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Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Cervical Cancer | Research article

Neutrophil-lymphocyte ratio as a predictor of oncologic outcomes in stage IVB, persistent, or recurrent cervical cancer patients treated by chemotherapy

Authors: Pornprom Ittiamornlert, Irene Ruengkhachorn

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Cervical cancer patients with stage IVB, persistent, or recurrent disease after complete primary treatment are usually treated with systemic chemotherapy. Circulating blood components have been a target of study relative to their ability to predict cancer outcomes; however, no previous study has focused on patients with advanced, persistent, or recurrent cervical carcinoma who were treated by chemotherapy, which adversely affects hematopoietic and immune activity. The predictive value of complete blood cell differential counts in patients with stage IVB, persistent, or recurrent cervical cancer treated by chemotherapy, may be able to triage these patients.

Methods

This retrospective chart review was conducted in cervical cancer patients with stage IVB disease, persistent disease, or recurrent disease who were treated by chemotherapy during January 2006 to January 2017 were reviewed. Follow-up data were collected through July 2017.

Results

A total of 355 cervical carcinoma patients were included. Of those, 63 patients received chemotherapy as primary treatment, and 292 patients received chemotherapy for persistent or recurrent disease. Mean age was 52.5 ± 10.3 years, median age was 51.9 years (IQR: 45.0–59.7), and mean BMI was 23.3 ± 4.9 kg/m2. Overall response rate was 37.5%, with a median progression free survival (PFS) of 5.7 months, and with a median overall survival (OS) of 38.1 months. Multivariate analysis revealed elevated platelet count (> 400,000/mm3), squamous cell carcinoma subtype, and distant metastasis to be associated with poorer PFS. Elevated neutrophil count (> 7000/mm3), elevated platelet count (> 400,000/mm3), squamous cell carcinoma subtype, and distant metastasis were found to be associated with poorer OS. Neutrophil-lymphocyte ratio ≥ 3.6 was the most valuable predictor of poor oncologic outcome relative to overall response rate (odds ratio = 1.642, 95% confidence interval [CI]: 1.048–2.572, P = 0.030), PFS (hazard ratio [HR] = 1.676, 95% CI: 1.334–2.107, P < 0.001), and OS (HR = 2.544, 95% CI: 1.672–3.870, P < 0.001).

Conclusions

Neutrophil-lymphocyte ratio ≥ 3.6 was identified as an independent predictor of poor oncologic outcome relative to overall response rate, PFS and OS.
Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRef Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRef
3.
go back to reference Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri. Int J Gynecol Obstet. 2018;143:22–36.CrossRef Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri. Int J Gynecol Obstet. 2018;143:22–36.CrossRef
4.
go back to reference Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a gynecologic oncology group study. J Clin Oncol. 2005;23:4626–33.CrossRef Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a gynecologic oncology group study. J Clin Oncol. 2005;23:4626–33.CrossRef
5.
go back to reference Monk BJ, Sill MW, DS MM, Cohn DE, Ramondetta LM, Boardman CH, et al. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a gynecologic oncology group study. J Clin Oncol. 2009;27:4649–55.CrossRef Monk BJ, Sill MW, DS MM, Cohn DE, Ramondetta LM, Boardman CH, et al. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a gynecologic oncology group study. J Clin Oncol. 2009;27:4649–55.CrossRef
6.
go back to reference Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004;22:3113–9.CrossRef Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004;22:3113–9.CrossRef
7.
go back to reference Donskov F. Immunomonitoring and prognostic relevance of neutrophils in clinical trials. Semin Cancer Biol. 2013;23:200–7.CrossRef Donskov F. Immunomonitoring and prognostic relevance of neutrophils in clinical trials. Semin Cancer Biol. 2013;23:200–7.CrossRef
8.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference Lee YY, Choi CH, Kim HJ, Kim TJ, Lee JW, Lee JH, et al. Pretreatment neutrophil:lymphocyte ratio as a prognostic factor in cervical carcinoma. Anticancer Res. 2012;32:1555–61.PubMed Lee YY, Choi CH, Kim HJ, Kim TJ, Lee JW, Lee JH, et al. Pretreatment neutrophil:lymphocyte ratio as a prognostic factor in cervical carcinoma. Anticancer Res. 2012;32:1555–61.PubMed
10.
go back to reference Lee YY, Choi CH, Sung CO, Do IG, Hub SJ, Kim HJ, et al. Clinical significance of changes in peripheral lymphocyte count after surgery in early cervical cancer. Gynecol Oncol. 2012;127:107–13.CrossRef Lee YY, Choi CH, Sung CO, Do IG, Hub SJ, Kim HJ, et al. Clinical significance of changes in peripheral lymphocyte count after surgery in early cervical cancer. Gynecol Oncol. 2012;127:107–13.CrossRef
11.
go back to reference Chen L, Zhang F, Sheng XG, Zhang SQ. Decreased pretreatment lymphocyte/monocyte ratio is associated with poor prognosis in stage Ib1-IIa cervical cancer patients who undergo radical surgery. Onco Targets Ther. 2015;8:1355–62.PubMedPubMedCentral Chen L, Zhang F, Sheng XG, Zhang SQ. Decreased pretreatment lymphocyte/monocyte ratio is associated with poor prognosis in stage Ib1-IIa cervical cancer patients who undergo radical surgery. Onco Targets Ther. 2015;8:1355–62.PubMedPubMedCentral
12.
go back to reference Zhang Y, Wang L, Liu Y, Wang S, Shang P, Gao Y, et al. Preoperative neutrophil-lymphocyte ratio before platelet-lymphocyte ratio predicts clinical outcome in patients with cervical cancer treated with initial radical surgery. Int J Gynecol Cancer. 2014;24:1319–25.CrossRef Zhang Y, Wang L, Liu Y, Wang S, Shang P, Gao Y, et al. Preoperative neutrophil-lymphocyte ratio before platelet-lymphocyte ratio predicts clinical outcome in patients with cervical cancer treated with initial radical surgery. Int J Gynecol Cancer. 2014;24:1319–25.CrossRef
13.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRef Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRef
14.
go back to reference Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, et al. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 1997;15:165–71.CrossRef Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, et al. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 1997;15:165–71.CrossRef
15.
go back to reference Bloss JD, Blessing JA, Behrens BC, Mannel RS, Rader JS, Sood AK, et al. Randomized trial of cisplatin and ifosfamide with or without bleomycin in squamous carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2002;20:1832–7.CrossRef Bloss JD, Blessing JA, Behrens BC, Mannel RS, Rader JS, Sood AK, et al. Randomized trial of cisplatin and ifosfamide with or without bleomycin in squamous carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2002;20:1832–7.CrossRef
16.
go back to reference Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, et al. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical Cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015;33:2129–35.CrossRef Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, et al. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical Cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015;33:2129–35.CrossRef
17.
go back to reference Ruengkhachorn I, Leelaphatanadit C, Therasakvichya S, Hunnangkul S. Oncologic outcomes of stage IVB or persistent or recurrent cervical carcinoma patients treated with chemotherapy at Siriraj hospital: Thailand's largest tertiary referral center. Int J Gynecol Cancer. 2016;26:1154–61.CrossRef Ruengkhachorn I, Leelaphatanadit C, Therasakvichya S, Hunnangkul S. Oncologic outcomes of stage IVB or persistent or recurrent cervical carcinoma patients treated with chemotherapy at Siriraj hospital: Thailand's largest tertiary referral center. Int J Gynecol Cancer. 2016;26:1154–61.CrossRef
18.
go back to reference Fernandes PC Jr, Garcia CB, Micheli DC, Cunha FQ, Murta EF, Tavares-Murta BM. Circulating neutrophils may play a role in the host response in cervical cancer. Int J Gynecol Cancer. 2007;17:1068–74.CrossRef Fernandes PC Jr, Garcia CB, Micheli DC, Cunha FQ, Murta EF, Tavares-Murta BM. Circulating neutrophils may play a role in the host response in cervical cancer. Int J Gynecol Cancer. 2007;17:1068–74.CrossRef
19.
go back to reference Younes G, Segev Y, Begal J, Auslender R, Goldberg Y, Amit A, et al. The prognostic significance of hematological parameters in women with uterine serous papillary carcinoma (USPC). Eur J Obstet Gynecol Reprod Biol. 2016;199:16–20.CrossRef Younes G, Segev Y, Begal J, Auslender R, Goldberg Y, Amit A, et al. The prognostic significance of hematological parameters in women with uterine serous papillary carcinoma (USPC). Eur J Obstet Gynecol Reprod Biol. 2016;199:16–20.CrossRef
20.
go back to reference Wu ES, Oduyebo T, Cobb LP, Cholakian D, Kong X, Fader AN, et al. Lymphopenia and its association with survival in patients with locally advanced cervical cancer. Gynecol Oncol. 2016;140:76–82.CrossRef Wu ES, Oduyebo T, Cobb LP, Cholakian D, Kong X, Fader AN, et al. Lymphopenia and its association with survival in patients with locally advanced cervical cancer. Gynecol Oncol. 2016;140:76–82.CrossRef
21.
go back to reference Williams KA, Labidi-Galy SI, Terry KL, Vitonis AF, Welch WR, Goodman A, et al. Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer. Gynecol Oncol. 2014;132:542–50.CrossRef Williams KA, Labidi-Galy SI, Terry KL, Vitonis AF, Welch WR, Goodman A, et al. Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer. Gynecol Oncol. 2014;132:542–50.CrossRef
22.
go back to reference Onal C, Guler OC, Yildirim BA. Prognostic use of pretreatment hematologic parameters in patients receiving definitive Chemoradiotherapy for cervical Cancer. Int J Gynecol Cancer. 2016;26:1169–75.CrossRef Onal C, Guler OC, Yildirim BA. Prognostic use of pretreatment hematologic parameters in patients receiving definitive Chemoradiotherapy for cervical Cancer. Int J Gynecol Cancer. 2016;26:1169–75.CrossRef
23.
go back to reference Mizunuma M, Yokoyama Y, Futagami M, Aoki M, Takai Y, Mizunuma H. The pretreatment neutrophil-to-lymphocyte ratio predicts therapeutic response to radiation therapy and concurrent chemoradiation therapy in uterine cervical cancer. Int J Clin Oncol. 2015;20:989–96.CrossRef Mizunuma M, Yokoyama Y, Futagami M, Aoki M, Takai Y, Mizunuma H. The pretreatment neutrophil-to-lymphocyte ratio predicts therapeutic response to radiation therapy and concurrent chemoradiation therapy in uterine cervical cancer. Int J Clin Oncol. 2015;20:989–96.CrossRef
24.
go back to reference Kumagai S, Marumo S, Shoji T, Sakuramoto M, Hirai T, Nishimura T, et al. Prognostic impact of preoperative monocyte counts in patients with resected lung adenocarcinoma. Lung Cancer. 2014;85:457–64.CrossRef Kumagai S, Marumo S, Shoji T, Sakuramoto M, Hirai T, Nishimura T, et al. Prognostic impact of preoperative monocyte counts in patients with resected lung adenocarcinoma. Lung Cancer. 2014;85:457–64.CrossRef
25.
go back to reference Machida H, De Zoysa MY, Takiuchi T, Hom MS, Tierney KE, Matsuo K. Significance of monocyte counts at recurrence on survival outcome of women with endometrial Cancer. Int J Gynecol Cancer. 2017;27:302–10.CrossRef Machida H, De Zoysa MY, Takiuchi T, Hom MS, Tierney KE, Matsuo K. Significance of monocyte counts at recurrence on survival outcome of women with endometrial Cancer. Int J Gynecol Cancer. 2017;27:302–10.CrossRef
26.
go back to reference Matsuo K, Hom MS, Moeini A, Machida H, Takeshima N, Roman LD, et al. Significance of monocyte counts on tumor characteristics and survival outcome of women with endometrial cancer. Gynecol Oncol. 2015;138:332–8.CrossRef Matsuo K, Hom MS, Moeini A, Machida H, Takeshima N, Roman LD, et al. Significance of monocyte counts on tumor characteristics and survival outcome of women with endometrial cancer. Gynecol Oncol. 2015;138:332–8.CrossRef
27.
go back to reference Lee YY, Choi CH, Sung CO, Do IG, Huh S, Song T, et al. Prognostic value of pre-treatment circulating monocyte count in patients with cervical cancer: comparison with SCC-ag level. Gynecol Oncol. 2012;124:92–7.CrossRef Lee YY, Choi CH, Sung CO, Do IG, Huh S, Song T, et al. Prognostic value of pre-treatment circulating monocyte count in patients with cervical cancer: comparison with SCC-ag level. Gynecol Oncol. 2012;124:92–7.CrossRef
28.
go back to reference Stone RL, Nick AM, McNeish IA, Balkwill F, Han HD, Bottsford-Miller J, et al. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med. 2012;366:610–8.CrossRef Stone RL, Nick AM, McNeish IA, Balkwill F, Han HD, Bottsford-Miller J, et al. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med. 2012;366:610–8.CrossRef
29.
go back to reference Zhang X, Lv Z, Yu H, Zhu J. The clinicopathological and prognostic role of thrombocytosis in patients with cancer: a meta-analysis. Oncol Lett. 2017;13:5002–8.CrossRef Zhang X, Lv Z, Yu H, Zhu J. The clinicopathological and prognostic role of thrombocytosis in patients with cancer: a meta-analysis. Oncol Lett. 2017;13:5002–8.CrossRef
30.
go back to reference Menczer J. Preoperative elevated platelet count and thrombocytosis in gynecologic malignancies. Arch Gynecol Obstet. 2017;295:9–15.CrossRef Menczer J. Preoperative elevated platelet count and thrombocytosis in gynecologic malignancies. Arch Gynecol Obstet. 2017;295:9–15.CrossRef
31.
go back to reference Hernandez E, Lavine M, Dunton CJ, Gracely E, Parker J. Poor prognosis associated with thrombocytosis in patients with cervical Cancer. Cancer. 1992;69:2975–7.CrossRef Hernandez E, Lavine M, Dunton CJ, Gracely E, Parker J. Poor prognosis associated with thrombocytosis in patients with cervical Cancer. Cancer. 1992;69:2975–7.CrossRef
32.
go back to reference Rodriguez GC, Clarke-Pearson DL, Soper JT, Berchuck A, Synan I, Dodge RK. The negative prognostic implications of thrombocytosis in women with stage IB cervical cancer. Obstet Gynecol. 1994;83:445–8.PubMed Rodriguez GC, Clarke-Pearson DL, Soper JT, Berchuck A, Synan I, Dodge RK. The negative prognostic implications of thrombocytosis in women with stage IB cervical cancer. Obstet Gynecol. 1994;83:445–8.PubMed
33.
go back to reference De Jonge ET, Viljoen E, Lindeque BG, Amant F, Nesland JM, Holm R. The prognostic significance of p53, mdm2, c-erbB-2, cathepsin D, and thrombocytosis in stage IB cervical cancer treated by primary radical hysterectomy. Int J Gynecol Cancer. 1999;9:198–205.CrossRef De Jonge ET, Viljoen E, Lindeque BG, Amant F, Nesland JM, Holm R. The prognostic significance of p53, mdm2, c-erbB-2, cathepsin D, and thrombocytosis in stage IB cervical cancer treated by primary radical hysterectomy. Int J Gynecol Cancer. 1999;9:198–205.CrossRef
34.
go back to reference Hernandez E, Donohue KA, Anderson LL, Heller PB, Stehman FB. The significance of thrombocytosis in patients with locally advanced cervical carcinoma: a gynecologic oncology group study. Gynecol Oncol. 2000;78:137–42.CrossRef Hernandez E, Donohue KA, Anderson LL, Heller PB, Stehman FB. The significance of thrombocytosis in patients with locally advanced cervical carcinoma: a gynecologic oncology group study. Gynecol Oncol. 2000;78:137–42.CrossRef
35.
go back to reference Zhao K, Deng H, Qin Y, Liao W, Liang W. Prognostic significance of pretreatment plasma fibrinogen and platelet levels in patients with early-stage cervical cancer. Gynecol Obstet Investig. 2015;79:25–33.CrossRef Zhao K, Deng H, Qin Y, Liao W, Liang W. Prognostic significance of pretreatment plasma fibrinogen and platelet levels in patients with early-stage cervical cancer. Gynecol Obstet Investig. 2015;79:25–33.CrossRef
36.
go back to reference Allensworth SK, Langstraat CL, Martin JR, Lemens MA, McGree ME, Weaver AL, et al. Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer. Gynecol Oncol. 2013;130:499–504.CrossRef Allensworth SK, Langstraat CL, Martin JR, Lemens MA, McGree ME, Weaver AL, et al. Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer. Gynecol Oncol. 2013;130:499–504.CrossRef
37.
go back to reference Kizer NT, Hatem H, Nugent EK, Zhou G, Moore K, Heller P, et al. Chemotherapy response rates among patients with endometrial Cancer who have elevated serum platelets. Int J Gynecol Cancer. 2015;25:1015–22.CrossRef Kizer NT, Hatem H, Nugent EK, Zhou G, Moore K, Heller P, et al. Chemotherapy response rates among patients with endometrial Cancer who have elevated serum platelets. Int J Gynecol Cancer. 2015;25:1015–22.CrossRef
Metadata
Title
Neutrophil-lymphocyte ratio as a predictor of oncologic outcomes in stage IVB, persistent, or recurrent cervical cancer patients treated by chemotherapy
Authors
Pornprom Ittiamornlert
Irene Ruengkhachorn
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5269-1

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