Abstract
Background: Recently, radioiodine refractory differentiated thyroid cancer (RR-DTC) has received increasing attention due to its poor prognosis. The roles of clinical, pathological, and molecular features in the development of RR-DTC remain controversial and require additional investigation. This study aimed to evaluate the association between these risk factors and the occurrence of RR-DTC.Methods: We performed a systematic search for relevant literature following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) in PubMed, EMBASE, Medline, SCOPUS, and Web of Science up to the July 15, 2020. Observational studies that investigated the risk factors for RR-DTC were included. Fixed- or random-effects models were used to calculate pooled odds ratios (ORs) or mean differences (MD) with corresponding 95% confidence intervals.Results: We included 13 eligible studies incorporating 1,431 cases, of which 603 were patients with RR-DTC. The pooled analysis indicated that four parameters significantly increased the risk of RR-DTC: extrathyroidal extension (ETE) (OR: 2.28, 95% CI: 1.43–3.64, I2 = 14%), BRAFV600E mutation (OR: 3.60, 95% CI: 1.74–7.46, I2 = 69%), TERT promoter mutation (OR: 9.84, 95% CI: 3.60–26.89, I2 = 61%) and high-risk histological subtype (OR: 1.94, 95% CI: 1.15–3.27, I2 = 15%), including tall cell variant papillary thyroid carcinoma (PTC), sclerosing diffuse PTC, hobnail variant PTC, follicular thyroid carcinoma (FTC) (including Hürthle cell), and poorly differentiated thyroid carcinoma (PDTC). However, there was no statistical significance regarding sex, age, tumor size, multifocality, or lateral lymph node metastasis. Subgroup and sensitivity analyses were conducted to further confirm the robustness of the results.Conclusions: Histological subtype, ETE, BRAFV600E mutation, and TERT promoter mutation could be considered clinicopathological factors and biomarkers. They could assist in risk stratification, prognostic prediction, and individual therapy options for RR-DTC.
Highlights
In recent decades, thyroid cancer (TC) has emerged as a striking health issue, and the global incidence of TC is 6.7 per 100,000 [1]
Forty-six remaining studies were retrieved for assessment, and a flow chart showed the process of literature retrieval (Figure 1)
There were 603 RR-differentiated thyroid carcinoma (DTC) and 828 controls involved in the present study
Summary
Thyroid cancer (TC) has emerged as a striking health issue, and the global incidence of TC is 6.7 per 100,000 [1]. Most DTC cases can be treated successfully by thyroidectomy, selective radioactive iodine (RAI) therapy, and thyroid stimulating hormone (TSH)-suppressive therapy and have a favorable prognosis. The incidences of local recurrence and distant metastases are ∼30 and 10% [2], respectively. Among these patients, one third show initial or gradual loss of iodine uptake and even a decrease in sodium iodide symporter (NIS) expression in the plasma membrane, indicating a status of dedifferentiation known as RAI-refractory DTC (RR-DTC) [3]. Radioiodine refractory differentiated thyroid cancer (RR-DTC) has received increasing attention due to its poor prognosis. This study aimed to evaluate the association between these risk factors and the occurrence of RR-DTC
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