Re-Irradiation Using Pulsed Reduced Dose Rate Radiation Therapy in 58 Patients with Recurrent Grade 2 Glioma

Abstract

<h3>Purpose/Objective(s)</h3> Patients with grade 2 glioma exhibit a markedly variable time course of survival ranging from months to over a decade. Re-irradiation for recurrent disease can be valuable for some patients but is less well studied than in the setting of high-grade glioma. We report treatment results of pulsed reduced dose rate (PRDR) radiation for patients with recurrent grade 2 glioma in an effort to prolong survival and limit normal tissue toxicity profiles. <h3>Materials/Methods</h3> We identified consecutive patients from an institutional database initially diagnosed with grade 2 glioma from 2000 to 2021 who underwent pulsed reduced dose rate radiation therapy. Radiation was delivered in 20 cGy pulses every three minutes, most commonly with a 3D conformal, three field technique, encompassing gross disease with a 1-2 cm margin. Kaplan Meier analysis was used to calculate overall survival and progression free survival. <h3>Results</h3> 58 patients with biopsy proven grade 2 glioma were identified. The median survival from initial date of surgery was 9.5 years (95% CI 6.3-12.7 yrs). 82% underwent at least a second resection and 86% received chemotherapy during their treatment course. 69% of patients showed malignant transformation to grade 3 (38%) or grade 4 (31%) glioma. Overall survival following PRDR was 12.6 months (95% CI 8.5-16.7 mo) and progression free survival was 6.3 months (95% CI 4.1-8.6 mo). Overall response rate based on post PRDR MRI was 36% with mixed or partial response, 29% with stable imaging findings, 11% with progression, and 9 cases with no post PRDR imaging. In patients who maintained grade 2 histology at recurrence, overall survival from PRDR was 22.0 months and five patients remain disease free, the longest of which are alive at 9.6 and 5.5 years. 1p19q co-deletion was associated with longer survival following PRDR with median survival for non-codeleted patients of 12.6 months (95% CI 7.9-17.3 mo) versus 33.7 months (95% CI 5.3-62.2 mo) in the co-deleted group (p = 0.18). PRDR was generally well tolerated, with four patients experiencing documented seizures and general fatigue reported as the most common complaint during treatment. <h3>Conclusion</h3> To our knowledge, this is the largest reported series of patients with recurrent grade 2 glioma treated with PRDR radiation for disease recurrence. We demonstrate promising survival efficacy and acceptable toxicity profiles following re-irradiation. In the cohort of patients who maintain grade 2 disease, prolonged survival (> 5 years) is observed in selected patients, 1p19q co-deletion is associated with longer survival.