{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:45:10Z","timestamp":1793411110951,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"9","funder":[{"DOI":"10.13039\/100014804","name":"Neurofibromatosis Therapeutic Acceleration Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Understanding the natural history of non-malignant peripheral nerve sheath tumors (PNSTs) in neurofibromatosis type 1 (NF1) is critical to optimal clinical care and the development of meaningful clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We longitudinally analyzed growth of plexiform neurofibromas (PNs) and of PNSTs with distinct nodular appearance (distinct nodular lesions [DNLs]) using volumetric MRI analysis in patients enrolled on a natural history study (NCT00924196).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DNLs were observed in 58\/122 (45.6%) patients (median 2 DNLs\/patient). In DNLs that developed during follow-up, median age of development was 17 years. A moderate negative correlation was observed between the estimated PN growth rate and patients\u2019 age at initial MRI (Spearman\u2019s r [95% CI]: \u22120.60 [\u22120.73, \u22120.43], n = 70), whereas only a weak correlation was observed for DNLs (Spearman\u2019s r [95% CI]: \u22120.25 [\u22120.47, 0.004]; n = 61). We observed a moderate negative correlation between tumor growth rate and baseline tumor volume for PNs and DNLs (Spearman\u2019s r [95% CI]: \u22120.52 [\u22120.67, \u22120.32] and \u22120.61 [\u22120.75, \u22120.42], respectively). Spontaneous tumor volume reduction was observed in 10 PNs and 7 DNLs (median decrease per year, 3.6% and 7.3%, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We corroborate previously described findings that most rapidly growing PNs are observed in young children. DNLs tend to develop later in life and their growth is minimally age related. Distinct growth characteristics of PNs and DNLs suggest that these lesions have a different biology and may require different clinical management and clinical trial design. In a subset of PNs and DNLs, slow spontaneous regression in tumor volume was seen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaa053","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T07:26:21Z","timestamp":1583479581000},"page":"1368-1378","source":"Crossref","is-referenced-by-count":87,"title":["Longitudinal evaluation of peripheral nerve sheath tumors in neurofibromatosis type 1: growth analysis of plexiform neurofibromas and distinct nodular lesions"],"prefix":"10.1093","volume":"22","author":[{"given":"Srivandana","family":"Akshintala","sequence":"first","affiliation":[{"name":"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Liewehr","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, NCI, NIH, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Goodwin","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaishri O","family":"Blakeley","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M","family":"Gross","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth M","family":"Steinberg","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, NCI, NIH, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Dombi","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte C","family":"Widemann","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,10]]},"reference":[{"issue":"1","key":"2020092909445824200_CIT0001","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/(SICI)1096-8628(19990326)89:1<31::AID-AJMG7>3.0.CO;2-W","article-title":"Plexiform neurofibromas","volume":"89","author":"Korf","year":"1999","journal-title":"Am J Med Genet."},{"key":"2020092909445824200_CIT0002","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.jpeds.2011.04.008","article-title":"Plexiform neurofibromas in children with neurofibromatosis type 1: frequency and associated clinical deficits","volume":"159","author":"Nguyen","year":"2011","journal-title":"J Pediatr."},{"issue":"9","key":"2020092909445824200_CIT0003","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1212\/01.wnl.0000250332.89420.e6","article-title":"NF1 plexiform neurofibroma growth rate by volumetric MRI: relationship to age and body weight","volume":"68","author":"Dombi","year":"2007","journal-title":"Neurology."},{"issue":"16","key":"2020092909445824200_CIT0004","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1212\/WNL.0b013e3181bd1326","article-title":"Characteristics of children enrolled in treatment trials for NF1-related plexiform neurofibromas","volume":"73","author":"Kim","year":"2009","journal-title":"Neurology."},{"issue":"4","key":"2020092909445824200_CIT0005","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1215\/15228517-2008-011","article-title":"Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1","volume":"10","author":"Mautner","year":"2008","journal-title":"Neuro Oncol."},{"issue":"3","key":"2020092909445824200_CIT0006","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jpeds.2011.08.051","article-title":"Pediatric plexiform neurofibromas: impact on morbidity and mortality in neurofibromatosis type 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Pediatr."},{"issue":"4","key":"2020092909445824200_CIT0013","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1517\/13543784.2013.772979","article-title":"Optimizing biologically targeted clinical trials for neurofibromatosis","volume":"22","author":"Gutmann","year":"2013","journal-title":"Expert Opin Investig Drugs."},{"issue":"21 Suppl 1","key":"2020092909445824200_CIT0014","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1212\/01.wnl.0000435744.57038.af","article-title":"Recommendations for imaging tumor response in neurofibromatosis clinical trials","volume":"81","author":"Dombi","year":"2013","journal-title":"Neurology."},{"key":"2020092909445824200_CIT0015","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/1750-1172-7-75","article-title":"Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1","volume":"7","author":"Nguyen","year":"2012","journal-title":"Orphanet J Rare 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