DataSheet_1_Predictive risk factors for distant metastasis in pediatric differentiated thyroid cancer from Saudi Arabia.docx

BackgroundDespite their excellent prognosis, children and young adults (CAYA) with differentiated thyroid cancer (DTC) tend to have more frequent occurrence of distant metastasis (DM) compared to adult DTC. Data about DM in CAYA from Middle Eastern ethnicity is limited.MethodsMedical records of 170 patients with DTC ≤18 years were retrospectively reviewed. Clinico-pathological factors associated with lung metastasis in CAYA, their clinical presentation and outcome were analyzed. Rick factors related to distant metastasis-free survival (DMFS) for the whole cohort were evaluated.ResultsDM was observed in 27 patients and all were lung metastasis. Lung metastasis was significantly associated with younger age (≤15 years), extrathyroidal extension (ETE), multifocal tumors, bilaterality, presence of lymph node (LN) disease and high post-operative stimulated thyroglobulin (sTg). Highest negative predictive values were seen with low post-operative sTg (97.9%), absence of LN disease (93.8%), absence of ETE (92.2%) and age older than 15 years (92.9%). Post-therapy whole body scan (WBS) identified most of the lung metastasis (21 of 27; 77.8%). Upon evaluating patients response according to ATA guidelines, excellent response was seen in only one patient, while biochemical persistence and structural persistence were seen in 11.1% (3/27) and 77.8% (21/27), respectively. Elevated post-operative sTg (>10ng/ml) was the only risk factor found to be significantly associated with both biochemical persistence (with or without structural persistence (p = 0.0143)) and structural persistence (p = 0.0433). Cox regression analysis identified age and post-operative sTg as independent risk factors related to DMFS. Based on these two risk factors for DMFS, patients were divided into 3 groups: low risk (no risk factors), intermediate risk (1 risk factor) and high risk (both risk factors). 20-year DMFS rates in the low-, intermediate- and high-risk groups were 100.0%, 81.3% and 23.7% respectively (p < 0.0001).ConclusionHigher suspicion for metastatic pediatric DTC should be considered in patients who are young, have LN disease, extrathyroidal extension and elevated post-operative sTg. Persistent disease, despite therapy, is very common and it appears to be related to post-operative sTg level. Hence, risk adaptive management is desirable in CAYA with DTC.

尽管分化型甲状腺癌（DTC）的预后良好，但与成年DTC相比，儿童和青少年（CAYA）的远处转移（DM）发生率更高。关于中东血统CAYA的DM数据有限。方法：回顾性审查了170名18岁以下DTC患者的病历。分析了与CAYA肺转移相关的临床病理因素、其临床表现和预后。评估了整个队列与无远处转移生存期（DMFS）相关的风险因素。结果：观察到27例远处转移，均为肺转移。肺转移与年龄（≤15岁）、甲状腺外扩展（ETE）、多灶性肿瘤、双侧性、存在淋巴结（LN）疾病和术后刺激甲状腺球蛋白（sTg）水平高显著相关。术后sTg低（97.9%）、无LN疾病（93.8%）、无ETE（92.2%）和年龄大于15岁（92.9%）的阴性预测值最高。治疗后的全身扫描（WBS）识别了大多数肺转移（27例中的21例；77.8%）。根据ATA指南评估患者反应，仅1例患者表现出良好反应，而在11.1%（3/27）的患者中观察到生化持续存在，在77.8%（21/27）的患者中观察到结构持续存在。术后sTg升高（>10ng/ml）是唯一与生化持续存在（无论是否存在结构持续存在，p = 0.0143）和结构持续存在（p = 0.0433）显著相关的风险因素。Cox回归分析确定了年龄和术后sTg是独立的风险因素，与DMFS相关。基于这两个DMFS风险因素，患者被分为三组：低风险组（无风险因素）、中风险组（1个风险因素）和高风险组（两个风险因素）。低风险、中风险和高风险组的20年DMFS率分别为100.0%、81.3%和23.7%（p < 0.0001）。结论：对于年轻、有LN疾病、甲状腺外扩展和术后sTg升高的患者，应考虑对转移性儿童DTC保持更高的警惕。尽管接受治疗，持续疾病非常常见，这似乎与术后sTg水平有关。因此，对CAYA中的DTC进行风险适应性管理是可取的。