The lung immune prognostic index (LIPI) has been proposed as a new categorical blood-based biomarker to select advanced non-small cell lung cancer (NSCLC) patients for anti-programmed cell death-1 (PD-1) or programmed death ligand 1 (PD-L1) therapy. In this study, we investigate for the first time to the best of our knowledge the prognostic and predictive utility of the LIPI in a multicenter nivolumab monotherapy-based cohort. We retrospectively analyzed the influence of the baseline LIPI on overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and overall response rate (ORR) among 153 patients of a cohort of 188 advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond. Worse LIPI was significantly associated with shorter OS in univariate [hazard ratio (HR) =3.12, 95% confidence interval (CI), 2.12-4.60; P<0.0001] and multivariate (HR =3.67, 95% CI, 1.96-6.86; P<0.0001) analyses. Worse LIPI was associated with shorter PFS (HR =1.45, 95% CI, 1.05-2.03; P=0.03), but this correlation did not reach statistical significance in multivariate analysis (HR =1.49, 95% CI, 0.94-2.38; P=0.09). Worse LIPI was associated with lower DCR in univariate [odds ratio (OR) =0.41, 95% CI, 0.24-0.70; P=0.001] and multivariate (OR =0.44, 95% CI, 0.25-0.78; P=0.005) analyses. This study confirms the utility of the LIPI in prognostication and disease control prediction in advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond.
Over the past decade a number of vascular complications have emerged, such as newly developed or worsened hypertension, in patients who were administered with new cancer treatments for several types of cancer that were untreatable earlier. Hypertension is emerging as one of the most common adverse effects of therapy with angiogenesis inhibitors. Small-molecule inhibitors of vascular endothelial growth factor signalling are associated with a high proportion of patients with hypertension. The mechanisms underlying the development of hypertension are not well known, although there seem to be several mechanisms. Physiopathology of hypertension implicates abnormalities in endothelial function and angiogenesis. Several features of hypertensive patients are reduced number of arterioles and capillaries, alterations of the microvascular network, decrease in vascular wall compliance and flexibility, reduced nitric oxide bioactivity and increases in plasma vascular endothelial growth factor. Treatment with tyrosine kinase inhibitors (TKIs) is associated with a significant and sustained increase in blood pressure. We suspect that TKIs exert their hypertensive effects directly at the level of the microvascular network through processes such as vascular rarefaction, endothelial dysfunction and/or altered nitric oxide metabolism. This study shows the vascular complications of treatment with a TKI, sunitinib (SU11248), with special emphasis on hypertension.
Identification of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is a standard diagnostic test in patients with advanced non-small cell lung cancer (NSCLC). The current study describes the experience of ALK rearrangement detection of a referral center in the public health care system of Galicia in North-Western Spain. The fluorescence in situ hybridization (FISH) patterns of the ALK gene and the clinical and pathological features of these patients are reported. This study is also of interest for comparative purposes due to the relative geographical isolation of the area, which could have contributed to particular genetic features. A total of 2,045 tissue samples from NSCLC patients were collected between October 2010 and July 2015 and tested for ALK rearrangements by FISH. Examination of 1,686 paraffin-embedded tissue specimens and 395 cytological samples (306 cell block preparations and 53 cytological smears) was conducted, and any associations between the FISH results and clinicopathological features were assessed. The rate of successful evaluation was marginally higher in tissue samples than in cytological samples (92.9% vs. 84.1%); this difference was not significant. ALK rearrangements were identified in 82 patients(4%): 65 (79.3%) in tissue specimens, 15 (18.3%) in cell block samples and 2 (2.4%) in cytological smears. This genetic translocation appeared to be associated with a non-smoking history, younger age, female gender, stage IV and adenocarcinoma histological type. The findings demonstrate that ALK evaluation by FISH is feasible in tissue and cytological samples. The clinical and pathological features of the ALK-positive series of patients are similar to those previously reported in the literature.
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