{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T06:31:41Z","timestamp":1777962701927,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T00:00:00Z","timestamp":1562630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Targeted therapies (TT), combination immunotherapy (CMI), and monoimmunotherapy (MI) in combination with radiotherapy (CRI) or not are commonly used in patients with melanoma brain metastases, but studies that directly compare these strategies are lacking. The current meta\u2010analysis aimed to better elucidate their activity and efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic search of MEDLINE, Embase, and conference proceedings up to January 2019 was performed to identify trials investigating combination TT, monotargeted TT (mono TT), MI, CMI, and CRI in melanoma brain metastases. The outcomes considered were progression\u2010free survival (PFS), overall survival (OS), and the objective response rate (ORR) as evaluated at both intracranial and extracranial sites. Random effects models were used to compare the different therapeutic strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 15 trials were included that provided 1132 patients for analyses. CMI demonstrated a statistically significant better OS compared with MI (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.03, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.05, and <jats:italic>P<\/jats:italic>\u00a0=\u00a0.03, respectively, at 6\u00a0months, 18\u00a0months, and 24\u00a0months) and combination TT (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.04 and <jats:italic>P<\/jats:italic>\u00a0=\u00a0.03, respectively, at 18\u00a0months and 24\u00a0months). CMI demonstrated a statistically significant better PFS compared with combination TT (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001 at 12\u00a0months and 18\u00a0months), MI (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.02, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.02, and <jats:italic>P<\/jats:italic>\u00a0=\u00a0.05, respectively, at 6\u00a0months, 12\u00a0months, and 18\u00a0months), and mono TT (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001 at 6\u00a0months, 12\u00a0months, and 18\u00a0months). The intracranial objective response rate was higher with CMI compared with mono TT (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) and MI (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), whereas there was no difference between CMI and combination TT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of the current meta\u2010analysis suggested that CMI increases long\u2010term PFS and OS compared with MI and combination TT. Combination TT and CMI are associated with a similar intracranial response rate. The role of systemic therapy in combination with radiotherapy remains to be better elucidated.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.32375","type":"journal-article","created":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T08:34:58Z","timestamp":1562661298000},"page":"3776-3789","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["The impact of targeted therapies and immunotherapy in melanoma brain metastases: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"125","author":[{"given":"Eliana","family":"Rulli","sequence":"first","affiliation":[{"name":"Department of Oncology Mario Negri IRCCS Institute for Pharmacological Research Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Legramandi","sequence":"additional","affiliation":[{"name":"Department of Oncology Mario Negri IRCCS Institute for Pharmacological Research Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-0392","authenticated-orcid":false,"given":"Lorenzo","family":"Salvati","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8846-8959","authenticated-orcid":false,"given":"Mario","family":"Mandala","sequence":"additional","affiliation":[{"name":"Unit of Medical Oncology, Department of Oncology and Hematology Pope John XXIII Cancer Center Hospital Bergamo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30946"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25634"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-803508-5.00019-6"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.1206"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.08.140"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12538"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60868-X"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003466"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60898-4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00083-2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412690"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503093"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)70076-8"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu577"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70431-X"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70090-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30053-5"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805453"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30429-1"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602018"},{"key":"e_1_2_8_24_1","unstructured":"National Institute for Health and Care Excellence (NICE).NICE quality assessment for case series.https:\/\/www.nice.org.uk\/guidance\/cg3\/documents\/appendix-4-quality-of-case-series-form2. 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