Pretreatment Neutrophil-to-Lymphocyte Ratio and Lactate Dehydrogenase Predict the Prognosis of Metastatic Cervical Cancer Treated with Combination Immunotherapy

Cheng, Mingxia; Li, Guiling; Liu, Zhongan; Yang, Qin; Jiang, Yao

doi:https://doi.org/10.1155/2022/1828473

Journal of Oncology

On this page

Abstract Introduction Materials and Methods Results Discussion Conclusions Abbreviations Data Availability Conflicts of Interest Authors’ Contributions Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2022 | Article ID 1828473 | https://doi.org/10.1155/2022/1828473

Pretreatment Neutrophil-to-Lymphocyte Ratio and Lactate Dehydrogenase Predict the Prognosis of Metastatic Cervical Cancer Treated with Combination Immunotherapy

Mingxia Cheng,¹Guiling Li,¹Zhongan Liu,¹Qin Yang,¹and Yao Jiang¹

Academic Editor: Jie Mei

Received07 Jul 2022

Accepted29 Sept 2022

Published18 Oct 2022

Abstract

Background. Immune checkpoint inhibitors have considerably changed the treatment paradigm for metastatic cervical cancer; nonetheless, only a proportion of patients achieve a durable response. Therefore, exploring the predictive biomarkers of immunotherapy response is of crucial importance. This study aimed to evaluate the predictive and prognostic value of hematological parameters in patients with metastatic cervical cancer treated with combination immunotherapy. Methods. Clinical data of patients with metastatic cervical cancer treated with combination immunotherapy between June 2019 and April 2021 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the cut-off values of continuous variables, and binary logistic analysis was conducted to compare the treatment response between groups. The Kaplan–Meier method was applied for survival analysis. A Cox proportional hazards regression model was used to identify factors associated with progression-free survival (PFS). Results. Seventy patients were included in this study. The cut-off values for the neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) were 5.33 and 195.00 U/L, respectively. High pretreatment NLR (≥5.33) was correlated with decreased objective response rate (53.19% vs. 78.26%, ). The survival analysis revealed that high pretreatment NLR (hazard ratio , 95% confidence interval [CI]: 1.151–5.009, ) and LDH level (, 95% CI: 1.029–3.835, ) were independent prognostic factors associated with short PFS. Conclusions. Our study suggested that high pretreatment NLR and LDH values were independently correlated with poor survival in patients with metastatic cervical cancer treated with combination immunotherapy. Pretreatment NLR and LDH values could serve as potential biomarkers that may aid in the selection of patients who would benefit from combination immunotherapy. Further prospective studies investigating the prognostic value of NLR and LDH are warranted. Trial registration number: UHCT22008.

1. Introduction

Cervical cancer ranks as the fourth leading cause of morbidity and mortality in women globally, with a 5-year survival rate of 18% in patients with metastatic disease [1, 2]. Recently, immune checkpoint inhibitors (ICIs) have considerably improved the treatment landscape for metastatic cervical cancer. PD-1 inhibitors, pembrolizumab and nivolumab, have been approved for second-line or subsequent therapy in metastatic cervical cancer with a modest response rate of approximately 15% [3, 4]. More recently, the combination of pembrolizumab and chemotherapy, plus or minus bevacizumab, has been approved for patients with metastatic cervical cancer [5]. However, only a proportion of patients achieve a durable response. Therefore, there is an urgent need to explore predictive biomarkers for immunotherapy efficacy.

Several predictive biomarkers for immunotherapy have been investigated in cervical cancer. Among them, PD-L1 expression, tumor mutational burden (TMB), and microsatellite instability (MSI) have been approved for selecting patients who would benefit from single-agent pembrolizumab [4, 6, 7]. However, the predictive role of these biomarkers in the context of combination immunotherapy is far from being clarified [8]. In the CHECKMATE-358 and CLAP studies, clinical efficacy was observed in patients treated with combination immunotherapy, irrespective of PD-L1 status [9, 10]. The predictive value of TMB and MSI for immunotherapy has also been reported [11, 12]. However, only 25% and 1.9% of patients with cervical cancer exhibit high TMB (≥10 mutations/Mb) or MSI, respectively [13]. Additionally, tumor tissue specimens are sometimes difficult to obtain, thus limiting the use of PD-L1, TMB, and MSI tests [14].

Recently, hematological parameters have been studied and exhibited potential for predicting immunotherapy efficacy. Routine blood tests have the advantage of being easily available and cost-effective. Increased neutrophil-to-lymphocyte ratio (NLR) or lactate dehydrogenase (LDH) predicted poor prognosis in patients treated with immunotherapy in various cancers [15–17]. In cervical cancer, elevated NLR and LDH levels have been reported to be correlated with adverse clinical outcomes [18–21]. However, previous studies mainly focused on the correlation between hematological parameters and clinical outcomes in patients with cervical cancer treated with conventional therapy, including surgery, chemotherapy, and radiotherapy [22–26]. The predictive value of hematological parameters in patients with cervical cancer treated with combination immunotherapy remains unclarified. Thus, this study was conducted to investigate the predictive and prognostic value of hematological parameters in patients with metastatic cervical cancer who underwent combination immunotherapy. The findings of this study may aid in identifying patients who would benefit most from combination immunotherapy.

2. Materials and Methods

2.1. Patients

Clinical data of patients with metastatic cervical cancer who underwent combination immunotherapy at the Cancer Center in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Wuhan, China) between June 2019 and April 2021 were reviewed. The inclusion criteria were as follows: (1) recurrent or metastatic cervical cancer, (2) treatment involving at least two cycles of combination immunotherapy, (3) at least one measurable lesion at baseline according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients who underwent single-agent immunotherapy, withdrew immunotherapy because of intolerable toxicities, lacked follow-up data, or received drugs that improved blood cell function within 2 weeks from the first dose of immunotherapy were excluded from the analysis.

Baseline clinicopathological data, including age, histology, metastatic sites, lines of prior systemic treatment, and hematological parameters, were retrieved from medical records. The NLR refers to the absolute neutrophil count divided by the lymphocyte count measured in peripheral blood, whereas the platelet-to-lymphocyte ratio (PLR) refers to the platelet count divided by the lymphocyte count. The monocyte-to-lymphocyte ratio (MLR) refers to the monocyte count divided by the lymphocyte count.

This retrospective study was conducted in accordance with the principles embodied in the 1964 Declaration of Helsinki and was performed with the patients’ understanding and consent. Furthermore, this study was approved by the Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (approval no.: 20220023).

2.2. Follow-Up and Evaluation

All patients were regularly followed up until their death or the cut-off date for this study (October 20, 2021). Baseline tumor assessment was performed before immunotherapy initiation. Subsequently, the patients underwent imaging examination every 8–12 weeks. Clinical responses (complete response, partial response, stable disease, and progressive disease) were evaluated using the RECIST criteria version 1.1. The objective response rate (ORR) refers to the percentage of patients who achieved complete and partial responses. The disease control rate refers to the percentage of patients who achieved complete response, partial response, and stable disease. Progression-free survival (PFS) refers to the duration from the date of immunotherapy initiation to disease progression or until the last follow-up visit.

2.3. Statistical Analyses

Statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). For descriptive analysis, continuous and categorical variables were expressed as medians (range) and percentages, respectively. Receiver operating characteristic (ROC) curve analysis was performed to identify the cut-off values of continuous variables. The median value was regarded as the cut-off value if the area under the ROC curve was less than 0.50. Binary logistic analysis was conducted to analyze the correlation between clinical response and baseline characteristics. The Kaplan–Meier method was applied for survival analysis. A Cox proportional hazards regression model was used for univariate and multivariate analyses. A two-sided was considered statistically significant.

3. Results

3.1. Clinical Characteristics and Treatment

Seventy patients with metastatic cervical cancer treated with combination immunotherapy between June 2019 and April 2021 were included in this study. The baseline demographic characteristics and hematological parameters of patients are presented in Table 1. The median patient age was 51 (29–77) years, and 54 (77.14%) patients had squamous cell carcinoma. The majority of patients (80.00%) previously received radiotherapy. Of these patients, 27 (38.57%) had only local recurrence, and 24 (34.29%) received two or more lines of systemic treatment before immunotherapy initiation. Of all patients, 21 (30.00%) were treated with a combination of PD-1 inhibitor plus chemotherapy, whereas 49 (70.00%) were treated with a combination of PD-1 inhibitor plus chemotherapy and antiangiogenic agents.

3.2. Relationship between Hematological Parameters and Clinical Response

Complete response, partial response, and stable disease were observed in 8 (11.43%), 35 (50.00%), and 13 (18.57%) patients, respectively. The ORR was 61.43%. The ROC curve analysis indicated that the cut-off values for NLR and LDH were 5.33 and 195.00 U/L, respectively. Patients with high NLR (≥5.33) showed lower ORR (53.19% vs. 78.26%, ). The treatment responses based on baseline clinical characteristics are shown in Table 2. The PLR, MLR, and albumin-to-globulin ratio, as well as the levels of squamous cell carcinoma-associated antigen, LDH, and alkaline phosphatase, were not significantly associated with the clinical response.

3.3. Prognostic Factors for PFS

The median PFS of all patients was 8.0 months (95% confidence interval [CI]: 3.274–12.726). The univariate analysis showed that histology, NLR, and LDH level were significant prognostic factors for PFS. Patients with adenocarcinoma had shorter PFS than those with squamous carcinoma (hazard ratio , ). Furthermore, patients with high NLR (≥5.33) had shorter PFS (,). Similarly, a high LDH (≥195.00 U/L) level was correlated with shorter PFS (, ). The multivariate analysis revealed that histology of adenocarcinoma (, 95% CI: 1.652–6.422, ), high NLR (, 95% CI: 1.151–5.009, ), and high LDH level (, 95% CI: 1.029–3.835, ) remained as independent predictive factors for inferior PFS (Table 3). The Kaplan–Meier curve for the PFS of patients grouped according to histology as well as pretreatment NLR and LDH values are presented in Figure 1.

4. Discussion

An increasing number of patients with metastatic cervical cancer are being treated with immunotherapy in clinical practice; however, only a proportion of patients achieve a durable response. Therefore, an investigation of the predictive biomarkers of immunotherapy response is important. Recently, several studies have shown that hematological parameters can predict immunotherapy response in various cancers [27–29]. Nevertheless, information on the prognostic value of routine blood parameters in cervical cancer after immunotherapy is scarce. In this study, we assessed the baseline hematological parameters in patients with metastatic cervical cancer who underwent combination immunotherapy and confirmed that high pretreatment NLR and LDH values were associated with inferior PFS.

Neutrophils, which play essential roles in tumor development and progression, can be mechanistically recruited to the tumor microenvironment, secrete proliferative factors, and suppress T-lymphocyte activity, thereby promoting tumor angiogenesis, invasion, and metastasis [30–33]. The NLR is a systemic inflammation indicator of the balance between antitumor immune response and protumor inflammation and is an independent prognostic biomarker in various malignancies [16, 19, 34, 35]. Lima et al. reported an adverse association between NLR and prognosis in cervical cancer [36], whereas Zhang et al. showed the correlation of preoperative NLR with unfavorable histopathological features and prognosis in patients with cervical cancer who underwent surgery [24]. Additionally, pretreatment NLR could be a prognostic factor after chemotherapy and radiotherapy for cervical cancer [19, 22, 37]. More recently, the adverse association between NLR and prognosis in patients treated with immunotherapy has been reported. Dharmapuri et al. reported that both pretreatment and posttreatment was correlated with inferior overall survival (OS) in patients with hepatocellular carcinoma after immunotherapy [15]. In a cohort comprising 175 patients with non-small-cell lung cancer (NSCLC) treated with nivolumab, pretreatment was predictive of poor PFS and OS [38]. Nevertheless, the predictive role of NLR in cervical cancer treated with combination immunotherapy has not been investigated. The results of our study indicated that pretreatment was significantly associated with worse ORR and was independently predictive of inferior PFS in patients with metastatic cervical cancer after combination immunotherapy. The cut-off value for NLR was similar to the value reported in the aforementioned studies.

LDH is a key metabolic enzyme involved in the glycolytic pathway, which converts pyruvate to lactate, thereby causing a hypoxia-inducible factor 1a cascade, establishing a hypoxic tumor microenvironment and promoting tumor angiogenesis and aggressiveness. Elevated LDH level correlates with high tumor burden and poor survival in various malignancies [39–41]. Li et al. observed that the serum LDH level was elevated in most patients with cervical cancer and was strongly correlated with adverse outcomes [23]. Wang et al. revealed that high preradiotherapy LDH level was associated with poor OS in patients with cervical cancer who underwent chemoradiotherapy [18]. An inverse correlation between baseline LDH level and survival outcomes has recently been reported in patients treated with immunotherapy [42, 43]. A single-center retrospective study that included 366 patients with NSCLC who received ICI monotherapy had confirmed that a low LDH level indicated superior OS [44]. Another cohort study involving 153 patients with solid tumors treated with ICI monotherapy or combination therapy showed that elevated LDH level was associated with poor prognosis, irrespective of tumor types [17]. However, the predictive role of LDH after combination immunotherapy in cervical cancer remains unclear. In this study, we showed that baseline was correlated with inferior PFS in patients with cervical cancer treated with combination immunotherapy. Notably, no consensus regarding the cut-off value for the LDH level has been reached in previous studies. A meta-analysis showed the correlation between high LDH level and inferior survival in several malignancies, and there was no correlation between the LDH cut-off value and the reported hazard risk for OS [45].

To our knowledge, this study is the first to explore the correlation between hematological parameters and combination immunotherapy efficacy in patients with cervical cancer. Our analysis demonstrated that high pretreatment NLR and LDH values predicted poor prognosis in patients with metastatic cervical cancer who underwent combination immunotherapy. The findings of our study may aid in the early identification of patients with metastatic cervical cancer who would benefit from combination immunotherapy.

This study had some limitations. First, it is a retrospective study with a relatively small number of patients, which might have led to selection bias. Second, other inflammation-related peripheral blood indicators, such as C-reactive protein, were not analyzed in this study because only a proportion of patients were tested for it. Therefore, further investigations involving other inflammation markers derived from peripheral blood are required to determine their prognostic significance. Finally, the dynamic change in hematological parameters, which may reflect the dynamic change in the balance between cancer-associated inflammation and host immune response, should be investigated. Considering these limitations, well-designed, multicenter, prospective studies are warranted.

5. Conclusions

Our study indicated that high baseline NLR and LDH values were correlated with poor survival in patients with metastatic cervical cancer who underwent combination immunotherapy. Pretreatment NLR and LDH values could serve as potential biomarkers that may aid in the early identification of patients who would benefit from combination immunotherapy. Further prospective studies are necessary to validate the clinical application of our findings.

Abbreviations

CI:	Confidence interval
HR:	Hazard ratio
ICI:	Immune checkpoint inhibitor
LDH:	Lactate dehydrogenase
MLR:	Monocyte-to-lymphocyte ratio
MSI:	Microsatellite instability
NLR:	Neutrophil-to-lymphocyte ratio
NSCLC:	Non-small-cell lung cancer
ORR:	Objective response rate
OS:	Overall survival
PFS:	Progression-free survival
PLR:	Platelet-to-lymphocyte ratio
RECIST:	Response evaluation criteria in solid tumors
ROC:	Receiver operating characteristic
TMB:	Tumor mutational burden.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that there is no conflict of interest regarding the publication of this article.

Authors’ Contributions

Mingxia Cheng and Guiling Li contributed equally to this work.

Acknowledgments

This work was supported by the National Natural Science Foundation of China [grant number 81902854].

References

H. Sung, J. Ferlay, R. L. Siegel et al., “Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA: a Cancer Journal for Clinicians, vol. 71, no. 3, pp. 209–249, 2021.
View at: Publisher Site | Google Scholar
M. Liontos, A. Kyriazoglou, I. Dimitriadis, M. A. Dimopoulos, and A. Bamias, “Systemic therapy in cervical cancer: 30 years in review,” Critical Reviews in Oncology/Hematology, vol. 137, pp. 9–17, 2019.
View at: Publisher Site | Google Scholar
R. W. Naumann, A. Hollebecque, T. Meyer et al., “Safety and efficacy of nivolumab monotherapy in recurrent or metastatic cervical, vaginal, or vulvar carcinoma: results from the phase I/II CheckMate 358 trial,” Journal of Clinical Oncology, vol. 37, no. 31, pp. 2825–2834, 2019.
View at: Publisher Site | Google Scholar
H. C. Chung, W. Ros, J. P. Delord et al., “Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study,” Journal of Clinical Oncology, vol. 37, no. 17, pp. 1470–1478, 2019.
View at: Publisher Site | Google Scholar
N. Colombo, C. Dubot, D. Lorusso et al., “Pembrolizumab for persistent, recurrent, or metastatic cervical cancer,” The New England Journal of Medicine, vol. 385, no. 20, pp. 1856–1867, 2021.
View at: Publisher Site | Google Scholar
D. T. Le, J. N. Uram, H. Wang et al., “PD-1 blockade in tumors with mismatch-repair deficiency,” The New England Journal of Medicine, vol. 372, no. 26, pp. 2509–2520, 2015.
View at: Publisher Site | Google Scholar
A. Marabelle, M. Fakih, J. Lopez et al., “Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study,” The Lancet. Oncology, vol. 21, no. 10, pp. 1353–1365, 2020.
View at: Publisher Site | Google Scholar
O. Klein, D. Kee, B. Markman et al., “Evaluation of TMB as a predictive biomarker in patients with solid cancers treated with anti-PD-1/CTLA-4 combination immunotherapy,” Cancer Cell, vol. 39, no. 5, pp. 592-593, 2021.
View at: Publisher Site | Google Scholar
R. W. Naumann, A. Oaknin, T. Meyer et al., “Efficacy and safety of nivolumab (Nivo) + ipilimumab (Ipi) in patients (pts) with recurrent/metastatic (R/M) cervical cancer: results from CheckMate 358,” Annals of Oncology, vol. 30, Supplement 5, pp. v898–v899, 2019.
View at: Publisher Site | Google Scholar
C. Lan, J. Shen, Y. Wang et al., “Camrelizumab plus apatinib in patients with advanced cervical cancer (CLAP): a multicenter, open-label, single-arm, phase II trial,” Journal of Clinical Oncology, vol. 38, no. 34, pp. 4095–4106, 2020.
View at: Publisher Site | Google Scholar
A. M. Goodman, S. Kato, L. Bazhenova et al., “Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers,” Molecular Cancer Therapeutics, vol. 16, no. 11, pp. 2598–2608, 2017.
View at: Publisher Site | Google Scholar
P. Zhao, L. Li, X. Jiang, and Q. Li, “Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy,” Journal of Hematology & Oncology, vol. 12, no. 1, p. 54, 2019.
View at: Publisher Site | Google Scholar
R. Huang, J. Haberberger, K. Murugesan et al., “Clinicopathologic and genomic characterization of PD-L1-positive uterine cervical carcinoma,” Modern pathology: an official journal of the United States and Canadian academy of pathology Inc, vol. 34, pp. 1425–1433, 2021.
View at: Google Scholar
M. Nishino, N. H. Ramaiya, H. Hatabu, and F. S. Hodi, “Monitoring immune-checkpoint blockade: response evaluation and biomarker development,” Nature Reviews. Clinical Oncology, vol. 14, no. 11, pp. 655–668, 2017.
View at: Publisher Site | Google Scholar
S. Dharmapuri, U. Özbek, J. Y. Lin et al., “Predictive value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in advanced hepatocellular carcinoma patients treated with anti–PD-1 therapy,” Cancer Medicine, vol. 9, no. 14, pp. 4962–4970, 2020.
View at: Publisher Site | Google Scholar
R. Kumar, E. Geuna, V. Michalarea et al., “The neutrophil-lymphocyte ratio and its utilisation for the management of cancer patients in early clinical trials,” British Journal of Cancer, vol. 112, no. 7, pp. 1157–1165, 2015.
View at: Publisher Site | Google Scholar
C. Criscitiello, A. Marra, S. Morganti et al., “Pretreatment blood parameters predict efficacy from immunotherapy agents in early phase clinical trials,” The Oncologist, vol. 25, no. 11, pp. e1732–e1742, 2020.
View at: Publisher Site | Google Scholar
H. Wang, M. S. Wang, Y. H. Zhou, J. P. Shi, and W. J. Wang, “Prognostic values of LDH and CRP in cervical cancer,” Oncotargets and Therapy, vol. 13, pp. 1255–1263, 2020.
View at: Publisher Site | Google Scholar
J. L. Ethier, D. N. Desautels, A. J. Templeton, A. Oza, E. Amir, and S. Lheureux, “Is the neutrophil-to-lymphocyte ratio prognostic of survival outcomes in gynecologic cancers? A systematic review and meta-analysis,” Gynecologic Oncology, vol. 145, no. 3, pp. 584–594, 2017.
View at: Publisher Site | Google Scholar
P. Zou, E. Yang, and Z. Li, “Neutrophil-to-lymphocyte ratio is an independent predictor for survival outcomes in cervical cancer: a systematic review and meta-analysis,” Scientific Reports, vol. 10, no. 1, article 21917, 2020.
View at: Publisher Site | Google Scholar
Y. Ye, M. Chen, X. Chen, J. Xiao, L. Liao, and F. Lin, “Clinical significance and prognostic value of lactate dehydrogenase expression in cervical cancer,” Genetic Testing and Molecular Biomarkers, vol. 26, no. 3, pp. 107–117, 2022.
View at: Publisher Site | Google Scholar
H. Trinh, S. P. Dzul, J. Hyder et al., “Prognostic value of changes in neutrophil-to-lymphocyte ratio (NLR), platelet- to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) for patients with cervical cancer undergoing definitive chemoradiotherapy (dCRT),” Clinica Chimica Acta, vol. 510, pp. 711–716, 2020.
View at: Publisher Site | Google Scholar
J. Li, M. F. Wu, H. W. Lu, Q. Chen, Z. Q. Lin, and L. J. Wang, “Pretreatment serum lactate dehydrogenase is an independent prognostic factor for patients receiving neoadjuvant chemotherapy for locally advanced cervical cancer,” Cancer Medicine, vol. 5, no. 8, pp. 1863–1872, 2016.
View at: Publisher Site | Google Scholar
Y. Zhang, L. Wang, Y. Liu et al., “Preoperative neutrophil-lymphocyte ratio before platelet-lymphocyte ratio predicts clinical outcome in patients with cervical cancer treated with initial radical surgery,” International Journal of Gynecological Cancer, vol. 24, no. 7, pp. 1319–1325, 2014.
View at: Publisher Site | Google Scholar
M. Mizunuma, Y. Yokoyama, M. Futagami, M. Aoki, Y. Takai, and H. Mizunuma, “The pretreatment neutrophil-to-lymphocyte ratio predicts therapeutic response to radiation therapy and concurrent chemoradiation therapy in uterine cervical cancer,” International Journal of Clinical Oncology, vol. 20, no. 5, pp. 989–996, 2015.
View at: Publisher Site | Google Scholar
A. Taguchi, Y. Nakajima, A. Furusawa et al., “High neutrophil-to-lymphocyte ratio is a predictor of short-term survival for patients with recurrent cervical cancer after radiation-based therapy,” The Journal of Obstetrics and Gynaecology Research, vol. 47, no. 5, pp. 1862–1870, 2021.
View at: Publisher Site | Google Scholar
A. Muhammed, C. Fulgenzi, S. Dharmapuri et al., “The systemic inflammatory response identifies patients with adverse clinical outcome from immunotherapy in hepatocellular carcinoma,” Cancers (Basel), vol. 14, no. 1, 2022.
View at: Google Scholar
L. Mezquita, E. Auclin, R. Ferrara et al., “Association of the lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced non-small cell lung cancer,” JAMA Oncology, vol. 4, no. 3, pp. 351–357, 2018.
View at: Publisher Site | Google Scholar
G. Fornarini, S. E. Rebuzzi, G. L. Banna et al., “Immune-inflammatory biomarkers as prognostic factors for immunotherapy in pretreated advanced urinary tract cancer patients: an analysis of the Italian SAUL cohort,” ESMO Open, vol. 6, no. 3, article 100118, 2021.
View at: Publisher Site | Google Scholar
E. Bonavita, M. R. Galdiero, S. Jaillon, and A. Mantovani, “Phagocytes as corrupted policemen in cancer-related inflammation,” Advances in Cancer Research, vol. 128, pp. 141–171, 2015.
View at: Publisher Site | Google Scholar
Y. H. Kusumanto, W. A. Dam, G. A. Hospers, C. Meijer, and N. H. Mulder, “Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor,” Angiogenesis, vol. 6, no. 4, pp. 283–287, 2003.
View at: Publisher Site | Google Scholar
E. Uribe-Querol and C. Rosales, “Neutrophils in cancer: two sides of the same coin,” Journal of Immunology Research, vol. 2015, Article ID 983698, 21 pages, 2015.
View at: Publisher Site | Google Scholar
S. Xiong, L. Dong, and L. Cheng, “Neutrophils in cancer carcinogenesis and metastasis,” Journal of Hematology & Oncology, vol. 14, no. 1, p. 173, 2021.
View at: Publisher Site | Google Scholar
R. Singh, M. K. Mishra, and H. Aggarwal, “Inflammation, immunity, and cancer,” Mediators of Inflammation, vol. 2017, Article ID 6027305, 1 page, 2017.
View at: Publisher Site | Google Scholar
K. Moses and S. Brandau, “Human neutrophils: their role in cancer and relation to myeloid-derived suppressor cells,” Seminars in Immunology, vol. 28, no. 2, pp. 187–196, 2016.
View at: Publisher Site | Google Scholar
P. Lima, P. Mantoani, E. Murta, and R. S. Nomelini, “Laboratory parameters as predictors of prognosis in uterine cervical neoplasia,” European Journal of Obstetrics, Gynecology, and Reproductive Biology, vol. 256, pp. 391–396, 2021.
View at: Publisher Site | Google Scholar
J. W. Lee and K. H. Seol, “Pretreatment neutrophil-to-lymphocyte ratio combined with platelet-to-lymphocyte ratio as a predictor of survival outcomes after definitive concurrent chemoradiotherapy for cervical cancer,” Journal of Clinical Medicine, vol. 10, no. 10, p. 2199, 2021.
View at: Publisher Site | Google Scholar
S. J. Bagley, S. Kothari, C. Aggarwal et al., “Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer,” Lung Cancer, vol. 106, pp. 1–7, 2017.
View at: Publisher Site | Google Scholar
T. Kiba, T. Ito, T. Nakashima et al., “Bortezomib and dexamethasone for multiple myeloma: higher AST and LDH levels associated with a worse prognosis on overall survival,” BMC Cancer, vol. 14, no. 1, p. 462, 2014.
View at: Publisher Site | Google Scholar
A. J. Armstrong, D. J. George, and S. Halabi, “Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin,” Journal of Clinical Oncology, vol. 30, no. 27, pp. 3402–3407, 2012.
View at: Publisher Site | Google Scholar
W. Sun, X. Zhang, X. Ding et al., “Lactate dehydrogenase B is associated with the response to neoadjuvant chemotherapy in oral squamous cell carcinoma,” PLoS One, vol. 10, no. 5, article e0125976, 2015.
View at: Publisher Site | Google Scholar
R. Lobefaro, G. Viscardi, R. Di Liello et al., “Immunotherapy in advanced non-small cell lung cancer patients with poor performance status: the role of clinical-pathological variables and inflammatory biomarkers,” Lung Cancer, vol. 152, pp. 165–173, 2021.
View at: Publisher Site | Google Scholar
G. L. Banna, R. Di Quattro, L. Malatino et al., “Neutrophil-to-lymphocyte ratio and lactate dehydrogenase as biomarkers for urothelial cancer treated with immunotherapy,” Clinical & translational oncology: official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, vol. 22, no. 11, pp. 2130–2135, 2020.
View at: Publisher Site | Google Scholar
S. Hashemi, M. F. Fransen, A. Niemeijer et al., “Surprising impact of stromal TIL's on immunotherapy efficacy in a real-world lung cancer study,” Lung cancer: journal of the International Association for the Study of Lung Cancer, vol. 153, pp. 81–89, 2021.
View at: Publisher Site | Google Scholar
J. Zhang, Y. H. Yao, B. G. Li, Q. Yang, P. Y. Zhang, and H. T. Wang, “Prognostic value of pretreatment serum lactate dehydrogenase level in patients with solid tumors: a systematic review and meta-analysis,” Scientific Reports, vol. 5, no. 1, p. 9800, 2015.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2022 Mingxia Cheng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

350

Downloads

562

Citations