Pulsed Reduced Dose Rate (PRDR) Intensity Modulated Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results

Abstract

<h3>Purpose/Objective(s)</h3> Pulsed reduced dose rate (PRDR) intensity-modulated radiotherapy (IMRT) is a reirradiation approach that may reduce the risk of toxicities in the setting of prior radiotherapy (RT) for recurrent central nervous system (CNS) malignancies. However, toxicities and cumulative doses (in EQD2) to CNS structures are not uniformly reported. We shared our institutional outcomes of PRDR and reported cumulative doses for CNS organs-at-risk (OARs) <h3>Materials/Methods</h3> Consecutive patients diagnosed with recurrent primary CNS tumors treated with PRDR from April 2017 to September 2021 were evaluated. Data collected included number of prior interventions, diagnosis, tumor grade, RT dose and fractionation, cumulative OAR doses, progression-free survival (PFS), overall survival (OS), and adverse events. A systematic review of literature was also performed, and results were compared to this study. <h3>Results</h3> Eighteen patients met inclusion criteria (11 WHO grade 4 glioma, 6 grade 3 glioma, and 1 grade 2 glioma). All patients had at least 1 surgery (range 1-4) and 2 systemic therapy regimens (range 2-6) before PRDR. The median dose for the first course of RT was 59.4 Gy (range: 50-75 Gy) in 33 fractions and the median time from the initial RT to PRDR was 35.6 months (range: 7.0-122.0 months). The median PRDR dose was 45 Gy (range: 36-59.4 Gy) in 25 fractions; the median cumulative EQD2 dose was 107.6 Gy (93.1-132.5 Gy). The median target volume was 134.9 cc (range: 17.9-696.6 cc). The median cumulative EQD2 Dmax values for the brain and brainstem were 111.4 Gy (range: 82.4-175.2 Gy), and 85.4 Gy (range: 14.8-111.6 Gy). At a median follow-up of 6.2 months, grade 2+ treatment-related toxicities were seen in 12 (66.7%) patients. Symptomatic radiation necrosis occurred in 3 (16.7%) patients, the median EQD2 brain Dmax for these patients was 115.9 Gy (110.4-156.7 Gy). In addition, two patients had grade 3 toxicity (fatigue and hearing impairment); no Grade 4+ toxicities were observed. The median PFS and OS after PRDR were 6.3 months (95% Cl: 0.9-11.6 months) and 8.6 months (95% Cl: 4.9-12.3 months), respectively. The systematic review analyzed 5 peer-reviewed studies reporting outcomes for reirradiation with PRDR for 188 patients. The median PRDR dose was 50 Gy (range: 22-60 Gy) in 25 fractions with a median cumulative dose of 110.3 Gy to a median tumor volume of 369.1 cc. At a median follow-up of 8.7 months, the total number of grade 3+ toxicities was 24, but time-dependent analyses were not uniformly reported. <h3>Conclusion</h3> This study supports PRDR reirradiation as a feasible and appropriate strategy for recurrent primary CNS tumors where other options have been exhausted. Despite high cumulative EQD2 to the OARs, the risk of developing high-grade toxicities remains acceptable; the median cumulative brain EQD2 dose for developing necrosis is 115.9 Gy.