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.
In this phase Ib study, four combination therapies of nivolumab 10 mg/kg and standard chemotherapy (cisplatin/gemcitabine, cisplatin/pemetrexed, carboplatin/paclitaxel/bevacizumab, or docetaxel) showed acceptable toxicity profiles in patients with advanced non-small-cell lung cancer. Furthermore, these combination therapies presented encouraging antitumor activities.
Abstract. Tumor-associated macrophages (TAMs) often assume an immunoregulatory M2 phenotype. Thus, the aim of the present study was to clarify the correlation of vascularity and TAMs, in particular the M2 phenotype in the stroma and tumor areas, with the clinical and pathological outcomes of patients with bladder cancer. The TAM counts and microvessel counts (MVCs) were determined immunohistochemically in 21 patients with bladder cancer. The number of infiltrating TAMs was measured using immunohistochemistry with anti-cluster of differentiation (CD)68 and anti-CD163 antibodies, to identify a macrophage lineage marker and an M2-polarized-specific cell surface receptor, respectively. CD68 + and CD163 + macrophages were evaluated in the stroma and tumor areas, and areas with a high density of infiltrating cell spots were counted. MVCs were determined using immunohistochemistry with anti-CD34 antibodies. The results revealed that the higher ratio of CD163 + /CD68 + macrophages in the stroma, tumor and total tumor tissues were correlated with a higher stage and grade (P<0.05). In addition, the low ratio of CD68 + /CD34 + microvessels was correlated with a higher stage (P<0.05). There was also a positive correlation between TAMs and MVC (r 2 =0.25; P<0.05). These results suggest that the TAM polarized M2 phenotype affects microvessels, pathological outcome, tumor grade and invasiveness.
Preoperative NLR elevation is significantly associated with poor outcomes in patients with metastatic RCC who underwent CN. Patients with NLR ≥4.0 and ECOG-PS ≥ 1 might not benefit from immediate CN after initial diagnosis.
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