{"doi":"10.1093/jnci/djaf057","title":"Radiotherapy results in decreased time to second cancer in children with Li Fraumeni syndrome","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Li Fraumeni syndrome (LFS) arising from germline TP53 mutation results in defective DNA repair and increased risk of multiple primary cancers beginning in childhood. Curative intent radiotherapy is often used to treat childhood cancer, but its impact on children with LFS has not been reviewed.</jats:p>\n               <jats:p>We undertook a retrospective case-series review of 47 children with a solid cancer diagnosed age less than 16 years to assess time and survival after second cancer diagnosis.</jats:p>\n               <jats:p>After radiotherapy for the first cancer diagnosis, median time to second primary cancer diagnosis was 13.3 years and median survival 9.7 years. Where no radiotherapy was received, median time to second primary cancer diagnosis was 25.1 years (χ2 = 14.8, P &amp;lt; .0001; Hazard Ratio = 7.9 [95% CI = 2.8 to 22.6]), and median survival of 29.2 years (χ2 = 12.5, P = .004, Hazard Ratio = 3.2 [95% CI = 1.5 to 6.6]).</jats:p>\n               <jats:p>Radiotherapy for first cancer in children with LFS is associated with adverse outcomes and ought to be considered only in the absence of other potentially curative options. Where unavoidable, second cancer risks must be minimized.</jats:p>","journal":"JNCI: Journal of the National Cancer Institute","year":2025,"id":610086,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":122400,"name":"John-Paul Kilday","orcid":"0000-0002-0539-215X","position":1,"is_corresponding":false},{"id":776020,"name":"Stephanie Ng","orcid":"0000-0003-1438-4263","position":2,"is_corresponding":false},{"id":1568422,"name":"Anna Kelsey","orcid":null,"position":3,"is_corresponding":false},{"id":52732,"name":"D. Gareth Evans","orcid":"0000-0002-8482-5784","position":4,"is_corresponding":false},{"id":1197412,"name":"Emma R. Woodward","orcid":"0000-0002-6297-2855","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Radiotherapy results in decreased time to second cancer in children with Li Fraumeni syndrome","abstract":"Li Fraumeni syndrome (LFS) arising from germline TP53 mutation results in defective DNA repair and increased risk of multiple primary cancers beginning in childhood. Curative intent radiotherapy is often used to treat childhood cancer, but its impact on children with LFS has not been reviewed. We undertook a retrospective case-series review of 47 children with a solid cancer diagnosed age less than 16 years to assess time and survival after second cancer diagnosis. After radiotherapy for the first cancer diagnosis, median time to second primary cancer diagnosis was 13.3 years and median survival 9.7 years. Where no radiotherapy was received, median time to second primary cancer diagnosis was 25.1 years (χ2 = 14.8, P < .0001; Hazard Ratio = 7.9 [95% CI = 2.8 to 22.6]), and median survival of 29.2 years (χ2 = 12.5, P = .004, Hazard Ratio = 3.2 [95% CI = 1.5 to 6.6]). Radiotherapy for first cancer in children with LFS is associated with adverse outcomes and ought to be considered only in the absence of other potentially curative options. Where unavoidable, second cancer risks must be minimized.","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40059635","pmcid":"PMC12505129","openalex_id":"https://openalex.org/W4408298288","authors":[],"funders":[{"funder_name":"Manchester Biomedical Research Centre","grant_id":"NIHR203308","title":null},{"funder_name":"Cancer Research UK","grant_id":"CDEPIL-Jan24/100007","title":null},{"funder_name":"National Institute for Health Research (NIHR)","grant_id":"","title":null}],"total_grants":3,"fwci":2.4629,"citation_percentile":0.8949488,"influential_citations":0,"citation_trend":[{"year":2026,"count":5}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://academic.oup.com/jnci/advance-article-pdf/doi/10.1093/jnci/djaf057/62361718/djaf057.pdf","host_type":"journal"},{"url":"https://academic.oup.com/jnci/advance-article-pdf/doi/10.1093/jnci/djaf057/62361718/djaf057.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/jnci/djaf057","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40059635","host_type":"repository"},{"url":"https://research.manchester.ac.uk/en/publications/ee516027-f5a0-49d3-b4a2-8f3f88f9003b","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12505129","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12505129/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12505129","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12505129?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer-related Molecular Pathways","Hedgehog Signaling Pathway Studies","Epigenetics and DNA Methylation"],"mesh_terms":["Adolescent","Child","Child, Preschool","Female","Humans","Infant","Male","Retrospective Studies","Time Factors","Tumor Suppressor Protein p53","Neoplasms, Second Primary","Li-Fraumeni Syndrome","Germ-Line Mutation"],"keywords":["Medicine","Li–Fraumeni syndrome","Radiation therapy","Cancer","Retrospective cohort study","Internal medicine","Primary cancer","Oncology","Germline mutation","Surgery","Pediatrics","Mutation"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T19:14:46.685520Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}