Baseline Neutrophil-to-lymphocyte Ratio Research Articles

Significance of inflammatory indexes in atezolizumab monotherapy outcomes in previously treated non-small-cell lung cancer patients

Cancer immunotherapy, including atezolizumab monotherapy, is a promising alternative strategy for patients with advanced non-small-cell lung cancer (NSCLC). Several inflammatory indices have been reported as potential biomarkers regarding the effectiveness of various treatments. This study aimed to analyze the efficacy of atezolizumab monotherapy using baseline inflammatory markers in NSCLC patients. We retrospectively enrolled 81 NSCLC patients who received atezolizumab monotherapy at six different medical institutions in Japan. The Cox proportional hazards model was used to assess the impact of the clinical variables, including inflammatory indexes, on clinical outcomes. Median progression-free survival (PFS) and overall survival (OS) were 60 days and 252 days, respectively. The objective response rate was 7.4%, and the disease control rate was 54.3%. Patients with high neutrophil to lymphocyte ratio (NLR), low lymphocyte to monocyte ratio (LMR), and/or high platelet to lymphocyte ratio (PLR), at baseline, demonstrated substantially shorter PFS and OS compared to those with a low NLR, high LMR, and/or low PLR. The multivariate analysis demonstrated that a high baseline NLR was substantially associated with short PFS and short OS. Our retrospective observations suggest that inflammatory indices may be a potential negative prognostic factor of atezolizumab monotherapy outcomes in NSCLC patients.

Neutrophil to lymphocyte ratio predicts glucocorticoid resistance in polymyalgia rheumatica.

Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) correlate with disease activity in several rheumatic diseases; however, their utility in polymyalgia rheumatica (PMR) remains unclear. This study evaluated their relationship with disease activity and glucocorticoid resistance in PMR. Data for disease activity (PMR-AS) and full blood examination was obtained from a prospective observational cohort comprising newly diagnosed, steroid-naïve PMR patients treated with low-dose glucocorticoid therapy. Glucocorticoid resistance was defined as non-response to prednisolone 15mg/d or initial response followed by flare (PMR-AS≥9.35 or ∆ ≥6.6) upon weaning to 5mg/d. Univariable Bayesian linear regression analysis of the relationship between PMR-AS (baseline and mean) and NLR and PLR was performed. Predictors of glucocorticoid resistance were identified using a multivariable outcome model, with variables derived from Bayesian model selection. Of the 32 included patients, 16 (50%) fulfilled the primary outcome measure of glucocorticoid resistance. These participants were older, typically female, and had higher baseline C-reactive protein than their glucocorticoid-responsive counterparts. A statistically significant relationship was identified between PMR-AS and both NLR (odds ratio [OR] 28.1; 95% CI 1.6-54.7) and PLR (OR 40.6; 95% CI 10.1-71.4) at baseline, with PLR also found to correlate with disease activity during follow-up (OR 15.6; 95% CI 2.7-28.2). Baseline NLR proved a statistically significant predictor of glucocorticoid-resistant PMR (OR 14.01; 95% CI 1.49-278.06). Baseline NLR can predict glucocorticoid resistance in newly diagnosed PMR patients. Both NLR and PLR may be reliable biomarkers of disease activity in PMR.

Prognostic value of the early change in neutrophil-to-lymphocyte ratio in metastatic pancreatic adenocarcinoma

In metastatic pancreatic adenocarcinoma, a high neutrophil-to-lymphocyte ratio (NLR) at diagnosis is a marker of poor prognosis. The prognostic role of baseline NLR and NLR change during first-line chemotherapy were determined. We conducted a retrospective study by using data from a single-center prospective cohort and a randomized open-label, multicenter, randomized trial. Two hundred and twelve patients were analyzed. Baseline NLR>5 was an independent marker of poor prognosis for overall survival (HR=2.01, 95% CI 1.33−3.05; P=0.001) and progression-free survival (PFS; HR=1.80, 95% CI 1.23–2.65; P=0.0026). According to NLR dynamics (n=172), patients with NLR≤5 on days 1 and 15 had a significantly better prognosis than those with NLR≤5 on day 1 and NLR>5 on day 15 (HR=2.23, 95% CI 1.18–4.21; P=0.013), NLR >5 on day 1 and NLR ≤5 on day 15 (HR=3.25, 95% CI 1.86–5.68; P<0.001), and NLR>5 on days 1 and 15 (HR=3.37, 95% CI 1.93–5.90; P<0.001). Over time, bad responders (PFS <6 months) had significantly higher mean NLR than good responders (PFS>6 months; group effect: P<0.0001). Seven out of eight patients with baseline NLR>5 had circulating tumor DNA. This study confirmed the independent prognostic value of baseline NLR >5 in metastatic pancreatic cancer. The change in NLR early during chemotherapy was also a prognostic indicator in patients with NLR ≤5.

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio associations with heart and body dose and their effects on patient outcomes in locally advanced non-small cell lung cancer treated with definitive radiotherapy.

BackgroundInflammation plays a vital role in tumor growth and progression and can be affected by radiotherapy (RT) and chemotherapy. We sought to investigate the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and their associations with dosimetric factors in locally advanced non-small cell lung cancer (LA-NSCLC).MethodsIn this retrospective study, subjects consisted of 244 patients who had received definitive RT ± chemotherapy for LA-NSCLC between 2012 and 2016. Absolute lymphocyte count (ALC), NLR and PLR recorded at pretreatment, during RT and post-RT were analyzed. Multivariable analysis (MVA) was performed to correlate clinical factors and inflammatory biomarkers with progression-free survival (PFS) and overall survival (OS) using a Cox regression model. Relationships between NLR or PLR with OS and PFS were evaluated with Kaplan-Meier analysis and compared with log-rank test results. Multiple stepwise linear regression was used to assess the associations between dosimetric factors and NLR or PLR.ResultsThe median PFS and OS for all patients were 8.6 and 15.8 months, respectively. On MVA for PFS and OS, higher 1-month post-RT start NLR [hazard ratio (HR) 1.049; 95% CI: 1.018–1.080; P=0.001] or higher 1-month post-RT start PLR (HR 1.001; 95% CI: 1.000–1.002; P<0.001) was associated with inferior PFS. Higher 1-month post-RT start NLR (HR 1.040; 95% CI: 1.013–1.069; P=0.004) or PLR (HR 1.001; 95% CI: 1.001–1.002; P<0.001) was also an independent predictor of OS. ALCmin, baseline NLR and PLR were not associated with treatment outcomes. Multiple stepwise linear regression analysis confirmed that baseline NLR (P<0.001), heart V20 (P<0.001), heart V40 (P<0.001), and mean body dose (MBD) were significantly associated with 1-month post-RT start NLR. Also, baseline PLR (P<0.001) and MBD (P<0.001) were significantly associated with 1-month post-RT start PLR.ConclusionsHigher NLR and PLR during treatment were associated with worse patient outcomes, and heart dose or body dose was correlated with NLR or PLR in advanced NSCLC patients treated with definitive RT.

Prognostic value of baseline and posttreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in head and neck squamous cell carcinoma receiving chemoradiotherapy

Objective: The aim of this study was to evaluate the prognostic value of baseline and posttreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in head and neck squamous cell carcinoma (HNSCC) receiving chemoradiotherapy (CRT).&#x0D; Material and methods: Ninety-two HNSCC patients who received adjuvant or primary radiotherapy (RT) between September 2014 and December 2019 were assessed retrospectively. Surgery was performed on 24 (26.1%) patients. Eight patients (8.7%) received induction chemotherapy (CT), 63 patients (68.5%) concomitant CT and 17 (19.5%) patients received adjuvant CT.&#x0D; Results: The median follow-up time was 19 months (range 1-61 months). The median overall survival (OS) and progression-free survival (PFS) were 16 and 13 months, respectively. High baseline NLR level was found to be significantly associated with advanced T stage. Survival was significantly poor if baseline NLR cut-off was above 2.7. No significant correlation was revealed between post-RT NLR, baseline PLR and post-RT PLR and OS. Advanced T stage, presence of metastasis and high post-RT PLR were found to be significant factors that decrease PFS.&#x0D; Conclusion: High baseline NLR level in HNSCC receiving CRT/RT was strongly associated with advanced T stage and poor prognosis. However, well designed, larger studies with longer follow-up are warranted.

Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor of Disease-free Survival in Postnephrectomy High-risk Locoregional Renal Cell Carcinoma: Analysis of the S-TRAC Trial.

In the S-TRAC trial, adjuvant sunitinib improved disease-free survival (DFS) compared with placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence. This post hoc exploratory analysis investigated the neutrophil-to-lymphocyte ratio (NLR) for predictive and prognostic significance in the RCC adjuvant setting. Kaplan-Meier estimates and Cox proportional analyses were performed on baseline NLR and change from baseline at week 4 to assess their association with DFS. Univariate P values were two-sided and based on an unstratified log-rank test. 609 of 615 patients had baseline NLR values; 574 patients had baseline and week 4 values. Sunitinib-treated patients with baseline NLR <3 had longer DFS versus placebo (7.1 vs. 4.7; HR, 0.71; P = 0.02). For baseline NLR ≥3, DFS was similar regardless of treatment (sunitinib 6.8 vs. placebo not reached; HR, 1.03; P = 0.91). A ≥25% NLR decrease at week 4 was associated with longer DFS versus no change (6.8 vs. 5.3 years; HR, 0.71; P = 0.01). A greater proportion of sunitinib-treated patients had ≥25% NLR decrease at week 4 (71.2%) versus placebo (17.4%). Patients with ≥25% NLR decrease at week 4 received a higher median cumulative sunitinib dose (10,137.5 mg) versus no change (8,168.8 mg) or ≥25% increase (6,712.5 mg). In the postnephrectomy high-risk RCC patient cohort, low baseline NLR may help identify those most suitable for adjuvant sunitinib. A ≥25% NLR decrease at week 4 may be an early indicator of those most likely to tolerate treatment and derive DFS benefit.

ROC Analysis Identifies Baseline and Dynamic NLR and dNLR Cut-Offs to Predict ICI Outcome in 402 Advanced NSCLC Patients

Background: Neutrophil-to-Lymphocyte Ratio (NLR) and derived Neutrophils-to-(Leukocytes minus neutrophils) Ratio (dNLR) have been proposed as possible biomarkers of response to immune checkpoint inhibitors (ICI). However, in non-small cell lung cancer (NSCLC) studies, various NLR and/or dNLR cut-offs have been used, manly based on previous reports on melanoma. Methods: In this Italian multicenter retrospective study, NLR, dNLR, platelet-to-lymphocyte ratio, albumin, and lactate dehydrogenase (LDH) were longitudinally assessed in patients with stage IV non-small cell lung cancer (NSCLC) treated with ICI. The primary objective was to evaluate if baseline parameters predicted response to ICI, using Receiver Operating Characteristic (ROC) curves. Secondary endpoint was to evaluate if dynamic changing of NLR and dNLR also predicted response. Results: Data of 402 patients were collected and analyzed. Among the baseline parameters considered, NLR and dNLR were the most appropriate biomarkers according to the ROC analyses, which also identified meaningful cut-offs (NLR = 2.46; dNLR = 1.61). Patients with low ratios reported a significantly improved outcome, in terms of overall survival (p = 0.0003 for NLR; p = 0.0002 for dNLR) and progression free survival (p = 0.0004 for NLR; p = 0.005 for dNLR). The role of NLR and dNLR as independent biomarkers of response was confirmed in the Cox regression model. When assessing NLR and dNLR dynamics from baseline to cycle 3, a decrease ≥1.04 for NLR and ≥0.41 for dNLR also predicted response. Conclusions in our cohort, we confirmed that NLR and dNLR, easily assessable on peripheral blood, can predict response at baseline and early after ICI initiation. For both baseline and dynamic assessment, we identified clinically meaningful cut-offs, using ROC curves.

Prognostic Roles of Neutrophil-to-Lymphocyte Ratio and Stromal Tumor-Infiltrating Lymphocytes and Their Relationship in Locally Advanced Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy

Introduction: The neutrophil-to-lymphocyte ratio (NLR) and stromal tumor-infiltrating lymphocytes (sTILs) are associated with immunogenicity and prognosis of patients with triple-negative breast cancer (TNBC). Objective: To investigated the prognostic roles of NLR and sTILs and their rela­tionship of TNBC patients treated with neoadjuvant chemotherapy (NAC). Methods: The clinical data of 170 patients with locally advanced TNBC who received NAC from January 2010 to December 2014 were collected. The difference among variables was calculated by χ² test. The association between essential clinicopathological characteristics, pathological complete response (pCR), NLR, and sTILs with disease-free survival (DFS) was analyzed. Kaplan-Meier and Cox analysis were performed to address the effects of clinical parameters on prognosis. Results: There was a trend that TNBC patients with lower baseline NLR (NLR1) or higher sTILs scoring would obtain a better pCR rate. NLR1 and sTILs were not associated (p > 0.05). Patients with low NLR1 or high sTILs scoring had a significantly improved DFS compared to those with high NLR1 or low sTILs scoring (p = 0.002 and p = 0.001, respectively). The increased lymphocyte count in peripheral blood after NAC was associated with the improved DFS outcome in both high and low NLR1 groups. Cox analysis revealed that NLR1 and sTILs were independent prognostic predictors of DFS outcome (p < 0.001). Conclusion: Low NLR1 and high sTILs were associated with better DFS outcome in locally advanced TNBC patients treated with NAC. Further studies are needed to explore the connection between systemic and local inflammatory/immune markers.

Prognostic value of neutrophil-to-lymphocyte ratio in human epidermal growth factor receptor 2-negative breast cancer patients who received neoadjuvant chemotherapy

We aimed to investigate the correlation between neutrophil-to-lymphocyte ratio (NLR) and pathologic complete response (pCR) and survival outcomes in human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who received neoadjuvant chemotherapy. The baseline NLR was evaluated in non-metastatic, HER2-negative breast cancer patients who received neoadjuvant chemotherapy. Baseline NLR was calculated as absolute neutrophil per lymphocyte count from pre-treatment blood samples. Any value ≥ 2.74 was considered to be a high NLR. In the 1,097 patients studied, 272 (24.4%) had high NLR and 825 (75.6%) had low NLR. The high NLR was an independent factor for pCR (OR 0.595; 95% CIs 0.398–0.890; P = 0.011). Furthermore, high NLR was a significant independent parameter affecting DFS (HR 2.298; 95% CIs 1.691–3.124; P < 0.001) and OS (HR 1.905; 95% CIs 1.167–3.108; P = 0.010). Regardless of the baseline NLR, survival outcomes were excellent in patients who achieved pCR, but high NLR was associated with worse survival for patients with residual invasive disease. Our study showed that NLR was predictive for treatment response and a prognostic factor in patients with HER2-negative breast cancer who received neoadjuvant chemotherapy. Moreover, we identified that high NLR was associated with poor survival outcomes in patients who did not achieve pCR.

Neutrophil-to-lymphocyte ratio in combination with PD-L1 or lactate dehydrogenase as biomarkers for high PD-L1 non-small cell lung cancer treated with first-line pembrolizumab.

The identification of prognostic and predictive biomarkers for high-programmed cell death-ligand 1 (PD-L1) advanced non-small cell lung cancer (aNSCLC) treated with first-line pembrolizumab could support the decision-making about possible combination therapies. To explore the baseline neutrophil-to-lymphocyte ratio (NLR) with the possible addition of PD-L1 tumour proportion score (TPS) level or lactate dehydrogenase (LDH) as possible prognostic biomarkers by a multicenter retrospective exploratory analysis aiming at identifying favourable-risk patients. Baseline NLR was available for all 132 high PD-L1 aNSCLC patients, PD-L1 level and LDH for 81 (61%) and 85 (64%) patients, respectively. NLR, PD-L1 and LDH cut-offs by receiver operating characteristic (ROC) curves were 4.9, 77.5% and 268.5, respectively. Seventy-one patients (54%) had NLR <5; 25 out of 81 NLR <5 (31%) had PD-L1 >80%, 26 out of 85 (31%) NLR <5 and normal LDH (nLDH). Median follow-up was 16.3 months. As compared to NLR >5, significantly better 2-year overall survival (OS) and progression-free survival (PFS) were observed with NLR <5 [62% vs. 41%, P=0.005, hazard ratio (HR) 0.45, and median of 12.0 vs. 5.7 months, P=0.01, HR 0.56, respectively], NLR <5 + PD-L1 >80% (81%, P=0.006, HR 0.20 and median of 14.7, P=0.03, HR 0.44, respectively), and NLR <5 + nLDH (74%, P=0.009, HR 0.25 and median of 14.7, P=0.02, HR 0.40, respectively). NLR <5 and NLR <5 + nLDH significantly associated with PD (P=0.008 and P=0.025, respectively) but not response rate (RR) (P=0.09 and P=0.07, respectively); NLR <5 + PD-L1 >80% both RR (P=0.03) and PD (P=0.02). NLR <5 ± PD-L1 >80% or nLDH could represent easy-to-assess tools to identify high PD-L1 aNSCLC patients with favourable outcome following first-line pembrolizumab monotherapy.

Prognostic role of baseline neutrophil-to-lymphocyte ratio in metastatic solid tumors.

High baseline neutrophil-to-lymphocyte ratio (NLR) has been associated with poor survival in a number of solid tumors, but has not been extensively investigated in the context of radiation oncology. Developing more robust models to predict survival would inform patient care for patients with metastatic solid tumors. The present study was undertaken to evaluate the effect of baseline NLR (using 4 as a cutoff) on survival in 320 consecutive patients with metastatic cancer who were referred to a single radiation oncologist between 2012 and 2015, with a median follow-up of 20.6 months. The median NLR was 4.4 (interquartile range, 2.8-7.2). Patients with a baseline NLR ≤4 had a median survival of 9.3 months compared to 4.1 months for NLR >4 (P<0.001). The number of active tumors, Eastern Cooperative Oncology Group performance status score, baseline albumin, primary tumor site, liver metastases and baseline NLR predicted overall survival on both univariate and multivariate analysis (P<0.05 for all). After adjusting for known prognostic factors for advanced solid tumors, baseline NLR >4 independently predicted adverse survival in this cohort.

Serum neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in prognosticating immunotherapy efficacy.

Aim: To examine neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in prognosticating immunotherapy efficacy. Methods: A retrospective study of 156 patients with metastatic melanoma and non-small-cell lung cancer on PD-1 inhibitors. Results: Baseline NLR≥5 was associated with worse progression-free survival (hazardratio [HR]: 1.53; 95% CI: 1.01-2.31; p = 0.043) but nonsignificant worse overall survival trend (HR: 1.51; 95% CI: 0.98-2.34; p = 0.064). PLR≥200 was associated with worse overall survival (HR: 1.94; 95% CI: 1.29-2.94; p = 0.002) and worse progression-free survival (HR: 1.894; 95% CI: 1.27-2.82; p = 0.002). NLR or PLR are prognosticating factors regardless of cancer types, with PLR having a stronger association with outcomes than NLR. Conclusion: High baseline NLR or PLR (alone and combined) were associated with worse immunotherapy efficacy regardless of cancer type, indicating their potential role as an agnostic marker for immunotherapy efficacy.

Pretreatment Neutrophil-to-Lymphocyte Ratio (NLR) May Predict the Outcomes of Advanced Non-small-cell Lung Cancer (NSCLC) Patients Treated With Immune Checkpoint Inhibitors (ICIs).

Background: Recent studies have demonstrated the predictive value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in advanced cancers; however, the role of NLR in patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) remained to be explored. Thus, we aimed to investigate whether pretreatment NLR was associated with the outcomes of advanced NSCLC patients treated with ICIs.Methods: A comprehensive literature research was first conducted in PubMed, the Cochrane Central Library, and Embase for studies that evaluated the association between pretreatment NLR and survival of advanced NSCLC patients with ICIs treatment. We then conducted a retrospective study in Chinese People's Liberation Army (PLA) General Hospital (Beijing, China) to validate these findings.Results: A total of 17 eligible studies with 2,106 patients were included in our meta-analysis, of which, 12 studies reported progression-free survival (PFS), and 13 studies reported overall survival (OS). The pooled results showed that high pretreatment NLR was significantly associated with poorer PFS (HR = 1.44, 95% CI 1.26–1.65; P < 0.001) and OS (HR = 2.86, 95% CI 2.11–3.87; P < 0.001) compared with those with low pretreatment NLR. Subgroup analysis demonstrated that the association between baseline NLR and PFS remained significant except that the cut-off value of NLR was 3 (HR = 1.48, 95% CI 0.93–2.37; P = 0.098) and region of Asia (HR = 1.55, 95% CI 1.00–2.39; P = 0.051). These results were further validated in our retrospective study that patients with pretreatment NLR ≥ 6.0 had shorter PFS (median: 5.0 vs. 9.1 months, HR = 1.39; 95% CI 1.01–1.91; P = 0.02) and OS (median: 10.0 vs. 17.3 months, HR = 1.71; 95% CI 1.18–2.46; P < 0.001) compared with those with NLR < 6.0. The associations between NLR and survival were consistent in subgroup analysis stratified by age, gender, ECOG PS, histology, stage, smoking history, treatment, and prior lines of therapy. Dynamics of NLR (dNLR) that increased ≥3.0 from baseline was also significantly associated with worse PFS (median: 3.1 vs. 9.1 months; P = 0.01) and OS (median: 6.8 vs. 17.0 months; P < 0.0001).Conclusions: Our study demonstrates that pretreatment NLR and dNLR from baseline are associated with the outcomes of advanced NSCLC patients treated with ICIs; however, it warrants further prospective studies.

Variation in neutrophil to lymphocyte ratio (NLR) as predictor of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (mNSCLC) patients treated with nivolumab.

An elevated pre-treatment neutrophil to lymphocytes ratio (NLR) is associated with poor prognosis in various malignancies. Optimal cut-off is highly variable across studies and could not be determined individually for a patient to inform his prognosis. We hypothesize that NLR variations could be more useful than baseline NLR to predict progression-free survival (PFS) and overall survival (OS) in patients (pts) receiving anti-PD1 treatment. All pts with metastatic renal cell carcinoma (mRCC) and metastatic non-small cell lung cancer (mNSCLC) who received anti-PD1 nivolumab monotherapy in second-line setting or later were included in this French multicentric retrospective study. NLR values were prospectively collected prior to each nivolumab administration. Clinical characteristics were recorded. Associations between baseline NLR, NLR variations and survival outcomes were determined using Kaplan-Meier's method and multivariable Cox regression models. 161 pts (86 mRCC and 75 mNSCLC) were included with a median follow-up of 18months. On the whole cohort, any NLR increase at week 6 was significantly associated with worse outcomes compared to NLR decrease, with a median PFS of 11months vs 3.7months (p < 0.0001), and a median OS of 28.5months vs. 18months (p = 0.013), respectively. In multivariate analysis, NLR increase was significantly associated with worse PFS (HR 2.2; p = 6.10-5)and OS (HR 2.1; p = 0.005). Consistent results were observed in each cohort when analyzed separately. Any NLR increase at week 6 was associated with worse PFS and OS outcomes. NLR variation is an inexpensive and dynamic marker easily obtained to monitor anti-PD1 efficacy.

Association of the neutrophil to lymphocyte ratio and clinical outcomes in patients with lung cancer receiving immunotherapy: a meta-analysis.

ObjectivesTo explore the relationship between the pretreatment or post-treatment neutrophil to lymphocyte ratio (NLR) and overall survival (OS)/progression-free survival (PFS) in patients with lung cancer receiving immunotherapy.DesignWe searched several databases to collect relevant studies conducted until July 2019. We carefully reviewed the full text of the included publications and combined the HRs and 95% CIs to assess the association between the NLR and survival time in patients with lung cancer receiving immunotherapy.Data sourcesPubMed, the Cochrane Library, Embase and Web of ScienceEligibility criteriaStudies reporting the prognostic value of the NLR in patients with lung cancer receiving immunotherapy were enrolled.Data extraction and synthesisBasic information on the articles and patients (NLR cut-off value, NLR at baseline and HRs with 95% CIs for OS and PFS) was extracted by two authors independently. The pooled HRs of OS and PFS were synthesised using the random effects or fixed effects model.ResultsTwenty-three studies with 2068 patients were enrolled. Among all patients, 1305 (64.0%) were men and 643 (31.4%) were diagnosed with squamous cell carcinoma (SCC). In a pooled analysis of OS and PFS from all studies, an elevated NLR predicted poor OS (HR=1.62; 95% CI: 1.41 to 1.87; p<0.001) and PFS (HR=1.47; 95% CI: 1.25 to 1.72; p<0.001). Subgroup analyses stratified showed that the post-treatment NLR was not significantly related to OS and that patients in Asia had significantly higher HRs than those in Europe and America. Furthermore, the proportion of SCC and baseline NLR could affect the prognostic value of the NLR.ConclusionsOur study found that an elevated NLR was associated with poor OS and PFS in patients with lung cancer receiving immunotherapy and that several clinical factors might have an impact on the predictive value of the NLR in the survival of patients with lung cancer.

Dynamic evaluation of neutrophil-to-lymphocyte ratio as prognostic factor in stage III non-small cell lung cancer treated with chemoradiotherapy

Locally advanced non-small cell lung cancer (LA-NSCLC) is frequently treated with chemoradiotherapy (CRT). Despite the efforts, long-term outcomes are poor, and novel therapies have been introduced to improve results. Biomarkers are needed to detect early treatment failure and plan future follow-up and therapies. Our aim is to evaluate the role of dynamics of neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced NSCLC treated with CRT. We retrospectively reviewed patients diagnosed with LA-NSCLC receiving definitive CRT at our center from 2010 to 2015. Baseline and post-treatment NLR were collected from our center database. NLR was dichotomized (threshold = 4) and patients were divided into two groups based on the variation from baseline to post-treatment NLR. The prognostic role and association with response were examined with logistic regression and multivariate Cox regression model, respectively. Ninety-two patients were included. Our analysis shows that NLR after treatment is associated with response to treatment [OR in the multivariate analysis 4.94 (1.01-24.48); p value = 0.048]. Furthermore, NLR and ECOG are independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Specifically, PFS was 25.79months for the good prognosis group and 12.09 for the poor prognosis group [HR 2.98 (CI 95% = 1.74-5.10), p < 0.001]; and OS was 42.94months and 18.86months, respectively [HR 2.81 (CI 95% = 1.62-4.90), p < 0.001]. Dynamics of NLR have a prognostic value in stage III NSCLC treated with definitive CRT. Pre- and post-CRT NLR should be evaluated in prospective clinical trials involving consolidation treatment with immunotherapy.

Neutrophil-lymphocyte score: A novel prognostic scoring system that utilized the dynamic change of neutrophil, lymphocyte, and albumin and its comparison to other indices.

3048 Background: Indications for immune checkpoint inhibitor (ICI) in cancer care are expanding rapidly. There is increasing need for accurate decision tool to better guide treatment. We have constructed a new prognostic scoring system, neutrophil-lymphocyte score (NRS), based on the nonlinear dynamic change of neutrophil to lymphocyte ratio (NLR) in relation to survival over the first cycle of ICI treatment. We compared this novel system to existing indices such as NLR, lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), Advanced Lung Cancer Inflammation Index (ALI), and Systemic Immune-inflammation Index (SII). Methods: This is a retrospective analysis of 837 patients at Ohio State University from 2011-18. Neutrophil (ANC), lymphocyte (ALC), platelet (plt), monocyte (AMC), albumin (alb), and body mass index (BMI) were collected at baseline. Repeat labs were collected at cycle 2. NLR = ANC/ALC, ALI = BMI x alb / NLR, LMR = ALC/AMC, SII = platelet x NLR, PLR = plt/ALC. NLR Ratio = baseline NLR / repeat NLR. Based on the association between NLR and the overall survival, we assigned 1 point (p) for baseline NLR &lt; 0.7, 6p for 0.7 to &lt; 2, 5p for 2 to &lt; 3, 4 p for 3 to &lt; 4, 3 for 4 to 5, 2p for 5 to &lt; 9, and 1p for ≥9. We also assigned 1p for NLR ratio &lt; 0.6, 2p for 0.6 to &lt; 0.8, 3p for 0.8 to &lt; 1.2, 5p for 1.25 to &lt; 1.4, 3p for 1.4 to &lt; 1.6, and 2p for ≥1.6. NLS = sum of these 2 scores . NLS_A = NLS*alb. Time-dependent receiver operator characteristic (ROC) curves with integrated time-dependent area under the curve (TD AUC) values were used to evaluate the predictive accuracy of each index for survival. Results: For baseline and repeat values, all indices were statistically significant (P &lt; 0.001) in predicting survival. Baseline integrated TD AUC were: ALI 0.704, NLR 0.692, SII 0.663, LMR 0.645, and PLR 0.612. All of the repeat indices at cycle 2 had higher prognostic value than their baseline counterparts. Integrated TD AUC for indices at cycle 2 were: ALI 0.740 (with baseline BMI), NLR 0.729, SII 0.694, LMR 0.671, and PLR 0.652. NLS_A was a composite score based on the dynamic change of NLR from cycle 1 to 2 and the treatment alb with integrated TD-AUC at 0.754. Conclusions: Indices constructed from ANC, ALC, AMC, Plt, alb, and BMI can be obtained inexpensively and provide great prognostic value for pts on ICI. We have constructed a novel scoring system (NLS_A) and demonstrated its improvement over the current prognostic indices. Studies with a larger cohort are needed to further improve and validate this system.

Association of neutrophil to lymphocyte ratio (NLR) with efficacy from JAVELIN Renal 101.

5061 Background: The phase 3 JAVELIN Renal 101 trial (NCT02684006) in treatment-naive patients with advanced renal cell carcinoma (aRCC) demonstrated significantly improved progression-free survival (PFS; hazard ratio [HR], 0.69; 95% CI, 0.56, 0.84; P &lt; 0.001) and higher objective response rate (ORR; 51.4% vs 25.7%) with avelumab + axitinib vs sunitinib (Motzer RJ, et al. N Engl J Med. 2019;380:1103-15). NLR has emerged as a potential prognostic biomarker in aRCC; elevated NLR is associated with poorer prognosis. Here, we describe the association of NLR with the efficacy of avelumab + axitinib from JAVELIN Renal 101. Methods: We examined baseline NLR and its association with efficacy outcomes. PFS, best overall response (per blinded independent central review using RECIST 1.1), and overall survival (OS) data from the avelumab + axitinib arm from the first interim analysis of JAVELIN Renal 101 were analyzed (data cutoff, June 20, 2018). Multivariate Cox regression analyses of PFS and OS were also conducted. Results: In the avelumab + axitinib arm, patients with &lt; median NLR (N = 217) had longer observed PFS (stratified HR, 0.85; 95% CI, 0.634, 1.153) and longer observed OS (stratified HR, 0.51; 95% CI, 0.300, 0.871) than patients with ≥ median NLR (N = 217). The ORR was 57.1% in patients with &lt; median NLR vs 47.5% in patients with ≥ median NLR, with complete response in 5.5% vs 1.4%. Multivariate analysis showed that low NLR was associated with longer PFS and OS by treating baseline NLR as either a continuous variable or a binary variable (dichotomized by median). Conclusions: Low NLR was associated with better observed treatment outcomes in patients with aRCC who received avelumab + axitinib. Clinical trial information: NCT02684006 .

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of tumor response in hepatocellular carcinoma after DEB-TACE.

To investigate the predictive value of quantifiable imaging and inflammatory biomarkers in patients with hepatocellular carcinoma (HCC) for the clinical outcome after drug-eluting bead transarterial chemoembolization (DEB-TACE) measured as volumetric tumor response and progression-free survival (PFS). This retrospective study included 46 patients with treatment-naïve HCC who received DEB-TACE. Laboratory work-up prior to treatment included complete and differential blood count, liver function, and alpha-fetoprotein levels. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were correlated with radiomic features extracted from pretreatment contrast-enhanced magnetic resonance imaging (MRI) and with tumor response according to quantitative European Association for the Study of the Liver (qEASL) criteria and progression-free survival (PFS) after DEB-TACE. Radiomic features included single nodular tumor growth measured as sphericity, dynamic contrast uptake behavior, arterial hyperenhancement, and homogeneity of contrast uptake. Statistics included univariate and multivariate linear regression, Cox regression, and Kaplan-Meier analysis. Accounting for laboratory and clinical parameters, high baseline NLR and PLR were predictive of poorer tumor response (p = 0.014 and p = 0.004) and shorter PFS (p = 0.002 and p < 0.001). When compared to baseline imaging, high NLR and PLR correlated with non-sphericaltumor growth (p = 0.001 and p < 0.001). This study establishes the prognostic value of quantitative inflammatory biomarkers associated with aggressive non-sphericaltumor growth and predictive of poorer tumor response and shorter PFS after DEB-TACE. • In treatment-naïve hepatocellular carcinoma (HCC), high baseline platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with non-nodular tumor growth measured as lowtumor sphericity. • High PLR and NLR are predictive of poorer volumetric enhancement-based tumor response and PFS after DEB-TACE in HCC. • This set of readily available, quantitative immunologic biomarkers can easily be implemented in clinical guidelines providing a paradigm to guide and monitor the personalized application of loco-regional therapies in HCC.

Peri-interventional Behavior of the Neutrophil to Lymphocyte Ratio in Patients with Intracranial Aneurysms

The neutrophil-to-lymphocyte ratio (NLR) has been investigated as an independent predictive marker for clinical outcomes in vascular diseases. This study aimed to investigate the peri-interventional behavior of the NLR in patients with ruptured and unruptured intracranial aneurysms (IAs). A total of 117 patients with IAs, who were treated at our department and had available complete data, were retrospectively identified during a 10-year period. Routine laboratory parameters, including the neutrophil and lymphocytes counts, were evaluated before and after treatment. The baseline NLR showed significant differences between patients with ruptured and unruptured IAs (6.3 vs. 1.8; P < 0.001). In patients with ruptured IAs, the baseline NLR decreased significantly during the follow-up visits, whereas in unruptured IAs, the NLR remained low. Furthermore, higher baseline NLR values could also be observed in patients with ruptured IAs and fatal outcome than in surviving patients (8.0 vs. 5.4; P= 0.220). In patients with poor functional outcome, defined as modified Rankin score ≥3, the NLR was significantly higher before treatment (P= 0.047), at day 10 (P= 0.025), and 1 month after treatment (P= 0.001). The peri-interventional NLR was significantly different between patients with ruptured and unruptured IAs. In patients with ruptured IAs, elevated baseline NLR levels were associated with poor postoperative functional outcomes and decreased postoperatively, implying the potential prognostic value of NLR in patients with IAs.