{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:29:11Z","timestamp":1773311351180,"version":"3.50.1"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Up to 10% of all pediatric cancer patients may have an underlying germline mutation which predisposed them to develop a malignancy. With more patients being tested for and diagnosed with genetic tumor predisposition syndromes, there has been improved characterization of their many nonmalignant manifestations. However, designing and implementing clinical trials to treat the nonmalignant tumor and non-tumor manifestations of these syndromes poses many unique challenges. Unlike trials for malignancies where tumor response and survival can be used as straightforward trial endpoints, the nonmalignant manifestations are often chronic, evolve more slowly over time, and may not be immediately life-threatening. Therefore, they will likely require a different approach to both testing and treatment with a focus on more functional and patient-reported outcome trial endpoints. The recent success of treatment trials for the benign tumors plexiform neurofibromas in the tumor predisposition syndrome neurofibromatosis type 1 (NF1) can be used as a model for the development of clinical trials in other tumor predisposition syndromes. In this article, we review the unique challenges associated with targeting the nonmalignant aspects of these conditions as well as some of the lessons learned from the NF1 experience which may be applied to other syndromes in the future.<\/jats:p>","DOI":"10.1093\/noajnl\/vdaa017","type":"journal-article","created":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T04:53:52Z","timestamp":1593147232000},"page":"i134-i140","source":"Crossref","is-referenced-by-count":7,"title":["Clinical trial design in neurofibromatosis type 1 as a model for other tumor predisposition syndromes"],"prefix":"10.1093","volume":"2","author":[{"given":"Andrea M","family":"Gross","sequence":"first","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte C","family":"Widemann","sequence":"first","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"issue":"16","key":"2020062600534655900_CIT0001","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1056\/NEJMoa1215134","article-title":"Chimeric antigen receptor-modified T cells for acute lymphoid leukemia","volume":"368","author":"Grupp","year":"2013","journal-title":"N Engl J Med."},{"issue":"8","key":"2020062600534655900_CIT0002","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1056\/NEJMoa1714448","article-title":"Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children","volume":"378","author":"Drilon","year":"2018","journal-title":"N Engl J Med."},{"issue":"9","key":"2020062600534655900_CIT0003","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1001\/jama.2015.10080","article-title":"Integrative clinical sequencing in the management of refractory or relapsed cancer in youth","volume":"314","author":"Mody","year":"2015","journal-title":"JAMA."},{"issue":"5","key":"2020062600534655900_CIT0004","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1001\/jamaoncol.2015.5699","article-title":"Diagnostic yield of clinical tumor and germline whole-exome sequencing for children with solid tumors","volume":"2","author":"Parsons","year":"2016","journal-title":"JAMA Oncol."},{"issue":"24","key":"2020062600534655900_CIT0005","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1056\/NEJMoa1508054","article-title":"Germline mutations in predisposition genes in pediatric cancer","volume":"373","author":"Zhang","year":"2015","journal-title":"N Engl J Med."},{"issue":"15","key":"2020062600534655900_CIT0006","first-page":"10503","article-title":"SPRINT: phase II study of the MEK 1\/2 inhibitor selumetinib (AZD6244, ARRY-142886) in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN)","volume":"36","author":"Gross","journal-title":"J Clin Oncol"},{"issue":"11","key":"2020062600534655900_CIT0007","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1158\/1078-0432.CCR-17-0702","article-title":"Pediatric cancer predisposition and surveillance: an overview, and a tribute to Alfred G. 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