Clinicopathological and prognostic differences of fusion oncogenes in papillary thyroid carcinoma: a meta-analysis of summary and individual patient data

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IntroductionFusion oncogenes (e.g., NTRK, RET, ALK, BRAF, PPARG) are rare genetic events in papillary thyroid carcinoma (PTC) and little is known about the similarities and differences in clinicopathological manifestations and prognostic outcomes of these genetic alterations. This meta-analysis aimed to investigate the clinicopathological significance and prognoses of different oncogenic fusions in PTC patients.MethodsWe performed a summary-level meta-analysis to compare the fusion-positive with fusion-negative PTCs and individual patient data meta-analysis to analyze the clinicopathological profiles of different oncogenic fusions. The odds ratio and their 95% confidence intervals were calculated using the random-effect model. Chi-square and Fisher’s exact tests were used to compare categorical variables while Wilcoxon rank-sum and analysis of variance (ANOVA) tests were utilized for continuous covariates.ResultsWe included 40 studies for meta-analyses. Compared to fusion-negative PTCs, cases with oncogenic fusions occurred at a younger age and had increased rates of multifocality, vascular invasion, extrathyroidal extension, and nodal/distant metastases. NTRK-, RET-, BRAF-, ALK-, and PPARG-rearranged PTCs had a unique demographic/clinicopathological profile but similar progression-free survival (PFS) and overall survival (OS). NTRK1-positive PTCs demonstrated more aggressive clinical behaviors and shorter PFS in comparison to NTRK3-positive PTCs whereas RET rearrangement variants shared comparable clinicopathological backgrounds.ConclusionThis study provides new insights and facilitates our current understanding of clinicopathological features and survival outcomes of different fusion oncogenes in PTCs. It may help clinicians better counsel the patients and tailor appropriate treatment decisions.