Skip to main content
Erschienen in: European Archives of Oto-Rhino-Laryngology 10/2019

16.07.2019 | Head and Neck

Systemic immune response in squamous cell carcinoma of the head and neck: a comparative concordance index analysis

verfasst von: Tristan Tham, Michael Wotman, Christopher Chung, Seungjun Ahn, Holly Dupuis, Vasiliki Gliagias, Tamara Movsesova, Dennis Kraus, Peter Costantino

Erschienen in: European Archives of Oto-Rhino-Laryngology | Ausgabe 10/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The objective of this study was to investigate the prognostic role of three inflammatory markers: the neutrophil to lymphocyte ratio (NLR), the lymphocyte to monocyte ratio (LMR), and the platelet to lymphocyte ratio (PLR) as prognostic indicators in squamous cell carcinoma of the head and neck (HNSCC).

Methods

Patients with HNSCC treated with primary surgery, with or without adjuvant radiochemotherapy were enrolled. The preoperative NLR, LMR, and PLR were recorded. Confounding variables were also recorded: age, sex, BMI, comorbidities, performance status, AJCC T and N stage and HPV status. Endpoints were overall survival (OS) and event-free survival (EFS). Survival analysis was performed using Kaplan–Meier analysis, and multivariable analysis was performed using Cox proportional hazards regression. Survival models were evaluated using Harrell’s concordance index (c-index).

Results

NLR (p = 0.2413), PLR (p = 0.1593), and LMR (p = 0.0552) were not significantly associated with OS in the multivariable analysis. With regard to EFS, low LMR (HR = 2.95, 95% CI 1.54–5.65, p = 0.001), high PLR (HR = 2.68, 95% CI 1.42–5.09, p = 0.003), and high NLR (HR = 3.37, 95% CI 1.7–6.69, p < 0.001) were associated with EFS. The multivariable c-index was highest for LMR (0.762), followed by NLR (0.761) and PLR (0.739).

Conclusion

The LMR, PLR, and NLR were not associated with OS, but were associated with EFS in HNSCC. These markers are easily obtainable, and in the age of individualized patient care and precision medicine, they might represent further risk stratification tools for HNSCC patients.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140(6):883–899CrossRef Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140(6):883–899CrossRef
2.
Zurück zum Zitat Naito Y, Saito K, Shiiba K et al (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58(16):3491–3494PubMed Naito Y, Saito K, Shiiba K et al (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58(16):3491–3494PubMed
3.
Zurück zum Zitat Sharma P, Shen Y, Wen S et al (2007) CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci 104(10):3967–3972CrossRef Sharma P, Shen Y, Wen S et al (2007) CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci 104(10):3967–3972CrossRef
4.
Zurück zum Zitat Jordanova ES, Gorter A, Ayachi O et al (2008) Human leukocyte antigen class I, MHC class I chain-related molecule A, and CD8+/regulatory T-cell ratio: which variable determines survival of cervical cancer patients? Clin Cancer Res 14(7):2028–2035CrossRef Jordanova ES, Gorter A, Ayachi O et al (2008) Human leukocyte antigen class I, MHC class I chain-related molecule A, and CD8+/regulatory T-cell ratio: which variable determines survival of cervical cancer patients? Clin Cancer Res 14(7):2028–2035CrossRef
5.
Zurück zum Zitat Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL (2004) Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck. Clin Cancer Res 10(11):3755–3762CrossRef Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL (2004) Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck. Clin Cancer Res 10(11):3755–3762CrossRef
6.
Zurück zum Zitat Tham T, Bardash Y, Herman SW, Costantino PD (2018) Neutrophil-to-lymphocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis. Head Neck 40(11):2546–2557CrossRef Tham T, Bardash Y, Herman SW, Costantino PD (2018) Neutrophil-to-lymphocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis. Head Neck 40(11):2546–2557CrossRef
7.
Zurück zum Zitat Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, Tredan O, Verweij J, Biron P, Labidi I, Guastalla JP (2009) Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res 69(13):5383–5391CrossRef Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, Tredan O, Verweij J, Biron P, Labidi I, Guastalla JP (2009) Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res 69(13):5383–5391CrossRef
8.
Zurück zum Zitat Hu K, Lou L, Ye J, Zhang S (2015) Prognostic role of the neutrophil–lymphocyte ratio in renal cell carcinoma: a meta-analysis. BMJ Open 5(4):e006404CrossRef Hu K, Lou L, Ye J, Zhang S (2015) Prognostic role of the neutrophil–lymphocyte ratio in renal cell carcinoma: a meta-analysis. BMJ Open 5(4):e006404CrossRef
9.
Zurück zum Zitat Paramanathan A, Saxena A, Morris DL (2014) 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 23(1):31–39CrossRef Paramanathan A, Saxena A, Morris DL (2014) 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 23(1):31–39CrossRef
10.
Zurück zum Zitat Templeton AJ, McNamara MG, Šeruga B et al (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106(6):dju124CrossRef Templeton AJ, McNamara MG, Šeruga B et al (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106(6):dju124CrossRef
11.
Zurück zum Zitat Teng J-J, Zhang J, Zhang T-Y, Zhang S, Li B-S (2016) Prognostic value of peripheral blood lymphocyte-to-monocyte ratio in patients with solid tumors: a meta-analysis. Onco Targets Ther 9:37PubMed Teng J-J, Zhang J, Zhang T-Y, Zhang S, Li B-S (2016) Prognostic value of peripheral blood lymphocyte-to-monocyte ratio in patients with solid tumors: a meta-analysis. Onco Targets Ther 9:37PubMed
12.
Zurück zum Zitat Wei Y, Jiang Y-Z, Qian W-H (2014) Prognostic role of NLR in urinary cancers: a meta-analysis. PLoS One 9(3):e92079CrossRef Wei Y, Jiang Y-Z, Qian W-H (2014) Prognostic role of NLR in urinary cancers: a meta-analysis. PLoS One 9(3):e92079CrossRef
13.
Zurück zum Zitat Xiao W-K, Chen D, Li S-Q et al (2014) Prognostic significance of neutrophil-lymphocyte ratio in hepatocellular carcinoma: a meta-analysis. BMC Cancer 14(1):117CrossRef Xiao W-K, Chen D, Li S-Q et al (2014) Prognostic significance of neutrophil-lymphocyte ratio in hepatocellular carcinoma: a meta-analysis. BMC Cancer 14(1):117CrossRef
14.
Zurück zum Zitat Zhao Q-T, Yang Y, Xu S et al (2015) Prognostic role of neutrophil to lymphocyte ratio in lung cancers: a meta-analysis including 7,054 patients. Onco Targets Ther 8:2731PubMedPubMedCentral Zhao Q-T, Yang Y, Xu S et al (2015) Prognostic role of neutrophil to lymphocyte ratio in lung cancers: a meta-analysis including 7,054 patients. Onco Targets Ther 8:2731PubMedPubMedCentral
15.
Zurück zum Zitat Tham T, Olson C, Khaymovich J, Herman SW, Costantino PD (2018) The lymphocyte-to-monocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol 275(7):1663–1670CrossRef Tham T, Olson C, Khaymovich J, Herman SW, Costantino PD (2018) The lymphocyte-to-monocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol 275(7):1663–1670CrossRef
16.
Zurück zum Zitat Takenaka Y, Oya R, Kitamiura T, Ashida N, Shimizu K, Takemura K, Yamamoto Y, Uno A (2018) Platelet count and platelet-lymphocyte ratio as prognostic markers for head and neck squamous cell carcinoma: a meta-analysis. Head Neck 40(12):2714–2723CrossRef Takenaka Y, Oya R, Kitamiura T, Ashida N, Shimizu K, Takemura K, Yamamoto Y, Uno A (2018) Platelet count and platelet-lymphocyte ratio as prognostic markers for head and neck squamous cell carcinoma: a meta-analysis. Head Neck 40(12):2714–2723CrossRef
17.
Zurück zum Zitat Harrell FE, Lee KL, Mark DB (1996) Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15(4):361–387CrossRef Harrell FE, Lee KL, Mark DB (1996) Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15(4):361–387CrossRef
18.
Zurück zum Zitat Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA (1982) Evaluating the yield of medical tests. JAMA 247(18):2543–2546CrossRef Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA (1982) Evaluating the yield of medical tests. JAMA 247(18):2543–2546CrossRef
19.
Zurück zum Zitat Harrell FE Jr, Lee KL, Califf RM, Pryor DB, Rosati RA (1984) Regression modelling strategies for improved prognostic prediction. Stat Med 3(2):143–152CrossRef Harrell FE Jr, Lee KL, Califf RM, Pryor DB, Rosati RA (1984) Regression modelling strategies for improved prognostic prediction. Stat Med 3(2):143–152CrossRef
20.
Zurück zum Zitat Uno H, Cai T, Pencina MJ, D'Agostino RB, Wei L (2011) On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data. Stat Med 30(10):1105–1117PubMedPubMedCentral Uno H, Cai T, Pencina MJ, D'Agostino RB, Wei L (2011) On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data. Stat Med 30(10):1105–1117PubMedPubMedCentral
21.
Zurück zum Zitat Rachidi S, Wallace K, Wrangle JM et al (2016) Neutrophil-to-lymphocyte ratio and overall survival in all sites of head and neck squamous cell carcinoma. Head Neck 38(Suppl 1):E1068–E1074CrossRef Rachidi S, Wallace K, Wrangle JM et al (2016) Neutrophil-to-lymphocyte ratio and overall survival in all sites of head and neck squamous cell carcinoma. Head Neck 38(Suppl 1):E1068–E1074CrossRef
22.
Zurück zum Zitat Kano S, Homma A, Hatakeyama H et al (2017) Pretreatment lymphocyte-to-monocyte ratio as an independent prognostic factor for head and neck cancer. Head Neck 39(2):247–253CrossRef Kano S, Homma A, Hatakeyama H et al (2017) Pretreatment lymphocyte-to-monocyte ratio as an independent prognostic factor for head and neck cancer. Head Neck 39(2):247–253CrossRef
23.
Zurück zum Zitat Sun W, Zhang L, Luo M et al (2016) Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma: neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. Head Neck 38(Suppl 1):E1332–E1340CrossRef Sun W, Zhang L, Luo M et al (2016) Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma: neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. Head Neck 38(Suppl 1):E1332–E1340CrossRef
24.
Zurück zum Zitat Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel EL Jr (2004) Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 291(20):2441–2447CrossRef Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel EL Jr (2004) Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 291(20):2441–2447CrossRef
25.
Zurück zum Zitat Amin MB, Edge SB, Greene FL et al (eds) (2017) AJCC Cancer staging manual, 8th edn. Springer, New York Amin MB, Edge SB, Greene FL et al (eds) (2017) AJCC Cancer staging manual, 8th edn. Springer, New York
26.
Zurück zum Zitat Michiels S, Le Maître A, Buyse M et al (2009) Surrogate endpoints for overall survival in locally advanced head and neck cancer: meta-analyses of individual patient data. Lancet Oncol 10(4):341–350CrossRef Michiels S, Le Maître A, Buyse M et al (2009) Surrogate endpoints for overall survival in locally advanced head and neck cancer: meta-analyses of individual patient data. Lancet Oncol 10(4):341–350CrossRef
27.
Zurück zum Zitat Youden WJ (1950) Index for rating diagnostic tests. Cancer 3(1):32–35CrossRef Youden WJ (1950) Index for rating diagnostic tests. Cancer 3(1):32–35CrossRef
28.
Zurück zum Zitat Harrell FE (2001) Regression modeling strategies, with applications to linear models, survival analysis and logistic regression. Springer, New York Harrell FE (2001) Regression modeling strategies, with applications to linear models, survival analysis and logistic regression. Springer, New York
29.
Zurück zum Zitat Ong HS, Gokavarapu S, Wang LZ, Tian Z, Zhang CP (2017) Low pretreatment lymphocyte-monocyte ratio and high platelet-lymphocyte ratio indicate poor cancer outcome in early tongue cancer. J Oral Maxillofac Surg 75(8):1762–1774CrossRef Ong HS, Gokavarapu S, Wang LZ, Tian Z, Zhang CP (2017) Low pretreatment lymphocyte-monocyte ratio and high platelet-lymphocyte ratio indicate poor cancer outcome in early tongue cancer. J Oral Maxillofac Surg 75(8):1762–1774CrossRef
30.
Zurück zum Zitat Eltohami YI, Kao H-K, Lao WW-K et al (2018) The prediction value of the systemic inflammation score for oral cavity squamous cell carcinoma. Otolaryngol Head Neck Surg 158(6): 1042–1050CrossRef Eltohami YI, Kao H-K, Lao WW-K et al (2018) The prediction value of the systemic inflammation score for oral cavity squamous cell carcinoma. Otolaryngol Head Neck Surg 158(6): 1042–1050CrossRef
31.
Zurück zum Zitat Park YM, Oh KH, Cho J-G et al (2018) A prognostic scoring system using inflammatory response biomarkers in oral cavity squamous cell carcinoma patients who underwent surgery-based treatment. Acta Otolaryngol 138(4):422–427CrossRef Park YM, Oh KH, Cho J-G et al (2018) A prognostic scoring system using inflammatory response biomarkers in oral cavity squamous cell carcinoma patients who underwent surgery-based treatment. Acta Otolaryngol 138(4):422–427CrossRef
32.
Zurück zum Zitat Yoo W, Mayberry R, Bae S et al (2014) A study of effects of multicollinearity in the multivariable analysis. Int J Appl Sci Technol 4(5):9PubMedPubMedCentral Yoo W, Mayberry R, Bae S et al (2014) A study of effects of multicollinearity in the multivariable analysis. Int J Appl Sci Technol 4(5):9PubMedPubMedCentral
33.
Zurück zum Zitat So YK, Lee G, Oh D, So YK, Lee G, Oh D, Byeon S, Park W, Chung MK (2018) Prognostic role of neutrophil-to-lymphocyte ratio in patients with human papillomavirus–positive oropharyngeal cancer. Otolaryngol Head Neck Surg 159(2):303–309CrossRef So YK, Lee G, Oh D, So YK, Lee G, Oh D, Byeon S, Park W, Chung MK (2018) Prognostic role of neutrophil-to-lymphocyte ratio in patients with human papillomavirus–positive oropharyngeal cancer. Otolaryngol Head Neck Surg 159(2):303–309CrossRef
34.
Zurück zum Zitat Compton C (2018) Precision medicine core: progress in prognostication—populations to patients. Ann Surg Oncol 25(2):349–350CrossRef Compton C (2018) Precision medicine core: progress in prognostication—populations to patients. Ann Surg Oncol 25(2):349–350CrossRef
35.
Zurück zum Zitat Li XH, Chang H, Xu BQ, Tao YL, Gao J, Chen C, Qu C, Zhou S, Liu SR, Wang XH, Zhang WW (2016) An inflammatory biomarker-based nomogram to predict prognosis of patients with nasopharyngeal carcinoma: an analysis of a prospective study. Cancer Med 6(1):310–319CrossRef Li XH, Chang H, Xu BQ, Tao YL, Gao J, Chen C, Qu C, Zhou S, Liu SR, Wang XH, Zhang WW (2016) An inflammatory biomarker-based nomogram to predict prognosis of patients with nasopharyngeal carcinoma: an analysis of a prospective study. Cancer Med 6(1):310–319CrossRef
Metadaten
Titel
Systemic immune response in squamous cell carcinoma of the head and neck: a comparative concordance index analysis
verfasst von
Tristan Tham
Michael Wotman
Christopher Chung
Seungjun Ahn
Holly Dupuis
Vasiliki Gliagias
Tamara Movsesova
Dennis Kraus
Peter Costantino
Publikationsdatum
16.07.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
European Archives of Oto-Rhino-Laryngology / Ausgabe 10/2019
Print ISSN: 0937-4477
Elektronische ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-019-05554-x

Weitere Artikel der Ausgabe 10/2019

European Archives of Oto-Rhino-Laryngology 10/2019 Zur Ausgabe

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.