{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:22:15Z","timestamp":1783113735908,"version":"3.54.6"},"reference-count":58,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Arteriovenous malformations (AVMs) are rare, high\u2010flow, vascular anomalies that can occur either sporadically or as part of a genetic syndrome. AVMs can progress with serious morbidity and even mortality if left unchecked. Sirolimus is an mTOR inhibitor that is effective in low\u2010flow vascular malformations; however, its role in AVMs is unclear. This scoping review investigates the current evidence base around the use of sirolimus for AVMs. Twenty\u2010one reports encompassing a total of 60 patients with AVMs treated with systemic sirolimus were included. Sirolimus was predominantly used as an adjunct or salvage therapy. Response was variable overall; however, there was a more consistent benefit in patients with PTEN hamartoma syndrome (PHTS)\u2010associated AVMs, where PI3K\/AKT\/mTOR pathway dysregulation provides a molecular basis for sirolimus efficacy. Standardised outcome reporting, routine molecular profiling, and larger multicentre collaboration are needed to better define the role of sirolimus for AVMs, particularly as part of multimodal care.<\/jats:p>","DOI":"10.1002\/1545-5017.70325","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:25:26Z","timestamp":1776407126000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sirolimus for Extracranial Arteriovenous Malformations: A Scoping Review of the Evidence in Syndromic and Non\u2010Syndromic Cases"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7730-8909","authenticated-orcid":false,"given":"Will","family":"Swansson","sequence":"first","affiliation":[{"name":"Department of Dermatology The Royal Melbourne Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Winship","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine The Royal Melbourne Hospital  Melbourne Victoria Australia"},{"name":"Department of Medicine The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Hammerschlag","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine The Royal Melbourne Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Scardamaglia","sequence":"additional","affiliation":[{"name":"Department of Dermatology The Royal Melbourne Hospital  Melbourne Victoria Australia"},{"name":"Department of Medicine The University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Dermatology Western Health  Melbourne Victoria Australia"},{"name":"Department of Dermatology The Royal Children's Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-41278-z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjps.2010.05.033"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jimed.2023.10.006"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.018"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otc.2017.09.006"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00585-z"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/379793"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.026886"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181ac9aea"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.048934"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)07946-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-199809010-00006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181d18070"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2007.087452"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2003.10.048"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2018.12.033"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2016.07.001"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-3257"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2019.06.217"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.6.1307"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000479632"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2018.3039"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.14841"},{"issue":"12","key":"e_1_2_10_25_1","first-page":"1105","article-title":"Efficacy and Tolerance of Sirolimus (Rapamycin) for Extracranial Arteriovenous Malformations in Children and Adults","volume":"99","author":"Gabeff R.","year":"2019","journal-title":"Acta Dermato\u2010Venereologica"},{"issue":"1","key":"e_1_2_10_26_1","first-page":"86","article-title":"Sirolimus in the Treatment of Vascular Anomalies","volume":"27","author":"Triana P.","year":"2017","journal-title":"European Journal of Pediatric Surgery"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2021.04.071"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2021-246265"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-1970"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-023-02732-3"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2024-262673"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvsv.2020.07.001"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.15435"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23098"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1661377"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-3262"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.31282"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/JOVA.0000000000000047"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000515168"},{"issue":"1","key":"e_1_2_10_40_1","first-page":"35","article-title":"Targeted Therapy With sirolimus in Vascular Malformations\u2013a Case Report","volume":"20","author":"Gueif\u00e3o I.","year":"2024","journal-title":"Angiologia e Cirurgia Vascular"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2018.4653"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2024.1434493"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.2174\/18763863-v16-23005050-2022-9"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.14853"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017-1044"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30758"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-023-02740-3"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2014.12.069"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI98589"},{"issue":"9","key":"e_1_2_10_50_1","first-page":"3065","article-title":"Inhibition of mTORC1 Leads to MAPK Pathway Activation Through a PI3K\u2010Dependent Feedback Loop in human Cancer","volume":"118","author":"Carracedo A.","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-022-09853-6"},{"key":"e_1_2_10_52_1","unstructured":"ClinicalTrials.gov \u201cTrametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation (ClinicalTrialsgov identifier NCT04258046) \u201dNCT 2025 https:\/\/clinicaltrials.gov\/study\/NCT04258046?cond=NCT04258046&rank=1."},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456\u2010024\u201009961\u20105"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI127425"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-3-200602070-00030"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15715"},{"key":"e_1_2_10_57_1","unstructured":"ClinicalTrials.gov \u201cSirolimus for Nosebleeds in HHT (ClinicalTrials.gov identifier NCT05269849) \u201dNCT 2025 https:\/\/clinicaltrials.gov\/study\/NCT05269849?cond=sirolimus%20hht&rank=1."},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2014.04.010"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1097\/JOVA.0000000000000065"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1545-5017.70325","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/1545-5017.70325","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1545-5017.70325","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:58:31Z","timestamp":1783112311000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/1545-5017.70325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":58,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/1545-5017.70325"],"URL":"https:\/\/doi.org\/10.1002\/1545-5017.70325","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"assertion":[{"value":"2026-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70325"}}