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Meta-Analysis
. 2017 Jul 25;8(30):49421-49442.
doi: 10.18632/oncotarget.17220.

Comparative analysis of diagnostic performance, feasibility and cost of different test-methods for thyroid nodules with indeterminate cytology

Salvatore Sciacchitano  1   2 , Luca Lavra  2 , Alessandra Ulivieri  2 , Fiorenza Magi  2 , Gian Paolo De Francesco  3 , Carlo Bellotti  4 , Leila B Salehi  2   5 , Maria Trovato  6 , Carlo Drago  7 , Armando Bartolazzi  8   9
Affiliations
Meta-Analysis

Comparative analysis of diagnostic performance, feasibility and cost of different test-methods for thyroid nodules with indeterminate cytology

Salvatore Sciacchitano et al. Oncotarget. .

Abstract

Since it is impossible to recognize malignancy at fine needle aspiration (FNA) cytology in indeterminate thyroid nodules, surgery is recommended for all of them. However, cancer rate at final histology is <30%. Many different test-methods have been proposed to increase diagnostic accuracy in such lesions, including Galectin-3-ICC (GAL-3-ICC), BRAF mutation analysis (BRAF), Gene Expression Classifier (GEC) alone and GEC+BRAF, mutation/fusion (M/F) panel, alone, M/F panel+miRNA GEC, and M/F panel by next generation sequencing (NGS), FDG-PET/CT, MIBI-Scan and TSHR mRNA blood assay.We performed systematic reviews and meta-analyses to compare their features, feasibility, diagnostic performance and cost. GEC, GEC+BRAF, M/F panel+miRNA GEC and M/F panel by NGS were the best in ruling-out malignancy (sensitivity = 90%, 89%, 89% and 90% respectively). BRAF and M/F panel alone and by NGS were the best in ruling-in malignancy (specificity = 100%, 93% and 93%). The M/F by NGS showed the highest accuracy (92%) and BRAF the highest diagnostic odds ratio (DOR) (247). GAL-3-ICC performed well as rule-out (sensitivity = 83%) and rule-in test (specificity = 85%), with good accuracy (84%) and high DOR (27) and is one of the cheapest (113 USD) and easiest one to be performed in different clinical settings.In conclusion, the more accurate molecular-based test-methods are still expensive and restricted to few, highly specialized and centralized laboratories. GAL-3-ICC, although limited by some false negatives, represents the most suitable screening test-method to be applied on a large-scale basis in the diagnostic algorithm of indeterminate thyroid lesions.

Keywords: diagnostic performance; indeterminate thyroid nodules; meta-analysis; systematic review; thyroid FNA cytology.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Flow of information of our systematic review for each test-method, through the four-phase flow, according to the PRISMA statement
Figure 2
Figure 2. Forest plots of individual studies and pooled odds ratio of the four test-methods for which more then 2 studies were selected from the systematic literature search
For each study the 95% confidence interval (95% CI) and the weight (%) were also reported. The open diamond at the bottom of the graph shows the average effect size of the examined studies.
Figure 3
Figure 3. Comparative two-dimensional scatterplot diagram of sensitivity and specificity of each test-method
Arbitrary cut-off lines at 80% of specificity and at 80% of sensitivity were included in the diagram.
Figure 4
Figure 4. Comparative two-dimensional scatterplot diagram of LR+ and LR- of each test-method
(LR+ Positive Likelihood Ratio, LR- Negative Likelihood Ratio). Arbitrary cut-off lines at 5 of LR+ and at 0.3 of LR- were included in the diagram.
Figure 5
Figure 5. Comparative two-dimensional scatterplot diagram of cost and accuracy of each test-method
Arbitrary cut-off lines at 80% of accuracy and at 1,000 and 2,000 USD were included in the diagram.
Figure 6
Figure 6. Comparative three-dimensional scatterplot diagram of cost, sensitivity and specificity of each test-method
Arbitrary cut-off lines at 80% of sensitivity, at 80% of specificity and at 1,500 of single test cost, expressed in USD, were included in the diagram.
Figure 7
Figure 7. Algorithm for management of thyroid nodules
See this image and copyright information in PMC

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