Prognostic value of neutrophil-to-lymphocyte ratio in advanced cancer patients receiving immunotherapy

Viñal, David; Gutiérrez-Sainz, Laura; Martı́nez, Daniel; Pedregosa, Javier Pérez; Villamayor, J.; Ostios, L.; Sanchez-Cabrero, Darío; Higuera, Oliver; Pinto, Álvaro; Rodrı́guez-Salas, Nuria; Espinosa, Enrique; Castro, Javier de; Feliú, Jaime

doi:10.1007/s12094-020-02509-1

Cited by 17 publications

(20 citation statements)

References 29 publications

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“…In fact, recently published studies about immunotherapy and the dynamics of NLR suggested the special role of early change in NLR in predicting the efficacy of immunotherapy and final survival outcomes [ 8 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. Specifically, they observed the following three points: (1) The trend in NLR (upward or downward) may be associated with the outcome of tumor response after ICI treatment.…”

Section: Introductionmentioning

confidence: 99%

Focus on the Dynamics of Neutrophil-to-Lymphocyte Ratio in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis and Systematic Review

Guo

Xiang

Wan

et al. 2022

Cancers

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Background: A number of studies have reported an association between the dynamics of neutrophil-to-lymphocyte ratio (NLR) and clinical efficacy in patients treated with immune checkpoint inhibitors (ICIs), but there is still a lack of a meta-analysis or systematic review. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched until September 2022 for studies reporting on the association between the change in NLR after ICI treatment and clinical outcomes. Outcome measures of interest included: change in NLR before and after treatment, overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: A total of 4154 patients in 38 studies were included. The pooled percentage of patients with increased NLR was 49.7% (95CI%: 43.7–55.8%). Six studies discussing the change in NLR in patients with different tumor responses all showed that the NLR level in patients without response to immunotherapy may increase after ICI treatment. The upward trend in NLR was associated with shorter OS (pooled HR: 2.05, 95%CI: 1.79–2.35, p < 0.001) and PFS (pooled HR: 1.89, 95%CI: 1.66–2.14, p < 0.001) and higher ORR (pooled OR: 0.27, 95%CI: 0.19–0.39, p < 0.001), and downward trend in NLR was associated with longer OS (pooled HR: 0.49, 95%CI: 0.42–0.58, p < 0.001) and PFS (pooled HR: 0.55, 95%CI: 0.48–0.63, p < 0.001) and lower ORR (pooled OR: 3.26, 95%CI: 1.92–5.53, p < 0.001). In addition, post-treatment high NLR was associated with more impaired survival than baseline high NLR (pooled HR of baseline high NLR: 1.82, 95%CI: 1.52–2.18; pooled HR of post-treatment high NLR: 2.93, 95%CI: 2.26–3.81), but the NLR at different time points may have a similar predictive effect on PFS (pooled HR of baseline high NLR: 1.68, 95%CI: 1.44–1.97; pooled HR of post-treatment high NLR: 2.00, 95%CI: 1.54–2.59). Conclusions: The NLR level of tumor patients after ICI treatment is stable overall, but the NLR level in patients without response to immunotherapy may increase after ICI treatment. Patients with an upward trend in NLR after ICI treatment were associated with worse clinical outcomes; meanwhile, the downward trend in NLR was associated with better clinical outcomes. Post-treatment high NLR was associated with more impaired survival than baseline high NLR.

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Section: Introductionmentioning

confidence: 99%

Focus on the Dynamics of Neutrophil-to-Lymphocyte Ratio in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis and Systematic Review

Guo

Xiang

Wan

et al. 2022

Cancers

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“…Viñal et al assessed the NLR at baseline and before the second dose of immunotherapy, but also the NLR trend in order to predict the response to treatment in advanced cancer patients treated with ICIs. They reported that the NLR at all three time points was a prognostic factor for survival [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Blood Parameters as Biomarkers for Response to Immune Checkpoint Inhibition in Metastatic Melanoma Patients

et al. 2022

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Objectives: We aimed to investigate whether inflammatory parameters in peripheral blood at baseline and during the first six months of treatment could predict the short- and long-term outcomes of metastatic melanoma patients treated with immune checkpoint inhibitors (ICIs). Methods: This single-center retrospective study considered patients with metastatic melanoma treated with either single or dual checkpoint inhibition. Blood sample tests were scheduled together with 18F-2-fluor-2-desoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans at baseline and at three and six months after initiation of ICI treatment. The short-term response to ICIs was assessed using FDG-PET/CT scans. The long-term response to ICIs was assessed using the overall survival OS and progression-free survival PFS as endpoints. Results: A total of 100 patients with metastatic melanoma were included (female, n = 31; male, n = 69). The median age was 68 years (interquartile range (IQR): 53–74 years). A total of 82% of the cohort displayed a disease control (DC), while 18% presented a progressive disease (PD) after six months of ICIs. Patients with DC after six months of ICIs showed a lower median of the neutrophils-to-lymphocytes ratio (NLR) toward patients with PD, with no significant prediction power of NLR neither in the short nor in the long term. The count of neutrophils at the baseline time point (TP 0) (p = 0.037) and erythrocytes three months after treatment start (TP 1) (p = 0.010) were strong predictive parameters of a DC six months after treatment start. Erythrocytes (p < 0.001) and lymphocytes (p = 0.021) were strong biomarkers predictive of a favorable OS. Erythrocytes (p = 0.013) and lymphocytes (p = 0.017) also showed a significant prediction power for a favorable PFS. Conclusions: Inflammatory blood parameters predicted the short- and long-term response to ICIs with a strong predictive power. Our results suggested the validation of inflammatory blood parameters as biomarkers that predict immunotherapies’ efficacity in metastatic melanoma patients. However, confounding factors that interfere with myelopoiesis should also be taken into consideration.

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“…Decades of research describe an elevation in circulating neutrophils of patients with cancer, with an elevated NLR being associated with poorer survival outcomes both before and after treatment. 71 , 72 Indeed, an elevation in NLR is associated with weight loss and cachexia in patients with advanced colon, lung, and prostate cancer. 43 Despite the abundance of associative data concerning elevated NLR and patient outcomes, the influence of this immunologic shift during cachexia remains incompletely understood, ultimately highlighting the need for pre‐clinical cachexia models that accurately reflect this immunologic shift for future mechanistic studies.…”

Section: Discussionmentioning

confidence: 99%

Physiologic and molecular characterization of a novel murine model of metastatic head and neck cancer cachexia

Olson

Norgard

Levasseur

et al. 2021

J cachexia sarcopenia muscle

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Background Cancer cachexia is a metabolic disorder characterized by the progressive loss of fat and lean mass that results in significant wasting, ultimately leading to reduced quality of life and increased mortality. Effective therapies for cachexia are lacking, potentially owing to the mismatch in clinically relevant models of cachexia. Specifically, cachexia observed in a clinical setting is commonly associated with advanced or late-stage cancers that are metastatic, yet pre-clinical metastatic models of cachexia are limited. Furthermore, the prevalence of cachexia in head and neck cancer patients is high, yet few pre-clinical models of head and neck cancer cachexia exist. In addition to these shortcomings, cachexia is also heterogeneous among any given cancer, whereas patients with similar disease burden may experience significantly different degrees of cachexia symptoms. In order to address these issues, we characterize a metastatic model of human papilloma virus (HPV) positive head and neck squamous cell carcinoma that recapitulates the cardinal clinical and molecular features of cancer cachexia. Methods Male and female C57BL/6 mice were implanted subcutaneously with oropharyngeal squamous cell carcinoma cells stably transformed with HPV16 E6 and E7 together with hRas and luciferase (mEERL) that metastasizes to the lungs (MLM). We then robustly characterize the physiologic, behavioural, and molecular signatures during tumour development in two MLM subclones. Results Mice injected with MLM tumour cells rapidly developed primary tumours and eventual metastatic lesions to the lungs. MLM3, but not MLM5, engrafted mice progressively lost fat and lean mass during tumour development despite the absence of anorexia (P < 0.05). Behaviourally, MLM3-implanted mice displayed decreased locomotor behaviours and impaired nest building (P < 0.05). Muscle catabolism programmes associated with cachexia, including E3 ubiquitin ligase and autophagy up-regulation, along with progressive adipose wasting and accompanying browning gene signatures, were observed. Tumour progression also corresponded with hypothalamic and peripheral organ inflammation, as well as an elevation in neutrophil-to-lymphocyte ratio (P < 0.05). Finally, we characterize the fat and lean mass sparing effects of voluntary wheel running on MLM3 cachexia (P < 0.05). Conclusions This syngeneic MLM3 allograft model of metastatic cancer cachexia is reliable, consistent, and readily recapitulates key clinical and molecular features and heterogeneity of cancer cachexia. Because few metastatic models of cachexia exist-even though cachexia often accompanies metastatic progression-we believe this model more accurately captures cancer cachexia observed in a clinical setting and thus is well suited for future mechanistic studies and pre-clinical therapy development for this crippling metabolic disorder.

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Prognostic value of neutrophil-to-lymphocyte ratio in advanced cancer patients receiving immunotherapy

Cited by 17 publications

References 29 publications

Focus on the Dynamics of Neutrophil-to-Lymphocyte Ratio in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis and Systematic Review

Focus on the Dynamics of Neutrophil-to-Lymphocyte Ratio in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis and Systematic Review

Inflammatory Blood Parameters as Biomarkers for Response to Immune Checkpoint Inhibition in Metastatic Melanoma Patients

Physiologic and molecular characterization of a novel murine model of metastatic head and neck cancer cachexia

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