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


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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    • "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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    • "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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