Shirali Aditya S, Hu Mimi I, Chiang Yi-Ju, Graham Paul H, Fisher Sarah B, Sosa Julie Ann, Perrier Nancy, Brown Spandana, Holla Vijaykumar R, Dadu Ramona, Busaidy Naifa, Sherman Steven I, Cabanillas Maria, Waguespack Steven G, Zafereo Mark E, Grubbs Elizabeth G
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
J Endocr Soc. 2024 Apr 24;8(6):bvae048. doi: 10.1210/jendso/bvae048. eCollection 2024 Apr 6.
Next-generation sequencing (NGS) analysis of sporadic medullary thyroid carcinoma (sMTC) has led to increased detection of somatic mutations, including M918T, which has been considered a negative prognostic indicator.
This study aimed to determine the association between clinicopathologic behavior and somatic mutation identified on clinically motivated NGS.
In this retrospective cohort study, patients with sMTC who underwent NGS to identify somatic mutations for treatment planning were identified. Clinicopathologic factors, time to distant metastatic disease (DMD), disease-specific survival (DSS), and overall survival (OS) were compared between somatic mutations.
Somatic mutations were identified in 191 sMTC tumors, including M918T (53.4%), other codons (10.5%), (18.3%), somatic indels (8.9%), and wild-type (WT) status (8.9%). The median age at diagnosis was 50 years (range, 11-83); 46.1% were female. When comparing patients with M918T, Other, and WT (which included and WT), there were no differences in sex, TNM category, systemic therapy use, time to DMD, DSS, or OS. On multivariate analysis, older age at diagnosis (HR 1.05, < .001; HR 1.06, .001) and M1 stage at diagnosis (HR 3.17, = .001; HR 2.98, = .001) were associated with decreased DSS and OS, respectively, but mutation cohort was not. When comparing M918T to indels there was no significant difference in time to DMD, DSS, or OS between the groups.
Somatic mutations do not portend compromised DSS or OS in a cohort of sMTC patients who underwent clinically motivated NGS.
散发性甲状腺髓样癌（sMTC）的下一代测序（NGS）分析已导致体细胞突变检测增加，包括M918T，其被认为是不良预后指标。
本研究旨在确定临床病理行为与基于临床目的的NGS检测到的体细胞突变之间的关联。
在这项回顾性队列研究中，纳入了因治疗计划而接受NGS以鉴定体细胞突变的sMTC患者。比较了体细胞突变之间的临床病理因素、远处转移疾病（DMD）时间、疾病特异性生存（DSS）和总生存（OS）。
在191例sMTC肿瘤中鉴定出体细胞突变，包括M918T（53.4%）、其他密码子（10.5%）、（18.3%）、体细胞插入缺失（8.9%）和野生型（WT）状态（8.9%）。诊断时的中位年龄为50岁（范围11 - 83岁）；46.1%为女性。比较M918T、其他和WT（包括和WT）患者时，性别、TNM分类、全身治疗使用、DMD时间、DSS或OS方面无差异。多因素分析显示，诊断时年龄较大（HR 1.05，<.001；HR 1.06，.001）和诊断时M1期（HR 3.17，=.001；HR 2.98，=.001）分别与DSS和OS降低相关，但突变队列无关。比较M918T和插入缺失时，两组之间的DMD时间、DSS或OS无显著差异。
在因临床目的接受NGS的sMTC患者队列中，体细胞突变并不预示DSS或OS受损。
