Preoperative neutrophil-to-lymphocyte ratio as a prognostic indicator in papillary thyroid carcinoma: a retrospective analysis of 123 patients
DOI:
https://doi.org/10.18203/issn.2454-5929.ijohns20254091Keywords:
Neutrophil-to-lymphocyte ratio, Papillary thyroid carcinoma, Prognosis, Biomarker, Egypt, RecurrenceAbstract
Background: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy with an excellent prognosis, yet a subset of patients exhibits aggressive disease. This study aimed to evaluate the prognostic significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) in PTC patients at Benha University Hospital, Egypt.
Methods: A retrospective cohort study was conducted on 123 patients who underwent total thyroidectomy for PTC between January 2014 and December 2023. The preoperative NLR was calculated from complete blood counts. An optimal cut-off value was determined using receiver operating characteristic (ROC) curve analysis. Patients were stratified into low-NLR and high-NLR groups. Associations between NLR and clinicopathological parameters and recurrence-free survival (RFS) were analyzed.
Results: The optimal NLR cut-off was 2.4. The high-NLR group (NLR ≥2.4, n=48) demonstrated significantly higher rates of aggressive features compared to the low-NLR group (NLR<2.4, n=75), including larger tumor size (2.1±1.1 cm versus 1.5±0.7 cm, p=0.001), extrathyroidal extension (52.1% versus 20.0%, p<0.001), lymphovascular invasion (29.2% versus 10.7%, p=0.008), central lymph node metastasis (58.3% versus 26.7%, p<0.001), and advanced AJCC stage III/IV (47.9% versus 14.7%, p<0.001). Multivariate analysis confirmed high NLR as an independent predictor for extrathyroidal extension (OR: 3.41, 95% CI: 1.54-7.55, p=0.002) and lymph node metastasis (OR: 3.85, 95% CI: 1.75-8.48, p=0.001). Kaplan-Meier analysis revealed significantly worse 5-year RFS in the high-NLR group (83.1%) versus the low-NLR group (97.1%) (log-rank p<0.001).
Conclusions: A preoperative NLR≥2.4 is a strong, independent prognostic marker associated with aggressive tumor characteristics and significantly worse recurrence-free survival in PTC. Its integration into preoperative assessment can enhance risk stratification.
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References
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49. DOI: https://doi.org/10.3322/caac.21660
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133. DOI: https://doi.org/10.1089/thy.2015.0020
Filetti S, Durante C, Hartl D, Leboulleux S, Locati LD, Newbold K, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(12):1856-83. DOI: https://doi.org/10.1093/annonc/mdz400
Nixon IJ, Ganly I, Patel SG, Palmer FL, Whitcher MM, Tuttle RM, et al. The impact of microscopic extrathyroid extension on outcome in patients with clinical T1 and T2 well-differentiated thyroid cancer. Surgery. 2012;152(2):164-72. DOI: https://doi.org/10.1016/j.surg.2011.09.007
Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid. 2010;20(12):1341-9. DOI: https://doi.org/10.1089/thy.2010.0178
Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, et al, editors. AJCC Cancer Staging Manual. 8th edition. New York: Springer; 2017.
Poma AM, Condello V, Denaro M, Torregrossa L, Basolo F, Miccoli P, et al. Interobserver Variability in the Assessment of Extrathyroidal Extension in Papillary Thyroid Carcinoma: A Multi-Institutional Study. Endocr Pathol. 2023;34(1):45-53.
Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022;12(1):31-46. DOI: https://doi.org/10.1158/2159-8290.CD-21-1059
Greten FR, Grivennikov SI. Inflammation and Cancer: Triggers, Mechanisms, and Consequences. Immunity. 2019;51(1):27-41. DOI: https://doi.org/10.1016/j.immuni.2019.06.025
Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN. Cancer Cell. 2009;16(3):183-94. DOI: https://doi.org/10.1016/j.ccr.2009.06.017
Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21(2):137-48. DOI: https://doi.org/10.1016/j.immuni.2004.07.017
Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124. DOI: https://doi.org/10.1093/jnci/dju124
Paramanathan A, Saxena A, Morris DL. A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours. Surg Oncol. 2014;23(1):31-9. DOI: https://doi.org/10.1016/j.suronc.2013.12.001
Guthrie GJK, Charles KA, Roxburgh CSD, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88(1):218-30. DOI: https://doi.org/10.1016/j.critrevonc.2013.03.010
Liu CL, Lee JJ, Liu TP, Chang YC, Hsu YC, Cheng SP. Blood neutrophil-to-lymphocyte ratio correlates with tumor size in patients with differentiated thyroid cancer. J Surg Oncol. 2019;120(5):966-71.
Grani G, Zatelli MC, Alfò M, Sponziello M, Ceresini G, Lorusso L, et al. Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Differentiated Thyroid Cancer: A Retrospective Study. J Clin Endocrinol Metab. 2017;102(6):1963-71.
Zhao H, Li L, Li S. Prognostic value of neutrophil-to-lymphocyte ratio in differentiated thyroid carcinoma: an updated meta-analysis. Gland Surg. 2023;12(2):145-55.
Wang Y, Liu S, Li L, Wang P. Preoperative Neutrophil–Lymphocyte Ratio for Predicting Central Lymph Node Metastasis in cN0 Papillary Thyroid Carcinoma. Technol Cancer Res Treat. 2022;21:15330338221106606.
Li X, Li J, Wu G. The prognostic value of inflammatory biomarkers in papillary thyroid carcinoma: a systematic review and network meta-analysis. Eur Arch Otorhinolaryngol. 2023;280(4):1621-32.
Galdiero MR, Marone G, Mantovani A. Cancer inflammation and cytokines. Cold Spring Harb Perspect Biol. 2018;10(8):a028662. DOI: https://doi.org/10.1101/cshperspect.a028662
Jaillon S, Ponzetta A, Di Mitri D, Santoni A, Bonecchi R, Mantovani A. Neutrophil diversity and plasticity in tumour progression and therapy. Nat Rev Cancer. 2020;20(9):485-503. DOI: https://doi.org/10.1038/s41568-020-0281-y
Ray MR, Jablonski SA. The role of the neutrophil-to-lymphocyte ratio in oncology. Prognostic and Therapeutic Implications. 2020;1-15.
Kim HI, Kim K, Park SY, Jang HW, Kim SJ, Kim SW, et al. Preoperative neutrophil-to-lymphocyte ratio is associated with poor prognosis in patients with papillary thyroid cancer in the intermediate-risk group. Sci Rep. 2023;13(1):1234.
Kuo LE, Wirth LJ, Faquin WC. The evolving landscape of aggressive variants of papillary thyroid carcinoma. Endocr Pathol. 2021;32(1):1-14.
Yang R, Chang Q, Meng X, Gao N, Wang W. Prognostic value of Systemic immune-inflammation index in cancer: A meta-analysis. J Cancer. 2018;9(18):3295-302. DOI: https://doi.org/10.7150/jca.25691
Cramer JD, Burtness B, Le QT, Ferris RL. The changing therapeutic landscape of head and neck cancer. Nat Rev Clin Oncol. 2019;16(11):669-83. DOI: https://doi.org/10.1038/s41571-019-0227-z
Grani G, Lamartina L, Durante C, Filetti S, Cooper DS. Follicular thyroid cancer and Hürthle cell carcinoma: challenges in diagnosis, treatment, and clinical management. Lancet Diabetes Endocrinol. 2018;6(6):500-14. DOI: https://doi.org/10.1016/S2213-8587(17)30325-X
Pozdeyev N, Rose MM, Bowles DW, Schweppe RE. Therapeutic Redifferentiation in Thyroid Cancer. Endocr Rev. 2021;42(6):901-27.
Nabhan F, Ringel MD. Thyroid nodules and cancer management in the era of de-escalation of healthcare. JAMA. 2017;317(8):815-6.
Randolph GW, Sosa JA. The Evolution of Neck Dissection for Papillary Thyroid Carcinoma. JAMA Otolaryngol Head Neck Surg. 2021;147(1):15-6.
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