Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2020, Vol. 34 ›› Issue (6): 36-41.doi: 10.6040/j.issn.1673-3770.0.2020.053

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Changes in and prognostic value of the inflammatory index before and after concurrent chemoradiotherapy for nasopharyngeal carcinoma

FAN Li, LI Yue, XU Ximing   

  1. Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430000, Hubei, China
  • Published:2021-01-11

Abstract: Objective To investigate the effect of the neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)in peripheral blood on the prognosis of nasopharyngeal carcinoma(NPC)before and after concurrent chemoradiotherapy. Methods Pre-/post-treatment and changes in neutrophil, platelet, and lymphocyte levels of 229 patients who were diagnosed with locally advanced NPC and received concurrent chemoradiotherapy in Renmin Hospital of Wuhan University were retrospectively analyzed. A receiver operating characteristic(ROC)analysis was performed to determine the optimal cutoff values of NLR, PLR, ΔNLR, and ΔPLR, and the patients were then divided into lower and higher groups according to the optimal cutoff values of ΔNLR and ΔPLR. A Kaplan-Meier analysis and Cox risk model were used to identify independent predictors of recurrence and prognosis. Results The areas under the ROC curve of PLR, NLR, ΔNLR, and ΔPLR in the diagnosis of tumor recurrence were 0.680, 0.678, 0.854, and 0.730, respectively, and the optimal cut-off values for each parameter were 2.730, 135.550, 4.982, and 122.553, respectively. Univariate analysis showed that TNM stages, clinical stages, PLR and NLR, ΔNLR, and ΔPLR were correlated with the recurrence of NPC, whereas the Cox regression model suggested that TNM stages, ΔNLR, and ΔPLR were independent risk factors for the recurrence of NPC. Kaplan-Meier analysis found that the 2-year recurrence-free survival rates of the ΔHNLR and ΔHPLR groups were lower than those of the ΔLNLR and ΔLPLR groups(ΔHNLR vs. ΔLNLR=0.488 vs. 0.993; ΔHPLR vs. ΔLPLR=0.476 vs. 0.935), and that the median recurrence-free survival time for both the ΔHNLR and ΔHPLR groups was 23 months. Conclusion Both NLR and PLR in patients with locally advanced NPC increased after concurrent chemoradiotherapy, and poorer prognosis was correlated with higher ΔNLR and ΔPLR values. Therefore, ΔNLR and ΔPLR can be used to assess risk for tumor recurrence in patients with locally advanced NPC.

Key words: Nasopharyngeal carcinoma, Concurrent chemoradiotherapy, Neutrophil-lymphocyte ratio, Platelet-lymphocyte ratio, Recurrence

CLC Number: 

  • R739.6
[1] Shalapour S, Karin M. Pas de deux: control of anti-tumor immunity by cancer-associated inflammation[J]. Immunity, 2019, 51(1): 15-26. doi:10.1016/j.immuni.2019.06.021.
[2] Dolan RD, Laird BJA, Klepstad P, et al. An exploratory study examining the relationship between performance status and systemic inflammation frameworks and cytokine profiles in patients with advanced cancer[J]. Medicine(Baltimore), 2019, 98(37): e17019. doi:10.1097/MD.0000000000017019.
[3] Derer A, Frey B, Fietkau R, et al. Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors[J]. Cancer Immunol Immunother, 2016, 65(7): 779-786. doi:10.1007/s00262-015-1771-8.
[4] Chajon E, Castelli J, Marsiglia H, et al. The synergistic effect of radiotherapy and immunotherapy: a promising but not simple partnership[J]. Crit Rev Oncol, 2017, 111: 124-132. doi:10.1016/j.critrevonc.2017.01.017.
[5] Toulany M. Targeting DNA double-strand break repair pathways to improve radiotherapy response[J]. Genes(Basel), 2019, 10(1): E25. doi:10.3390/genes10010025.
[6] Ma YT, Pitt JM, Li QQ, et al. The renaissance of anti-neoplastic immunity from tumor cell demise[J]. Immunol Rev, 2017, 280(1): 194-206. doi:10.1111/imr.12586.
[7] Lumniczky K, Sáfrány G. The impact of radiation therapy on the antitumor immunity: local effects and systemic consequences[J]. Cancer Lett, 2015, 356(1): 114-125. doi:10.1016/j.canlet.2013.08.024.
[8] Candéias SM, Testard I. The many interactions between the innate immune system and the response to radiation[J]. Cancer Lett, 2015, 368(2): 173-178. doi:10.1016/j.canlet.2015.02.007.
[9] Murata M. Inflammation and cancer[J]. Environ Health Prev Med, 2018, 23(1): 50. doi:10.1186/s12199-018-0740-1.
[10] Shalapour S, Lin XJ, Bastian IN, et al. Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity[J]. Nature, 2017, 551(7680): 340-345. doi:10.1038/nature24302.
[11] Dolan RD, McSorley ST, Horgan PG, et al. The role of the systemic inflammatory response in predicting outcomes in patients with advanced inoperable cancer: Systematic review and meta-analysis[J]. Crit Rev Oncol Hematol, 2017, 116: 134-146. doi:10.1016/j.critrevonc.2017.06.002.
[12] Yodying H, Matsuda A, Miyashita M, et al. Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: a systematic review and meta-analysis[J]. Ann Surg Oncol, 2016, 23(2): 646-654. doi:10.1245/s10434-015-4869-5.
[13] Zhao Z, Zhao XR, Lu JJ, et al. Prognostic roles of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in ovarian cancer: a meta-analysis of retrospective studies[J]. Arch Gynecol Obstet, 2018, 297(4): 849-857. doi:10.1007/s00404-018-4678-8.
[14] Lorente L. New prognostic biomarkers of mortality in patients undergoing liver transplantation for hepatocellular carcinoma[J]. World J Gastroenterol, 2018, 24(37): 4230-4242. doi:10.3748/wjg.v24.i37.4230.
[15] Rossi S, Basso M, Strippoli A, et al. Are markers of systemic inflammation good prognostic indicators in colorectal cancer?[J]. Clin Colorectal Cancer, 2017, 16(4): 264-274. doi:10.1016/j.clcc.2017.03.015. 019, 26(1): 31-47. doi:10.1111/iju.13801.
[16] Ohno Y. Role of systemic inflammatory response markers in urological malignancy[J]. International journal of urology: official journal of the Japanese Urological Association,2019,26(1):31-47. doi: 10.1111/iju.13801.
[17] Su L, Zhang MW, Zhang WJ, et al. Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis[J]. Medicine(Baltimore), 2017, 96(11): e6364. doi:10.1097/MD.0000000000006364.
[18] Sridharan V, Margalit DN, Lynch SA, et al. Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer[J]. Br J Cancer, 2016, 115(2):252-260. doi: 10.1038/bjc.2016.166.
[19] Burnette BC, Liang H, Lee Y, et al. The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity[J]. Cancer Res. 2011, 71(7):2488-2496. doi: 10.1158/0008-5472.CAN-10-2820.
[20] Chen J, Cao Y, Markelc B, et al. Type Ⅰ IFN protects cancer cells from CD8+ T cell-mediated cytotoxicity after radiation[J]. I Clin Invest, 2019, 129(10):4224-4238. doi: 10.1172/JCI127458.
[21] Schuler PJ, Harasymczuk M, Schilling B, et al. Effects of adjuvant chemoradiotherapy on the frequency and function of regulatory T cells in patients with head and neck cancer[J]. Clin Cancer Res, 2013, 19(23):6585-6596. doi: 10.1158/1078-0432.CCR-13-0900.
[22] Al-Taei S, Banner R, Powell N, et al. Decreased HPV-specific T cell responses and accumulation of immunosuppressive influences in oropharyngeal cancer patients following radical therapy[J]. Cancer Immunol Immunother, 2013, 62(12):1821-1830.
[23] van Meir H, Nout RA, Welters MJP, et al. Impact of(chemo)radiotherapy on immune cell composition and function in cervical cancer patients[J]. Oncoimmunology, 2017,6(2):e1267095. doi: 10.1080/2162402X.2016.1267095.
[24] Wennerberg E, Lhuillier C, Vanpouille-Box C, et al. Barriers to radiation-induced In situ tumor vaccination[J]. Front Immunol, 2017, 8: 229. doi:10.3389/fimmu.2017.00229.
[25] Menon H, Ramapriyan R, Cushman TR, et al. Role of radiation therapy in modulation of the tumor stroma and microenvironment[J]. Front Immunol, 2019, 10: 193. doi:10.3389/fimmu.2019.00193.
[26] Wang H, Jiang H, van De Gucht M, et al. Hypoxic radioresistance: can ROS be the key to overcome it?[J]. Cancers(Basel), 2019, 11(1): E112. doi:10.3390/cancers11010112.
[27] Rückert M, Deloch L, Fietkau R, et al. Immune modulatory effects of radiotherapy as basis for well-reasoned radioimmunotherapies[J]. Strahlenther Onkol, 2018, 194(6): 509-519. doi:10.1007/s00066-018-1287-1.
[28] McLaren PJ, Bronson NW, Hart KD, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios can predict treatment response to neoadjuvant therapy in esophageal cancer[J]. J Gastrointest Surg, 2017, 21(4): 607-613. doi:10.1007/s11605-016-3351-4.
[29] Stöth M, Freire Valls A, Chen MY, et al. Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation[J]. Int J Cancer, 2019, 145(9): 2509-2520. doi:10.1002/ijc.32378.
[30] Ocana A, Nieto-Jiménez C, Pandiella A, et al. Neutrophils in cancer: prognostic role and therapeutic strategies[J]. Mol Cancer, 2017, 16(1): 137. doi:10.1186/s12943-017-0707-7.
[31] Pucci F, Rickelt S, Newton AP, et al. PF4 promotes platelet production and lung cancer growth[J]. Cell Rep, 2016, 17(7): 1764-1772. doi:10.1016/j.celrep.2016.10.031.
[32] Ménétrier-Caux C, Ray-Coquard I, Blay JY, et al. Lymphopenia in cancer patients and its effects on response to immunotherapy: an opportunity for combination with cytokines?[J]. J Immunother Cancer, 2019, 7(1): 85. doi:10.1186/s40425-019-0549-5.
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