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Predictive Factors of Recurrence for Multifocal Papillary Thyroid Microcarcinoma With Braf^v600e Mutation: A Single Center Study of 1,207 Chinese Patients.

ABSTRACT: Background: The American Thyroid Association (ATA) guidelines risk stratify Braf^v600e mutated multifocal papillary thyroid microcarcinoma (BMPTMC) into different recurrence risk groups by the extent of extrathyroidal extension (ETE). These findings and modifications for BMPTMC need to be verified in additional studies. Methods: A retrospective cohort study was conducted in BMPTMC patients who underwent total thyroidectomy (TT) and central lymph node dissection (CLND) from 2008 to 2013. Overall, 1,207 patients were included, and predictive factors were identified by univariate and multivariate analysis over a mean 7.5-year follow up. Results: BMPTMC with ETE to capsule shows the same recurrence rate (3.8%) with intrathyroidal BMPTMC. Moreover, BMPTMC with ETE only to strap muscle, which belongs to high-risk group according to ATA guideline, shows relatively lower recurrence rate (13.3%) compared with some intermediate risk categories such as cN1 and >5 pN1. Multivariate analysis using a Cox proportional hazards regression model shows that total tumor diameter (TTD) is associated with significantly higher recurrence for BMPTMC with or without other risk factors (Hazard Ratio (HRO) = 9.86 [95%CI 5.35-18.20], p = 0.00; HRO = 2.32 [95%CI 1.12-4.85], p = 0.02; respectively), while Hashimoto thyroiditis (HT) is found to be protective against the recurrence (HRO = 0.51 [95%CI 0.33-0.79], p = 0.00; HRO = 0.47 [95%CI 0.25-0.89], p = 0.02; respectively). Conclusions: Taken together, capsular ETE and gross ETE to the strap muscles did not have the expected significant influence on recurrence for Chinese BMPTMC patients who underwent TT and CLND. Rather than the extent of ETE, TTD and the lack of HT were identified as predictors for recurrence among BMPTMC with or without other risk factors (vascular invasion, cN1, pN1>5, pN1>3 cm).

SUBMITTER: Xue S

PROVIDER: S-EPMC6607364 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Predictive Factors of Recurrence for Multifocal Papillary Thyroid Microcarcinoma With Brafv600e Mutation: A Single Center Study of 1,207 Chinese Patients.

Xue Shuai S Zhang Li L Wang Peisong P Liu Jia J Yin Yue Y Jin Meishan M Guo Liang L Zhou Yuhua Y Chen Guang G

Frontiers in endocrinology 20190626

Background: The American Thyroid Association (ATA) guidelines risk stratify Brafv600e mutated multifocal papillary thyroid microcarcinoma (BMPTMC) into different recurrence risk groups by the extent of extrathyroidal extension (ETE). These findings and modifications for BMPTMC need to be verified in additional studies. Methods: A retrospective cohort study was conducted in BMPTMC patients who underwent total thyroidectomy (TT) and central lymph node dissection (CLND) fro ...[more]

PMID: 31297091

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Project description:BackgroundUltrasound, cytology, and BRAFV600E mutation analysis were applied as valuable tools in the differential diagnosis of thyroid nodules. The aim of the present study was to evaluate the diagnostic efficiency of the three methods and their combined use in screening for papillary thyroid microcarcinoma (PTMC).MethodsA total of 1,081 patients with 1,157 thyroid nodules (0.5-1 cm in maximum diameter) classified as thyroid imaging reporting and data system (TIRADS) 4-5 were recruited. All patients underwent ultrasound, fine-needle aspiration (FNA) examination, and an additional BRAFV600E mutation test. TIRADS and Bethesda System for Reporting Thyroid Cytopathology (BSRTC) were adopted to judge the ultrasound and cytological results. The receiver operating characteristic (ROC) curve was established to assess the diagnostic values of different methods.ResultsOf the 1,157 nodules, 587 were benign and 570 were PTMCs. BRAFV600E mutation test had highest sensitivity (85.4%), specificity (97.1%), accuracy (91.4%), and area under the ROC curve (Az) value (0.913) among the three methods. The combination of BSRTC and BRAFV600E mutation analysis yielded a considerably high sensitivity (96.0%), accuracy (94.3%), and negative predictive value (95.9%) than either BSRTC or BRAFV600E mutation alone (P < 0.0001 for all comparisons). Of all the methods, the combined use of the three methods produced the best diagnostic performance (Az = 0.967), which was significantly higher than that (Az = 0.943) for the combination of BSRTC and BRAFV600E mutation (P < 0.0001). The diagnostic accuracy of the molecular method in the 121 nodules with indeterminate cytology was 90.1% (109/121), which was significantly higher than that of TIRADS classification, 74.4% (90/121) (P = 0.002).ConclusionThe combined use of ultrasound, cytology, and BRAFV600E mutation analysis is the most efficient and objective method for diagnosing PTMC. Both BRAFV600E mutation and TIRADS classification are potentially useful adjuncts to differentiate thyroid nodules, especially indeterminate samples classified as BSRTC III.

Project description:BackgroundOver the past ten years, the incidence rate of papillary thyroid carcinoma (PTC) worldwide has been increasing rapidly year by year, with the incidence rate increasing 6% annually. PTC has become the malignant tumor with the highest growth rate in the world that fourteen PTC-related mutant genes have been identified. Whether the BRAFV600E mutation related to more aggressive clinicopathologic features and worse outcome in PTC remains variable and controversial. We aim to investigate the risk factors that may predict the BRAFV600E mutation potential of these lesions and new prevention strategies in PTC patients.MethodsA total of 9,908 papillary thyroid carcinoma patients with average 74.6% BRAFV600E mutations were analyzed (RevMan 5.3 software) in this study. The PubMed, Embase, and ISI Web of Science databases were systematically searched for works published through December 15, 2021.ResultsThe following variables were associated with an increased risk of BRAFV600E mutation in PTC patients: age ≥ 45 years (OR = 1.39, 95%CI = 1.21-1.60, p < 0.00001), male gender (OR = 1.13, 95%CI = 0.99-1.28, p = 0.06), multifocality (OR = 1.22, 95%CI = 1.07-1.40, p = 0.004), lymph node metastasis (OR = 1.33, 95%CI = 0.79-2.23, p = 0.28), extrathyroidal extension + (OR = 1.61, 95%CI = 1.06-2.44, p = 0.03), vascular invasion + (OR = 2.04, 95%CI = 1.32-3.15, p = 0.001), and tumor node metastasis stage (OR = 1.61, 95%CI = 1.38-1.88, p < 0.00001). In addition, tumor size (>1 cm) (OR = 0.51, 95%CI = 0.32-0.81, p = 0.005) and distant metastasis (OR = 0.69, 95%CI = 0.22-2.21, p = 0.54) had no association or risk with BRAFV600E mutation in PTC patients.ConclusionOur systematic review identified the following significant risk factors of BRAFV600E mutation in PTC patients: age (≥45 years), gender (male), multifocality, lymph node metastasis, vascular invasion, extrathyroidal extension, and advanced tumor node metastasis stage (stages III and IV). Tumor size (>1 cm) and distant metastasis do not appear to be correlated with BRAFV600E mutation in PTC patients.

Project description:BackgroundCurrently, less aggressive treatment or even active surveillance of papillary thyroid microcarcinoma (PTMC) is widely accepted and recommended as a therapeutic management option. However, there are some concerns about these approaches. We investigated whether there are any demographic, clinical and ultrasound characteristics of PTMC patients that are easy to obtain and clinically available before surgery to help clinicians make proper therapeutic decisions.MethodsWe performed a retrospective chart review of 5,021 patients with thyroid tumors surgically treated in one center in 2008-2018. Finally, 182 (3.62%) PTMC patients were selected (158 (86.8%) females and 24 (13.2%) males, mean age 48.8±15.4 years). We analyzed the disease-free survival (DFS) time of the PTMC patients according to demographic and histopathological parameters. Univariate and multivariate logistic regression analyses were used to assess the relationships of demographic, clinical and ultrasound characteristics with aggressive histopathological features.ResultsAge ≥55 years, hypoechogenicity, microcalcifications, irregular tumor shape, smooth margins and high vascularity significantly increased the risk for minimal extrathyroidal extension (minETE), lymph node metastasis (LNM), and capsular and vascular invasion (p<0.0001). Multivariate logistic regression analysis demonstrated a statistically significant risk of LNM (OR = 5.98, 95% CI: 2.32-15.38, p = 0.0002) and trends toward significantly higher rates of minETE and capsular and vascular invasion (OR = 2.24, 95% CI: 0.97-5.19, p = 0.056) in patients ≥55 years than in their younger counterparts. The DFS time was significantly shorter in patients ≥55 years (p = 0.015), patients with minETE and capsular and vascular invasion (p = 0.001 for all), patients with tumor size >5 mm (p = 0.021), and patients with LNM (p = 0.002).ConclusionsThe absence of microcalcifications, irregular tumor shape, blunt margins, hypoechogenicity and high vascularity in PTMC patients below 55 years and with tumor diameters below 5 mm may allow clinicians to select individuals with a low risk of local recurrence so that they can receive less aggressive management.

Dataset Information

Predictive Factors of Recurrence for Multifocal Papillary Thyroid Microcarcinoma With Braf^v600e Mutation: A Single Center Study of 1,207 Chinese Patients.

Publications

Predictive Factors of Recurrence for Multifocal Papillary Thyroid Microcarcinoma With Braf<sup>v600e</sup> Mutation: A Single Center Study of 1,207 Chinese Patients.

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