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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 3  |  Page : 437-444

Exploring the prognostic significance of the pretreatment inflammatory markers in hypopharyngeal cancers: A retrospective analysis


1 Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
2 Department of Medical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
3 Department of Radiation Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India

Date of Submission11-Apr-2020
Date of Decision25-May-2020
Date of Acceptance07-Jul-2020
Date of Web Publication19-Sep-2020

Correspondence Address:
Arvind Krishnamurthy
Department of Surgical Oncology, Cancer Institute (WIA), 38, Sardar Patel Rd., Adyar, Chennai - 600 036, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_152_20

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  Abstract 


Background: There is increasing evidence pertaining to the prognostic significance of pretreatment inflammatory markers such as platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and the combination of platelet count and neutrophil-to-lymphocyte ratio (COP-NLR) in many solid tumors, including head and neck cancers. However, there are limited data related to these markers in hypopharyngeal cancers.
Objectives: We aimed to explore the association of the pretreatment inflammatory markers with survival outcomes in our cohort of hypopharyngeal cancers.
Materials and Methods: The electronic medical records for the consecutive patients with carcinoma of the hypopharynx, treated at our center between January 1, 2016, and December 31, 2016, were accessed. The association between the clinico-demographic-laboratory variables and pretreatment inflammatory markers was analyzed using the Chi-square test, and the survival analysis was performed using the Kaplan–Meier method.
Results: Seventy-nine eligible patients were included in the study. The median age of our cohort was 45 years; the male-to-female ratio was 2.9:1. There was a significant association of NLR with sex, hemoglobin, and the primary site; however, no such association was observed between PLR and these variables. Further, our study showed that higher values of NLR, PLR, and COP-NLR were predictive of poor outcomes, both in terms of the disease-free and overall survival.
Conclusion: The readily available pretreatment systemic inflammatory markers, such as NLR, PLR, and COP-NLR, can be used as prognostic tools in patients with squamous cell carcinoma of the hypopharynx. The role of these potential markers, especially PLR, appears interesting and warrants further evaluation in other subsites of the head and neck as well.

Keywords: Carcinoma hypopharynx, combination of platelet count and neutrophil to lymphocyte ratio, head and neck squamous cell carcinoma, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, prognosis, NLR, COP-NLR


How to cite this article:
Mittal S, Krishnamurthy A, Kothandaraman SK, Dhanushkodi M, John A. Exploring the prognostic significance of the pretreatment inflammatory markers in hypopharyngeal cancers: A retrospective analysis. Cancer Res Stat Treat 2020;3:437-44

How to cite this URL:
Mittal S, Krishnamurthy A, Kothandaraman SK, Dhanushkodi M, John A. Exploring the prognostic significance of the pretreatment inflammatory markers in hypopharyngeal cancers: A retrospective analysis. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Oct 28];3:437-44. Available from: https://www.crstonline.com/text.asp?2020/3/3/437/295533




  Introduction Top


Hypopharyngeal cancers are considered biologically more aggressive than malignancies arising from the other sub-sites of the head-and-neck region. Apart from the tumor node metastasis (TNM) staging, various other tumor-and patient-related factors have been studied in an attempt to better prognosticate the outcomes for patients with hypopharyngeal cancers. These factors include age, sex, habits, tumor grade, performance status, and comorbidities among others; however, several studies have shown their limited utility in prognostication. Human papillomavirus positivity and p16 immunoexpression are important prognostic factors in oropharyngeal cancers, but their prognostic value in hypopharyngeal cancers is limited and unclear.[1],[2]

Several studies have suggested a strong relationship between inflammation and cancer.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] Furthermore, studies have shown that the complex interplay between inflammation, immunity, and cancer can impact tumor initiation, progression, and treatment response.[3],[4] It has been suggested that the presence of neutrophils in the tumor microenvironment plays a pro-tumor role through the formation of neutrophil extracellular traps, the release of reactive oxygen species, secretion of pro-tumor cytokines and chemokines, and promotion of immunosuppression.[12] The lymphocytes act as anti-tumor agents by inhibiting proliferation and inducing cytotoxic cell death.[11],[12],[13] A recent meta-analysis has shown a favorable prognostic role of tumor-infiltrating lymphocytes in head neck cancers.[14] A few studies have shown poor survival with pretreatment thrombocytosis across many cancer sites, including those in the head and neck.[15],[16],[17],[18],[19],[20]

Based on the promising preclinical data, the prognostic value of the various inflammatory markers has been explored in different solid tumors. The inflammatory markers include the pretreatment platelet counts, neutrophils, monocytes, lymphocytes, platelet-to-lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), and the combination of platelet count and NLR (COP-NLR) among others. There is growing evidence regarding the prognostic significance of pretreatment PLR, NLR, and COP-NLR in several solid tumors, including head and neck cancers.[5],[6],[7],[8],[9],[10] However, the use of these inflammation-based prognostic markers in hypopharyngeal cancers has not been well documented. Therefore, in this study, we have attempted to explore their prognostic significance in hypopharyngeal cancers.


  Materials and Methods Top


General study details

We performed a retrospective analysis of the data from patients with carcinoma of the hypopharynx managed in the Department of Head and Neck Services of the Cancer Institute (WIA), the regional cancer center in Chennai, Tamil Nadu. The study was conducted in accordance with the principles of the International Conference on Harmonization Good Clinical Practice guidelines, the Declaration of Helsinki, and the guidelines laid down by the Indian Council of Medical Research and was approved by our Institutional Ethics Committee (IEC/2020/May 02, approved on 6th May 2020). The trial protocol is available as Supplementary Appendix 1. Informed consent was obtained from all the patients for the use of their anonymized data for research and publication purposes. As this was a retrospective analysis, the ethics committee waived the need for obtaining additional written informed consent from each patient. The study was not registered in a public clinical trials registry.

Participants

The electronic medical records of all the consecutive patients with carcinoma of the hypopharynx, who received treatment at our center between January 1, 2016, and December 31, 2016, were accessed and retrospectively analyzed. The said time period was chosen to ensure an adequate follow-up to capture the survival outcomes. The inclusion criteria were a histologically proven squamous cell carcinoma of the hypopharynx, availability of the pretreatment complete blood counts, treatment with potentially curative intent, and completion of the intended definitive treatment at our center. The exclusion criteria were active infection, documented chronic inflammation, and unavailability of follow-up details.

Variables

The primary aims of the study were to evaluate the clinico-demographic profile and the relationship to the inflammatory biomarkers in patients with hypopharyngeal cancers, and to study the association of the inflammatory biomarkers with the survival outcomes.

Study methodology

We recorded the demographic data; clinical stage; complete hemogram; platelet count; absolute neutrophil count (ANC); absolute lymphocyte count (ALC); NLR, defined as the ratio of ANC to ALC; PLR, defined as the ratio of platelet count to ALC; treatment received (primary, adjuvant, salvage); last follow-up date; and condition at that time. Disease-free survival (DFS) was defined as the time from treatment completion to recurrence, disease progression, or death. Overall survival (OS) was defined as the time from treatment completion to death.

The pretreatment NLR, PLR, and platelet count were divided into the low and high categories according to the values described by Nakahira etal., which are <3 and ≥3, <150 and ≥150, and <300 × 109/L and ≥300 × 109/L, respectively.[10] In addition, the COP-NLR was calculated. A platelet count of ≥300 × 109/L and an NLR≥3 were assigned to COP-NLR 2. Patients with only one value raised and no value raised were assigned to COP-NLR 1 and COP-NLR 0, respectively.[10]

Statistics

As this was a retrospective analysis, a sample size was not calculated. We included all patients who fulfilled the inclusion and exclusion criteria during the study period.

The association of clinico-demographic-laboratory variables, namely the TNM stage, T group, N group, and tumor grade with the pretreatment NLR and PLR were analyzed using the Chi-square test. The median follow-up was calculated, including the surviving as well as the deceased patients. Survival analysis (univariate) was performed using the Kaplan–Meier method. For analysis of the OS, the time from treatment completion to the date of the last follow-up or date of death was considered.[21] Prognostic factors in the treatment groups were analyzed using the Cox proportional univariate regression analysis.[22],[23] A P-value of less than 0.05 was considered significant. All the statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS version 20, IBM Corp., Armonk, NY, USA).


  Results Top


A total of 93 patients with carcinoma of the hypopharynx received treatment at our center between January 1, 2016, and December 31, 2016. Of these, 79 fulfilled the eligibility criteria and were included in the analysis [Figure 1]. The median age of our cohort was 45 years (range, 29–69 years), 67% of the patients were men, and the male-to-female ratio was 2.9:1. A vast majority of the patients (86.3%) had stage III/IV disease, and 96.2% of the patients received upfront nonsurgical treatment (concurrent chemoradiation in 62% and radical radiation in 34.2%, as per the decision of a multi-disciplinary tumor board). The preferred regimen for chemoradiation was 66 Gy of external beam radiation along with cisplatin (100 mg/m2, once in 3 weeks). The cisplatin-ineligible patients were considered for carboplatin (area under the curve 2). The median follow-up of our cohort was 19 months (1.13–41.53 months).
Figure 1: Flow chart of patient selection for the study

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The demographic variables of our cohort have been elaborated in [Table 1]. A significant association of pretreatment NLR was noted with sex (P = 0.001), hemoglobin (P = 0.005), and primary sub-site (P = 0.043). However, the pretreatment PLR was not found to be associated with the above variables.
Table 1: Demographic variables of the patient cohort

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The median DFS was 17.17 months (95% confidence interval [CI], 15.00–21.01 months), while the median OS was 19 months (95% CI, 16.94–22.53 months). On univariate analysis, the factors that were found to have a significant association with DFS and OS were pretreatment NLR (P = 0.025 and P = 0.037, respectively), pretreatment PLR (P = 0.001 and P = 0.004, respectively), pretreatment COP–NLR (P = 0.006 and P = 0.002, respectively), TNM stage (P = 0.037 and P = 0.047, respectively), and nodal stage (P = 0.045 and P = 0.043, respectively). Higher TNM stage, nodal stage, NLR, PLR, and COP–NLR were associated with poor DFS and OS [Figure 2], [Figure 3], [Figure 4]. There was a statistically significant association between the platelet count and OS (P = 0.025), but not with DFS (P = 0.088). Moreover, there was a significant difference in the DFS (P = 0.031) of patients who had received radiation and concurrent chemoradiation, but the difference in their OS was not significant (P = 0.98). The association of the clinico-demographic-laboratory variables with the survival outcomes is described in [Table 2]. A formal multivariate analysis of all the variables that showed significance on univariate analysis could not be performed as there were many interdependent variables. However, a multivariate analysis after adjustment for known prognostic variables showed PLR to be a significant predictor of both DFS and OS [Table 3].
Figure 2: Kaplan–Meier estimate of the overall survival stratified by neutrophil to lymphocyte ratio

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Figure 3: Kaplan–Meier estimate of the overall survival stratified by platelet to lymphocyte ratio

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Figure 4: Kaplan–Meier estimate of the overall survival stratified by the combination of platelet count and neutrophil to lymphocyte ratio

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Table 2: Association of the clinico-demographic-laboratory variables with the survival outcomes

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Table 3: Multivariate analysis after adjustment for known prognostic variables showed platelet-to-lymphocyte ratio to be a significant predictor of both disease free as well as overall survival

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  Discussion Top


Analysis of the clinico-demographic-laboratory variables in our cohort revealed a significant association of the pretreatment NLR with sex, hemoglobin, and the primary site. However, no association of the pretreatment PLR was noted with these variables. There are several other studies that have evaluated the association between clinico-demographic-laboratory variables and the pretreatment NLR and PLR. However, they have shown mixed results, thus precluding any definitive conclusions.[10],[18],[24],[25],[26],[27],[28],[29],[30],[31],[32]

The cutoff value for NLR that can consistently categorize the patients with head and neck cancers into different prognostic groups is still unclear. A meta-analysis of the prognostic significance of the pretreatment NLR values from 24 studies suggested that categorizing the patients into three groups based on the NLR values (<2, 2–6, and ≥6) could better predict the differences in their survival outcomes.[33] In our cohort, the pretreatment NLR, PLR, platelet counts, and COP-NLR were categorized according to the values described by Nakahira etal.

The prognostic significance of pretreatment NLR and PLR has been explored in many clinical studies involving patients with head and neck cancers (including the hypopharynx as well as other sub-sites), but with contradictory results. Many studies have shown a significant association between the pretreatment NLR and survival outcomes in patients with head and neck cancers, where a higher NLR predicted a poor outcome.[24],[25],[26],[27],[28],[29],[30],[31],[32] Similarly, a few other studies have shown a significant association between the pretreatment PLR and survival outcomes.[6] A few meta-analyses have explored the prognostic role of NLR in head and neck cancers.[34],[35],[36],[37] In addition, some studies have assessed the prognostic significance of the pretreatment NLR and PLR in exclusive cohorts of patients with hypopharyngeal cancers;[27],[28],[29],[30],[31],[32] the salient findings of these studies have been summarized in [Table 4].
Table 4: Association of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with survival outcomes from studies focusing exclusively on hypopharyngeal cancers

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Ishizuka et al. evaluated the prognostic significance of COP-NLR in gastric and colorectal cancers and observed COP-NLR to be a useful predictor of survival.[8],[9] Further, Nakayama et al. investigated the role of COP-NLR in hypopharyngeal cancers and concluded that COP-NLR could be a useful prognostic marker.[10] Our results mirrored those of Nakayama etal.'s study, with a higher pretreatment COP-NLR predicting poor survival.

The limitations of our study are the modest size of our cohort and its retrospective design. It would have been interesting to know what the NLR, PLR, and COP-NLR were posttreatment, especially in patients who had poorer DFS and OS and to evaluate whether there was any correlation with outcomes. Unfortunately, these values were not consistently available for all patients across specific time points, and this could not be evaluated. However, our study was focused on a single sub-site (hypopharynx) and used the readily available pretreatment laboratory inflammatory markers to predict the outcomes, which add to its merits. Pretreatment NLR, PLR, and COP-NLR are easy to calculate and can be used even in a resource-constrained setting for aiding in prognostication. The positive correlation of PLR with outcomes in our cohort of patients with hypopharyngeal cancers appears exciting and needs to be explored further.


  Conclusion Top


The study has shown that the readily available pretreatment laboratory inflammatory markers, namely the NLR, PLR, and COP-NLR, can be used as prognostic tools in patients with squamous cell carcinoma of the hypopharynx. The role of these markers, especially the PLR, appears interesting. However, our findings need to be validated in a larger cohort of patients. Moreover, similar studies can be performed in patients with other solid cancers, especially those in the other sub-sites of the head and neck.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.


  Supplementary Appendix 1 Top



  Retrospective Study of the role of inflammatory markers in Head and Neck Cancers Top


Background and Rationale: Head and Neck cancers are a significant cause of morbidity and mortality globally and more so in the Indian Sub-continent. Apart from the Tumour Node Metastasis (TNM) staging, various other tumour and patient related factors have been studied, in an attempt to better prognosticate patients with head and neck cancers. These factors include age, gender, habits, grade, performance status, co-morbidities among others, however many studies have shown their limited utility in prognostication. Inflammation is considered to be one of the hallmarks of cancer. A few of the inflammatory markers are being explored as possible prognostic biomarkers across various solid cancers. The inflammatory markers include neutrophils, lymphocytes, monocytes and platelet counts studied either as individual values or as ratios to each other i.e. neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) among others. There is a growing body of evidence pertaining to the prognostic significance of NLR and PLR in head and neck cancers and we wish to further explore this association.

Aims:

  1. To study the clinic-demographic profile and their relationship to the inflammatory biomarkers.
  2. To study the association of the inflammatory biomarkers with the survival outcomes


Study design: Retrospective study of patients treated in our institution for head and neck squamous cell carcinomas from 2014-2016. These will be further divided into sub-cohorts for comparative analysis.

For this study, the following data from the Electronic Medical Records will be collated:

  • Clinical parameters including age, gender, site of primary tumour
  • Laboratory Parameters including complete hemogram, platelet counts, absolute neutrophil counts, absolute lymphocyte counts
  • Primary tumor characteristics include tumour diameter (mm), margins of resection tumour thickness, presence of bone invasion, presence of perineural invasion (PNI), presence of lymphovascular invasion (LVI) and degree of differentiation (well, moderate or poor)
  • Neck nodes pathological characteristics include the presence of nodal metastasis (N0 versus N1-3), number of involved nodes (single versus multiple) and the presence of extracapsular nodal spread (ECS).
  • Treatment details including Surgery and the administration of radiotherapy and/or chemotherapy
  • Survival outcomes.


Statistical analysis: Disease free survival was defined as time from treatment completion till occurrence of first event defined as recurrence, disease progression or death. Overall survival was defined as time from treatment completion till death. Hazard ratios and interactions between age and prognostic variables will be calculated using Cox proportional hazard models and Kaplan-Meier curves generated for graphical analysis.

The generated data will be anonymous and no patient identifiers will ever be shared.


  References Top


  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646–74
  2. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140:883-99.
  3. Guthrie GJK, Charles AK, Roxburgh CSD, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil–lymphocyte ratio: Experience in patients with cancer. Oncology/Hematology 2013;88:218-230.
  4. 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;42:665-677.
  5. Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A. Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Solid Tumors: A Systematic Review and Meta-Analysis. J Natl Cancer Inst 2014;106: dju124.




 
  References Top

1.
Dahm V, Haitel A, Kaider A, Stanisz I, Beer A, Lill C. Cancer stage and pack-years, but not p16 or HPV, are relevant for survival in hypopharyngeal and laryngeal squamous cell carcinomas. Eur Arch Otorhinolaryngol 2018;275:1837-43.  Back to cited text no. 1
    
2.
Murthy V, Calcuttawala A, Chadha K, d'Cruz A, Krishnamurthy A, Mallick I, et al. Human papillomavirus in head and neck cancer in India: Current status and consensus recommendations. South Asian J Cancer 2017;6:93-8.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011;144:646-74.  Back to cited text no. 3
    
4.
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883-99.  Back to cited text no. 4
    
5.
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;88:218-30.  Back to cited text no. 5
    
6.
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;42:665-77.  Back to cited text no. 6
    
7.
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:dju124.  Back to cited text no. 7
    
8.
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;110:935-41.  Back to cited text no. 8
    
9.
Ishizuka M, Nagata H, Takagi K, Iwasaki Y, Kubota K. Combination of platelet count and neutrophil to lymphocyte ratio is a useful predictor of postoperative survival in patients with colorectal cancer. Br J Cancer 2013;109:401-7.  Back to cited text no. 9
    
10.
Nakahira M, Sugasawa M, Matsumura S, Kuba K, Ohba S, Hayashi T, et al. Prognostic role of the combination of platelet count and neutrophil-lymphocyte ratio in patients with hypopharyngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 2016;273:3863-7.  Back to cited text no. 10
    
11.
Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-7.  Back to cited text no. 11
    
12.
Wu L, Saxena S, Awaji M, Singh RK. Tumor-associated neutrophils in cancer: Going pro. Cancers (Basel) 2019;11:564.  Back to cited text no. 12
    
13.
Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454:436-44.  Back to cited text no. 13
    
14.
de Ruiter EJ, Ooft ML, Devriese LA, Willems SM. The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis. Oncoimmunology 2017;6:e1356148.  Back to cited text no. 14
    
15.
Menter DG, Tucker SC, Kopetz S, Sood AK, Crissman JD, Honn KV. Platelets and cancer: A casual or causal relationship: Revisited. Cancer Metastasis Rev 2014;33:231-69.  Back to cited text no. 15
    
16.
Schlesinger M. Role of platelets and platelet receptors in cancer metastasis. J Hematol Oncol 2018;11:125.  Back to cited text no. 16
    
17.
Ikeda M, Furukawa H, Imamura H, Shimizu J, Ishida H, Masutani S, et al. Poor prognosis associated with thrombocytosis in patients with gastric cancer. Ann Surg Oncol 2002;9:287-91.  Back to cited text no. 17
    
18.
Long Y, Wang T, Gao Q, Zhou C. Prognostic significance of pretreatment elevated platelet count in patients with colorectal cancer: A meta-analysis. Oncotarget 2016;7:81849-61.  Back to cited text no. 18
    
19.
Yu M, Liu L, Zhang BL, Chen Q, Ma XL, Wu YK, et al. Pretreatment thrombocytosis as a prognostic factor in women with gynecologic malignancies: A meta-analysis. Asian Pac J Cancer Prev 2012;13:6077-81.  Back to cited text no. 19
    
20.
Chen MH, Chang PM, Chen PM, Tzeng CH, Chu PY, Chang SY, et al. Prognostic significance of a pretreatment hematologic profile in patients with head and neck cancer. J Cancer Res Clin Oncol 2009;135:1783-90.  Back to cited text no. 20
    
21.
Chakraborty S. A step-wise guide to performing survival analysis. Cancer Res Stat Treat 2018;1:41-5.  Back to cited text no. 21
  [Full text]  
22.
Dessai S, Simha V, Patil V. Stepwise cox reg ression analysis in SPSS. Cancer Res Stat Treat 2018;1:167-70.  Back to cited text no. 22
  [Full text]  
23.
Dessai S, Patil V. Testing and interpreting assumptions of COX regression analysis. Cancer Res Stat Treat 2019;2:108-11.  Back to cited text no. 23
  [Full text]  
24.
Bojaxhiu B, Templeton AJ, Elicin O, Shelan M, Zaugg K, Walser M, et al. Relation of baseline neutrophil-to-lymphocyte ratio to survival and toxicity in head and neck cancer patients treated with (chemo-) radiation. Radiat Oncol 2018;13:216.  Back to cited text no. 24
    
25.
Cho Y, Kim JW, Yoon HI, Lee CG, Keum KC, Lee IJ. The prognostic significance of neutrophil-to-lymphocyte ratio in head and neck cancer patients treated with radiotherapy. J Clin Med 2018;7:512.  Back to cited text no. 25
    
26.
Rachidi S, Wallace K, Wrangle JM, Day TA, Alberg AJ, Li Z. Neutrophil-to-lymphocyte ratio and overall survival in all sites of head and neck squamous cell carcinoma. Head Neck 2016;38 Suppl 1:E1068-74.  Back to cited text no. 26
    
27.
Kuo C, Hsueh WT, Wu YH, Yang MW, Cheng YJ, Pao TH, et al. The role of pretreatment serum neutrophil-to-lymphocyte ratio in hypopharyngeal cancer treated with definitive chemoradiotherapy: A pilot study. Sci Rep 2019;9:1618.  Back to cited text no. 27
    
28.
Lau H, Hsueh C, Chen Q, Tao L, Zhou L, Deng W, et al. Prognostic values of preoperative plateletW, aryngeal cancer treated with definitive chemoradiotherapy: A pilot study.pilot study.pilot study.cer.gastClin Otolaryngol 2020;45:221-30.  Back to cited text no. 28
    
29.
Kuwahara T, Takahashi H, Sano D, Matsuoka M, Hyakusoku H, Hatano T, et al. Fibrinogen and neutrophil-to-lymphocyte ratio predicts survival in patients with advanced hypopharyngeal squamous cell carcinoma. Anticancer Res 2018;38:5321-30.  Back to cited text no. 29
    
30.
Lo WC, Wu CT, Wang CP, Yang TL, Lou PJ, Ko JY, et al. The pretreatment neutrophil-to-lymphocyte ratio is a prognostic determinant of T3-4 hypopharyngeal squamous cell carcinoma. Ann Surg Oncol 2017;24:1980-8.  Back to cited text no. 30
    
31.
Ikeguchi M. Glasgow prognostic score and neutrophil-lymphocyte ratio are good prognostic indicators after radical neck dissection for advanced squamous cell carcinoma in the hypopharynx. Langenbecks Arch Surg 2016;401:861-6.  Back to cited text no. 31
    
32.
Song Y, Liu H, Gao L, Liu X, Ma L, Lu M, et al. Preoperative neutrophil-to-lymphocyte ratio as prognostic predictor for hypopharyngeal squamous cell carcinoma after radical resections. J Craniofac Surg 2015;26:e137-40.  Back to cited text no. 32
    
33.
Cho JK, Kim MW, Choi IS, Moon UY, Kim MJ, Sohn I, et al. Optimal cutoff of pretreatment neutrophil-to-lymphocyte ratio in head and neck cancer patients: A meta-analysis and validation study. BMC Cancer 2018;18:969.  Back to cited text no. 33
    
34.
Yang L, Huang Y, Zhou L, Dai Y, Hu G. High pretreatment neutrophil-to-lymphocyte ratio as a predictor of poor survival prognosis in head and neck squamous cell carcinoma: Systematic review and meta-analysis. Head Neck 2019;41:1525-35.  Back to cited text no. 34
    
35.
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;40:2546-57.  Back to cited text no. 35
    
36.
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;40:647-55.  Back to cited text no. 36
    
37.
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;40:2714-23.  Back to cited text no. 37
    


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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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