Determinants of lung metastasis in pediatric and young adult differentiated thyroid cancer: A meta-analytic study.

Abstract

e18107 Background: Distant metastases from differentiated thyroid cancer (DTC) occur more frequently in children and young adults (CAYA) than in older adults, with the lung as the most common metastatic site. This meta-analysis provides a comprehensive assessment of factors associated with lung metastasis at diagnosis, during follow-up, and lung metastasis–free survival in CAYA with DTC. Methods: This study was registered in PROSPERO. A systematic search of PubMed, Scopus, OVID, Cochrane, and Web of Science was conducted in February 2024. Retrospective, prospective, and case-control studies evaluating lung metastasis in patients aged ≤21 years with DTC were included. Lung metastasis was confirmed by imaging and/or pathology. Two reviewers independently performed study selection and data extraction. Random-effects meta-analyses evaluated demographic, pathological, and molecular predictors. Results: Thirty-two studies were included. At diagnosis, younger age, advanced T stage, nodal involvement, lateral lymph node metastasis, extrathyroidal extension (ETE), and multifocality were significantly associated with lung metastasis. Wild-type BRAF status was associated with a higher risk of lung metastasis compared with BRAF V600E . During follow-up, male sex, nodal disease, lateral lymph node metastasis, and ETE were significant predictors. Age ≤15 years was associated with worse lung metastasis–free survival. Conclusions: Nodal disease, ETE, advanced T stage, younger age, and multifocality are key predictors of lung metastasis in CAYA with DTC, while BRAF V600E mutation status appears protective. Factors predicting lung metastasis at diagnosis. No. of studies No. of patients OR/mean difference 95% CI P- value I 2 Male (vs. female) 11 1177 1.28 [0.87, 1.87] 0.21 18% Average age (years) 8 490 -1.65 [-2.46, -0.84] 0.0001 0% Age ≤10 years (vs. >10) 9 1558 2.35 [1.72, 3.22] 0.00001 0% Age ≤15 years (vs. >15) 8 1394 2.50 [1.56, 4.02] 0.0002 12% Papillary thyroid cancer (vs. follicular) 7 716 1.52 [0.59, 3.89] 0.39 20% T3/T4 (vs. T1/T2) 7 345 2.86 [1.45, 5.64] 0.002 0% pN1(vs. pN0) 8 984 4.14 [2.68, 6.39] 0.00001 0% Lateral lymph node (vs. no) 3 256 10.70 [3.71, 30.90] 0.0001 0% Average tumor size (cm) 4 617 0.70 [-0.07, 1.47] 0.070 72% ETE (vs. no) 3 792 2.55 [1.80, 3.61] 0.00001 0% Multifocal (vs. unifocal) 3 518 2.42 [1.56, 3.76] 0.0001 0% Wild type BRAF (vs. mutation) 6 419 5.71 [2.05, 15.87] 0.0008 0% Lung Metastasis on follow-up Male (vs. female) 6 549 2.39 [1.30, 4.41] 0.005 0% Average age (years) 3 211 -1.45 [-3.57, 0.67] 0.180 67% Papillary thyroid cancer (vs. follicular) 5 487 2.07 [0.60, 7.13] 0.250 0% T3/T4 (vs. T1/T2) 4 313 2.62 [0.81, 8.52] 0.110 15% pN1(vs. pN0) 5 479 3.89 [1.72, 8.83] 0.001 0% cN+(vs cN0) 2 246 7.02 [3.42, 14.40] 0.00001 0% Lateral lymph node (vs. no) 3 287 3.48 [1.79, 6.76] 0.0002 0% ETE (vs. no) 3 284 12.6 [4.74, 33.85] 0.00001 0% Total thyroidectomy (vs no) 3 281 2.46 [0.31, 19.55] 0.400 67%