PMID- 29378267 OWN - NLM STAT- MEDLINE DCOM- 20190403 LR - 20220409 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 13 IP - 4 DP - 2018 Apr TI - Safety of Combined PD-1 Pathway Inhibition and Intracranial Radiation Therapy in Non-Small Cell Lung Cancer. PG - 550-558 LID - S1556-0864(18)30039-X [pii] LID - 10.1016/j.jtho.2018.01.012 [doi] AB - INTRODUCTION: Intracranial metastases are a common cause of morbidity and mortality in patients with advanced NSCLC, and are frequently managed with radiation therapy (RT). The safety of cranial RT in the setting of treatment with immune checkpoint inhibitors (ICIs) has not been established. METHODS: We identified patients with advanced NSCLC with brain metastases who received cranial RT and were treated with or without programmed cell death 1/programmed death ligand 1 inhibitors between August 2013 and September 2016. RT-related adverse events (AEs) were retrospectively evaluated and analyzed according to ICI treatment status, cranial RT type, and timing of RT with respect to ICI. RESULTS: Of 163 patients, 50 (31%) received ICIs, whereas 113 (69%) were ICI naive. Overall, 94 (58%), 28 (17%), and 101 (62%) patients received stereotactic radiosurgery, partial brain irradiation, and/or whole brain RT, respectively. Fifty percent of patients received more than one radiation course. We observed no significant difference in rates of all-grade AEs and grade 3 or higher AEs between the ICI-naive and ICI-treated patients across different cranial RT types (grade >/=3 AEs in 8% of ICI-naive patients versus in 9% of ICI-treated patients for stereotactic radiosurgery [p = 1.00] and in 8% of ICI-naive patients versus in 10% of ICI-treated patients for whole brain RT [p = 0.71]). Additionally, there was no difference in AE rates on the basis of timing of ICI administration with respect to RT. CONCLUSIONS: Treatment with an ICI and cranial RT was not associated with a significant increase in RT-related AEs, suggesting that use of programmed cell death 1/programmed death ligand 1 inhibitors in patients receiving cranial RT may have an acceptable safety profile. Nonetheless, additional studies are needed to validate this approach. CI - Copyright (c) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. FAU - Hubbeling, Harper G AU - Hubbeling HG AD - Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. FAU - Schapira, Emily F AU - Schapira EF AD - Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Horick, Nora K AU - Horick NK AD - Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts. FAU - Goodwin, Kelly E H AU - Goodwin KEH AD - Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. FAU - Lin, Jessica J AU - Lin JJ AD - Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. FAU - Oh, Kevin S AU - Oh KS AD - Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Shaw, Alice T AU - Shaw AT AD - Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. FAU - Mehan, William A AU - Mehan WA AD - Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Shih, Helen A AU - Shih HA AD - Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Gainor, Justin F AU - Gainor JF AD - Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: jgainor@partners.org. LA - eng GR - C06 CA059267/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20180131 PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Programmed Cell Death 1 Receptor) SB - IM CIN - J Thorac Oncol. 2018 Apr;13(4):475-477. PMID: 29576287 MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/pathology/*radiotherapy MH - Combined Modality Therapy/*methods MH - Cranial Irradiation/methods MH - Female MH - Humans MH - Immunotherapy/*methods MH - Lung Neoplasms/pathology/*radiotherapy MH - Male MH - Middle Aged MH - Programmed Cell Death 1 Receptor/*antagonists & inhibitors OTO - NOTNLM OT - Brain metastases OT - Immunotherapy OT - NSCLC OT - PD-1 inhibitor OT - Radiation EDAT- 2018/01/30 06:00 MHDA- 2019/04/04 06:00 CRDT- 2018/01/30 06:00 PHST- 2017/11/01 00:00 [received] PHST- 2018/01/05 00:00 [revised] PHST- 2018/01/15 00:00 [accepted] PHST- 2018/01/30 06:00 [pubmed] PHST- 2019/04/04 06:00 [medline] PHST- 2018/01/30 06:00 [entrez] AID - S1556-0864(18)30039-X [pii] AID - 10.1016/j.jtho.2018.01.012 [doi] PST - ppublish SO - J Thorac Oncol. 2018 Apr;13(4):550-558. doi: 10.1016/j.jtho.2018.01.012. Epub 2018 Jan 31.