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Neutrophil to lymphocyte ratio influences impact of steroids on efficacy of immune checkpoint inhibitors in lung cancer brain metastases.

ABSTRACT: Steroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM). Steroids and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with decreased overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI). We retrospectively investigated patients treated with ICI after the diagnosis of NSCLCBM at a single tertiary care institution examing the impact of steroids and NLR. Overall survival (OS) and intracranial progression-free survival (PFS) were analyzed. 171 patients treated with ICI for NSCLCBM were included. Thirty-six received steroids within 30 days of the start of ICI, and 53 patients had an NLR ≥ 5 before the start of ICI. Upfront steroids was associated with decreased OS on multivariable analysis (median OS 10.5 vs. 17.9 months, p = .03) and intracranial PFS (5.0 vs. 8.7 months, p = .045). NLR ≥ 5 was indicative of worse OS (10.5 vs. 18.4 months, p = .04) but not intracranial PFS (7.2 vs. 7.7 months, p = .61). When NLR and upfront steroids are modeled together, there is a strong interaction (p = .0008) indicating that the impact of steroids depended on the patient's NLR. In a subgroup analysis, only in patients with NLR < 4 was there a significant difference in OS with upfront steroids (26.1 vs. 15.6 months, p = .032). The impact of steroids on the efficacy of ICI in patients with NSCLCBM is dependent on the patient's NLR underscoring its importance in these patients. Patients with a low NLR, steroid use decreases the efficacy of ICI. These results can inform clinicians about the impact of steroids in patients treated with ICI.

SUBMITTER: Lauko A

PROVIDER: S-EPMC8021556 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe role of platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) as independent prognostic markers in different tumors is well established. However, there is a limited review of the potential of NLR and PLR as predictors of treatment outcomes from immune checkpoint inhibitors (ICIs).ObjectiveTo establish a correlation between NLR and PLR and the potential of clinical benefit from ICIs.MethodsThe literature search was performed for studies that reported the association between NLR, PLR, and treatment outcomes among cancer patients treated with ICIs. The outcomes of interest were objective response rate (ORR), disease control rate (DCR), and progressive disease (PD). ORR was the summation of patients who achieved complete response and partial response. DCR included patients who achieved stable disease. PD was the proportion of patients who progressed, relapsed, or discontinued the treatment. Statistical analysis was performed using the STATA 12.0 package. Heterogeneity was determined by the I2 value. Quality assessment was performed using the Newcastle-Ottawa Scale. Egger's test was used to establish publication bias and sensitivity analysis.ResultsA total of 40 papers that met the inclusion criteria were included in the systematic review. However, only 17 studies were used in the meta-analysis to determine the correlation between NLR, PLR, and treatment response. We found that treatment with ICIs and monitoring of outcomes and adverse events using PLR and NLR parameters have been studied in different tumors. Our analysis showed that low NLR correlated with higher ORR (OR = 0.62 (95% CI 0.47-0.81, p = 0.001) and higher DCR (OR = 0.23, 95% CI 0.14-0.36, p < 0.001). Higher NLR predicted a higher probability of PD (OR = 3.12, 95% CI 1.44, 6.77, p = 0.004). Similarly, low PLR correlated with higher ORR (OR = 0.69, 95% CI 0.5, 0.95, p = 0.025). Generally, patients with low NLR and PLR were more likely to achieve clinical benefit and better response (p-value < 0.001). Meanwhile, patients with high ratios were more likely to progress (p-value < 0.005), although there was significant heterogeneity among studies. There was no significant publication bias observed.ConclusionThe study showed that high NLR and PLR either at baseline or during treatment is associated with poorer treatment outcome. Therefore, these ratios can be utilized in clinical practice with other markers to determine treatment efficacy from immunotherapy.

Project description:ObjectivesDerived neutrophil-to-lymphocytes ratio (dNLR) has recently been reported as a novel potential biomarker associated with prognosis of non-small cell lung cancer (NSCLC). However, evidence for the prognostic utility of dNLR in patients with NSCLC treated with immune checkpoint inhibitors (ICIs) remains inconsistent. The objective of this work was to evaluate the association between pretreatment dNLR and prognosis of patients with NSCLC treated with ICIs.DesignThis study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesPubMed, EMBASE, Web of Science and the Cochrane Library were searched for eligible studies up to 16 October 2020. ELIGIBILITY CRITERIA: (1) Human subjects receiving ICIs therapy and who had been diagnosed with NSCLC; (2) the baseline values of dNLR were obtained; (3) the objective of the study was to investigate the relationships between dNLR and overall survival (OS) or progression-free survival (PFS) in NSCLC and (4) HR and 95% CI were displayed in the original article or could be extracted from Kaplan-Meier curves.Data extraction and synthesisTwo investigators extracted data independently. Data synthesis was performed via systematic review and meta-analysis of eligible cohort studies. Meta-analysis was performed with Cochran's Q test and I2 statistics. Publication bias of studies was assessed by Begg's test and Egger's test. We used V.12.0 of the Stata statistical software.ResultsThis analysis included eight studies (2456 cases) on the prognostic utility of dNLR in ICI therapy for NSCLC. The results indicate that higher dNLR significantly predicted poor OS (HR=1.65, 95% CI 1.46 to 1.88; p<0.001) and PFS (HR=1.38, 95% CI 1.23 to 1.55; p<0.001). Subgroup analyses of OS-related studies indicated that there were similar results in stratifications by ethnicity, sample size, type of HR and dNLR cut-off value. As for PFS-related studies, subgroup analyses showed no significant difference in Asian populations. Publication biases were not detected using Begg's test and Egger's linear regression test.ConclusionsThis meta-analysis indicated that elevated pretreatment dNLR may be a negative prognostic predictor for patients with NSCLC treated with ICIs. More large-sample and higher-quality studies are warranted to support our findings.Prospero registration numberCRD42021214034.

Project description:BACKGROUND:There is an unmet need to determine factors predictive of clinical benefit, to guide therapeutic sequencing and selection in metastatic RCC (mRCC). We evaluated clinical factors such as the neutrophil lymphocyte ratio (NLR) and duration of prior anti-vascular endothelial growth factor (VEGF) inhibitors, as predictors of response rate, progression free survival (PFS) and overall survival (OS) in mRCC patients treated with immune checkpoint inhibitor (ICI). METHODS:Regulatory approval was obtained. A single center retrospective chart review of mRCC patients at Karmanos Cancer Institute, treated with ICI based therapy (PD-1/PD-L1 inhibitors) was conducted. Data were collected on demographics, smoking status, prognostic scoring (Memorial Sloan Kettering and Heng criteria), NLR pretherapy, post 1 and 4 doses of ICI, and duration of prior anti-VEGF therapy ?6 months or <6. RESULTS:42 patients were evaluated with median age of 61 years (range, 24-85). Pretherapy NLR < 3 and ?3 was seen in 19 (45%) and 23 (55%) patients, respectively. 24 (57%) and 18 (43%) patients had prior anti-VEGF inhibitors for a duration of ?6 months and <6 months, respectively. 12 (29%), 22 (52%) and 8 (19%) patients had favorable, intermediate and poor risk disease based on Heng criteria, respectively. Multivariable analysis showed pretherapy NLR ?3 was predictive of shorter PFS and OS when treated with ICI with median 3.08 months and 13.50 months, respectively, versus 15.57 months and not reached for NLR < 3 (adjusted p-values =0.003 and 0.025, respectively). Prior anti-VEGF therapy <6 months was predictive of increased likelihood of benefit from ICI therapies (adjusted p = 0.028). The median PFS was 3.72 months and 14.33 months, respectively, in cases with prior anti-VEGF therapy for ?6 months and <6 months. CONCLUSION:Pretherapy NLR <3 and duration of prior anti-VEGF therapy of <6 months, are independent statistically significant predictors of longer PFS and OS with ICI therapy in mRCC. Validation is required in a larger sample size with multi-institutional collaboration.

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Neutrophil to lymphocyte ratio influences impact of steroids on efficacy of immune checkpoint inhibitors in lung cancer brain metastases.

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