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中性粒细胞和淋巴细胞比值与宫颈癌放疗过程中放射性肠炎的相关性
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Abstract:
本研究旨在分析中性粒细胞与淋巴细胞比值(NLR)是否与宫颈癌患者的放射线肠道炎症(RE)有关联。我们选择的是从2020年10月至2021年7月期间接受了放射疗法的39名宫颈癌病人作为我们的研究群体，并根据其NLR的最优切割点将其划分为低NLR组和高NLR组。分别根据RTOG标准和GSRS量表对患者RE严重程度进行评估，将RTOG分级为1级定义为轻度RE，2级定义为中度RE，3级和4级的定义为严重RE。分析放疗前NLR水平与宫颈癌患者放疗过程中RE严重程度之间的联系。经过对ROC曲线的分析后，我们确定了放射治疗前的NLR的最优切割点数值是2.76。基于RTOG与GSRS评分系统的结果显示，高NLR的患者比那些较低NLR的患者更易发生严重的RE，并且他们的GSRS评分也明显更高(P < 0.05)。在logistics单因素回归分析中，临床分期、N分期、NLR水平与患者发生中重度RE显著相关，logistic多因素回归分析表明影响患者发生中重度RE的独立危险因素为NLR水平、N分期；NLR对宫颈癌放疗患者中重度RE的发生具有一定的预测价值(均P < 0.05)。NLR与RE严重程度具有一定的相关性，是中重度RE的一种潜在的预测因子。
The aim of this study is to explore the connection between the neutrophil to lymphocyte ratio (NLR) and radiation enteritis (RE) in patients undergoing radiation therapy for cervical cancer. 39 patients with cervical cancer who received radiotherapy between October 2020 and July 2021 were analyzed in this study. They were categorized into low and high NLR groups based on the optimal NLR cut-off value in the ROC curve. The assessment of patients’ RE severity was determined using the RTOG criteria (Radiation Therapy Oncology Group) criteria and GSRS (Gastrointestinal Symptoms Rating Scales) respectively, and grade 1 of RTOG was defined as mild RE, grade 2 as moderate RE, grade 3 and 4 as severe RE. In this study, we examined how the level of NLR prior to radiotherapy is linked to the intensity of radiation esophagitis in cervical cancer patients. The ROC curve analysis revealed that the ideal threshold for NLR before radiotherapy was determined to be 2.76. The RTOG criteria and GSRS scale revealed that the high NLR group had a greater proportion of patients with severe RE than their low NLR counterparts, as well as an increased GSRS score (all P < 0.05). Clinical stage, N stage, and NLR level were found to have significant associations with the development of moderate-severe RE in logistic univariate regression analysis. However, in logistic multivariate regression analysis, it was revealed that the independent risk factors for moderate-severe RE occurrence were NLR level and N stage. NLR was determined to have diagnostic value for predicting moderate-severe RE in cervical cancer patients undergoing radiotherapy (P < 0.05). NLR is associated with the severity of RE during radiotherapy for cervical cancer patients, and it shows a certain predictive value for the occurrence of moderate-severe RE.
| [1] | Arbyn, M., Weiderpass, E., Bruni, L., de Sanjosé, S., Saraiya, M., Ferlay, J., et al. (2020) Estimates of Incidence and Mortality of Cervical Cancer in 2018: A Worldwide Analysis. The Lancet Global Health, 8, e191-e203. https://doi.org/10.1016/s2214-109x(19)30482-6 |
| [2] | Johnson, C.A., James, D., Marzan, A. and Armaos, M. (2019) Cervical Cancer: An Overview of Pathophysiology and Management. Seminars in Oncology Nursing, 35, 166-174. https://doi.org/10.1016/j.soncn.2019.02.003 |
| [3] | Landoni, F., Maneo, A., Colombo, A., Placa, F., Milani, R., Perego, P., et al. (1997) Randomised Study of Radical Surgery versus Radiotherapy for Stage Ib-IIa Cervical Cancer. The Lancet, 350, 535-540. https://doi.org/10.1016/s0140-6736(97)02250-2 |
| [4] | van Nagell, J.R., Parker, J.C., Maruyama, Y., Utley, J., Hager, W.D., Donaldson, E.S., et al. (1977) The Effect of Pelvic Inflammatory Disease on Enteric Complications Following Radiation Therapy for Cervical Cancer. American Journal of Obstetrics and Gynecology, 128, 767-771. https://doi.org/10.1016/0002-9378(77)90718-9 |
| [5] | Waddell, B.E., Rodriguez-Bigas, M.A., Lee, R.J., Weber, T.K. and Petrelli, N.J. (1999) Prevention of Chronic Radiation Enteritis. Journal of the American College of Surgeons, 189, 611-624. https://doi.org/10.1016/s1072-7515(99)00199-4 |
| [6] | Sher, M.E. and Bauer, J. (1990) Radiation-Induced Enteropathy. American Journal of Gastroenterology, 85, 121-128. |
| [7] | Andreyev, H.J.N., Vlavianos, P., Blake, P., Dearnaley, D., Norman, A.R. and Tait, D. (2005) Gastrointestinal Symptoms after Pelvic Radiotherapy: Role for the Gastroenterologist? International Journal of Radiation Oncology∙Biology∙Physics, 62, 1464-1471. https://doi.org/10.1016/j.ijrobp.2004.12.087 |
| [8] | Fang, H., Huang, X.Y., Chien, H., Chang, J.T., Liao, C., Huang, J., et al. (2013) Refining the Role of Preoperative C‐reactive Protein by Neutrophil/Lymphocyte Ratio in Oral Cavity Squamous Cell Carcinoma. The Laryngoscope, 123, 2690-2699. https://doi.org/10.1002/lary.24105 |
| [9] | Charles, K.A., Harris, B.D.W., Haddad, C.R., Clarke, S.J., Guminski, A., Stevens, M., et al. (2016) Systemic Inflammation Is an Independent Predictive Marker of Clinical Outcomes in Mucosal Squamous Cell Carcinoma of the Head and Neck in Oropharyngeal and Non-Oropharyngeal Patients. BMC Cancer, 16, Article No. 124. https://doi.org/10.1186/s12885-016-2089-4 |
| [10] | Sato, H., Tsubosa, Y. and Kawano, T. (2012) Correlation between the Pretherapeutic Neutrophil to Lymphocyte Ratio and the Pathologic Response to Neoadjuvant Chemotherapy in Patients with Advanced Esophageal Cancer. World Journal of Surgery, 36, 617-622. https://doi.org/10.1007/s00268-011-1411-1 |
| [11] | Sarraf, K.M., Belcher, E., Raevsky, E., Nicholson, A.G., Goldstraw, P. and Lim, E. (2009) Neutrophil/Lymphocyte Ratio and Its Association with Survival after Complete Resection in Non-Small Cell Lung Cancer. The Journal of Thoracic and Cardiovascular Surgery, 137, 425-428. https://doi.org/10.1016/j.jtcvs.2008.05.046 |
| [12] | Azab, B., Bhatt, V.R., Phookan, J., Murukutla, S., Kohn, N., Terjanian, T., et al. (2011) Usefulness of the Neutrophil-to-Lymphocyte Ratio in Predicting Short-and Long-Term Mortality in Breast Cancer Patients. Annals of Surgical Oncology, 19, 217-224. https://doi.org/10.1245/s10434-011-1814-0 |
| [13] | Yamanaka, T., Matsumoto, S., Teramukai, S., Ishiwata, R., Nagai, Y. and Fukushima, M. (2007) The Baseline Ratio of Neutrophils to Lymphocytes Is Associated with Patient Prognosis in Advanced Gastric Cancer. Oncology, 73, 215-220. https://doi.org/10.1159/000127412 |
| [14] | Bhatti, I., Peacock, O., Lloyd, G., Larvin, M. and Hall, R.I. (2010) Preoperative Hematologic Markers as Independent Predictors of Prognosis in Resected Pancreatic Ductal Adenocarcinoma: Neutrophil-Lymphocyte versus Platelet-Lymphocyte Ratio. The American Journal of Surgery, 200, 197-203. https://doi.org/10.1016/j.amjsurg.2009.08.041 |
| [15] | Halazun, K.J., Aldoori, A., Malik, H.Z., Al-Mukhtar, A., Prasad, K.R., Toogood, G.J., et al. (2008) Elevated Preoperative Neutrophil to Lymphocyte Ratio Predicts Survival Following Hepatic Resection for Colorectal Liver Metastases. European Journal of Surgical Oncology, 34, 55-60. https://doi.org/10.1016/j.ejso.2007.02.014 |
| [16] | Gondo, T., Nakashima, J., Ohno, Y., Choichiro, O., Horiguchi, Y., Namiki, K., et al. (2012) Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Establishment of Novel Preoperative Risk Stratification Model in Bladder Cancer Patients Treated with Radical Cystectomy. Urology, 79, 1085-1091. https://doi.org/10.1016/j.urology.2011.11.070 |
| [17] | Cho, H., Hur, H.W., Kim, S.W., Kim, S.H., Kim, J.H., Kim, Y.T., et al. (2008) Pre-Treatment Neutrophil to Lymphocyte Ratio Is Elevated in Epithelial Ovarian Cancer and Predicts Survival after Treatment. Cancer Immunology, Immunotherapy, 58, 15-23. https://doi.org/10.1007/s00262-008-0516-3 |
| [18] | Kawashita, Y., Kitamura, M., Soutome, S., Ukai, T., Umeda, M. and Saito, T. (2021) Association of Neutrophil-to-Lymphocyte Ratio with Severe Radiation-Induced Mucositis in Pharyngeal or Laryngeal Cancer Patients: A Retrospective Study. BMC Cancer, 21, Article No. 1064. https://doi.org/10.1186/s12885-021-08793-6 |
| [19] | 中国抗癌协会妇科肿瘤专业委员会. 宫颈癌诊断与治疗指南(第四版) [J]. 中国实用妇科与产科杂志, 2018, 34(6): 613-622. |
| [20] | Cox, J.D., Stetz, J. and Pajak, T.F. (1995) Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (eortc). International Journal of Radiation Oncology∙Biology∙Physics, 31, 1341-1346. https://doi.org/10.1016/0360-3016(95)00060-c |
| [21] | 冯钟煦, 孟维山, 苏忠, 等. 两种腹腔镜不同取石术式对胆总管结石患者肝功能及GS RS评分的影响[J]. 贵州医科大学学报, 2022, 47(9): 1087-1091, 1096. |
| [22] | Rubin, S.C. (2001) Cervical Cancer: Successes and Failures. CA: A Cancer Journal for Clinicians, 51, 89-91. https://doi.org/10.3322/canjclin.51.2.89 |
| [23] | Abu-Rustum, N.R., Yashar, C.M., Bean, S., Bradley, K., Campos, S.M., Chon, H.S., et al. (2020) NCCN Guidelines Insights: Cervical Cancer, Version 1.2020. Journal of the National Comprehensive Cancer Network, 18, 660-666. https://doi.org/10.6004/jnccn.2020.0027 |
| [24] | Daly, P.E., Samiee, S., Cino, M., Gryfe, R., Pollett, A., Ng, A., et al. (2016) High Prevalence of Adenomatous Colorectal Polyps in Young Cancer Survivors Treated with Abdominal Radiation Therapy: Results of a Prospective Trial. Gut, 66, 1797-1801. https://doi.org/10.1136/gutjnl-2016-311501 |
| [25] | Churnratanakul, S., Wirzba, B., Lam, T., Walker, K., Fedorak, R. and Thomson, A.B.R. (1990) Radiation and the Small Intestine. Digestive Diseases, 8, 45-60. https://doi.org/10.1159/000171239 |
| [26] | Keefe, D.M.K. (2004) Gastrointestinal Mucositis: A New Biological Model. Supportive Care in Cancer, 12, 6-9. https://doi.org/10.1007/s00520-003-0550-9 |
| [27] | Jung, E., Perrone, E.E., Brahmamdan, P., McDonough, J.S., Leathersich, A.M., Dominguez, J.A., et al. (2013) Inhibition of Intestinal Epithelial Apoptosis Improves Survival in a Murine Model of Radiation Combined Injury. PLOS ONE, 8, e77203. https://doi.org/10.1371/journal.pone.0077203 |
| [28] | Sun, H., Cai, H., Fu, Y., Wang, Q., Ji, K., Du, L., et al. (2020) The Protection Effect of Resveratrol against Radiation-Induced Inflammatory Bowel Disease via NLRP-3 Inflammasome Repression in Mice. Dose-Response, 18. https://doi.org/10.1177/1559325820931292 |
| [29] | Shadad, A.K. (2013) Gastrointestinal Radiation Injury: Prevention and Treatment. World Journal of Gastroenterology, 19, 199-208. https://doi.org/10.3748/wjg.v19.i2.199 |
| [30] | Lu, L., Jiang, M., Zhu, C., He, J. and Fan, S. (2019) Amelioration of Whole Abdominal Irradiation-Induced Intestinal Injury in Mice with 3,3′-Diindolylmethane (DIM). Free Radical Biology and Medicine, 130, 244-255. https://doi.org/10.1016/j.freeradbiomed.2018.10.410 |
| [31] | Bhat, K., Duhachek-Muggy, S., Ramanathan, R., Saki, M., Alli, C., Medina, P., et al. (2019) 1-[(4-Nitrophenyl)Sulfonyl]-4-Phenylpiperazine Increases the Number of Peyer’s Patch-Associated Regenerating Crypts in the Small Intestines after Radiation Injury. Radiotherapy and Oncology, 132, 8-15. https://doi.org/10.1016/j.radonc.2018.11.011 |
| [32] | Harb, A.H., Abou Fadel, C. and Sharara, A.I. (2014) Radiation Enteritis. Current Gastroenterology Reports, 16, Article No. 383. https://doi.org/10.1007/s11894-014-0383-3 |
| [33] | Imtiaz, F., Shafique, K., Mirza, S., Ayoob, Z., Vart, P. and Rao, S. (2012) Neutrophil Lymphocyte Ratio as a Measure of Systemic Inflammation in Prevalent Chronic Diseases in Asian Population. International Archives of Medicine, 5, Article 2. https://doi.org/10.1186/1755-7682-5-2 |
| [34] | Templeton, A.J., McNamara, M.G., Šeruga, B., Vera-Badillo, F.E., Aneja, P., Ocaña, A., et al. (2014) Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Solid Tumors: A Systematic Review and Meta-Analysis. JNCI: Journal of the National Cancer Institute, 106, dju124. https://doi.org/10.1093/jnci/dju124 |
| [35] | Günay, E., Sarınç Ulaşlı, S., Akar, O., Ahsen, A., Günay, S., Koyuncu, T., et al. (2013) Neutrophil-to-Lymphocyte Ratio in Chronic Obstructive Pulmonary Disease: A Retrospective Study. Inflammation, 37, 374-380. https://doi.org/10.1007/s10753-013-9749-1 |
| [36] | Coffelt, S.B., Wellenstein, M.D. and de Visser, K.E. (2016) Neutrophils in Cancer: Neutral no More. Nature Reviews Cancer, 16, 431-446. https://doi.org/10.1038/nrc.2016.52 |
| [37] | Gentles, A.J., Newman, A.M., Liu, C.L., Bratman, S.V., Feng, W., Kim, D., et al. (2015) The Prognostic Landscape of Genes and Infiltrating Immune Cells across Human Cancers. Nature Medicine, 21, 938-945. https://doi.org/10.1038/nm.3909 |
| [38] | Lorente, D., Mateo, J., Templeton, A.J., Zafeiriou, Z., Bianchini, D., Ferraldeschi, R., et al. (2015) Baseline Neutrophil-Lymphocyte Ratio (NLR) Is Associated with Survival and Response to Treatment with Second-Line Chemotherapy for Advanced Prostate Cancer Independent of Baseline Steroid Use. Annals of Oncology, 26, 750-755. https://doi.org/10.1093/annonc/mdu587 |
| [39] | Ethier, J., Desautels, D., Templeton, A., Shah, P.S. and Amir, E. (2017) Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Breast Cancer: A Systematic Review and Meta-Analysis. Breast Cancer Research, 19, Article No. 2. https://doi.org/10.1186/s13058-016-0794-1 |
| [40] | Doi, H., Nakamatsu, K., Anami, S., Fukuda, K., Inada, M., Tatebe, H., et al. (2018) Neutrophil-to-Lymphocyte Ratio Predicts Survival after Whole-Brain Radiotherapy in Non-Small Cell Lung Cancer. In Vivo, 33, 195-201. https://doi.org/10.21873/invivo.11459 |
| [41] | Suzuki, R., Takagi, T., Hikichi, T., Konno, N., Sugimoto, M., Watanabe, K., et al. (2016) Derived Neutrophil/Lymphocyte Ratio Predicts Gemcitabine Therapy Outcome in Unresectable Pancreatic Cancer. Oncology Letters, 11, 3441-3445. https://doi.org/10.3892/ol.2016.4381 |
| [42] | Homa-Mlak, I., Brzozowska, A., Mlak, R., Szudy-Szczyrek, A. and Małecka-Massalska, T. (2021) Neutrophil-to-Lymphocyte Ratio as a Factor Predicting Radiotherapy Induced Oral Mucositis in Head Neck Cancer Patients Treated with Radiotherapy. Journal of Clinical Medicine, 10, Article 4444. https://doi.org/10.3390/jcm10194444 |
