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MO_13_2794 - Report of Neurotoxicity after Concurrent Whole Brain Radiation Therapy and Checkpoint Blockade Immunotherapy for Patients with Brain Metastases

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Report of Neurotoxicity after Concurrent Whole Brain Radiation Therapy and Checkpoint Blockade Immunotherapy for Patients with Brain Metastases
R. H. Press1, Z. S. Buchwald2, C. Steuer3, R. Pillai3, T. K. Owonikoko3, S. Ramalingam3, W. J. Curran Jr1, and K. A. Higgins1; 1Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 2Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 3Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA

Purpose/Objective(s): For patients with brain metastases, whole brain radiation therapy (WBRT) is a standard of care. Additionally, the use of checkpoint blockade immunotherapy (IO) in advanced malignancies is increasing. The attributable cumulative rate of Grade 3+ (G3+) neurotoxicity after WBRT alone has been reported at 2% (RTOG 9508, Andrews et al. 2004), however the safety of administering WBRT in close temporal proximity to IO is poorly defined. Therefore, the purpose of this analysis was to determine whether concurrent delivery of WBRT and IO increases the G3+ neurotoxicity risk.

Materials/Methods: All patients with brain metastases who received WBRT and IO at our institution from 1/2013–12/2017 were evaluated. 41 patients were identified, of whom 19 received both therapies within 21 days of each other. For this cohort, we described patient and treatment characteristics as well as reported the incidence of neurotoxicity per CTCAE version 5.0.

Results: The median age was 62 (range 27-84) and median follow-up after WBRT was 10.8 months (range 1-24 months). Non-small cell lung cancer (n=5) and melanoma (n=14) were the primary histologies. Median WBRT dose was 30 Gy (range 30-37.5 Gy). 11 patients had previous treatment with stereotactic radiosurgery (SRS). IO included ipilimumab (n=8), nivolumab (n=3), and ipilimumab/nivolumab (n=3). Patients received IO either before WBRT (n=3), after WBRT (n=5), or both before and after WBRT (n=11). The median time from WBRT to IO was 6 days (range 0-21 days). The crude rate of G3+ radiation necrosis (RN) was 26% (n=5), however 2 instances occurred in lesions previously treated with SRS, 1 occurred after new treatment with SRS, and 1 occurred after a second course of WBRT. Therefore, the attributable G3+ RN rate was 5% (n=1) with a time to RN of 1.3 months. Two patients developed G3+ intracranial hemorrhage and 1 patient developed G3+ cognitive dysfunction, all occurring after intracranial progression. Additionally, no patients developed attributable G3+ seizures, strokes, headaches, or ataxia.

Conclusion: The delivery of IO within 21 days of WBRT appears well tolerated. The cumulative attributable rate of G3+ neurotoxicity after concurrent WBRT and IO was 5%, which is comparable to historic rates after WBRT alone.

Author Disclosure: R.H. Press: None. Z.S. Buchwald: None. C. Steuer: None. T.K. Owonikoko: None. W.J. Curran: Board Member; ASCO. K.A. Higgins: Consultant; Astra Zeneca.

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