F18-Fluorodeoxyglucose–Positron Emission Tomography/Computed Tomography Screening in Li-Fraumeni Syndrome

Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 04/2008; 299(11):1315-9. DOI: 10.1001/jama.299.11.1315
Source: PubMed

ABSTRACT Individuals with Li-Fraumeni syndrome (LFS) have an inherited cancer predisposition to a diverse array of malignancies beginning early in life; survivors of one cancer have a markedly elevated risk of additional primary tumors. The underlying genetic defect in the majority of the families is a germline mutation in the TP53 tumor suppressor gene. The diversity of tumors and rarity of families have contributed to the difficulty in devising effective screening recommendations for members of LFS kindreds.
To gather preliminary data with which to evaluate F18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging as a potential surveillance modality to detect early malignancies in asymptomatic members of LFS kindreds.
Members of LFS families with documented germline TP53 mutations or obligate carrier status, no history of cancer within 5 years of enrollment, and no symptoms of cancer or ill-health were offered FDG-PET/CT scanning as a screening test in a comprehensive US cancer center from 2006 to 2007. Scans were initially reviewed clinically, then centrally reviewed by an expert radiologist.
The primary outcome was the detection of new primary cancers using FDG-PET/CT scanning.
Of 15 individuals, baseline FDG-PET/CT scan identified asymptomatic cancers in 3 (20%). Two individuals had papillary thyroid cancers (stage II and stage III) and one individual had stage II esophageal adenocarcinoma.
These preliminary data provide the first evidence for a potential cancer surveillance strategy that may be worthy of further investigation for patients with LFS. Concerns about radiation exposure and other challenges inherent in screening high-risk patients will require further consideration.

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Available from: Lisa M Digianni, Sep 26, 2015
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    • "In a recent study by Villani et al., patients with LFS that were under enhanced surveillance with low-dose radiation exposure imaging (whole body MRIs, ultrasounds) had a statistically significant 3-year survival advantage (100% vs. 21% with routine follow up) [23] and this mode of surveillance is encouraged by NCCN. On the other hand, the role of Positron Emission Tomography/Computed Tomography (PET/CT) scanning is yet to be determined [24]. "
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    ABSTRACT: Approximately 5-10% of breast cancer cases might be inheritable, up to 30% of which are due to BRCA1/2 mutations. During the past few years and thanks to technology evolution, we have been witnesses of an intensive search of additional genes with similar characteristics, under the premise that successful gene discovery will provide substantial opportunities for primary and secondary prevention of breast cancer. Consequently, new genes have emerged as breast cancer susceptibility genes, including rare germline mutations in high penetrant genes, such as TP53 and PTEN, and more frequent mutations in moderate penetrant genes, such as CHEK2, ATM and PALB2. This review will summarize current data on new findings in breast cancer susceptibility genes.
    Cancer Treatment Reviews 11/2014; 41(1). DOI:10.1016/j.ctrv.2014.10.008 · 7.59 Impact Factor
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    • "Given the wide range of tumor sites and age of onset, it is difficult to have effective periodic surveillance. Novel surveillance imaging techniques for LFS, such as full body MRI scan in thick slices and FDG-PET/CT scans, are currently being investigated [11]. However, at present, the only surveillance method that is thought to be effective is regular surveillance for breast cancer in women aged 20–25 or older. "
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    ABSTRACT: Li Fraumeni Syndrome (LFS) is a hereditary cancer syndrome characterized by a high risk of developing various types of cancer from birth through late adulthood. Clinical benefits of surveillance for LFS are limited. The aim of this study is to investigate which advice for regular surveillance, if any, is given to high risk LFS individuals, adherence to that advice, and any psychological gain or burden derived from surveillance. Fifty-five high risk individuals (proven carriers and those at 50% risk) from families with a p53 germline mutation were invited to participate, of whom 82% completed a self-report questionnaire assessing advice for regular surveillance, compliance, perceived benefits and barriers of screening and LFS-related distress (IES) and worries (CWS). In total, 71% of the high risk family members received advice to undergo regular surveillance for LFS. The majority (78%) reported adherence with the recommended advice. All high risk women aged 25 or older reported having been advised to undergo annual breast cancer surveillance (n = 11), of whom 64% (n = 7) in specific received advice to undergo a mammography. Seventy-eight percent of respondents indicated having received tailored surveillance advice based on family cancer history. The large majority of respondents believed in the value of surveillance to detect tumors at an early stage (90%) and reported that it gave them a sense of control (84%) and security (70%). Despite its limited clinical benefits, the majority of high risk LFS family are advised to undergo, and are adherent to, and report psychological benefit from, regular surveillance programs.
    Familial Cancer 12/2010; 9(4):647-54. DOI:10.1007/s10689-010-9368-z · 1.98 Impact Factor
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