Bhatia S, Chen Y, Wong FL, et al. - Researchers here addressed the fundamental gaps in knowledge concerning the risk of subsequent neoplasms (SNs) in children with pathogenic neurofibromatosis type 1 (NF1) variants exposed to radiation and/or alkylator chemotherapy. For the SN risk, they assessed 167 NF1-affected vs 1,541 non–NF1-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’s Hospital of Philadelphia exposed to radiation and/or chemotherapy. NF1 childhood cancer survivors in the Childhood Cancer Survivor Study cohort exhibited the 20-year cumulative incidence of SNs of 7.3%, compared with 2.9% in the non-NF1 childhood cancer survivors; this suggests a 2.4-fold higher risk of SN in the NF1-affected individuals. Among NF1-affected children with a primary tumor, an increased risk of SNs was noted in correlation with therapeutic radiation, but not with alkylating agents. These findings may assist in the evidence-based clinical management of primary tumors in NF1-affected children.