Table 3.
Overview of the studies investigating the role of serum inflammation-based scores in different endocrine tumors
| Endocrine tumor type | Study (first author, year, reference) | Study population | Summary of the main findings of the study per serum inflammation-based score |
|---|---|---|---|
| Parathyroid tumors | Zeren 2015 (85) | 32 pts with primary hyperparathyroidism | • Preoperative NLR was 2.1 ± 0.9, with positive correlations between preoperative NLR and adenoma size, presence of carcinoma, calcium levels and PTH levels |
| Yang 2018 (86) | 213 secondary hyperparathyroidism pts after parathyroidectomy | • There were correlations between preoperative NLR and PLR and levels of serum phosphorous (rho = 0.17; P = 0.015 and rho = 0.19; P = 0.007, respectively) and calcium-phosphorus product (rho = 0.14; P = 0.046 and rho = 0.17; P = 0.014) | |
| • Postoperative PTH levels correlated with both NLR and PLR at follow-up (rho = 0.29; P = 0.004 and rho = 0.24; P = 0.023, respectively) | |||
| • NLR and PLR significantly decreased after successful parathyroidectomy (P = 0.0006 and P = 0.0003, respectively), while pts who had persistent or recurrent hyperparathyroidism had no significant changes | |||
| Lam 2019 (87) | 95 pts with primary hyperparathyroidism | • A correlation was observed between preoperative NLR and serum PTH (r = 0.274; P = 0.013) and calcium (r = 0.376; P = 0.001) levels | |
| • Pts had a decrease in median NLR after successful parathyroidectomy from 2.26 (IQR: 1.70-3.00) to 1.77 (IQR: 1.59-2.61) (P = 0.037) | |||
| Toraman 2019 (88) | 301 pts with high PTH levels | • A positive correlation was observed between serum NLR (but not PLR) and PTH and creatinine levels | |
| • There was a significant negative correlation between NLR (and PLR) and serum calcium levels | |||
| • Main determinants of NLR were PTH, albumin, LDL-cholesterol, hemoglobin and gender | |||
| Adrenal tumors | Bagante 2015 (89) | 84 ACC pts | • Pts with preoperative NLR > 5 (34.5%) had higher proportions of tumors > 5cm (100% vs 86%), resection of metastasis in other organs (69% vs 38%), incomplete resection R1/R2 (56% vs 26%), post-surgical complications (56% vs 27%) and readmissions within 90 days after operation (41% vs 14%) |
| • Pts with NLR > 5 had lower 5-year recurrence-free survival rates (10.5% vs 14.2%) | |||
| • NLR independently predicted both disease-specific (HR = 2.21) and recurrence-free survival (HR = 1.99) | |||
| • No significant differences in glucocorticoid excess rates between pts with NLR ≤ 5 and pts with NLR > 5 (38.1% vs 61.9%; P = 0.201) | |||
| • Pts with preoperative PLR > 190 (38.1%) had higher proportion of tumors > 5cm (100% vs 84%) and resection of metastasis in other organs (69% vs 36%) | |||
| • Pts with PLR > 190 had lower 5-year recurrence-free survival rates (5.2% vs 19.4%) | |||
| • PLR independently predicted recurrence-free survival (HR = 1.72) | |||
| • No significant differences in glucocorticoid excess rates between pts with PLR ≤ 190 and pts with PLR > 190 (61.9% vs 38.1%; P = 0.826) | |||
| Mochizuki 2017 (90) | 46 benign adrenal tumor pts, 13 malignant adrenal tumor pts (9 ACC) | • Preoperative NLR was higher in pts with malignant than those with benign adrenal disease (4.8 ± 2.9 vs 3.0 ± 1.8; P = 0.016) | |
| • Median NLR was 2.84 in adrenocortical adenomas; 2.03 in pheochromocytomas; 6.02 in ACC; 3.30 in lymphomas | |||
| • NLR was an independent predictor of malignant adrenal disease, with best cut-off estimated at 3.15 (area under ROC of 0.668) | |||
| • Among ACC pts, those with preoperative NLR ≥ 5 had a poorer survival (median survival of 174 vs 917 days; P = 0.032) | |||
| Gaitanidis 2019 (19) | 25 recurrent ACC pts after surgery | • A shorter disease-specific survival was seen in ACC pts with LMR < 4 (41 ± 7.4 vs 71 ± 12.3 months; P = 0.023) | |
| • LMR < 4 was independently associated with worse disease-specific survival (HR = 4.18; 95% CI: 1.18-14.76; P = 0.027) | |||
| • No associations between NLR or PLR and disease-specific survival | |||
| Pituitary tumors | Marques 2020 (91) | 68 prolactinoma pts, 72 acromegaly pts, 70 CD pts, 208 NFPA pts and 6 thyrotrophinoma pts after surgery | • CD pts had significantly higher preoperative NLR, SII and NPS in comparison to other pituitary tumor types |
| • Within Cushing’s disease pts: | |||
| • There was an association between elevated GPS and 24h-UFC or ACTH levels | |||
| • There were no association between inflammation-based scores and features/outcomes suggestive of clinically challenging disease, but pts who had multimodal treatment had fewer platelets (242 ± 50 vs 304 ± 86 x109/L; P = 0.001), with a platelet count <299.5x109/L predicting multimodal treatment | |||
| • Within prolactinoma + acromegaly + thyrotrophinoma pts. | |||
| • Pts with GPS ≥ 1 had higher rates of hypopituitarism (25% vs 4%; P = 0.048) and suprasellar extension (25% vs 4%; P = 0.048) | |||
| • Pts with NPS ≥ 1 had higher rates of suprasellar extension (15% vs 6%; P = 0.028) | |||
| • Lower PLR was observed in pts with macroadenomas (P = 0.039) | |||
| • PNI was lower in pts requiring multiple treatments (35.9 ± 23.1 vs 55.4 ± 5.1; P = 0.048) including radiotherapy (39.7 ± 20.6 vs 54.1 ± 9.7; P = 0.024) | |||
| • Within NFPA pts: | |||
| • Pts with GPS ≥ 1 had higher rates of apoplexy (40% vs 6%; P = 0.001) | |||
| • Pts with visual field defects at presentation had higher NLR (2.6 ± 2.1 vs 1.2 ± 0.3; P = 0.024) and lower LMR (3.8 ± 1.9 vs 5.5 ± 1.1; P = 0.031) | |||
| • Pts with tumor remnant on MRI within 1yr after operation had higher PLR (109 ± 65 vs 1317 ± 46; P = 0.021) | |||
| • Higher NLR was seen in reoperated pts (3.2 ± 1.0 vs 2.2 ± 1.3; P = 0.017) and in those requiring multiple treatments (3.1 ± 1.0 vs 2.2 ± 1.3; P = 0.049) | |||
| • Pts with active disease at last follow-up had lower PNI (25.9 ± 22.3 vs 54.7 ± 6.1; P = 0.021) | |||
| Craniopharyngiomas | Chen 2018 (6) | 197 CP pts, 57 RCC pts, 371 pituitary tumor pts, 682 HCs | • Papillary CP were associated with higher NLR and lower PNI compared to adamantinomatous CP (1.78 vs 1.39; P < 0.05, and 54.7 vs 55.8; P < 0.05, respectively), but there were no differences between primary or recurrent CP regarding other scores |
| • A papillary CP pts, time to recurrence correlated with PLR (r = -0.783; P < 0.05), MLR (r = -0.674; P < 0.05) and PNI (r = 0.577; P < 0.05) | |||
| • CP pts had higher PNI than pituitary tumor and RCC pts and HCs (55.7 vs 51.7 vs 52.8 vs 54.3, respectively; P < 0.05) | |||
| • CP pts had lower MLR than pituitary tumor pts and HCs (0.15 vs 0.18 vs 0.16, respectively; P < 0.05) | |||
| • NLR was higher in pituitary tumor pts than in RCC pts or HCs (1.58 vs 1.39 vs 1.49, respectively; P < 0.05) | |||
| • PNI alone showed good accuracy in predicting a CP (AUC of 0.616; 95% CI 0.568-0.663), but the best predictive value was obtained for the combinations NLR + PNI, dNLR + PNI and PLR + PNI (AUCs of 0.635, 0.6131 and 0.627, respectively) | |||
| • A predictive value for papillary CP (in comparison to other subgroups) was seen for NLR+PLR (AUC of 0.713; 95% CI 0.621-0.805) and dNLR + PLR (AUC of 0.703; 95% CI 0.610-0.797) | |||
| Zhang 2018 (36) | 149 CP pts | • A positive correlation was observed between preoperative NLR and 5-year overall (HR = 1.44, 95% CI 1.16-1.79; P = 0.001) and 5-year progression-free survival (HR = 1.46, 95% CI 1.22-1.74; P < 0.001). | |
| • Best predictive cut-off predicting poor outcome was NLR ≥ 4 | |||
| • Pts with NLR ≥ 4 had larger lesions (5.6 ± 3.5 vs 4.1 ± 1.6 cm2; P = 0.001), lower rates of gross total resection (42 vs 76%; P < 0.001), worse quality of life (2.7 ± 2.0 vs 3.5 ± 1.6 ASBS-Q score; P = 0.039), lower 5-year overall (67 vs 86%; P = 0.009) and 5-year progression-free survival rate (44 vs 86%; P < 0.001) |
ACC, adrenocortical carcinoma; ACTH, adrenocorticotropic hormone; ASBS-Q, anterior skull base surgery questionnaire; AUC, area under curve; CD, Cushing’s disease; CI, confidence interval; CP, craniopharyngioma; CRP, C-reactive protein; dNLR, derived neutrophil-to-lymphocyte ratio; DTC, differentiated thyroid cancer; eGFR, estimated glomerular filtration rate; GPS, Glasgow prognostic score; HCs, healthy controls; HR, hazard ratio; IQR, interquartile ranges; LDL, low-density lipoprotein; LMR, lymphocyte-to-monocyte ratio; MLR, monocyte-to-lymphocyte ratio; NFPA, nonfunctioning pituitary adenoma; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; PNI, prognostic nutritional index; PTH, parathyroid hormone; pts, patients; RCC, Rathke’s cleft cyst; ROC, receiver operative characteristic curve; SII, systemic inflammation index; UFC, urinary free cortisol.