101 Diagnostic utility of molecular and imaging biomarkers 2 BRAF mutation RAS mutation PAX8/PPARγ rearrangement BRAF/RAS combined 7-gene GMP Afirma® GEC Galectin-3 HBME-1 Cytokeratin 19 Galectin-3/HBME-1 combined (and/orI) Galectin-3/HBME-1 combined (dualII) Qualitative elastosonography Qualitative elastosonography (score >1III) Semi-quantitative elastosonography 99mTc-MIBI scintigraphy FDG-PET(/CT) scan 3,886 6,071 2,212 3,036 1,696 2,215 2,199 3,272 1,513 1,664 958 1,665 1,016 1,044 411 419 175 175 263 263 263 263 865 865 713 713 867 867 199 199 434 434 number of studies ni all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case all (nH) best/worst case positive likelihood ratio, (95% CI) negative likelihood ratio, (95% CI) 51 20 13 19 10 13 12 7 3 4 4 10 6 6 3 10 0 20 10 5 15 195.22 (28.77-1,324) 201.03 (67.64-597.44) 14,962 (44.69-5,009,532) 4.87 (2.67-8.90) 9.70 (5.21-18.06) 1.55 (0.61-3.95) 20.13 (2.98-135.82) 35.69 (4.50-283.32) 8.84 (0.92-84.83) 8.69 (5.41-13.96) 15.61 (8.33-29.24) 3.29 (1.28-8.47) 7.22 (4.08-12.76) 9.75 (5.56-17.10) 3.42 (1.41-8.33) 1.14 (1.06-1.23) 2.26 (1.75-2.91) 0.47 (0.32-0.71) 7.07 (4.25-14.95) 8.79 (4.41-17.52) 5.67 (3.16-10.18) 6.77 (4.46-10.27) 6.98 (4.62-10.56) 6.06 (3.79-9.69) 6.07 (3.18-11.57)* 6.07 (3.18-11.57)* 6.07 (3.18-11.57)* 4.51 (2.92-6.97) 4.51 (2.92-6.97) 4.51 (2.92-6.97) 13.47 (3.60-50.42) 13.47 (3.60-50.42) 13.47 (3.60-50.42) 4.27 (1.38-13.23) 4.27 (1.38-13.23) 4.27 (1.38-13.23) 1.20 (0.84-1.70) 1.20 (0.84-1.70) 1.20 (0.84-1.70) 14.04 (5.22-37.79) 14.04 (5.22-37.79) 14.04 (5.22-37.79) 2.09 (0.83-n.a.c.)* 2.09 (0.83-n.a.c.)* 2.09 (0.83-n.a.c.)* 1.76 (1.40-2.21) 1.76 (1.40-2.21) 1.76 (1.40-2.21) 0 1 0,50 0,25 0,75 0.80 (0.73-0.88) 0.80 (0.72-0.88) 0.91 (0.88-0.95) 0.77 (0.66-0.89) 0.69 (0.58-0.82) 0.95 (0.84-1.07) 0.94 (0.92-0.97) 0.94 (0.92-0.97) 0.98 (0.96-1.00) 0.55 (0.45-0.68) 0.51 (0.41-0.63) 0.80 (0.66-0.96) 0.44 (0.37-0.52) 0.52 (0.42-0.63) 0.77 (0.60-0.97) 0.18 (0.09-0.37) 0.03 (0.01-0.09) 5.54 (2.86-10.76) 0.29 (0.20-0.42) 0.27 (0.19-0.38) 0.37 (0.20-0.68) 0.22 (0.14-0.36) 0.22 (0.13-0.35) 0.27 (0.16-0.44) 0.26 (0.17-0.38)* 0.26 (0.17-0.38)* 0.26 (0.17-0.38)* 0.04 (0.01-0.12) 0.04 (0.01-0.12) 0.04 (0.01-0.12) 0.25 (0.15-0.41) 0.25 (0.15-0.41) 0.25 (0.15-0.41) 0.25 (0.14-0.45) 0.25 (0.14-0.45) 0.25 (0.14-0.45) 0.08 (0.01-0.73) 0.08 (0.01-0.73) 0.08 (0.01-0.73) 0.08 (0.01-0.75) 0.08 (0.01-0.75) 0.08 (0.01-0.75) 0.49 (0.18-1.31)* 0.49 (0.18-1.31)* 0.49 (0.18-1.31)* 0.12 (0.04-0.40) 0.12 (0.04-0.40) 0.12 (0.04-0.40) Results for RET/PTC rearrangement analysis, next generation sequencing, microRNA, and DWI-MRI are not included in this figure, because no meta-analysis could be performed. Forest plots for US characteristics and various subgroup analysis are provided in separate figures. *: pooled estimates using random effects model in case the number of studies is smaller than four. I: results shown are for test considered positive if sample was positive for one or both of the immunostains. II: results shown are for test considered positive if both immunostains were positive. III: results shown are for qualitative elastosonography using an alternative threshold score of >1 for a suspicious nodule. n.a.c., not able to calculate; ni, number of indeterminate nodules; nH, number of indeterminate nodules with available histopathology.
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