, CI 0.31-0.56), re-RT dose <4140 cGy (HR 0.50, CI 0.33-0.66), PTV = 200cc (HR 1.42, CI 1.06-1.91), and = grade 3 lymphopenia (HR 1.77, CI 1.19-2.63) during or within 1 month after re-RT were associated with shorter OS. On multivariate analysis, < 24 mo between RT sessions (HR 0.43, CI 0.30-0.62), re-RT dose <4140 cGy (HR 0.59, CI 0.41-0.87), and = grade 3 lymphopenia (HR 1.77, CI 1.14-2.75) remained associated with shorter OS. No cases of radiation injury to the optics were reported. 8.9% of patients experienced RN. Re-RT dose > 4140 cGy (p=0.18) and re-RT PTV >200 cc (p=0.62) were not significantly associated with RN.
Conclusion: These data support the safety and efficacy of conventionally fractionated re-RT for recurrent HGG and suggest that dose escalation may be feasible, including for large treatment volumes.