{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:42:23Z","timestamp":1792255343331,"version":"4.4.0"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Metastasis"],"DOI":"10.1007\/s10585-026-10439-5","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:05:37Z","timestamp":1792224337000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PD-1\/ PD-l1 Inhibitors and Stereotactic Radiosurgery for Brain Metastases: a systematic review and meta-analysis"],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7825-6355","authenticated-orcid":false,"given":"Yara","family":"Alswaiti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghena","family":"Shahwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakr","family":"Alhayek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Absi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Alzyoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dua\u2019a","family":"Kanaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badr","family":"Nawar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad Mahmoud","family":"Whdan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Gutierrez-Valencia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1567-3182","authenticated-orcid":false,"given":"Ayah","family":"Erjan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,17]]},"reference":[{"key":"10439_CR1","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_433694","volume":"44","author":"A Amouzegar","year":"2024","unstructured":"Amouzegar A, Haig S, Kahn AM et al (2024) Navigating the complexities of brain metastases management. Am Soc Clin Oncol Educ Book 44:e433694. https:\/\/doi.org\/10.1200\/EDBK_433694","journal-title":"Am Soc Clin Oncol Educ Book"},{"key":"10439_CR2","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.1200\/JCO.2004.12.149","volume":"22","author":"JS Barnholtz-Sloan","year":"2004","unstructured":"Barnholtz-Sloan JS, Sloan AE, Davis FG et al (2004) Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 22:2865\u20132872. https:\/\/doi.org\/10.1200\/JCO.2004.12.149","journal-title":"J Clin Oncol"},{"key":"10439_CR3","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1093\/neuonc\/nox077","volume":"19","author":"DN Cagney","year":"2017","unstructured":"Cagney DN, Martin AM, Catalano PJ et al (2017) Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro-Oncol 19:1511\u20131521. https:\/\/doi.org\/10.1093\/neuonc\/nox077","journal-title":"Neuro-Oncol"},{"key":"10439_CR4","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1200\/JCO.2011.38.0527","volume":"30","author":"PW Sperduto","year":"2012","unstructured":"Sperduto PW, Kased N, Roberge D et al (2012) Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30:419\u2013425. https:\/\/doi.org\/10.1200\/JCO.2011.38.0527","journal-title":"J Clin Oncol"},{"key":"10439_CR5","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1016\/S1470-2045(09)70263-3","volume":"10","author":"EL Chang","year":"2009","unstructured":"Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:1037\u20131044. https:\/\/doi.org\/10.1016\/S1470-2045(09)70263-3","journal-title":"Lancet Oncol"},{"key":"10439_CR6","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.prro.2022.02.003","volume":"12","author":"V Gondi","year":"2022","unstructured":"Gondi V, Bauman G, Bradfield L et al (2022) Radiation therapy for brain metastases: an ASTRO clinical practice guideline. Pract Radiat Oncol 12:265\u2013282. https:\/\/doi.org\/10.1016\/j.prro.2022.02.003","journal-title":"Pract Radiat Oncol"},{"key":"10439_CR7","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1016\/j.wneu.2017.07.062","volume":"107","author":"MA Ali","year":"2017","unstructured":"Ali MA, Hirshman BR, Wilson B et al (2017) Survival patterns of 5750 stereotactic radiosurgery-treated patients with brain metastasis as a function of the number of lesions. World Neurosurg 107:944-951.e1. https:\/\/doi.org\/10.1016\/j.wneu.2017.07.062","journal-title":"World Neurosurg"},{"key":"10439_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-023-01518-1","volume":"16","author":"D Zhou","year":"2023","unstructured":"Zhou D, Gong Z, Wu D et al (2023) Harnessing immunotherapy for brain metastases: insights into tumor\u2013brain microenvironment interactions and emerging treatment modalities. J Hematol Oncol 16:121. https:\/\/doi.org\/10.1186\/s13045-023-01518-1","journal-title":"J Hematol Oncol"},{"key":"10439_CR9","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/S1470-2045(16)30091-2","volume":"17","author":"R Rosell","year":"2016","unstructured":"Rosell R, Karachaliou N (2016) Trends in immunotherapy for brain metastases. Lancet Oncol 17:859\u2013860. https:\/\/doi.org\/10.1016\/S1470-2045(16)30091-2","journal-title":"Lancet Oncol"},{"key":"10439_CR10","doi-asserted-by":"publisher","first-page":"e498","DOI":"10.1016\/S1470-2045(15)00007-8","volume":"16","author":"AB Sharabi","year":"2015","unstructured":"Sharabi AB, Lim M, DeWeese TL, Drake CG (2015) Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol 16:e498\u2013e509. https:\/\/doi.org\/10.1016\/S1470-2045(15)00007-8","journal-title":"Lancet Oncol"},{"key":"10439_CR11","doi-asserted-by":"publisher","first-page":"373","DOI":"10.3171\/2014.10.JNS141610","volume":"123","author":"PK Sneed","year":"2015","unstructured":"Sneed PK, Mendez J, Vemer-van Den Hoek JGM et al (2015) Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors. J Neurosurg 123:373\u2013386. https:\/\/doi.org\/10.3171\/2014.10.JNS141610","journal-title":"J Neurosurg"},{"key":"10439_CR12","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1097\/WCO.0000000000000756","volume":"32","author":"TT Tran","year":"2019","unstructured":"Tran TT, Jilaveanu LB, Omuro A et al (2019) Complications associated with immunotherapy for brain metastases. Curr Opin Neurol 32:907\u2013916. https:\/\/doi.org\/10.1097\/WCO.0000000000000756","journal-title":"Curr Opin Neurol"},{"key":"10439_CR13","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.3171\/2023.4.JNS2349","volume":"139","author":"S Yomo","year":"2023","unstructured":"Yomo S, Oda K, Oguchi K (2023) Synergistic effects of immune checkpoint inhibitors in combination with stereotactic radiosurgery for patients with lung cancer and brain metastases: a propensity score\u2013matched analysis. J Neurosurg 139:1628\u20131637. https:\/\/doi.org\/10.3171\/2023.4.JNS2349","journal-title":"J Neurosurg"},{"key":"10439_CR14","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71","author":"MJ Page","year":"2021","unstructured":"Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. https:\/\/doi.org\/10.1136\/bmj.n71","journal-title":"BMJ"},{"key":"10439_CR15","volume-title":"Cochrane handbook for systematic reviews of interventions version 6.5 (updated August 2024)","author":"JPT Higgins","year":"2024","unstructured":"Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ et al (2024) Cochrane handbook for systematic reviews of interventions version 6.5 (updated August 2024). Cochrane"},{"key":"10439_CR16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1236398","volume":"14","author":"G Antelo","year":"2023","unstructured":"Antelo G, Comas S, Casas F et al (2023) Clinical outcomes and timing on the combination of focal radiation therapy and immunotherapy for the treatment of brain metastases. Front Immunol 14:1236398. https:\/\/doi.org\/10.3389\/fimmu.2023.1236398","journal-title":"Front Immunol"},{"key":"10439_CR17","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/s12967-023-04089-4","volume":"21","author":"W Tian","year":"2023","unstructured":"Tian W, Chu X, Tanzhu G, Zhou R (2023) Optimal timing and sequence of combining stereotactic radiosurgery with immune checkpoint inhibitors in treating brain metastases: clinical evidence and mechanistic basis. J Transl Med 21:244. https:\/\/doi.org\/10.1186\/s12967-023-04089-4","journal-title":"J Transl Med"},{"key":"10439_CR18","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14051240","volume":"14","author":"M Trommer","year":"2022","unstructured":"Trommer M, Adams A, Celik E et al (2022) Oncologic outcome and immune responses of radiotherapy with anti-PD-1 treatment for brain metastases regarding timing and benefiting subgroups. Cancers 14:1240. https:\/\/doi.org\/10.3390\/cancers14051240","journal-title":"Cancers"},{"key":"10439_CR19","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.radonc.2018.08.025","volume":"130","author":"EJ Lehrer","year":"2019","unstructured":"Lehrer EJ, Peterson J, Brown PD et al (2019) Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: an international meta-analysis of individual patient data. Radiother Oncol 130:104\u2013112. https:\/\/doi.org\/10.1016\/j.radonc.2018.08.025","journal-title":"Radiother Oncol"},{"key":"10439_CR20","unstructured":"National Heart, Lung, and Blood Institute. Quality assessment tool for observational cohort and cross-sectional studies. National Institutes of Health. Published 2013. https:\/\/www.nhlbi.nih.gov\/health-topics\/study-quality-assessment-tools"},{"key":"10439_CR21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1471-2288-12-9","volume":"12","author":"P Guyot","year":"2012","unstructured":"Guyot P, Ades A, Ouwens MJ, Welton NJ (2012) Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol 12:9. https:\/\/doi.org\/10.1186\/1471-2288-12-9","journal-title":"BMC Med Res Methodol"},{"key":"10439_CR22","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1080\/00207454.2021.1900843","volume":"133","author":"L Andring","year":"2023","unstructured":"Andring L, Squires B, Seymour Z et al (2023) Radionecrosis (RN) in patients with brain metastases treated with stereotactic radiosurgery (SRS) and immunotherapy. Int J Neurosci 133:186\u2013193. https:\/\/doi.org\/10.1080\/00207454.2021.1900843","journal-title":"Int J Neurosci"},{"key":"10439_CR23","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.jtho.2018.01.012","volume":"13","author":"HG Hubbeling","year":"2018","unstructured":"Hubbeling HG, Schapira EF, Horick NK et al (2018) Safety of combined PD-1 pathway inhibition and intracranial radiation therapy in non-small cell lung cancer. J Thorac Oncol 13:550\u2013558. https:\/\/doi.org\/10.1016\/j.jtho.2018.01.012","journal-title":"J Thorac Oncol"},{"key":"10439_CR24","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.cllc.2020.10.014","volume":"22","author":"TL Enright","year":"2021","unstructured":"Enright TL, Witt JS, Burr AR et al (2021) Combined immunotherapy and stereotactic radiotherapy improves neurologic outcomes in patients with non-small-cell lung cancer brain metastases. Clin Lung Cancer 22:110\u2013119. https:\/\/doi.org\/10.1016\/j.cllc.2020.10.014","journal-title":"Clin Lung Cancer"},{"key":"10439_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.adro.2021.100798","volume":"6","author":"KA Ahmed","year":"2021","unstructured":"Ahmed KA, Kim Y, Arrington JA et al (2021) Nivolumab and stereotactic radiosurgery for patients with breast cancer brain metastases: a nonrandomized, open-label phase 1b study. Adv Radiat Oncol 6:100798. https:\/\/doi.org\/10.1016\/j.adro.2021.100798","journal-title":"Adv Radiat Oncol"},{"key":"10439_CR26","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1068592","volume":"13","author":"S Bashir","year":"2023","unstructured":"Bashir S, Wen L, Zhang P et al (2023) Efficacy and safety of combined immunotherapy and stereotactic radiosurgery in NSCLCBM patients and a novel prognostic nomogram: a real-world study. Front Oncol 13:1068592. https:\/\/doi.org\/10.3389\/fonc.2023.1068592","journal-title":"Front Oncol"},{"key":"10439_CR27","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1093\/neuonc\/noz046","volume":"21","author":"R Kotecha","year":"2019","unstructured":"Kotecha R, Kim JM, Miller JA et al (2019) The impact of sequencing PD-1\/PD-L1 inhibitors and stereotactic radiosurgery for patients with brain metastasis. Neuro-Oncol 21:1060\u20131068. https:\/\/doi.org\/10.1093\/neuonc\/noz046","journal-title":"Neuro-Oncol"},{"key":"10439_CR28","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1093\/neuonc\/noab129","volume":"23","author":"S Scoccianti","year":"2021","unstructured":"Scoccianti S, Olmetto E, Pinzi V et al (2021) Immunotherapy in association with stereotactic radiotherapy for non-small cell lung cancer brain metastases: results from a multicentric retrospective study on behalf of AIRO. Neuro-Oncol 23:1750\u20131764. https:\/\/doi.org\/10.1093\/neuonc\/noab129","journal-title":"Neuro-Oncol"},{"key":"10439_CR29","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.canrad.2021.01.007","volume":"25","author":"C Cabanie","year":"2021","unstructured":"Cabanie C, Biau J, Durando X et al (2021) Toxicity and time lapse between immunotherapy and stereotactic radiotherapy of brain metastases. Cancer Radiother 25:432\u2013440. https:\/\/doi.org\/10.1016\/j.canrad.2021.01.007","journal-title":"Cancer Radiother"},{"key":"10439_CR30","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdad018","volume":"5","author":"P Wong","year":"2023","unstructured":"Wong P, Masucci L, Florescu M et al (2023) Phase II multicenter trial combining nivolumab and radiosurgery for NSCLC and RCC brain metastases. Neuro-oncol Adv 5:vdad018. https:\/\/doi.org\/10.1093\/noajnl\/vdad018","journal-title":"Neuro-oncol Adv"},{"key":"10439_CR31","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s11060-024-04895-w","volume":"172","author":"AS Marwaha","year":"2025","unstructured":"Marwaha AS, Liang Y, Shepard MJ et al (2025) Patterns of failure after stereotactic radiosurgery for brain metastases from small cell lung cancer: outcomes in the immunotherapy era. J Neurooncol 172:177\u2013183. https:\/\/doi.org\/10.1007\/s11060-024-04895-w","journal-title":"J Neurooncol"},{"key":"10439_CR32","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s11060-022-03951-7","volume":"157","author":"M Abdulhaleem","year":"2022","unstructured":"Abdulhaleem M, Johnston H, D\u2019Agostino R et al (2022) Local control outcomes for combination of stereotactic radiosurgery and immunotherapy for non-small cell lung cancer brain metastases. J Neurooncol 157:101\u2013107. https:\/\/doi.org\/10.1007\/s11060-022-03951-7","journal-title":"J Neurooncol"},{"key":"10439_CR33","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1097\/CMR.0000000000000413","volume":"28","author":"C Nardin","year":"2018","unstructured":"Nardin C, Mateus C, Texier M et al (2018) Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed cell death-1 (pembrolizumab) for melanoma brain metastases. Melanoma Res 28:111\u2013119. https:\/\/doi.org\/10.1097\/CMR.0000000000000413","journal-title":"Melanoma Res"},{"key":"10439_CR34","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003730","volume":"9","author":"G Minniti","year":"2021","unstructured":"Minniti G, Lanzetta G, Capone L et al (2021) Leptomeningeal disease and brain control after postoperative stereotactic radiosurgery with or without immunotherapy for resected brain metastases. J Immunother Cancer 9:e003730. https:\/\/doi.org\/10.1136\/jitc-2021-003730","journal-title":"J Immunother Cancer"},{"key":"10439_CR35","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3340\/jkns.2020.0135","volume":"64","author":"MH Lee","year":"2021","unstructured":"Lee MH, Cho K-R, Choi JW et al (2021) Immune checkpoint inhibitors for non-small-cell lung cancer with brain metastasis: the role of gamma knife radiosurgery. J Korean Neurosurg Soc 64:271\u2013281. https:\/\/doi.org\/10.3340\/jkns.2020.0135","journal-title":"J Korean Neurosurg Soc"},{"key":"10439_CR36","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123668","volume":"12","author":"A Cho","year":"2020","unstructured":"Cho A, Untersteiner H, Hirschmann D et al (2020) Gamma knife radiosurgery for brain metastases in non-small cell lung cancer patients treated with immunotherapy or targeted therapy. Cancers 12:3668. https:\/\/doi.org\/10.3390\/cancers12123668","journal-title":"Cancers"},{"key":"10439_CR37","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10092249","volume":"10","author":"J Porte","year":"2022","unstructured":"Porte J, Saint-Martin C, Frederic-Moreau T et al (2022) Efficacy and safety of combined brain stereotactic radiotherapy and immune checkpoint inhibitors in non-small-cell lung cancer with brain metastases. Biomedicines 10:2249. https:\/\/doi.org\/10.3390\/biomedicines10092249","journal-title":"Biomedicines"},{"key":"10439_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0282-x","volume":"5","author":"ES Anderson","year":"2017","unstructured":"Anderson ES, Postow MA, Wolchok JD et al (2017) Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment. J Immunother Cancer 5:76. https:\/\/doi.org\/10.1186\/s40425-017-0282-x","journal-title":"J Immunother Cancer"},{"key":"10439_CR39","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.ijrobp.2018.02.175","volume":"101","author":"E Schapira","year":"2018","unstructured":"Schapira E, Hubbeling H, Yeap BY et al (2018) Improved overall survival and locoregional disease control with concurrent PD-1 pathway inhibitors and stereotactic radiosurgery for lung cancer patients with brain metastases. Int J Radiat Oncol Biol Phys 101:624\u2013629. https:\/\/doi.org\/10.1016\/j.ijrobp.2018.02.175","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"10439_CR40","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0588-y","volume":"7","author":"G Minniti","year":"2019","unstructured":"Minniti G, Anzellini D, Reverberi C et al (2019) Stereotactic radiosurgery combined with nivolumab or ipilimumab for patients with melanoma brain metastases: evaluation of brain control and toxicity. J Immunother Cancer 7:102. https:\/\/doi.org\/10.1186\/s40425-019-0588-y","journal-title":"J Immunother Cancer"},{"key":"10439_CR41","doi-asserted-by":"publisher","first-page":"512","DOI":"10.3171\/2018.10.JNS181371","volume":"132","author":"C Singh","year":"2020","unstructured":"Singh C, Qian JM, Yu JB, Chiang VL (2020) Local tumor response and survival outcomes after combined stereotactic radiosurgery and immunotherapy in non\u2013small cell lung cancer with brain metastases. J Neurosurg 132:512\u2013517. https:\/\/doi.org\/10.3171\/2018.10.JNS181371","journal-title":"J Neurosurg"},{"key":"10439_CR42","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s11060-017-2437-5","volume":"133","author":"KA Ahmed","year":"2017","unstructured":"Ahmed KA, Kim S, Arrington J et al (2017) Outcomes targeting the PD-1\/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases. J Neurooncol 133:331\u2013338. https:\/\/doi.org\/10.1007\/s11060-017-2437-5","journal-title":"J Neurooncol"},{"key":"10439_CR43","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14174069","volume":"14","author":"P Saiag","year":"2022","unstructured":"Saiag P, Molinier R, Roger A et al (2022) Efficacy of large use of combined hypofractionated radiotherapy in a cohort of anti-PD-1 monotherapy-treated melanoma patients. Cancers (Basel) 14:4069. https:\/\/doi.org\/10.3390\/cancers14174069","journal-title":"Cancers (Basel)"},{"key":"10439_CR44","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.radonc.2017.06.006","volume":"124","author":"LRG Pike","year":"2017","unstructured":"Pike LRG, Bang A, Ott P et al (2017) Radiation and PD-1 inhibition: favorable outcomes after brain-directed radiation. Radiother Oncol 124:98\u2013103. https:\/\/doi.org\/10.1016\/j.radonc.2017.06.006","journal-title":"Radiother Oncol"},{"key":"10439_CR45","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-011432","volume":"13","author":"KA Ahmed","year":"2025","unstructured":"Ahmed KA, Kim Y, Kim S et al (2025) Nivolumab and stereotactic radiosurgery for patients with breast cancer brain metastases: long-term results and biomarker analysis from a non-randomized, open-label, phase Ib study. J Immunother Cancer 13:e011432. https:\/\/doi.org\/10.1136\/jitc-2024-011432","journal-title":"J Immunother Cancer"},{"key":"10439_CR46","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.646328","volume":"11","author":"S Wu","year":"2021","unstructured":"Wu S, Yuan C, Chen L et al (2021) Survival benefits of anti-PD-1 therapy in combination with radiotherapy in Chinese melanoma patients with brain metastasis. Front Oncol 11:646328. https:\/\/doi.org\/10.3389\/fonc.2021.646328","journal-title":"Front Oncol"},{"key":"10439_CR47","doi-asserted-by":"publisher","first-page":"685","DOI":"10.3171\/2019.4.JNS19822","volume":"133","author":"MJ Shepard","year":"2020","unstructured":"Shepard MJ, Xu Z, Donahue J et al (2020) Stereotactic radiosurgery with and without checkpoint inhibition for patients with metastatic non\u2013small cell lung cancer to the brain: a matched cohort study. J Neurosurg 133:685\u2013692. https:\/\/doi.org\/10.3171\/2019.4.JNS19822","journal-title":"J Neurosurg"},{"key":"10439_CR48","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.ejca.2020.04.028","volume":"135","author":"R Carron","year":"2020","unstructured":"Carron R, Gaudy-Marqueste C, Amatore F et al (2020) Stereotactic radiosurgery combined with anti-PD1 for the management of melanoma brain metastases: a retrospective study of safety and efficacy. Eur J Cancer 135:52\u201361. https:\/\/doi.org\/10.1016\/j.ejca.2020.04.028","journal-title":"Eur J Cancer"},{"key":"10439_CR49","doi-asserted-by":"publisher","first-page":"4026","DOI":"10.1002\/cam4.3021","volume":"9","author":"B Gatterbauer","year":"2020","unstructured":"Gatterbauer B, Hirschmann D, Eberherr N et al (2020) Toxicity and efficacy of Gamma Knife radiosurgery for brain metastases in melanoma patients treated with immunotherapy or targeted therapy\u2014a retrospective cohort study. Cancer Med 9:4026\u20134036. https:\/\/doi.org\/10.1002\/cam4.3021","journal-title":"Cancer Med"},{"key":"10439_CR50","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.ejca.2017.01.007","volume":"75","author":"ES Choong","year":"2017","unstructured":"Choong ES, Lo S, Drummond M et al (2017) Survival of patients with melanoma brain metastasis treated with stereotactic radiosurgery and active systemic drug therapies. Eur J Cancer 75:169\u2013178. https:\/\/doi.org\/10.1016\/j.ejca.2017.01.007","journal-title":"Eur J Cancer"},{"key":"10439_CR51","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.1093\/annonc\/mdw417","volume":"27","author":"KA Ahmed","year":"2016","unstructured":"Ahmed KA, Abuodeh YA, Echevarria MI et al (2016) Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF\/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy. Ann Oncol 27:2288\u20132294. https:\/\/doi.org\/10.1093\/annonc\/mdw417","journal-title":"Ann Oncol"},{"key":"10439_CR52","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1007\/s11060-025-05026-9","volume":"173","author":"AY Fu","year":"2025","unstructured":"Fu AY, Bernstein K, Zhang J et al (2025) Outcomes of concurrent versus non-concurrent immune checkpoint inhibition with stereotactic radiosurgery for melanoma brain metastases. J Neurooncol 173:619\u2013625. https:\/\/doi.org\/10.1007\/s11060-025-05026-9","journal-title":"J Neurooncol"},{"key":"10439_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2025.108813","volume":"210","author":"L Frehner","year":"2025","unstructured":"Frehner L, Sch\u00e4r S, Hayoz S et al (2025) First-line immunotherapy \u00b1 chemotherapy with or without upfront stereotactic radiotherapy (SRT) in patients with non-small cell lung cancer (NSCLC) with asymptomatic brain metastases. Lung Cancer 210:108813. https:\/\/doi.org\/10.1016\/j.lungcan.2025.108813","journal-title":"Lung Cancer"},{"key":"10439_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.113287","volume":"192","author":"AE Dohm","year":"2023","unstructured":"Dohm AE, Nakashima JY, Kalagotla H et al (2023) Stereotactic radiosurgery and anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF\/MEK inhibitors, BRAF inhibitors, or conventional chemotherapy for the management of melanoma brain metastases. Eur J Cancer 192:113287. https:\/\/doi.org\/10.1016\/j.ejca.2023.113287","journal-title":"Eur J Cancer"},{"key":"10439_CR55","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/S1470-2045(20)30111-X","volume":"21","author":"SB Goldberg","year":"2020","unstructured":"Goldberg SB, Schalper KA, Gettinger SN et al (2020) Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. Lancet Oncol 21:655\u2013663. https:\/\/doi.org\/10.1016\/S1470-2045(20)30111-X","journal-title":"Lancet Oncol"},{"key":"10439_CR56","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/S1470-2045(18)30139-6","volume":"19","author":"GV Long","year":"2018","unstructured":"Long GV, Atkinson V, Lo S et al (2018) Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol 19:672\u2013681. https:\/\/doi.org\/10.1016\/S1470-2045(18)30139-6","journal-title":"Lancet Oncol"},{"key":"10439_CR57","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s13566-015-0217-4","volume":"4","author":"W Jiang","year":"2015","unstructured":"Jiang W, Tang C, Chang JY (2015) Radiation with immunotherapy: an emerging combination for cancer treatment. J Radiat Oncol 4:331\u2013338. https:\/\/doi.org\/10.1007\/s13566-015-0217-4","journal-title":"J Radiat Oncol"},{"key":"10439_CR58","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1080\/02688697.2021.2022098","volume":"37","author":"S Badrigilan","year":"2023","unstructured":"Badrigilan S, Meola A, Chang SD et al (2023) Stereotactic radiosurgery with immune checkpoint inhibitors for brain metastases: a meta-analysis study. Br J Neurosurg 37:1533\u20131543. https:\/\/doi.org\/10.1080\/02688697.2021.2022098","journal-title":"Br J Neurosurg"},{"key":"10439_CR59","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s11060-022-04038-z","volume":"158","author":"A Le","year":"2022","unstructured":"Le A, Mohammadi H, Mohammed T et al (2022) Local and distant brain control in melanoma and NSCLC brain metastases with concurrent radiosurgery and immune checkpoint inhibition. J Neurooncol 158:481\u2013488. https:\/\/doi.org\/10.1007\/s11060-022-04038-z","journal-title":"J Neurooncol"},{"key":"10439_CR60","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111621","volume":"22","author":"M Rodr\u00edguez Pl\u00e1","year":"2021","unstructured":"Rodr\u00edguez Pl\u00e1 M, Dualde Beltr\u00e1n D, Ferrer Albiach E (2021) Immune checkpoints inhibitors and SRS\/SBRT synergy in metastatic non-small-cell lung cancer and melanoma: a systematic review. Int J Mol Sci 22:11621. https:\/\/doi.org\/10.3390\/ijms222111621","journal-title":"Int J Mol Sci"},{"key":"10439_CR61","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1177\/0271678X16630991","volume":"36","author":"HC Helms","year":"2016","unstructured":"Helms HC, Abbott NJ, Burek M et al (2016) In vitro models of the blood\u2013brain barrier: an overview of commonly used brain endothelial cell culture models and guidelines for their use. J Cereb Blood Flow Metab 36:862\u2013890. https:\/\/doi.org\/10.1177\/0271678X16630991","journal-title":"J Cereb Blood Flow Metab"},{"key":"10439_CR62","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1714089115","author":"D Taggart","year":"2018","unstructured":"Taggart D, Andreou T, Scott KJ et al (2018) Anti\u2013PD-1\/anti\u2013CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8+ T cell trafficking. Proc Natl Acad Sci. https:\/\/doi.org\/10.1073\/pnas.1714089115","journal-title":"Proc Natl Acad Sci"},{"key":"10439_CR63","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/labinvest.2016.35","volume":"96","author":"E Vandenhaute","year":"2016","unstructured":"Vandenhaute E, Drolez A, Sevin E et al (2016) Adapting coculture in vitro models of the blood\u2013brain barrier for use in cancer research: maintaining an appropriate endothelial monolayer for the assessment of transendothelial migration. Lab Invest 96:588\u2013598. https:\/\/doi.org\/10.1038\/labinvest.2016.35","journal-title":"Lab Invest"},{"key":"10439_CR64","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1016\/j.ijrobp.2009.06.006","volume":"77","author":"BJ Blonigen","year":"2010","unstructured":"Blonigen BJ, Steinmetz RD, Levin L et al (2010) Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol 77:996\u20131001. https:\/\/doi.org\/10.1016\/j.ijrobp.2009.06.006","journal-title":"Int J Radiat Oncol"},{"key":"10439_CR65","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1002\/cncr.34087","volume":"128","author":"EJ Lehrer","year":"2022","unstructured":"Lehrer EJ, Gurewitz J, Bernstein K et al (2022) Radiation necrosis in renal cell carcinoma brain metastases treated with checkpoint inhibitors and radiosurgery: an international multicenter study. Cancer 128:1429\u20131438. https:\/\/doi.org\/10.1002\/cncr.34087","journal-title":"Cancer"},{"key":"10439_CR66","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2025.124390","volume":"202","author":"HB Walker","year":"2025","unstructured":"Walker HB, Casey K, Ricci S et al (2025) A systematic review and meta-analysis of radiation necrosis incidence in brain metastasis treated by gamma knife and cyberknife stereotactic radiosurgery. World Neurosurg 202:124390. https:\/\/doi.org\/10.1016\/j.wneu.2025.124390","journal-title":"World Neurosurg"},{"key":"10439_CR67","doi-asserted-by":"publisher","first-page":"4114","DOI":"10.1007\/s00330-020-07514-0","volume":"31","author":"PH Kim","year":"2021","unstructured":"Kim PH, Suh CH, Kim HS et al (2021) Immune checkpoint inhibitor therapy may increase the incidence of treatment-related necrosis after stereotactic radiosurgery for brain metastases: a systematic review and meta-analysis. Eur Radiol 31:4114\u20134129. https:\/\/doi.org\/10.1007\/s00330-020-07514-0","journal-title":"Eur Radiol"},{"key":"10439_CR68","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1007\/s00066-022-01973-8","volume":"198","author":"D Bernhardt","year":"2022","unstructured":"Bernhardt D, K\u00f6nig L, Grosu A-L et al (2022) DEGRO practical guideline for central nervous system radiation necrosis part 2: treatment. Strahlenther Onkol 198:971\u2013980. https:\/\/doi.org\/10.1007\/s00066-022-01973-8","journal-title":"Strahlenther Onkol"},{"key":"10439_CR69","doi-asserted-by":"publisher","unstructured":"Vaios EJ, Winter SF, Shih HA, et al. Novel Mechanisms and Future Opportunities for the Management of Radiation Necrosis in Patients Treated for Brain Metastases in the Era of Immunotherapy. Cancers (Basel). 2023;15(9):2432. Published 2023 Apr 24. 10.3390\/cancers15092432 https:\/\/doi.org\/10.3390\/cancers15092432","DOI":"10.3390\/cancers15092432"}],"container-title":["Clinical & Experimental Metastasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10585-026-10439-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10585-026-10439-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10585-026-10439-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:02:44Z","timestamp":1792252964000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10585-026-10439-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,17]]},"references-count":69,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["10439"],"URL":"https:\/\/doi.org\/10.1007\/s10585-026-10439-5","relation":{},"ISSN":["1573-7276"],"issn-type":[{"value":"1573-7276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,17]]},"assertion":[{"value":"27 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"None to declare.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Due to the nature of this study, being a systematic review and meta-analysis of previously published literature, it does not involve the direct participation of human subjects or the collection of primary individual patient data, no Internal Review Board\u00a0(IRB) was obtained.","order":3,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"58"}}