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](/media/14004370/80469_-bhatia.jpg)
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.