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Universal newborn genetic screening for pediatric cancer predisposition syndromes: model-based insights
Jennifer M Yeh1,2, Natasha K Stout3,4, Aeysha Chaudhry5
1Harvard Medical School, Boston, MA, USA. jennifer.yeh@childrens.harvard.edu.
Insights
Genetic testing for pediatric cancer predisposition syndromes (CPS) in newborns could significantly decrease cancer deaths. This approach may become cost-effective as genetic sequencing expenses decrease.
Area of Science:
- Genetics
- Pediatrics
- Oncology
Background:
- Pediatric cancer predisposition syndromes (CPS) are rare genetic disorders that increase the risk of developing various childhood cancers.
- Current newborn screening programs do not routinely include comprehensive genetic testing for CPS.
- The potential benefits and costs of implementing universal genetic screening for CPS in newborns are not well-established.
Purpose of the Study:
- To evaluate the potential benefits and cost-effectiveness of universal genetic screening for a panel of pediatric cancer predisposition syndromes (CPS) in newborns.
- To model the impact of early identification and surveillance on cancer mortality and survival rates.
Main Methods:
- A simulation model was developed to assess universal screening versus usual care for US newborns.
- Pathogenic/likely pathogenic (P/LP) variants in 11 key genes (RET, RB1, TP53, DICER1, SUFU, PTCH1, SMARCB1, WT1, APC, ALK, PHOX2B) were assigned at birth.
- Survival benefits were calculated based on reductions in advanced disease, cancer deaths, and treatment-related mortality, assuming 100% adherence to surveillance protocols.
Main Results:
- In a cohort of 3.7 million newborns, universal screening identified 13.3% at birth as at-risk for CPS.
- This strategy resulted in a 53.5% decrease in cancer deaths among P/LP heterozygotes and a 7.8% decrease in the overall cohort by age 20.
- The cost-effectiveness varied with test price, ranging from $99,430 to $244,860 per life-year gained for tests costing $20 and $55, respectively.
Conclusions:
- Population-based genetic testing for CPS in newborns shows promise in reducing pediatric cancer mortality.
- Universal screening for CPS could be a cost-effective strategy, particularly as the cost of genetic sequencing continues to decline.
- Early identification through genetic screening enables timely surveillance, potentially improving outcomes for children at high risk of cancer.
Purpose:
Genetic testing for pediatric cancer predisposition syndromes (CPS) could augment newborn screening programs, but with uncertain benefits and costs.
Methods:
We developed a simulation model to evaluate universal screening for a CPS panel. Cohorts of US newborns were simulated under universal screening versus usual care. Using data from clinical studies, ClinVar, and gnomAD, the presence of pathogenic/likely pathogenic (P/LP) variants in RET, RB1, TP53, DICER1, SUFU, PTCH1, SMARCB1, WT1, APC, ALK, and PHOX2B were assigned at birth. Newborns with identified variants underwent guideline surveillance. Survival benefit was modeled via reductions in advanced disease, cancer deaths, and treatment-related late mortality, assuming 100% adherence.
Results:
Among 3.7 million newborns, under usual care, 1,803 developed a CPS malignancy before age 20. With universal screening, 13.3% were identified at birth as at-risk due to P/LP variant detection and underwent surveillance, resulting in a 53.5% decrease in cancer deaths in P/LP heterozygotes and a 7.8% decrease among the entire cohort before age 20. Given a test cost of $55, universal screening cost $244,860 per life-year gained; with a $20 test, the cost fell to $99,430 per life-year gained.
Conclusion:
Population-based genetic testing of newborns may reduce mortality associated with pediatric cancers and could be cost-effective as sequencing costs decline.
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