Masciari Serena, Van den Abbeele Annick D, Diller Lisa R, Rastarhuyeva Iryna, Yap Jeffrey, Schneider Katherine, Digianni Lisa, Li Frederick P, Fraumeni Joseph F, Syngal Sapna, Garber Judy E
Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
JAMA. 2008 Mar 19;299(11):1315-9. doi: 10.1001/jama.299.11.1315.
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.
DESIGN, SETTING, AND PARTICIPANTS: 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.
李-佛美尼综合征（LFS）患者具有遗传性癌症易感性，在生命早期就易患多种恶性肿瘤；患过一种癌症的幸存者患其他原发性肿瘤的风险显著升高。大多数家族的潜在遗传缺陷是TP53肿瘤抑制基因的种系突变。肿瘤的多样性和家族的罕见性导致为LFS家族成员制定有效的筛查建议存在困难。
收集初步数据，以评估18F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（FDG-PET/CT）成像作为一种潜在的监测方式，用于检测LFS家族无症状成员中的早期恶性肿瘤。
设计、地点和参与者：2006年至2007年期间，在美国一家综合癌症中心，对有记录的种系TP53突变或确定携带者状态、入组前5年内无癌症病史且无癌症或健康问题症状的LFS家族成员进行FDG-PET/CT扫描作为筛查测试。扫描最初由临床医生进行评估，然后由一名专家放射科医生进行集中评估。
主要观察指标是使用FDG-PET/CT扫描检测新的原发性癌症。
15名个体中，基线FDG-PET/CT扫描发现3例（20%）无症状癌症。2例患有甲状腺乳头状癌（II期和III期），1例患有II期食管腺癌。
这些初步数据为一种潜在的癌症监测策略提供了首个证据，该策略可能值得对LFS患者进行进一步研究。对辐射暴露的担忧以及筛查高危患者所固有的其他挑战需要进一步考虑。
