(OA12) Pulsed Reduced Dose Rate Re-Irradiation (PRDR) Using Modulated ARC (MARC) IMRT for Recurrent Gliomas: Initial Clinical Outcomes of a Novel Technique

Abstract

Limited salvage options exist for patients with recurrent malignant brain tumors after standard treatment. Pulsed reduced dose rate re-irradiation (PRDR) is a biologically-unique strategy that lowers the effective dose rate, potentially decreasing toxicity by allowing for greater sublethal damage repair in normal tissue. It has been shown to be safe and effective in patients with recurrent gliomas using a 3DRT technique. We developed a novel technique using PRDR with modulated arc (mARC) IMRT delivery to further reduce the amount of normal tissue exposed. We report our initial clinical results using mARC PRDR in patients with previously-irradiated recurrent gliomas. We conducted a retrospective review of all brain tumor patients treated with mARC PRDR at our Institution. All mARC PRDR plans were generated with Monaco (Elekta Inc) using 1/10 of the total prescription dose. For each treatment fraction a total of 10 identical treatment beams were delivered with a minimum time interval of 3 min between beam initiations. This technique allows for the entire treatment volume to receive exactly 1/10 of the prescription dose every 3 min while limiting the prescription dose rate to less than 0.0667 Gy/min. A total of 34 patients were treated with mARC PRDR. Primary histology included grade 2 (n=6), grade 3 (n=10), and grade 4 (n=15) gliomas. Median dose at initial RT was 60 Gy (range 48 – 70) at 1.8 – 2 Gy per fraction. Patients were heavily pre-treated with a mean of 3 prior recurrences (range 1 – 7) before PRDR. Nineteen patients had repeat resection at recurrence including 6 just prior to PRDR. Bevacizumab was previously given to 16 patients with 26 patients receiving bevacizumab while undergoing PRDR (dose 10 mg/kg or 5 mg/kg q2 weeks). All patients had a KPS of 70 or greater. Mean age at PRDR was 53 (range 3 – 71). Median interval between initial RT and PRDR was 4.75 years (range 0.5 – 18.3). Median total dose was 54 Gy (range 30 – 60) at 2 Gy per fraction. At a mean follow-up of 9.3 months (range 0.5 - 19.3), 6-month OS was 70.5% and 1-year was OS 23.5%. Median time to progression was 6 months with 6-month PFS 47% and 1-year PFS 17.6%. Five of the 34 patients did not finish treatment due to clinical decline and/or tumor progression. No acute G3 toxicities were seen from PRDR. This is the first clinical report of mARC IMRT PRDR for recurrent gliomas. This technique appears to be safe, feasible, and well-tolerated for previously-irradiated patients with recurrent gliomas. We await long-term clinical data to better define efficacy and toxicity.