{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:45:29Z","timestamp":1790711129295,"version":"4.1.0"},"reference-count":15,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"32","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2019,11,10]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Fundamental gaps in knowledge regarding the risk of subsequent neoplasms (SNs) in children with pathogenic neurofibromatosis type 1 (NF1) variants exposed to radiation and\/or alkylator chemotherapy have limited the use of these agents. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> We addressed these gaps by determining the SN risk in 167 NF1-affected versus 1,541 non\u2013NF1-affected 5-year childhood cancer survivors from the Childhood Cancer Survivor Study and 176 nonoverlapping NF1-affected individuals with primary tumors from University of Alabama at Birmingham and Children\u2019s Hospital of Philadelphia exposed to radiation and\/or chemotherapy. Proportional subdistribution hazards multivariable regression analysis was used to examine risk factors, adjusting for type and age at primary tumor diagnosis and therapeutic exposures. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> In the Childhood Cancer Survivor Study cohort, the 20-year cumulative incidence of SNs in NF1 childhood cancer survivors was 7.3%, compared with 2.9% in the non-NF1 childhood cancer survivors ( P = .003), yielding a 2.4-fold higher risk of SN (95% CI, 1.3 to 4.3; P = .005) in the NF1-affected individuals. In the University of Alabama at Birmingham and Children\u2019s Hospital of Philadelphia cohort, among NF1-affected individuals with a primary tumor, the risk of SNs was 2.8-fold higher in patients with irradiated NF1 (95% CI, 1.3 to 6.0; P = .009). In contrast, the risk of SNs was not significantly elevated after exposure to alkylating agents (hazard ratio, 1.27; 95% CI, 0.3 to 3.0; P = .9). <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Children with NF1 who develop a primary tumor are at increased risk of SN when compared with non-NF1 childhood cancer survivors. Among NF1-affected children with a primary tumor, therapeutic radiation, but not alkylating agents, confer an increased risk of SNs. These findings can inform evidence-based clinical management of primary tumors in NF1-affected children. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.19.00114","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T19:59:21Z","timestamp":1568836761000},"page":"3050-3058","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":49,"title":["Subsequent Neoplasms After a Primary Tumor in Individuals With Neurofibromatosis Type 1"],"prefix":"10.1200","volume":"37","author":[{"given":"Smita","family":"Bhatia","sequence":"first","affiliation":[{"name":"University of Alabama at Birmingham, Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham, Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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