Predicting Risk of Subsequent CNS Tumors in Survivors of Childhood Cancer

Key Points

  • Inclusion of genetic variants increased the ability to predict risk of subsequent CNS tumors in survivors of childhood cancer.
  • The combined model had a sensitivity of 87.5% and a specificity of 83.5% for predicting highest or lowest risk.

As reported in the Journal of Clinical Oncology, Wang et al have developed a model for predicting risk of subsequent central nervous system (CNS) tumors in survivors of childhood cancer.

Study Details

In the study, matched childhood cancer survivors with (n = 82) and without (n = 228) subsequent CNS tumors form the COG ALTE03N1 study were assessed for genetic variants associated with adult-onset primary CNS tumors. Prediction models were developed and tested for identification of high and low risk for subsequent CNS tumors using genetic information and clinical variables. Models were validated in a matched sample of 25 cases and 54 controls.

Predictive Ability

Association of risk for subsequent CNS tumors in survivors was found for six single nucleotide polymorphisms: rs15869 in BRCA2, rs1805389 in LIG4, rs8079544 in TP53, rs25489 in XRCC1, rs1673041 in POLD1, and rs11615 in ERCC1. Inclusion of these genetic variants in a model containing age at primary cancer, sex, and cranial radiation therapy dose resulted in an AUC for predictive ability of 0.81, greater than that observed with a model containing clinical variables alone (AUC = 0.73; P = .002). In the validation cohort, AUC values were 0.89 for the final combined model vs 0.73 for the clinical model (P = .07). The combined prediction model had a sensitivity of 87.5% and a specificity of 83.5% for predicting highest or lowest risk of subsequent CNS tumors.

The investigators concluded: “It is possible to identify survivors of childhood cancer at high or low risk for subsequent CNS tumors on the basis of genetic and clinical information. This information can be used to inform surveillance for early detection of subsequent CNS tumors.”

The study was supported by grants and awards from the National Cancer Institute, Leukemia and Lymphoma Society, Mathew Larson Foundation, and St. Baldrick’s Foundation.

Smita Bhatia, MD, MPH, of the Institute for Cancer Outcomes and Survivorship, School of Medicine, University of Alabama at Birmingham, is the corresponding author of the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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