(OA16) Repeat Whole Brain Radiation Therapy Using a Pulsed Reduced Dose Rate Technique

Abstract

Limited salvage options exist for patients with multiple recurrent brain metastases previously treated with whole brain radiation therapy (WBRT). Pulsed reduced dose rate radiation therapy (PRDR) is a biologically-unique irradiation strategy that lowers the effective dose rate, potentially decreasing toxicity to normal tissue by allowing for sublethal damage repair. PRDR has been shown to be safe and effective in patients with gliomas receiving partial brain re-irradiation. To our knowledge, this technique has not been reported before in patients with brain metastases who have received repeat WBRT with PRDR. We report our early outcomes using repeat WBRT with PRDR. We conducted a retrospective review of all brain tumor patients treated with PRDR at our institution. We further analyzed patients with brain metastases previously treated with WBRT who received repeat WBRT with PRDR at the time of clinical and/or radiographic progression. PRDR treatments were delivered with a series of 0.20 Gy pulses given over a 3-minute period, resulting in an apparent dose rate of 0.0667 Gy/min. Patients were treated with parallel-opposed whole brain lateral fields with dose prescribed to isocenter. We identified 26 patients who received WBRT with PRDR from 2012 to 2017 . We excluded 4 patients from further analysis as 2 patients had not received prior WBRT and 2 patient expired during treatment course due to extracranial disease. Primary histology included breast cancer (n=8), melanoma (n=5), NSCLC (n=6), non-seminomatous testicular cancer (n=1), SCLC (n=1) and sarcoma (n=1). Initial WBRT dose regimens included 30 Gy in 10 fractions (n=14), 37.5 Gy in 15 fractions (n=7), and 39.6 Gy in 18 fractions (n=1). KPS was 70-100 for all patients at time of first WBRT. Median time to progression after first WBRT was 7.7 months (range 1.3 - 54.8 months) at which time patients underwent repeat WBRT with PRDR. Patients received daily fractions of 2 – 3 Gy (median = 2 Gy) to a total dose of 20 Gy - 30 Gy (median = 24 Gy). KPS at repeat irradiation was 70-100 and age ranged from 28.3 yrs to 77.0 yrs (mean = 55.38 yrs). With a mean follow-up of 7.1 months (range 0.63 – 33.4 months), mean time to intracranial progression after repeat WBRT with PRDR was 4.7 months (range 0.53 – 15.5 months). Four patients had intracranial disease control after repeat WBRT with PRDR for > 6 months and 1 patient is still alive at the time of this review. No acute grade 3 toxicities were seen as a result of reirradiation based on CTCAE v4.03. Grade 1/2 toxicities included fatigue, anorexia, and alopecia. To our knowledge, this is the first report of repeat WBRT with PRDR. This technique appears to be a safe and feasible option for patients with multiple brain metastases who previously received WBRT. Future prospective studies using this technique are being considered.