Harvard Medical School, Boston, MA, USA.
Boston Children's Hospital, Boston, MA, USA.
Genet Med. 2021 Jul;23(7):1366-1371. doi: 10.1038/s41436-021-01124-x. Epub 2021 Mar 25.
Genetic testing for pediatric cancer predisposition syndromes (CPS) could augment newborn screening programs, but with uncertain benefits and costs.
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.
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.
Population-based genetic testing of newborns may reduce mortality associated with pediatric cancers and could be cost-effective as sequencing costs decline.
儿科癌症易感性综合征（CPS）的遗传检测可以增强新生儿筛查计划，但收益和成本不确定。
我们开发了一个模拟模型来评估 CPS 面板的通用筛查。在通用筛查与常规护理下，对美国新生儿队列进行了模拟。使用来自临床研究、ClinVar 和 gnomAD 的数据，在出生时分配 RET、RB1、TP53、DICER1、SUFU、PTCH1、SMARCB1、WT1、APC、ALK 和 PHOX2B 中致病性/可能致病性（P/LP）变异的存在。确定有变异的新生儿接受指南监测。通过降低晚期疾病、癌症死亡和治疗相关的晚期死亡率来建模生存获益，假设 100%的依从性。
在 370 万新生儿中，在常规护理下，有 1803 人在 20 岁之前患上 CPS 恶性肿瘤。通过通用筛查，有 13.3%的人因 P/LP 变异检测而在出生时被确定为高危人群，并接受了监测，导致 P/LP 杂合子的癌症死亡率降低了 53.5%，整个队列在 20 岁之前的死亡率降低了 7.8%。考虑到检测成本为 55 美元，通用筛查的每获得一个生命年的成本为 244860 美元；如果检测成本为 20 美元，每获得一个生命年的成本则降至 99430 美元。
基于人群的新生儿基因检测可能会降低与儿科癌症相关的死亡率，并且随着测序成本的降低，可能具有成本效益。
