Abstract
Comprehensive annual screening reduces cancer-related mortality in Li-Fraumeni syndrome (LFS), a cancer-prone disorder caused by pathogenic germline TP53 variants. Blood tests at months 4 and 8 between annual screening are recommended but their effectiveness in early cancer detection has not been established. Interim blood counts and inflammatory biomarkers were evaluated in 132 individuals with LFS (112 adults, 87 female, median age 36 years [range 3–68], median follow-up 37 months [range 2–70]) and test abnormalities were observed in 225 (35%). Thirteen cancers in 12 individuals were diagnosed between annual screenings but only one cancer (colorectal adenocarcinoma) was diagnosed due to an abnormal interim blood test. Fisher’s exact test and generalized estimating equation models found no statistical associations between cancer diagnoses and any test abnormality. Four- and 8-monthly interim screening blood tests may not be of independent benefit for cancer detection in LFS, but annual cancer screening and personalized follow-up remain essential.
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References
Mai PL, Best AF, Peters JA et al (2016) Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer 122(23):3673–3681. https://doi.org/10.1002/cncr.30248
Amadou A, Waddington Achatz MI, Hainaut P (2018) Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: temporal phases of Li-Fraumeni syndrome. Curr Opin Oncol 30(1):23–29. https://doi.org/10.1097/CCO.0000000000000423
Bougeard G, Renaux-Petel M, Flaman JM et al (2015) Revisiting Li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol 33(21):2345–2352. https://doi.org/10.1200/JCO.2014.59.5728
Porter CC, Druley TE, Erez A et al (2017) Recommendations for surveillance for children with leukemia-predisposing conditions. Clin Cancer Res 23(11):e14–e22. https://doi.org/10.1158/1078-0432.CCR-17-0428
Kratz CP, Achatz MI, Brugieres L et al (2017) Cancer screening recommendations for individuals with Li-Fraumeni syndrome. Clin Cancer Res 23(11):e38–e45. https://doi.org/10.1158/1078-0432.CCR-17-0408
Villani A, Shore A, Wasserman JD et al (2016) Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol 17(9):1295–1305. https://doi.org/10.1016/S1470-2045(16)30249-2
Ballinger ML, Best A, Mai PL et al (2017) Baseline surveillance in Li-Fraumeni syndrome using whole-body magnetic resonance imaging: a meta-analysis. JAMA Oncol 3(12):1634–1639. https://doi.org/10.1001/jamaoncol.2017.1968
Young JL, Pantaleao A, Zaspel L et al (2019) Couples coping with screening burden and diagnostic uncertainty in Li-Fraumeni syndrome: connection versus independence. J Psychosoc Oncol 37(2):178–193. https://doi.org/10.1080/07347332.2018.1543376
Ross J, Bojadzieva J, Peterson S et al (2017) The psychosocial effects of the Li-Fraumeni Education and Early Detection (LEAD) program on individuals with Li-Fraumeni syndrome. Genet Med 19(9):1064–1070. https://doi.org/10.1038/gim.2017.8
Hanson H, Brady AF, Crawford G et al (2020) UKCGG Consensus Group guidelines for the management of patients with constitutional TP53 pathogenic variants. J Med Genet. https://doi.org/10.1136/jmedgenet-2020-106876
Frebourg T, Bajalica Lagercrantz S, Oliveira C, Magenheim R, Evans DG, European Reference Network G (2020) Guidelines for the Li-Fraumeni and heritable TP53-related cancer syndromes. Eur J Hum Genet 28(10):1379–1386. https://doi.org/10.1038/s41431-020-0638-4
Mai PL, Khincha PP, Loud JT et al (2017) Prevalence of cancer at baseline screening in the National Cancer Institute Li-Fraumeni Syndrome cohort. JAMA Oncol 3(12):1640–1645. https://doi.org/10.1001/jamaoncol.2017.1350
R Core Team (2018) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. Available online at https://www.R-project.org/
Acknowledgements
We thank the study participants, their families, and referring physicians for their valuable contributions to this study. Janet Bracci, RN, Kathryn Nichols, RN, Maureen Risch, RN and Nicole Dupree of Westat, Inc., provided outstanding study support.
Funding
This work was supported by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health and through contract HHSN261201800004C with Westat, Inc.
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Oba, L., Best, A.F., Mai, P.L. et al. Utility of interim blood tests for cancer screening in Li-Fraumeni syndrome. Familial Cancer 21, 333–336 (2022). https://doi.org/10.1007/s10689-021-00265-x
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DOI: https://doi.org/10.1007/s10689-021-00265-x