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?
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.
Prevalent cancers were common among this cohort and institution of cancer screening for individuals with pathogenic germline TP53 variants is warranted.
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.
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.
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.
Phuong L. Mai, Payal P. Khincha, Jennifer T. Loud, Rosamma M. DeCastro, Renée C. Bremer, June A. Peters, Chia-Ying Liu, David A. Bluemke, Ashkan A. Malayeri, Sharon A. Savage. Prevalence of Cancer at Baseline Screening in the National Cancer Institute Li-Fraumeni Syndrome Cohort. JAMA Oncol. Published online August 03, 2017. doi:10.1001/jamaoncol.2017.1350