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Original Investigation
August 3, 2017

Prevalence of Cancer at Baseline Screening in the National Cancer Institute Li-Fraumeni Syndrome Cohort

Author Affiliations
  • 1Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 2Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
  • 3Radiology and Imaging Sciences, Clinical Center, Department of Health and Human Services, National Institutes of Health, Bethesda, Maryland
JAMA Oncol. Published online August 3, 2017. doi:10.1001/jamaoncol.2017.1350
Key Points

Question  What is the prevalence of cancer at baseline examination in a cancer surveillance program for individuals with Li-Fraumeni syndrome, a rare, highly penetrant cancer predisposition syndrome?

Findings  In this cohort study of 116 individuals with Li-Fraumeni syndrome caused by pathogenic germline TP53 variants, 40 individuals had a finding on baseline screening examination with rapid whole-body, brain, or breast magnetic resonance imaging that required further evaluation, and 8 of these individuals were diagnosed with a new primary cancer. Non-magnetic resonance imaging techniques, including baseline blood tests, abdominal ultrasonography in children, mammography, and colonoscopy, did not lead to a diagnosis of prevalent cancer in the cohort.

Meaning  Prevalent cancers were common among this cohort and institution of cancer screening for individuals with pathogenic germline TP53 variants is warranted.

Abstract

Importance  Establishment of an optimal cancer surveillance program is important to reduce cancer-related morbidity and mortality in individuals with Li-Fraumeni syndrome, a rare, highly penetrant cancer predisposition syndrome.

Objective  To determine the feasibility and efficacy of a comprehensive cancer screening regimen in Li-Fraumeni syndrome, using multiple radiologic techniques, including rapid whole-body magnetic resonance imaging (MRI) and laboratory measurements.

Design, Setting, and Participants  Baseline evaluation of a prospective cancer screening study was conducted from June 1, 2012, to July 30, 2016, at the National Cancer Institute, National Institutes of Health (an academic research facility). Participants included 116 individuals with Li-Fraumeni syndrome with a germline TP53 pathogenic variant who were aged 3 years or older at the time of baseline screening and had not received active cancer therapy at least 6 months prior to screening.

Main Outcomes and Measures  Detection of prevalent cancer with multimodal screening techniques and the need for additional evaluation.

Results  Of the 116 study participants, 77 (66.4%) were female; median age was 37.6 years (range, 3-68 years). Baseline cancer screening led to the diagnosis of cancer in 8 (6.9%) individuals (2 lung adenocarcinomas, 1 osteosarcoma, 1 sarcoma, 1 astrocytoma, 1 low-grade glioma, and 2 preinvasive breast cancers [ductal carcinoma in situ]); all but 1 required only resection for definitive treatment. A total of 40 (34.5%) participants required additional studies to further investigate abnormalities identified on screening, with 32 having incidental, benign, or normal findings, resulting in a false-positive rate of 29.6%. Non-MRI techniques, including baseline blood tests, abdominal ultrasonography in children, mammography, and colonoscopy, did not lead to a diagnosis of prevalent cancer in our cohort.

Conclusions and Relevance  This study describes the establishment and feasibility of an intensive cancer surveillance protocol for individuals with Li-Fraumeni syndrome. Prevalent cancers were detected at an early stage with baseline whole-body, brain, and breast MRI. Prospective screening of the participants is under way.

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