In a study reported in the Journal of Clinical Oncology, Smita Bhatia, MD, MPH, and colleagues found that childhood cancer survivors with pathogenic neurofibromatosis type 1 (NF1) variants had a greater risk of subsequent neoplasms than survivors without NFI variants and that radiotherapy was associated with an increased risk.
Smita Bhatia, MD, MPH
As stated by the investigators, “Fundamental gaps in knowledge regarding the risk of subsequent neoplasms in children with … NF1 variants exposed to radiation and/or alkylator chemotherapy have limited the use of these agents.”
Study Details
In the study, risk of subsequent neoplasms was assessed in 167 NF1-affected vs 1,541 non–NF1-affected 5-year childhood cancer survivors from the Childhood Cancer Survivor Study and a separate cohort of 176 NF1-affected patients with primary tumors from the University of Alabama at Birmingham and Children’s Hospital of Philadelphia who received radiation therapy and/or chemotherapy. Multivariate analysis of risk factors adjusted for the type of primary tumor, age at diagnosis, and therapeutic exposures.
Increased Risk
The 20-year cumulative incidence of subsequent neoplasms was 7.3% among NF1-affected childhood cancer survivors vs 2.9% among non–NF1-affected survivors (P = .003) in the Childhood Cancer Survivor Study cohort. On multivariate analysis, the hazard ratio (HR) for subsequent neoplasms was 2.42 (P = .005).
On multivariate analysis in the University of Alabama at Birmingham/Children’s Hospital of Philadelphia cohort, the risk of subsequent neoplasms was significantly increased among patients who received radiation therapy (HR = 2.78, P = .01). On univariate analysis, the risk among patients receiving alkylating agents was not significantly increased (HR = 1.27, P = .6), with the association being further weakened on multivariate analysis (HR = 1.0, P = .9).
KEY POINTS
- Risk of subsequent neoplasms was significantly increased among survivors with NF1.
- Radiotherapy, but not alkylating chemotherapy, was associated with increased risk.
The investigators concluded, “Children with NF1 who develop a primary tumor are at increased risk of [subsequent neoplasms] when compared with non–NF1-[affected] childhood cancer survivors. Among NF1-affected children with a primary tumor, therapeutic radiation, but not alkylating agents, confer an increased risk of [subsequent neoplasms]. These findings can inform evidence-based clinical management of primary tumors in NF1-affected children.”
Dr. Bhatia, of the University of Alabama at Birmingham, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by a grant from the National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.
