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

Abstract

Simple SummaryPulsed-reduced dose rate (PRDR) is a technique used to safely deliver re-irradiation by targeting dividing neoplastic cells while permitting intra-therapy sublethal damage repair in previously irradiated normal tissues. However, treatment-related toxicities are not uniformly reported in previous PRDR studies; thus, it is unclear whether the cumulative thresholds (EQD2) for CNS organs-at-risk (OARs) can be designated in a “safe” category. In this study, we evaluated dosimetric data for patients treated with PRDR IMRT for recurrent primary CNS malignancies, generated accumulated equivalent uniform doses with rigid registration of all intracranial treatments, and investigated toxicity as a function of cumulative EQD2. We found that PRDR IMRT re-irradiation is a safe and feasible strategy for appropriately selected recurrent primary CNS tumor patients after exhausting other options. The clinical outcomes were favorable given the unique population treated with this approach (ineligible for other salvage treatments or enrollment onto clinical trials), and the toxicities observed were mild to moderate.Purpose: The objective was to describe PRDR outcomes and report EQD2 OAR toxicity thresholds. Methods: Eighteen patients with recurrent primary CNS tumors treated with PRDR at a single institution between April 2017 and September 2021 were evaluated. The radiotherapy details, cumulative OAR doses, progression-free survival (PFS), overall survival (OS), and toxicities were collected. Results: The median PRDR dose was 45 Gy (range: 36–59.4 Gy); the median cumulative EQD2 prescription dose was 102.7 Gy (range: 93.8–120.4 Gy). The median cumulative EQD2 D0.03cc for the brain was 111.4 Gy (range: 82.4–175.2 Gy). Symptomatic radiation necrosis occurred in three patients, for which the median EQD2 brain D0.03cc was 115.9 Gy (110.4–156.7 Gy). The median PFS and OS after PRDR were 6.3 months (95%CI: 0.9–11.6 months) and 8.6 months (95%CI: 4.9–12.3 months), respectively. The systematic review identified five peer-reviewed studies with a median cumulative EQD2 prescription dose of 110.3 Gy. At a median follow-up of 8.7 months, the median PFS and OS were 5.7 months (95%CI: 2.1–15.4 months) and 6.7 months (95%CI: 3.2–14.2 months), respectively. Conclusion: PRDR re-irradiation is a relatively safe and feasible treatment for recurrent primary CNS tumors. Despite high cumulative dose to OARs, the risk of high-grade, treatment-related toxicity within the first year of follow-up remains acceptable.