Blood Profiles in the Prediction of Radioiodine Refractory Papillary Thyroid Cancer: A Case–Control Study

Figures & data

Figure 1 The flow chart of patient selection.

Abbreviations: LIS, laboratory information system; PTC, papillary thyroid cancer; RAI, radioactive iodine.

Table 1 Demographical and Clinicopathological Characteristics of Included Patients

Parameter	Total	RAIR group	Control Group	p-value
Number of patients	36	12	24
Age (years, SD)	40.58 (9.262)	40.58 (9.539)	40.58 (9.329)	1.000
≥55y (%)	6 (16.7)	2 (16.7)	4 (16.7)	1.000
Sex (female, %)	21 (58.3)	7 (58.3)	14 (58.3)	1.000
BMI (kg/m^2, SD)	24.94 (3.786)	25.56 (4.159)	24.63 (3.639)	0.497
Hashimoto’s thyroiditis (%)	4 (11.1)	1 (8.3)	3 (12.5)	0.708
Hypertension (%)	5 (13.9)	1 (8.3)	4 (16.7)	0.496
Diabetes (%)	4 (11.1)	2 (16.7)	2 (8.3)	0.453
Smoking (%)	6 (16.7)	3 (25.0)	3 (12.5)	0.343
Alcohol consumption (%)	5 (13.9)	3 (25.0)	2 (8.3)	0.173
Cumulative I-131 dose (mCi) ^a	220 (220, 235)	220 (220, 220)	415 (225, 570)	<0.001 ***
Histological subtype (%) ^b
Classical	34 (94.4)	11 (91.7)	23 (95.8)	0.607
Follicular variant	8 (22.2)	3 (25.0)	5 (20.8)	0.777
Tall cell variant/solid variant	2 (5.6)	2 (16.7)	0 (0.0)	0.040 *
Tumor size (cm, SD)	1.60 (0.971)	1.57 (1.053)	1.61 (0.950)	0.896
Multifocality (%)	26 (72.2)	10 (83.3)	16 (66.7)	0.293
Extrathyroidal extension (%)	19 (52.8)	7 (58.3)	12 (50.0)	0.637
TNM (%)
T1-3	22 (61.1)	7 (58.3)	15 (62.5)	0.809
T4	14 (38.9)	5 (41.7)	9 (37.5)
N0	3 (8.3)	1 (8.3)	2 (8.3)	1.000
N1	33 (91.7)	11 (91.7)	22 (91.7)
M0	31 (86.1)	7 (58.3)	24 (100.0)	0.001 **
M1	5 (13.9)	5 (41.7)	0 (0.0)

Notes: Bold font: significant difference. * p<0.05, ** p <0.01, *** p <0.001. ^aAll continuous data were displayed as means and SDs except for cumulative I-131 dose, which was presented as median and IQR. ^bSeven patients had more than one subtypes in their primary lesions.

Abbreviations: BMI, body mass index; IQR, interquartile range; RAIR, radioactive iodine refractory thyroid cancer; SD, standard deviation.

Figure 2 The heatmap of sixteen blood biomarkers with statistical significance.

Abbreviations: AGPK, anion gap; BASO#, basophil count; FDP, fibrin/fibrinogen degradation products; LDL-Ch/TCh, low-density lipoprotein cholesterol-to-total cholesterol ratio; Na, serum sodium; NA/na, not applicable; Neu#, neutrophil count; TCO2, total carbon dioxide, Tg2/Tg1, stimulated thyroglobulin at the second I-131-to-stimulated thyroglobulin at the first I-131 ratio; TG-Ab, thyroglobulin antibody; TGB, thyroglobulin; TPO-Ab, thyroid peroxidase antibody; TT, thrombin time; WBC, white blood cell; VitD3, 25-hydroxyvitamin D3.

Table 2 Logistic Regression Analysis for the Association Between Blood Biomarkers and RAIR

Variable	Admission	Univariate		Multivariate
		OR (95% CI)	p-value	β value	OR (95% CI)	p-value
AGPK	Surgery	1.392 (1.001, 1.936)	0.049 *			0.161
LDL-Ch/TCh	Surgery	4.606e+6 (8.277, 2.564e+12)	0.023 *	19.750	3.778e+8 (31.953, 4.466e+15)	0.017 *
Na	Surgery	1.549 (1.060, 2.262)	0.024 *			0.246
Neu#	Surgery	0.480 (0.228, 1.012)	0.054			0.535
TT	Surgery	2.125 (1.106, 4.084)	0.024 *			0.274
WBC	Surgery	0.622 (0.370, 1.044)	0.072	−0.627	0.534 (0.292, 0.979)	0.042 *
FDP	First I-131	0.924 (0.692, 1.233)	0.591
TGB	First I-131	1.042 (0.982, 1.106)	0.172
TPO-Ab	First I-131	1.003 (1.000, 1.006)	0.083
VitD3	First I-131	1.130 (0.994, 1.284)	0.061
AGPK	Second I-131	1.356 (0.982, 1.874)	0.065
BASO#	Second I-131	0.000 (0.000, 105.915)	0.077
TCO2	Second I-131	0.684 (0.482, 0.969)	0.033 ^*,a
TG-Ab	Second I-131	1.043 (0.992, 1.097)	0.101
TGB	Second I-131	1.034 (0.962, 1.111)	0.367
Tg2/Tg1	NA	3.861 (0.683, 21.808)	0.126

Notes: Bold font: significant difference. * p<0.05. ^aThe data of TCO2 at the admission for the second I-131 ablation were not input into multivariate analysis since it could not be acquired in the early stage of treatment.

Abbreviations: AGPK, anion gap; BASO#, basophil count; CI, confidence interval; FDP, fibrin/fibrinogen degradation products; LDL-Ch/TCh, low density lipoprotein cholesterol-to-total cholesterol ratio; Na, serum sodium; NA, not applicable; Neu#, neutrophil count; OR, odd ratio; RAIR, radioactive iodine refractory thyroid cancer; TCO2, total carbon dioxide, Tg2/Tg1, stimulated thyroglobulin at the second I-131-to-stimulated thyroglobulin at the first I-131 ratio; TG-Ab, thyroglobulin antibody; TGB, thyroglobulin; TPO-Ab, thyroid peroxidase antibody; TT, thrombin time; WBC, leukocyte; VitD3, 25-hydroxyvitamin D3.

Table 3 Predictive Accuracy of the Blood Markers and the Scoring System Based on the ROC Curve

Variable	AUC	p-value	Cut-off Value	Sensitivity	Specificity	Youden Index
AGPK	0.701	0.052	12.17	0.833	0.500	0.333
LDL-Ch/TCh	0.759	0.012 *	0.551	0.917	0.625	0.542
Na	0.740	0.021 *	142.25	0.583	0.875	0.458
Neu# ^a	0.726	0.029 *	4.205	0.583	1.000	0.583
TT	0.858	0.001 **	17.15	1.000	0.750	0.750
WBC ^a	0.674	0.093	7.355	0.458	1.000	0.458
Scoring system	0.861	<0.001 ***	8.341	0.833	0.875	0.708

Notes: Bold font: significant difference. *p<0.05, **p<0.01, ***p<0.001. ^aNeutrophil and leukocyte count were negatively correlated with the RAIR. Hence their AUCs were calculated on the condition that the control group was defined as the state variable.

Abbreviations: AGPK, anion gap; AUC, area under the curve; LDL-Ch/TCh, low density lipoprotein cholesterol-to-total cholesterol ratio; Na, serum sodium; Neu#, neutrophil count; ROC, receiver operating characteristics; TT, thrombin time; WBC, leukocyte.

Figure 3 The comparison of scores between the two groups. The medians and interquartile ranges were displayed here. The Mann–Whitney U-test was applied.

Abbreviation: RAIR, radioactive iodine refractoriness.

Figure 4 The ROC curve of the scoring system.