Usefulness of pre-thyroidectomy neutrophil–lymphocyte, platelet–lymphocyte, and monocyte–lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer

Riguetto, Cínthia Minatel; Barreto, Icléia Siqueira; Maia, Frederico Fernandes Ribeiro; Assumpção, Lígia Vera Montali da; Zantut-Wittmann, Denise Engelbrecht

doi:10.6061/clinics/2021/e3022

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ORIGINAL ARTICLE • Clinics 76 • 2021 • https://doi.org/10.6061/clinics/2021/e3022 copy

Usefulness of pre-thyroidectomy neutrophil–lymphocyte, platelet–lymphocyte, and monocyte–lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer

Authorship SCIMAGO INSTITUTIONS RANKINGS

OBJECTIVE:

This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC).

METHODS:

This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively.

RESULTS:

PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity).

CONCLUSION:

Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.

Neutrophil-Lymphocyte Ratio; Platelet-Lymphocyte Ratio; Monocyte-Lymphocyte Ratio; Distant Metastasis; Differentiated Thyroid Cancer

Patients’ characteristics		n=390
Gender	Female	324 (83.08%)
Gender	Male	66 (16.92%)
Age (years)		46.65±15.41
Age	<55 years	262 (67.18%)
Age	≥55 years	128 (32.82%)
Follow-up (months)		82.83±54.17
Platelets (×10³/µL)		250±63
White blood cells (×10³/µL)		7.20±1.91
Neutrophils (×10³/µL)		4.16±1.48
Lymphocytes (×10³/µL)		2.26±0.76
Monocytes (×10³/µL)		0.52±0.20
Neutrophil-lymphocyte ratio		2.05±1.12
Platelet-lymphocyte ratio		120.56±45.65
Monocyte-lymphocyte ratio		0.25±0.11
DTC characteristics		n=390
Thyroid cancer	Papillary	357 (91.54%)
Thyroid cancer	Follicular	33 (8.46%)
Papillary thyroid cancer variants	Classic	144 (40.45%)
	Follicular	153 (42.98%)
	Tall cell	59 (16.57%)
Diameter of the largest tumor focus (cm)		2.31±1.96
Microcarcinoma		101 (25.96%)
Multifocality		202 (52.06%)
Invasion	Extrathyroidal extension	92 (23.71%)
	Capsular	87 (22.42%)
	Vascular	83 (21.39%)
	No invasion	126 (32.48%)
Metastatic lymph nodes		126 (32.31%)
Distant metastasis	Lung	29 (7.44%)
	Bone	4 (1.03%)
	Lung and bone	4 (1.03%)
T1		181 (46.53%)
T2		69 (17.74%)
T3		86 (22.11%)
T4		53 (13.62%)
N0		263 (67.61%)
N1		116 (32.39%)
M0		351 (90.23%)
M1		38 (9.77%)
TNM staging (eighth edition)	I	296 (76.09%)
	II	58 (14.91%)
	III	16 (4.11%)
	IV	19 (4.88%)
ATA risk	Low	195 (50%)
	Intermediate	101 (25.90%)
	High	94 (24.10%)
Radioiodine therapy		366 (94.33%)
Radioiodine activities		195.16±198.34
Anti-thyroglobulin antibody detectable		17 (4.36%)
Response to treatment	Excellent	307 (78.72%)
	Biochemical incomplete	20 (5.13%)
	Structural incomplete	32 (8.21%)
	Indeterminate	31 (7.95%)
Tumor outcome	Disease-free status	307 (78.72%)
	Persistent disease	76 (19.49%)
	Disease-related death	7 (1.79%)

	Patients	Neutrophil-lymphocyte ratio		Platelet-lymphocyte ratio		Monocyte-lymphocyte ratio
	Patients	Mean	p-value	Mean	p-value	Mean	p-value
Thyroid Cancer
Papillary	357	2.05±1.15	0.4491	120.11±44.66	0.7714	0.25±0.12	0.2949
Follicular	33	2.04±0.73		125.45±55.89		0.25±0.09
Variants
Classic PTC	144	2.04±1.18	0.8484	118.76±39.65	0.9810	0.23±0.09	0.6133
Follicular	153	2.06±1.22		120.98±48.76		0.26±0.13
Tall cell	59	2.01±0.87		120.74±46		0.26±0.14
Capsular invasion
Yes	87	1.91±0.74	0.6555	119.16±45.91	0.7353	0.25±0.12	0.8818
No	301	2.08±1.20		120.81±45.76		0.25±0.11
Angiolymphatic invasion
Yes	83	2.06±1.15	0.7962	120.39±41.86	0.6194	0.25±0.12	0.5674
No	305	2.04±1.11		120.45±46.81		0.25±0.11
Extrathyroidal invasion
Yes	92	2.06±1.19	0.8269	118.81±41.33	0.9478	0.25±0.13	0.9550
No	296	2.04±1.10		120.95±47.08		0.25±0.11
Lymph node metastasis
Yes	126	2.04±1.08	0.9334	115.58±38.14	0.3197	0.24±0.11	0.7524
No	264	2.05±1.14		122.94±48.72		0.25±0.12
Distant metastasis
Yes	37	2.15±0.91	0.1786	133.15±43.95	0.0345	0.24±0.08	0.4285
No	353	2.03±1.14		119.24±45.69		0.25±0.12
Tumor Size
<1 cm	288	2.03±1.04	0.9992	118.38±41.74	0.7888	0.25±0.10	0.4843
≥1 cm	101	2.05±1.15		121.25±47.05		0.25±0.12
Age
<55 years	262	2.04±1.17	0.3177	121.17±44.69	0.3688	0.24 ± 0.12	0.0379
≥55 years	128	2.06±1.00		119.31±47.72		0.26 ± 0.10
TNM staging (eighth edition)
Stages I and II	354	2.04±1.15	0.4112	119.20±45	0.1004	0.25±0.12	0.0986
Stages III and IV	35	2.06±0.8		132.64±50.53		0.26±0.10
ATA risk
Low	195	2.09±1.22	0.8286	121.85±48.66	0.4852	0.25±0.12	0.4317
Intermediate	101	1.98±0.96		115.44±40.44		0.24±0.13
High	94	2.09±1.22		121.85±48.66		0.25±0.12
Radioiodine therapy
Yes	361	2.06±1.13	0.3018	120.46±45.50	0.8120	0.25±0.12	0.8856
No	32	1.80±0.84		118.47±49.47		0.24±0.08
Response to treatment
Excellent	307	2.01±1.11	0.3453	117.72±44.70	0.0717	0.24±0.11	0.4423
Biochemical incomplete	20	2.27±1.30		128.54±44.41		0.27±0.12
Structural incomplete	32	2.05±0.77		130.46±49.54		0.25±0.10
Indeterminate	31	2.25±1.36		133.34±49.64		0.27±0.16
Disease outcome
Disease-free status	307	2.01±1.11	0.0812	117.72±44.70	0.0089	0.24±0.11	0.1219
Persistent disease and disease-related death	83	2.18±1.14		131.07±47.85		0.26±0.13

Variables	p-value	HR	95% CI
Cox univariate analysis
NLR	0.4074	1.072	0.909-1.265
PLR	0.0247	1.004	1.001-1.008
MLR	0.0904	4.272	0.796-22.944
Tumor size of ≥1 cm versus <1 cm	0.0038	2.942	1.416-6.113
Age≥55 years versus <55 years	0.0179	1.701	1.096-2.640
TNM stages III and IV versus I and II	<0.0001	3.268	1.982-5.389
Papillary variant
Tall cell versus follicular	0.0221	2.016	1.106-3.676
Classic versus follicular	0.9494	1.018	0.590-1.756
High versus low ATA risk	<0.0001	6.652	3.583-12.352
Intermediate versus low ATA risk	<0.0001	4.916	2.509-9.631
Cox multivariate analysis
MLR	0.0147	8.775	1.532-50.273
High versus low ATA risk	<0.0001	5.998	3.126-11.505
Intermediate versus low ATA risk	<0.0001	4.892	2.492-9.605

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E-mail: clinics@hc.fm.usp.br

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[1] *Corresponding author. E-mail: zantutw@unicamp.br