(0707) Predictors of Distant Metastasis From Differentiated Thyroid Cancer in Children and Young Adults: A Meta-analysis

Introduction: It is widely known that distant metastases (DM) from differentiated thyroid cancer (DTC) are more commonly found in children compared to adults, though the factors that predict DM in children have not been well elucidated. This meta-analysis represents the first comprehensive examination of factors predicting DM at presentation and follow-up in children and young adults (CAYA) with DTC.

Methods: Our study was registered with PROSPERO (ID: CRD42024498913). We conducted a systematic review using PubMed, Scopus, OVID, Cochrane, and Web of Science in November 2023. Retrospective, prospective, and case-control studies exploring DM in DTC patients aged 21 years or younger were included, excluding national database studies, case reports, and case series. Two authors independently screened and extracted data from the selected studies. Random-effect meta-analyses were used to assess demographic, clinical, and pathological features associated with DM at presentation and follow-up.

Results: In total, 22 studies were included in the meta-analyses. In CAYA with DTC, male gender, younger age, nodal involvement, larger tumor size, and the presence of extra thyroidal extension (ETE) emerged as significant risk factors for DM at diagnosis (p < 0.05). Notably, ETE stood out as the strongest predictor of DM (OR 5.38, p < 0.0001). Patients with ETE and nodal involvement were significantly more likely to develop DM during follow-up after surgery (HR 4.01 and 6.59, respectively). Though prevalence of BRAF mutations is known to be lower in CAYA compared to adults with DTC, patients with BRAF V600E mutation were less likely to present with DM (p = 0.02). Meta-analyses demonstrated high homogeneity across studies (I^2 = 0% in all, except in two meta-analyses with 23% and 50%).

Conclusions: ETE and nodal involvement strongly predict DM in young patients with DTC. Unlike in adults, the presence of BRAF V600E mutation may have a protective effect against DM in CAYA.