Prognostic value of post-radiotherapy neutrophil-to-lymphocyte ratio in locally advanced nasopharyngeal carcinoma

  • Dan Ou
  • Xiaoshen Wang
  • Mingyao Wu
  • Fen Xue
  • Yujiao Li
  • Chaosu HuEmail author
  • Xiayun HeEmail author
Original Article



To explore the temporal profile of the peripheral neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced nasopharyngeal carcinoma (LANPC) and the potential prognostic value of its dynamic changes.


Complete blood count of 112 patients from a previous phase II study were retrospectively collected at the timepoints of the initiation of induction chemotherapy (pre-IC), within 1 week before radiotherapy started (pre-RT), and within 1 week after radiotherapy finished (post-RT). Data of 103 patients were fully recorded and Cox regression analysis was used to analyze the correlations of potential risk factors with 5‑year overall survival (OS). The performance of the prognostic factor was validated in another independent cohort of 103 matched (by T and N stage) patients selected from 236 consecutive NPC patients treated with IC and concurrent chemoradiation.


Multivariate analysis (MVA) identified patient age >50 years old (hazard ratio [HR] = 3.4, p = 0.02), weight loss during RT >7.5% (HR = 3.2, p = 0.03), and post-RT peripheral NLR >7.05 (vs. NLR ≤7.05, HR = 2.5, p = 0.04, 5‑year OS 71.4% vs. 87.8%) as unfavorable prognostic factors for OS. There was also a non-significant trend in the MVA that patients with post-RT peripheral NLR >7.05 showed worse progression-free survival (PFS; HR = 1.9, p = 0.06, 5‑year PFS 64.1% vs. 81.8%). Post-RT NLR had a good prognostic performance in the validation cohort (concordance index = 0.73, standard error 0.10; p = 0.02, Wilcoxon test).


Post-RT NLR is an independent prognostic factor for OS in LANPC patients. The dynamic change of the routinely tested inflammatory variable could help selection of appropriate treatment options and follow-up strategies.


Neutrophil-to-lymphocyte ratio Complete blood count Nasopharyngeal carcinoma Prognostic factor Radiotherapy 

Prognostischer Wert des Verhältnisses von Neutrophilen zu Lymphozyten nach Strahlentherapie bei lokal fortgeschrittenem Nasopharynxkarzinom



Untersuchung des zeitlichen Verlaufs der peripheren NLR („neutrophil-to-lymphocyte ratio“) bei Patienten mit lokal fortgeschrittenem Nasopharynxkarzinom (LANPC) und des potenziellen prognostischen Werts seiner dynamischen Veränderungen.


Das vollständige Blutbild von 112 Patienten aus einer früheren Phase-II-Studie wurde zum Zeitpunkt des Beginns der Induktionschemotherapie (Pre-IC), innerhalb einer Woche vor Beginn der Strahlentherapie (Pre-RT) und innerhalb einer Woche nach beendeter Strahlentherapie (post-RT) retrospektiv erhoben. Die Daten von 103 Patienten wurden vollständig aufgezeichnet und die Cox-Regressionsanalyse wurde verwendet, um die Korrelationen des potenziellen Risikofaktors mit dem 5‑Jahres-Gesamtüberleben (OS) zu analysieren. Die Leistung des Prognosefaktors wurde in einer anderen unabhängigen Kohorte von 103 (nach T‑ und N‑Stadium) passenden Patienten validiert, die aus 236 konsekutiven NPC-Patienten ausgewählt wurden, die mit IC und gleichzeitiger Radiochemotherapie behandelt wurden.


Die multivariate Analyse (MVA) identifizierte ein Patientenalter >50 Jahre (Hazard Ratio [HR] = 3,4; p = 0,02), einen Gewichtsverlust während RT >7,5% (HR = 3,2; p = 0,03) und eine periphere NLR nach RT >7,05 (NLR ≤7,05; HR = 2,5; p = 0,04; 5‑Jahres-OS 71,4% vs. 87,8%) als ungünstige Prognosefaktoren für das OS. Es gab auch einen nichtsignifikanten Trend in der MVA, dass Patienten mit peripherer NLR nach RT >7,05 ein schlechteres progressionsfreies Überleben (PFS) zeigten (HR = 1,9; p = 0,06; 5‑Jahres-PFS 64,1% vs. 81,8%). Post-RT-NLR zeigte eine gute Prognoseleistung in der Validierungskohorte (Konkordanzindex = 0,73, Standardfehler 0,10; p = 0,02, Wilcoxon-Test).


Post-RT-NLR ist ein unabhängiger Prognosefaktor für das OS bei LANPC-Patienten. Die dynamische Änderung der routinemäßig getesteten entzündlichen Variablen könnte dazu beitragen, geeignete Behandlungsoptionen und Follow-up-Strategien zu entwickeln.


Verhältnis von Neutrophilen zu Lymphozyten Komplettes Blutbild Nasopharynxkarzinom Prognosefaktor Strahlentherapie 



This study was supported by the Shanghai Anticancer Association EYAS PROJECT (grant no: SACA-CY1A02) and an institutional grant from the Fudan University Shanghai Cancer Center (grant no: YJ201703).

Conflict of interest

D. Ou, X. Wang, M. Wu, F. Xue, Y. Li, C. Hu, and X. He declare that they have no competing interests.

Supplementary material

66_2019_1529_MOESM1_ESM.docx (941 kb)
In Supplemental Table 1 we provide the baseline clinicopathological characteristics of the 133 discarded patients from the validation cohort. In Supplemental Table 2 and Supplemental Figure 1, we provide data of NLR and EBV DNA of another group of 80 patients treated between May 2018 and March 2019 in our department, to provide an idea about the NLR range and preliminary result of the correlation between EBV DNA and NLR.


  1. 1.
    Yu MC, Yuan JM (2002) Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol 12:421–429CrossRefGoogle Scholar
  2. 2.
    Perri F, Bosso D, Buonerba C, Lorenzo GD, Scarpati GD (2011) Locally advanced nasopharyngeal carcinoma: current and emerging treatment strategies. World J Clin Oncol 2:377–383CrossRefGoogle Scholar
  3. 3.
    Sun X, Su S, Chen C, Han F, Zhao C, Xiao W, Deng X, Huang S, Lin C, Lu T (2014) Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol 110:398–403CrossRefGoogle Scholar
  4. 4.
    Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ (2011) Natural innate and adaptive immunity to cancer. Annu Rev Immunol 29:235–271CrossRefGoogle Scholar
  5. 5.
    Chang H, Gao J, Xu BQ, Guo SP, Lu RB, Li G, Huang SM, Han F, Liu ZG, Tao YL, Tu ZW, Chen C, Li XH, Xia YF (2013) Haemoglobin, neutrophil to lymphocyte ratio and platelet count improve prognosis prediction of the TNM staging system in nasopharyngeal carcinoma: development and validation in 3,237 patients from a single institution. Clin Oncol 25:639–646CrossRefGoogle Scholar
  6. 6.
    Lin YH, Chang KP, Lin YS, Chang TS (2017) Pretreatment combination of platelet counts and neutrophil-lymphocyte ratio predicts survival of nasopharyngeal cancer patients receiving intensity-modulated radiotherapy. Onco Targets Ther 10:2751–2760CrossRefGoogle Scholar
  7. 7.
    Xu C, Chen YP, Liu X, Li WF, Chen L, Mao YP, Zhang Y, Guo R, Zhou GQ, Tang LL, Lin AH, Sun Y, Ma J (2017) Establishing and applying nomograms based on the 8th edition of the UICC/AJCC staging system to select patients with nasopharyngeal carcinoma who benefit from induction chemotherapy plus concurrent chemoradiotherapy. Oral Oncol 69:99–107CrossRefGoogle Scholar
  8. 8.
    Jelonek K, Pietrowska M, Widlak P (2017) Systemic effects of ionizing radiation at the proteome and metabolome levels in the blood of cancer patients treated with radiotherapy: the influence of inflammation and radiation toxicity. Int J Radiat Biol 93:683–696CrossRefGoogle Scholar
  9. 9.
    Wu M, Ou D, He X, Hu C (2017) Long-term results of a phase II study of gemcitabine and cisplatin chemotherapy combined with intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma. Oral Oncol 73:118–123CrossRefGoogle Scholar
  10. 10.
    He X, Ou D, Ying H, Zhu G, Hu C, Liu T (2012) Experience with combination of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol 269:1027–1033CrossRefGoogle Scholar
  11. 11.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674CrossRefGoogle Scholar
  12. 12.
    Schmitz S, Machiels JP (2016) Targeting the Tumor Environment in Squamous Cell Carcinoma of the Head and Neck. Curr Treat Options Oncol 17:37CrossRefGoogle Scholar
  13. 13.
    Ferris RL (2015) Immunology and Immunotherapy of Head and Neck Cancer. J Clin Oncol 33:3293–3304CrossRefGoogle Scholar
  14. 14.
    Ou D, Adam J, Garberis I, Blanchard P, Nguyen F, Levy A, Casiraghi O, Gorphe P, Breuskin I, Janot F, Temam S, Scoazec JY, Deutsch E, Tao Y (2017) Clinical relevance of tumor infiltrating lymphocytes, PD-L1 expression and correlation with HPV/p16 in head and neck cancer treated with bio- or chemo-radiotherapy. OncoImmunology 6(9):e1341030CrossRefGoogle Scholar
  15. 15.
    Cunha LL, Marcello MA, Ward LS (2014) The role of the inflammatory microenvironment in thyroid carcinogenesis. Endocr Relat Cancer 21:R85–R103CrossRefGoogle Scholar
  16. 16.
    Zilio S, Serafini P (2016) Neutrophils and granulocytic MDSC: the Janus God of cancer immunotherapy. Vaccines 4:31CrossRefGoogle Scholar
  17. 17.
    Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ (2013) The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol 88:218–230CrossRefGoogle Scholar
  18. 18.
    Schernberg A, Blanchard P, Chargari C, Deutsch E (2017) Neutrophils, a candidate biomarker and target for radiation therapy? Acta Oncol 56:1522–1530CrossRefGoogle Scholar
  19. 19.
    Gorphe P, Chekkoury Idrissi Y, Tao Y, Schernberg A, Ou D, Temam S, Casiraghi O, Blanchard P, Mirghani H (2018) Anemia and neutrophil-to-lymphocyte ratio are prognostic in p16-positive oropharyngeal carcinoma treated with concurrent chemoradiation. Papillomavirus Res 5:32–37CrossRefGoogle Scholar
  20. 20.
    Cho KM, Park H, Oh DY, Kim TY, Lee KH, Han SW, Im SA, Kim TY, Bang YJ (2017) Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and their dynamic changes during chemotherapy is useful to predict a more accurate prognosis of advanced biliary tract cancer. Oncotarget 8:2329–2341PubMedGoogle Scholar
  21. 21.
    Takenaka Y, Kitamura T, Oya R, Ashida N, Shimizu K, Takemura K, Yamamoto Y, Uno A (2017) Prognostic role of neutrophil-lymphocyte ratio in nasopharyngeal carcinoma: a meta-analysis. PLoS ONE 12:e181478CrossRefGoogle Scholar
  22. 22.
    Su L, Zhang M, Zhang W, Cai CH (2017) Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis. Medicine 96:e6364CrossRefGoogle Scholar
  23. 23.
    Hui L, Chen Y (2015) Tumor microenvironment: sanctuary of the devil. Cancer Lett 368:7–13CrossRefGoogle Scholar
  24. 24.
    Marabelle A, Filatenkov A, Sagiv-Barfi I, Kohrt H (2015) Radiotherapy and toll-like receptor agonists. Semin Radiat Oncol 25:34–39CrossRefGoogle Scholar
  25. 25.
    Demaria S, Coleman CN, Formenti SC (2016) Radiotherapy: changing the game in immunotherapy. Trends Cancer 2:286–294CrossRefGoogle Scholar
  26. 26.
    Tabachnyk M, Distel LV, Büttner M, Grabenbauer GG, Nkenke E, Fietkau R, Lubgan D (2012) Radiochemotherapy induces a favourable tumour infiltrating inflammatory cell profile in head and neck cancer. Oral Oncol 48:594–601CrossRefGoogle Scholar
  27. 27.
    Xu C, Yang SP, Zhang Y, Tang LL, Zhou GQ, Liu X, Mao YP, Guo R, Li WF, Chen L, Lin AH, Sun Y, Ma J (2017) Neutropenia during the first cycle of induction chemotherapy is prognostic for poor survival in locoregionally advanced nasopharyngeal carcinoma: a real-world study in an endemic area. Cancer Res Treat 50:777–790CrossRefGoogle Scholar
  28. 28.
    Blanchard P, Lee A, Marguet S, Leclercq J, Ng WT, Ma J, Chan AT, Huang PY, Benhamou E, Zhu G, Chua DT, Chen Y, Mai HQ, Kwong DL, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Zhang L, Hui EP, Lu TX, Bourhis J, Pignon JP, MAC-NPC Collaborative Group (2015) Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol 16:645–655CrossRefGoogle Scholar
  29. 29.
    Ribassin-Majed L, Marguet S, Lee AWM, Ng WT, Ma J, Chan ATC, Huang PY, Zhu G, Chua DTT, Chen Y, Mai HQ, Kwong DLW, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Bourhis J, Pignon JP, Blanchard P (2017) What is the best treatment of locally advanced nasopharyngeal carcinoma? An individual patient data network meta-analysis. J Clin Oncol 35:498–505CrossRefGoogle Scholar
  30. 30.
    Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF (1998) Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 16:1310–1317CrossRefGoogle Scholar
  31. 31.
    Lee AW, Tung SY, Ngan RK, Chappell R, Chua DT, Lu TX, Siu L, Tan T, Chan LK, Ng WT, Leung TW, Fu YT, Au GK, Zhao C, O’Sullivan B, Tan EH, Lau WH (2011) Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: combined analyses of NPC-9901 and NPC-9902 trials. Eur J Cancer 47:656–666CrossRefGoogle Scholar
  32. 32.
    Yin J, Qin Y, Luo YK, Feng M, Lang JY (2017) Prognostic value of neutrophil-to-lymphocyte ratio for nasopharyngeal carcinoma: a meta-analysis. Medicine 96:e7577CrossRefGoogle Scholar
  33. 33.
    Kim KY, Le QT, Yom SS, Pinsky BA, Bratman SV, Ng RH, El Mubarak HS, Chan KC, Sander M, Conley BA (2017) Current state of PCR-based Epstein-Barr virus DNA testing for nasopharyngeal cancer. J Natl Cancer Inst. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Yip TT, Ngan RK, Fong AH, Law SC (2014) Application of circulating plasma/serum EBV DNA in the clinical management of nasopharyngeal carcinoma. Oral Oncol 50:527–538CrossRefGoogle Scholar
  35. 35.
    Le QT, Zhang Q, Cao H, Cheng AJ, Pinsky BA, Hong RL, Chang JT, Wang CW, Tsao KC, Lo YD, Lee N, Ang KK, Chan AT, Chan KC (2013) An international collaboration to harmonize the quantitative plasma Epstein-Barr virus DNA assay for future biomarker-guided trials in nasopharyngeal carcinoma. Clin Cancer Res 19:2208–2215CrossRefGoogle Scholar
  36. 36.
    Balermpas P, Rödel F, Rödel C, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Gkika E, Stuschke M, Avlar M, Grosu AL, Abdollahi A, Debus J, Bayer C, Stangl S, Belka C, Pigorsch S, Multhoff G, Combs SE, Mönnich D, Zips D, Fokas E (2016) CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: a multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG). Int J Cancer 138:171–181CrossRefGoogle Scholar
  37. 37.
    Stangl S, Tontcheva N, Sievert W, Shevtsov M, Niu M, Schmid TE, Pigorsch S, Combs SE, Haller B, Balermpas P, Rödel F, Rödel C, Fokas E, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Stuschke M, Grosu AL, Abdollahi A, Debus J, Belka C, Maihöfer C, Mönnich D, Zips D, Multhoff G (2018) Heat shock protein 70 and tumor-infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: a multicentre retrospective study of the German cancer consortium radiation oncology group (DKTK-ROG). Int J Cancer 142:1911–1925CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
  2. 2.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina

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