Dynamic changes of inflammatory markers and their effects on the prognosis of patients with laryngeal and hypopharyngeal cancer submitted to total pharyngolaryngectomy
DOI:
https://doi.org/10.34631/sporl.1038Keywords:
Systemic inflammatory response, laryngeal carcinoma, hypopharyngeal carcinoma, platelet-lymphocyte ratio, survivalAbstract
Introduction: The use of prognostic markers to decide the most appropriate therapies to perform in each case is assumed as one of the pillars of the approach to the patient with squamous cell carcinoma (SCC) of the hypopharynx and larynx. In addition to the clinical and pathological stage determined by the classification system TNM, there is evidence that the tumor-related systemic inflammatory response (SIR) has implications for tumor aggressiveness and progression. However, its value as an independent prognostic factor remains ambiguous.
Aims: To analyze the tumor SIR, its perioperative dynamic changes and after adjuvant treatment and its prognostic value in patients with SCC of the larynx and hypopharynx undergoing total pharyngolaryngectomy.
Methods: Retrospective analysis of clinico- pathological data of patients undergoing total pharyngolaryngectomy between January 2013 and December 2018 in a tertiary-level hospital. SIR was assessed using the following parameters: lymphocyte-monocyte ratio (LMR), platelets-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR) and systemic immuno-inflammatory index (SII). Kaplan-Meier analysis and Cox regression were used to analyze survival outcomes and associated risks.
Results: 59 patients were included in the study, with a mean age of 59.2 years. The mean follow- up time was 49.2 months. Preoperative PLR was the best predictor of overall survival (OS) at 5 years (area under the curve (AUC) 0.796, p<0.005). The optimal cutoff value was determined for each inflammatory parameter analyzed preoperatively, postoperatively and after adjuvant treatment (LMR: 2.6, 2.8 and 2.2, respectively; PLR: 125.0, 162.6 and 57.2, respectively; NLR: 2.3, respectively; 2.3, 2.8 and 3.9, respectively; SSI: 931.4, 732.8 and 931.43, respectively). Multivariate survival analysis showed that OS and distant metastasis-f ree survival (MFS) were statistically lower in patients with preoperative PLR >125.0 (HR 4.39, p<0.005 and HR 17.65, p <0.005, respectively). There was a significantdecrease in SIR after complete treatment with surgery with or without adjuvant chemoradiation. However, the pattern of parameters variation with treatments had no influence on OS or MFS. Patients with preoperative LPR >125.0 tend to have higher NLR and SII (p<0.005), although these did not prove to be independent predictors of survival.
Conclusions: A high preoperative PLR was significantly associated with worse OS and MFS in patients undergoing total pharyngolaryngectomy. Still, the use of this marker in our current clinical practice to predict postoperative outcomes must be performed in a critical way.
References
Bardash Y, Olson C, Herman W, Khaymovich J, Costantino P, Tham T. Platelet-lymphocyte ratio as a predictor of prognosis in head and neck cancer: A systematic review and meta-analysis. Oncol Res Treat. 2019;42(12):665-677. doi: 10.1159/000502750.
Elmusrati A, Wang J, Wang CY. Tumor microenvironment and immune evasion in head and neck squamous cell carcinoma. Int J Oral Sci. 2021 Aug 2;13(1):24. doi: 10.1038/s41368-021-00131-7
Machiels JP, René Leemans C, Golusinski W, Grau C, Licitra L, Gregoire V. et al. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Nov;31(11):1462-1475. doi: 10.1016/j.annonc.2020.07.011.
Bradford CR, Ferlito A, Devaney KO, Mäkitie AA, Rinaldo A. Prognostic factors in laryngeal squamous cell carcinoma. Laryngoscope Investig Otolaryngol. 2020 Jan 27;5(1):74-81. doi: 10.1002/lio2.353.
Huo M, Zhang Y, Chen Z, Zhang S, Bao Y, Li T. Tumor microenvironment characterization in head and neck cancer identifies prognostic and immunotherapeutically relevant gene signatures. Sci Rep. 2020 Jul 7;10(1):11163. doi: 10.1038/s41598-020-68074-3.
Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocana A. et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: A systematic review and meta-analysis J Natl Cancer Inst. 2014 May 29;106(6):dju124. doi: 10.1093/jnci/dju124.
Yokota M, Katoh H, Nishimiya H, Kikuchi M, Kosaka Y, Sengoku N. et al. Lymphocyte-monocyte ratio significantly predicts recurrence in papillary thyroid cancer. J Surg Res. 2020 Feb;246:535-543. doi: 10.1016/j.jss.2019.09.034.
Nishijima TF, Muss HB, Shachar SS, Tamura K, Takamatsu Y. Prognostic value of lymphocyte-to-monocyte ratio in patients with solid tumors: A systematic review and meta-analysis. Cancer Treat Rev. 2015 Dec;41(10):971-8. doi: 10.1016/j.ctrv.2015.10.003.
Ishizuka M, Oyama Y, Abe A, Kubota K. Combination of platelet count and neutrophil to lymphocyte ratio is a useful predictor of postoperative survival in patients undergoing surgery for gastric cancer. J Surg Oncol. 2014 Dec;110(8):935-41. doi: 10.1002/jso.23753.
Tham T, Olson C, Khaymovich J, Herman SW, Costantino PD. The lymphocyte-to-monocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol. 2018 Jul;275(7):1663-1670. doi: 10.1007/s00405-018-4972-x.
Takenaka Y, Oya R, Kitamiura T, Ashida N, Shimizu K, Takemura K. et al. Prognostic role of neutrophil-to-lymphocyte ratio in head and neck cancer: A meta-analysis. Head Neck. 2018 Mar;40(3):647-655. doi: 10.1002/hed.24986.
Caudell JJ, Gillison ML, Maghami E, Spencer S, Pfister DG, Adkins D. et. al. NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022. J Natl Compr Canc Netw. 2022 Mar;20(3):224-234. doi: 10.6004/jnccn.2022.0016.
Dʼsouza G, Carey TE, William WN Jr, Nguyen ML, Ko EC, Riddell J 4th. et al. Epidemiology of head and neck squamous cell cancer among HIV-infected patients. J Acquir Immune Defic Syndr. 2014 Apr 15;65(5):603-10. doi: 10.1097/QAI.0000000000000083.
Rabinovics N, Mizrachi A, Hadar T, Ad-El D, Feinmesser R, Guttman D. et. al. Cancer of the head and neck region in solid organ transplant recipients. Head Neck. 2014 Feb;36(2):181-6. doi: 10.1002/hed.23283.
Takenaka Y, Oya R, Kitamiura T, Ashida N, Shimizu K, Takemura K. et al. Platelet count and platelet-lymphocyte ratio as prognostic markers for head and neck squamous cell carcinoma: Meta-analysis. Head Neck. 2018 Dec;40(12):2714-2723. doi: 10.1002/hed.25366.
Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW. The prognostic influence of tumour-infiltrating lymphocytes in cancer: A systematic review with meta-analysis. Br J Cancer. 2011 Jun 28;105(1):93-103. doi: 10.1038/bjc.2011.189.
Tham T, Wotman M, Chung C, Ahn S, Dupuis H, Gliagias V. et al. Systemic immune response in squamous cell carcinoma of the head and neck: a comparative concordance index analysis. Eur Arch Otorhinolaryngol. 2019 Oct;276(10):2913-2922. doi: 10.1007/s00405-019-05554-x.
Saroul N, Puechmaille M, Lambert C, Hassan AS, Biau J, Lapeyre M. et al. Prognosis in head and neck cancer: importance of nutritional and biological inflammatory status. Otolaryngol Head Neck Surg. 2022 Jan;166(1):118-127. doi: 10.1177/01945998211004592.
Grivennikov SI, Greten FR, Karin M. Immunity, Inflammation, and Cancer. Cell. 2010 Mar 19;140(6):883-99. doi: 10.1016/j.cell.2010.01.025.
Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: Experience in patients with cancer. Crit Rev Oncol Hematol. 2013 Oct;88(1):218-30. doi: 10.1016/j.critrevonc.2013.03.010.
Du J, Liu J, Zhang X, Chen X, Yu R, Gu D. et al. Pre-treatment neutrophil-to-lymphocyte ratio predicts survival in patients with laryngeal cancer. Oncol Lett. 2018 Feb;15(2):1664-1672. doi: 10.3892/ol.2017.7501.
Tham T, Bardash Y, Herman SW, Costantino PD. Neutrophil-to-lymphocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis. Head Neck. 2018 Nov;40(11):2546-2557. doi: 10.1002/hed.25324.
Zhang X, Ran Y. Prognostic role of elevated platelet count in patients with lung cancer: A systematic review and meta-analysis. Int J Clin Exp Med. 2015 Apr 15;8(4):5379-87.
Men H, Liang C, Yu M. Thrombocytosis as a prognostic factor in patients with renal cell carcinoma: a meta-analysis of literature. J Cancer Res Ther. Jan-Mar 2015;11(1):67-72. doi: 10.4103/0973-1482.150345.
Feng JF, Huang Y, Zhao Q, Chen QX. Clinical significance of preoperative neutrophil lymphocyte ratio versus platelet lymphocyte ratio in patients with small cell carcinoma of the esophagus. ScientificWorldJournal. 2013 Sep 5;2013:504365. doi: 10.1155/2013/504365.
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