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Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non-small cell lung cancer.

ABSTRACT: Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation-related parameters) on progression-free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27-87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin <3.7 g/dL, neutrophil-to-lymphocyte ratio ≥4, and ALI <18 were significantly associated with poor PFS and early progression on univariate analysis. Multivariate analyses revealed that pretreatment ALI <18 was independently associated with inferior PFS (median, 1.4 vs. 3.7 months, P < 0.001) and a higher likelihood of early progression (odds ratio, 2.76; 95% confidence interval 1.44-5.34; P = 0.002). The pretreatment ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice.

SUBMITTER: Shiroyama T

PROVIDER: S-EPMC5773945 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose The advanced lung cancer inflammation index (ALI) is a novel inflammatory and nutritional index that exerts prognostic value in various types of cancer. A previous study demonstrated that ALI at discharge could predict the prognosis in patients with acute decompensated heart failure (ADHF). However, the long-term prognostic value of ALI on admission in elderly heart failure (HF) inpatients remains unclear. Materials and methods We retrospectively collected HF inpatients over 65-year-old who were hospitalized in our cardiology center during the whole year of 2015. ALI was calculated as body mass index (BMI) × serum albumin (Alb)/neutrophil-to-lymphocyte ratio (NLR). Patients were divided into two groups by the optimal cutoff value of ALI for predicting all-cause mortality using time-dependent receiver operating characteristic (ROC) curves. The Spearman rank correlation coefficient was computed to evaluate the correlation between ALI and the geriatric nutritional risk index (GNRI). Kaplan–Meier curves, Cox survival analyses, time-dependent ROC analyses, and net reclassification improvement (NRI) analyses were used to assess the prognostic effect of ALI on all-cause mortality and cardiovascular mortality. Results Over a 28-month median follow-up, all-cause and cardiovascular mortality occurred in 192 (35.4%) and 132 (24.3%) out of 543 patients, respectively. The optimal cutoff value of ALI for predicting all-cause mortality at 2 years was 25.8. Spearman’s correlation coefficient showed a moderate positive linear correlation between ALI and GNRI (r = 0.44, p < 0.001). The Kaplan–Meier analysis revealed that the cumulative incidences of both all-cause and cardiovascular mortalities were significantly higher in patients with lower ALI (log-rank test, all-cause mortality: p < 0.0001; cardiovascular mortality: p < 0.0001). The multivariate Cox proportional hazard analyses indicated that ALI was an independent predictor for both all-cause mortality (HR 0.550, 95% CI 0.349–0.867, p = 0.01) and cardiovascular mortality (HR 0.536, 95% CI 0.302–0.953, p = 0.034). Time-dependent ROC analyses showed that ALI was comparable to GNRI in predicting long-term all-cause mortality (AUC: ALI 0.625, GNRI 0.641, p = 0.976) and cardiovascular mortality (AUC: ALI 0.632, GNRI 0.626, p = 0.999) at 2 years. However, the estimated NRI indicated that the addition of ALI could not significantly improve risk stratification of base models for all-cause mortality (categorical NRI 4.9%, p = 0.433, continuous NRI 25%, p = 0.022) or cardiovascular mortality (categorical NRI 6.5%, p = 0.223, continuous NRI 27.5%, p = 0.029). Conclusion Higher ALI was significantly associated with lower all-cause and cardiovascular mortalities in elderly HF patients. ALI on admission could be a competent nutrition-inflammation marker with independent predictive value for evaluating the long-term mortality of HF in elder population.

Project description:Lung cancer is a product of inflammation and a dysfunctional immune system, and depression has similar dysregulation. Depression disproportionately affects lung cancer patients, having the highest rates of all cancers. Systemic inflammation and depression are both predictive of non-small cell lung cancer (NSCLC) survival, but the existence and extent of any co-occurrence is unknown. Studied is the association between systemic inflammation ratio (SIR) biomarker levels and patients' depressive symptoms, with the hypothesis that depression severity would be significantly associated with prognostically poor inflammation. Newly diagnosed stage-IV non-small cell lung cancer (NSCLC; N = 186) patients were enrolled (ClinicalTrials.gov Identifier: NCT03199651) and blood draws and depression self-reports (Patient Health Questionnaire-9) were obtained. For SIRs, cell counts of neutrophils (N), lymphocytes (L), and platelets (P) were abstracted for ratio (R) calculations for NLR, PLR, and the Advanced Lung cancer Inflammation Index (ALI). Patients were followed and biomarkers were tested as predictors of 2-year overall survival (OS) to confirm their relevance. Next, multivariate linear regressions tested associations of depression with NLR, PLR, and ALI. Overall 2-year mortality was 61% (113/186). Cox model analyses confirmed higher NLR [hazard ratio (HR) = 1.91; p = 0.001] and PLR (HR = 2.08; p<0.001), along with lower ALI (HR = 0.53; p = 0.005), to be predictive of worse OS. Adjusting for covariates, depression was reliably associated with biomarker levels (p ≤ 0.02). Patients with moderate/severe depressive symptoms were 2 to 3 times more likely to have prognostically poor biomarker levels. Novel data show patients' depressive symptoms were reliably associated with lung-relevant systemic inflammation biomarkers, all assessed at diagnosis/pretreatment. The same SIRs were found prognostic for patients' 2-year OS. Intensive study of depression, combined with measures of cell biology and inflammation is needed to extend these findings to discover mechanisms of depression toxicity for NSCLC patients' treatment responses and survival.

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Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non-small cell lung cancer.

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