{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T16:14:03Z","timestamp":1785600843224,"version":"3.56.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01HD090019-04"],"award-info":[{"award-number":["5R01HD090019-04"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Identification of children and infants with Li-Fraumeni syndrome prompts tumor surveillance and allows potential early cancer detection. We assessed the clinical benefits and cost-effectiveness of population-wide newborn screening for TP53 variants (TP53-NBS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We simulated the impact of TP53-NBS using data regarding TP53-associated pediatric cancers and pathogenic or likely pathogenic (P\/LP) TP53 variants from Surveillance, Epidemiology, and End Results; ClinVar and gnomAD; and clinical studies. We simulated an annual US birth cohort under usual care and TP53-NBS and estimated clinical benefits, life-years, and costs associated with usual care and TP53-NBS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Under usual care, of 4 million newborns, 608 (uncertainty interval [UI] = 581-636) individuals would develop TP53-associated cancers before age 20\u2009years. Under TP53-NBS, 894 individuals would have P\/LP TP53 variants detected. These individuals would undergo routine surveillance after detection of P\/LP TP53 variants decreasing the number of cancer-related deaths by 7.2% (UI\u2009=\u20094.0%-12.1%) overall via early malignancy detection. Compared with usual care, TP53-NBS had an incremental cost-effectiveness ratio of $106\u200a009 per life-year gained. Probabilistic analysis estimated a 40% probability that TP53-NBS would be cost-effective given a $100\u200a000 per life-year gained willingness-to-pay threshold. Using this threshold, a value of information analysis found that additional research on the prevalence of TP53 variants among rhabdomyosarcoma cases would resolve most of the decision uncertainty, resulting in an expected benefit of 349 life-years gained (or $36.6 million).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We found that TP53-NBS could be cost-effective; however, our findings suggest that further research is needed to reduce the uncertainty in the potential health outcomes and costs associated with TP53-NBS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djac013","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T20:10:34Z","timestamp":1642191034000},"page":"722-731","source":"Crossref","is-referenced-by-count":11,"title":["Population-Based Newborn Screening for Germline <i>TP53<\/i> Variants: Clinical Benefits, Cost-Effectiveness, and Value of Further Research"],"prefix":"10.1093","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2409-4246","authenticated-orcid":false,"given":"Natalia","family":"Kunst","sequence":"first","affiliation":[{"name":"Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7946-5649","authenticated-orcid":false,"given":"Natasha K","family":"Stout","sequence":"additional","affiliation":[{"name":"Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Boston Children\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-776X","authenticated-orcid":false,"given":"Kurt D","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA"},{"name":"Broad Institute of MIT and Harvard, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1607-8411","authenticated-orcid":false,"given":"Pamela M","family":"McMahon","sequence":"additional","affiliation":[{"name":"Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0599-9063","authenticated-orcid":false,"given":"Ann Chen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA"},{"name":"Department of Pediatrics, Boston Children\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa R","family":"Diller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2724-7404","authenticated-orcid":false,"given":"Jennifer M","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Boston Children\u2019s Hospital, Boston, MA, USA"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"issue":"25","key":"2022051008265380100_djac013-B1","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1056\/NEJMsr1804754","article-title":"The major causes of death in children and adolescents in the United States","volume":"379","author":"Cunningham","year":"2018","journal-title":"N Engl J Med"},{"issue":"1","key":"2022051008265380100_djac013-B2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"2022051008265380100_djac013-B3"},{"issue":"9","key":"2022051008265380100_djac013-B4","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1093\/jnci\/djx030","article-title":"Annual report to the nation on the status of cancer. 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