Li-Fraumeni综合征相关肺癌的临床特征与诊疗管理
Clinical characteristics and management of Li-Fraumeni syndrome-associated lung cancer.
作者
作者单位
- Department of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address: kotaishioka@gmail.com.
- Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
- Department of Pathology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
- Department of Thoracic Surgical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
- Department of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
摘要
中文
Li-Fraumeni综合征（LFS）由致病性胚系TP53变异引起，日益被认为是肺腺癌（LUAD）的易感因素，但其临床特征尚未充分明确。我们回顾性分析了2000年至2025年间在我院确诊的LFS患者，在32例LFS患者中鉴定出5例原发性LUAD。确诊中位年龄为34岁（范围29-53岁），其中4例从未吸烟。3例有肺癌家族史，3例存在多个同步肺病灶。值得注意的是，所有4例接受检测的患者均检出活化EGFR变异。临床病程具有异质性：1例晚期患者接受lazertinib联合amivantamab治疗获得持续疾病控制，另1例患者通过序贯EGFR酪氨酸激酶抑制剂获得长期获益，在获得EGFR T790M突变后接受gefitinib治疗34个月、osimertinib治疗51个月。相比之下，1例既往已知LFS的患者接受监测，检出两处早期肺癌，随后接受根治性手术，术后恢复良好。5例患者中有2例不符合2015年Chompret标准。这些探索性发现提示，LFS相关LUAD可能未被充分认识，其特征为早发、非吸烟状态、多灶性疾病和频繁EGFR变异，需在更大队列中验证。
English
Li-Fraumeni syndrome (LFS), caused by pathogenic germline TP53 variants, is increasingly recognized as a predisposition to lung adenocarcinoma (LUAD); however, its clinical features remain insufficiently defined. Patients diagnosed with LFS at our institution between 2000 and 2025 were retrospectively reviewed, and five patients with primary LUAD were identified among 32 individuals with LFS. The median age at diagnosis was 34 years (range, 29-53 years), and four patients had never smoked. Three patients had a family history of lung cancer, and three had multiple synchronous lung lesions. Notably, activating EGFR alterations were identified in all four tested cases. The clinical course was heterogeneous: one patient with advanced disease achieved ongoing disease control with lazertinib plus amivantamab, whereas another patient achieved prolonged benefit from sequential EGFR tyrosine kinase inhibitors, with 34 months on gefitinib and 51 months on osimertinib after the acquisition of EGFR T790M. In contrast, surveillance of a patient with previously recognized LFS led to the detection of two early-stage lung cancers, followed by curative-intent surgery and a favorable postoperative course. Two of the five patients did not fulfill the 2015 Chompret criteria. These exploratory findings suggest that LFS-associated LUAD may be under-recognized and characterized by early-onset presentation and never-smoking status, multifocal disease, and frequent EGFR alterations, warranting validation in larger cohorts.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 5.3
- 新锐分区
- 2区