OBJECTIVE: To describe the clinical presentations and long-term outcomes of a large cohort of children and young adults with sMTC compared with hereditary MTC (hMTC).
METHODS: Retrospective study of 144 patients diagnosed with MTC between 1961 and 2019 at an age ≤ 21 years and evaluated at a tertiary referral center.
RESULTS: In contrast to hMTC (n = 124/144, 86%), patients with sMTC (n = 20/144, 14%) are older (P < .0001), have larger tumors (P < .0001), a higher initial stage grouping (P = .001) and have more structural disease (P = .0045) and distant metastases (DM) (P = .00084) at last follow-up, but are not more likely to die from MTC (P = .42). Among 77 patients diagnosed clinically, not by family history (20/20 sMTC and 57/124 hMTC), there was no difference in the initial stage (P = .27), presence of DM at diagnosis (P = 1.0), disease status at last follow-up (P = .13), overall survival (P = .57), or disease-specific survival (P = .87). Of the 12 sMTC tumors that underwent somatic testing, 11 (91%) had an identifiable alteration: 10 RET gene alterations and 1 ALK fusion.
CONCLUSIONS: sMTC is primarily a RET-driven disease that represents 14% of childhood-onset MTC in this cohort. Pediatric sMTC patients are older, present with clinical disease at a more advanced TNM classification, and have more persistent disease at last follow-up compared with hMTC, but these differences disappear when comparing those presenting clinically. Somatic molecular testing should be considered in sMTC patients who would benefit from systemic therapy.
目的:描述与遗传性MTC(hMTC)相比,大量儿童和年轻人sMTC的临床表现和长期结局。
方法:对1961-2019年间诊断为MTC且年龄≤21岁的144例患者进行回顾性研究,并在三级转诊中心进行评估。
结果:与hMTC(n=124/144,86%)相反,sMTC患者(n=20/144,14%)年龄较大(p<0.0001),有较大的肿瘤(p<0.0001),较高的初始阶段分组(p=0.001)和更多的结构性疾病(p=0.0045)和远处转移(DM)(p=0.00084)在最后一次随访,但不会更容易死于MTC(p=0.42)。在临床诊断的77名患者中,不是家族史(20/20sMTC和57/124hMTC),在初始阶段没有差异(p=0.27),诊断时存在DM(p=1.0),末次随访时的疾病状态(p=0.13),总生存率(p=0.57),或疾病特异性生存率(p=0.87)。在12个接受体细胞测试的sMTC肿瘤中,11个(91%)具有可识别的改变:10个RET基因改变和1个ALK融合。
结论:sMTC主要是RET驱动的疾病,在该队列中占儿童发作MTC的14%。儿科sMTC患者年龄较大,以更先进的TNM分类呈现临床疾病,与hMTC相比,在最后一次随访中有更多的持续性疾病,但是当比较临床上出现的差异时,这些差异消失了。应考虑将从全身治疗中受益的sMTC患者进行体细胞分子检测。