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Analysis Finds Sibling Cascade Testing Could Be Cost Effective in Pediatric Cancer

NEW YORK — Cascade testing of siblings of newborns with cancer susceptibility gene variants could be cost-effective, according to a new analysis.

Previous analyses of cascade testing have largely focused on testing adults, but researchers from Boston Children's Hospital and elsewhere have now analyzed the effects of testing siblings of newborns found to have a genetic susceptibility to cancer.

By analyzing a simulated cohort of 3.7 million newborns and their siblings, the researchers explored the effects of genetic testing on siblings of newborns with pathogenic or likely pathogenic variants in one of 11 different pediatric cancer genes. As they reported in JAMA Network Open on Monday, the researchers found that cascade testing would identify nearly 800 siblings with a pathogenic or likely pathogenic variant. Surveillance would then prevent about 15 childhood cancer deaths among those siblings. Depending on the gene, the researchers estimated that such sibling cascade testing could be cost effective.

"Our findings demonstrate how sibling cascade testing would enhance newborn screening efforts and how targeted screening approaches may be more efficient than universal screening to achieve population-level benefits," senior author Ann Wu, a pediatrician at Boston Children's and an associate professor of population medicine at Harvard Medical School, said in an email.

For their analysis, Wu and colleagues focused on 11 genes in which pathogenic variants are associated with cancer predisposition syndromes and an increased risk of early-onset pediatric cancers. This set included, for instance, RET, RB1, and TP53, among others. The researchers assumed in their initial analysis that de novo variants were rare and that siblings had a 50 percent chance of having the same germline variant as the initial case. They also assumed that each newborn found to have a pathogenic or likely pathogenic variant had a sibling.

If 3.7 million newborns were eligible for screening, the researchers calculated that 1,584 newborns with a pathogenic or likely pathogenic variant would be found. Sibling cascade testing would then uncover 792 siblings with pathogenic or likely pathogenic variants. Of these siblings, 116 would develop cancer before turning 20 years old. If usual care had been followed, they estimated that there would have been 29 cancer deaths among siblings, but that genetic screening would avert 15 of them, or 52 percent.

Overall, the researchers found sibling cascade testing would lead to an incremental cost-effectiveness ratio of $16,910 per life-year gained, as compared to usual care. That ICER varied based on the particular gene involved, ranging from being cost-saving for genes like ALK, RET, and WT1, among others, to a cost of $52,100 for TP53.

The costs for cascade testing included $200 for Sanger sequencing and $188 for a clinical visit before initiating surveillance, and surveillance costs were then based on 2018 Medicare reimbursement rates.

Wu and colleagues also conducted a number of other simulations in which they varied different parameters, such as the rate of de novo variants, but noted that the modifications did not lead to substantial changes in ICER.

According to the researchers, these findings are in line with studies conducted in adults of the cost-effectiveness of cascade screening, compared to standard screening.

Wu said that they plan to next include other diseases and genes in their analysis and noted that they would also like to examine the costs and benefits of cascade testing of parents, in addition to siblings.