O'Neill Allison F, Voss Stephan D, Jagannathan Jyothi P, Kamihara Junne, Nibecker Callie, Itriago-Araujo Elena, Masciari Serena, Parker Erin, Barreto Mauricio, London Wendy B, Garber Judy E, Diller Lisa
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Radiology, Boston Children's Hospital, Boston, Massachusetts.
Pediatr Blood Cancer. 2018 Feb;65(2). doi: 10.1002/pbc.26822. Epub 2017 Oct 27.
Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline mutations in the TP53 gene and a high risk of childhood-onset malignancies. Cancer surveillance is challenging in pediatric mutation carriers given the anatomic spectrum of malignancies and young age of onset. Whole-body magnetic resonance imaging (WB-MRI) may provide an acceptable method for early cancer detection.
We conducted a prospective feasibility pilot study of pediatric subjects (age < 18 years) with LFS to determine return rates for annual WB-MRI scan. Secondary objectives included characterization of incident cancers (and how they were detected).
Forty-five WB-MRI scans in 20 subjects were performed over 5 years; two patients enrolled without subsequently undergoing scans. Eighty-nine percent of participants scanned (95% confidence interval: 67-99%) returned for second examinations. Fifty-five percent of participants required general anesthesia, which was well tolerated in all cases. Six patients required dedicated follow-up imaging. One participant required biopsy of a detected brain lesion; pathology demonstrated reactive gliosis. Another participant, with prior choroid plexus carcinoma, had a new brain lesion detected on clinical follow-up MRI not seen on WB-MRI 6 months prior. All other participants remain well (median: 3 years, range: 0.08-4 years).
WB-MRI in pediatric subjects is a well-tolerated approach to cancer surveillance despite the need for general anesthesia in some patients. A large multicenter trial would determine true test characteristics and efficacy of this approach for early cancer detection in children at high cancer risk.
李-佛美尼综合征（LFS）是一种常染色体显性遗传性癌症综合征，与TP53基因的种系突变以及儿童期发病恶性肿瘤的高风险相关。鉴于恶性肿瘤的解剖范围和发病年龄较小，对儿科突变携带者进行癌症监测具有挑战性。全身磁共振成像（WB-MRI）可能为早期癌症检测提供一种可接受的方法。
我们对患有LFS的儿科受试者（年龄<18岁）进行了一项前瞻性可行性试点研究，以确定年度WB-MRI扫描的返回率。次要目标包括对新发癌症的特征描述（以及它们是如何被检测到的）。
在5年时间里，对20名受试者进行了45次WB-MRI扫描；两名患者登记后未进行后续扫描。89%的接受扫描的参与者（95%置信区间：67-99%）返回进行第二次检查。55%的参与者需要全身麻醉，所有病例中耐受性良好。6名患者需要进行专门的随访成像。一名参与者需要对检测到的脑部病变进行活检；病理显示为反应性胶质增生。另一名先前患有脉络丛癌的参与者，在临床随访MRI上发现了一个新的脑部病变，而6个月前的WB-MRI上未发现。所有其他参与者情况良好（中位数：3年，范围：0.08-4年）。
尽管有些患者需要全身麻醉，但儿科受试者的WB-MRI是一种耐受性良好的癌症监测方法。一项大型多中心试验将确定这种方法在高癌症风险儿童早期癌症检测中的真正测试特征和疗效。
