{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:08:32Z","timestamp":1793405312868,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Ministry of Health and Welfare, Republic of Korea","award":["HR21C0198"],"award-info":[{"award-number":["HR21C0198"]}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["NRF-2022R1A2C2091689"],"award-info":[{"award-number":["NRF-2022R1A2C2091689"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1 manifestations (eg, neurocognitive function, growth reduction, and caf\u00e9-au-lait spots) are unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This open-label, phase II trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (\u22653 cm). Selumetinib was administered at doses of 20 or 25 mg\/m2 or 50 mg q 12 hours for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, caf\u00e9-au-lait spots, and quality of life (QoL) were evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Fifty-nine children and 30 adults (median age, 16 years; range, 3\u201347) received an average of 22\u2005\u00b1\u20055 (4\u201326) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%\u201392.2%), and 81 (91%) patients showed partial response (\u226520% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P\u2005&amp;lt;\u2005.05). Prepubertal patients showed increases in height score and growth velocity (P\u2005&amp;lt;\u2005.05). Caf\u00e9-au-lait spot intensity decreased significantly (P\u2005&amp;lt;\u2005.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Selumetinib decreases PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in nonmalignant diverse NF1 manifestations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial Registration<\/jats:title>\n                  <jats:p>Cris.nih.go.kr Identifier (KCT0003700).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noae121","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T12:13:51Z","timestamp":1720440831000},"page":"2352-2363","source":"Crossref","is-referenced-by-count":36,"title":["Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma"],"prefix":"10.1093","volume":"26","author":[{"given":"Hyery","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Asan Medical Center Children\u2019s Hospital, University of Ulsan College of Medicine , Seoul ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Mang","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Radiology and Research Institute of Radiology, Asan Medical Center Children\u2019s Hospital, University of Ulsan College of Medicine , Seoul ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Key","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Asan Medical Center Children\u2019s Hospital, University of Ulsan College of Medicine , Seoul ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young 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