Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study
Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study
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DOI：
10.1016/s1470-2045(11)70119-x
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发表时间：
2011-06-01
期刊：
影响因子：
51.1
通讯作者：
Malkin, David
中科院分区：
文献类型：
--
作者：
Villani, Anita;Tabori, Uri;Malkin, David
Li-Fraumeni综合征患者一生中患癌症的风险很高。我们评估了对患有该综合征的家庭中无症状TP 53突变携带者进行全面监测方案的可行性和潜在临床效果。方法我们于2004年1月1日实施了一项临床监测方案，使用频繁的生化和成像研究，对无症状TP 53突变携带者进行监测。并对8个患有Li-Fraumeni综合征的家庭成员进行了前瞻性观察研究，这些家庭成员要么选择接受监测，要么选择不接受监测。主要结果指标是新癌症的检测。结果：截至2010年11月1日，确定了33名TP 53突变携带者，其中18人接受了监测。监测方案在7名患者中检测到10个无症状肿瘤，包括小的高级别肿瘤和低级别或癌前病变肿瘤。所有7名突变携带者在中位随访24个月（IQR 22-65个月）后均存活。在非监测组的10个个体中，发生了12个高级别、高阶段肿瘤，其中2人（20%）在随访结束时存活（与监测组的存活率相比，p=0.0417）。3-年总生存率在监测组中为100%，在非监测组中为21%（95%CI 4-48%）（p=0.0155）。解释我们的研究结果显示了临床监测方案用于检测具有生殖系TP 53突变的个体中的无症状肿瘤的可行性。这一战略为受影响的个人提供了一种管理选择，其好处是支持对有风险的个人和家庭进行早期基因检测。
Background Individuals with Li-Fraumeni syndrome have a high lifetime risk of developing cancer. We assessed the feasibility and potential clinical effect of a comprehensive surveillance protocol in asymptomatic TP53 mutation carriers in families with this syndrome.Methods We implemented a clinical surveillance protocol, using frequent biochemical and imaging studies, for asymptomatic TP53 mutation carriers on Jan 1, 2004, and did a prospective observational study of members of eight families with Li-Fraumeni syndrome who either chose to undergo surveillance or chose not to undergo surveillance. The primary outcome measure was detection of new cancers. The secondary outcome measure was overall survival.Findings As of Nov 1, 2010, 33 TP53 mutation carriers were identified, 18 of whom underwent surveillance. The surveillance protocol detected ten asymptomatic tumours in seven patients, including small, high-grade tumours and low-grade or premalignant tumours. All seven mutation carriers were alive after a median follow-up of 24 months (IQR 22-65 months). 12 high-grade, high-stage tumours developed in 10 individuals in the non-surveillance group, two of whom (20%) were alive at the end of follow-up (p=0.0417 for comparison with survival in the surveillance group). 3-year overall survival was 100% in the surveillance group and 21% (95% CI 4-48%) in the non-surveillance group (p=0.0155).Interpretation Our findings show the feasibility of a clinical surveillance protocol for the detection of asymptomatic neoplasms in individuals with germline TP53 mutations. This strategy offers a management option for affected individuals, and its benefits lend support to the use of early genetic testing of at-risk individuals and families.