Abstract 6502: Impact of immune checkpoint inhibition combined with stereotactic radiotherapy in treatment of brain metastases
Authors: Khedkar Sonal , Kennedy Andrew S. , Hunt D Edward , Gray James , Johnson Melissa L. , Chollet-Lipscomb Casey , McKean Meredith , Stevens Brian J. , Spigel David 
Published: September 2020

Abstract
Introduction: Stereotactic radiosurgery and radiotherapy (SRS-SRT) is a valuable treatment for brain metastases (BMs) due to its specificity to the patient and reduction of toxic effects compared to whole brain radiation. Immune checkpoint inhibition (ICI) is also an important treatment option utilizing anti-cytotoxic T-lymphocyte-associated protein 4 and anti-programed cell death protein 1 receptors in cancer cells. However, few published studies are available describing how combined immunotherapy and SRS-SRT affect patient outcomes. The purpose of this study was to retrospectively analyze how SRS-SRT given in combination with immunotherapy affects toxicity and survivorship in patients with metastatic brain tumors.
Methods: A retrospective review was completed of patients with BMs treated with linac-based SRS-SRT and ICI from 2010-2019 at a community cancer program. IRB exempt status was established. Timing of ICI in relation to SRS-SRT was characterized as prior (ended 6 months before), concurrent (delivered within 2 weeks before or during), and following (initiated more than 3 months) after radiation. Total radiation dose, fractionation, number of BMs treated, and conformality index (CI) in relation to ICI drug(s) and incidence of acute and delayed toxicities via RTOG criteria, were analyzed to identify predictors of toxicity and tumor control. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier survival curves and Cox proportional hazards models were used for multivariate analysis. Brain MRI with contrast was completed every 3 months post-radiation. Patients were evaluated via ROS and physical exam q2-3 months until death.
Results: The final sample consisted of 417 patients, 178M, 239F, with the mean age of 62.6 years (range 17-90). Primary tumor sites of BMs were lung (NSCLC and SCLC) 56%, Other 16.6%, breast 12.9%, melanoma 8.8%, and colon 5.5%. There were a total of 986 BMs treated, median dose was 2000 cGy in 3 fractions. A total of 71 pts (17%) received ICIs concurrent with SRS-SRT. Median RTOG toxicity score was 0.73, (SD 1.049). Neurotoxicity grade 3 occurred in 6.2% of all patients. Concurrent use of either Ipilimumab or Pembrolizumab with SRS-SRT showed significantly increased acute RTOG toxicity scores compared to either pre or post radiation ICI use of any drug. No grade 4 or 5 toxicities occurred. PFS and OS were not significantly associated with use of concurrent ICI with radiotherapy.
Conclusions: The use of ICI prior to, during or after SRS-SRT for BMs appears to be safe in both acute and delayed toxicity evaluation. However a small but statistically significant increase in acute toxicities was observed when concurrent Ipilimumab or Pembrolizumab were given.
Citation Format: Sonal Khedkar, Andrew S. Kennedy, D Edward Hunt, James Gray, Melissa L. Johnson, Casey Chollet-Lipscomb, Meredith McKean, Brian J. Stevens, David Spigel. Impact of immune checkpoint inhibition combined with stereotactic radiotherapy in treatment of brain metastases [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6502.