{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:18:39Z","timestamp":1790857119867,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We report on six patients with NF\u20101 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Subjects were 21\u00a0months to 14\u00a0years old at the time of initiation of trametinib therapy and 3\/6 subjects are male. Duration of therapy was 4\u201328\u00a0months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life\u2010threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6\u00a0months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1\u20132 paronychia or dermatitis in 5\/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF\u20101 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.3910","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T10:11:08Z","timestamp":1620036668000},"page":"3556-3564","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Trametinib therapy for children with neurofibromatosis type 1 and life\u2010threatening plexiform neurofibroma or treatment\u2010refractory low\u2010grade glioma"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3961-3042","authenticated-orcid":false,"given":"Rebecca","family":"Ronsley","sequence":"first","affiliation":[{"name":"Division of Hematology, Oncology &amp; BMT Department of Pediatrics University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine D.","family":"Hounjet","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology &amp; BMT Department of Pediatrics University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8005-2641","authenticated-orcid":false,"given":"Shahrad Rod","family":"Rassekh","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology &amp; BMT Department of Pediatrics University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology Department of Pediatrics University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Dunham","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology Department of Pathology University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Gardiner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Ophthalmology Department of Surgery University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvindera","family":"Ghag","sequence":"additional","affiliation":[{"name":"Division of Pediatric Orthopedic Surgery Department of Surgery University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Ludemann","sequence":"additional","affiliation":[{"name":"Division of Pediatric Otolaryngology Department of Surgery University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wensley","sequence":"additional","affiliation":[{"name":"Division of Pediatric Respiratory Medicine Department of Pediatrics University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wingfield","family":"Rehmus","sequence":"additional","affiliation":[{"name":"Division of Dermatology Department of Pediatrics University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Sargent","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neuro\u2010Radiology Department of Radiology University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Hukin","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology &amp; BMT Department of Pediatrics University of British Columbia Vancouver Canada"},{"name":"Division of Neurology Department of Pediatrics University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.08.051"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.04.008"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(97)70092-1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1995.82.4.0572"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.131.8.712"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.36.6054"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/not154"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.68.1585"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-0334"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3911"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0239-0"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2015.00054"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.32.15_suppl.10065"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1912735"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/now282"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30277-3"},{"key":"e_1_2_11_18_1","doi-asserted-by":"crossref","unstructured":"McCowageGB MuellerS PratilasCA et al.Trametinib in pediatric patients with neurofibromatosis type 1 (NF\u20101)\u2013associated plexiform neurofibroma: A phase I\/IIa study [abstract]. In: 2018 ASCO Annual Meeting; 2018 Jun 1\u20105; Chicago Il. Alexandria (VA): ASCO; 2018. Abstract nr 10504.","DOI":"10.1200\/JCO.2018.36.15_suppl.10504"},{"key":"e_1_2_11_19_1","doi-asserted-by":"crossref","unstructured":"BouffetE KieranE HargraveD et al.Trametinib therapy in pediatric patients with low\u2010grade gliomas (LGG) with BRAF gene fusion; A\u00a0disease\u2010specific cohort in the first pediatric testing of trametinib [abstract]. In: ISPNO 2018; 2018 Jun 30\u2010Jul 3; Denver Co. Cary (NC): Oxford University Press; 2018. Abstract nr 46.","DOI":"10.1093\/neuonc\/noy059.387"},{"key":"e_1_2_11_20_1","unstructured":"ManoharanN ChoiJ ChordasC et al.Trametinib for the treatment of recurrent\/progressive pediatric low grade glioma: A single institution experience [abstract]. In: SNO\u2019s 5th Pediatric Neuro\u2010Oncology Basic and Translational Research Conference; 2019 May 3\u20104; San Francisco CA. Cary (NC): Oxford University Press; 2019. 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