Search results for "progressive"
showing 10 items of 281 documents
A phase II study of the PI3K inhibitor taselisib (GDC-0032) combined with fulvestrant (F) in patients (pts) with HER2-negative (HER2-), hormone recep…
2016
520Background: The PI3K pathway is activated in HR+ BC, often via gain-of-function mutations in PIK3CA that occur in ~40% of HR+ BC. Taselisib is a potent and selective PI3K inhibitor, with greater selectivity against mutant PI3Kα isoforms than wild type (WT) PI3Kα. Phase Ib data demonstrated good tolerability and preliminary efficacy for taselisib + F in HR+ BC. Methods: This Phase II, open-label, single-arm study enrolled post-menopausal pts with HER2-, HR+ locally advanced or metastatic BC (mBC) who had progression or non-response to ≥ 1 prior endocrine therapy in adjuvant or mBC settings. Pts received taselisib (6 mg capsule PO qd) plus F (500 mg IM on Cycle 1 Day 1, Cycle 1 Day 15, the…
Metronomic oral vinorelbine in patients with advanced non-small cell lung cancer progressing after nivolumab immunotherapy: a retrospective analysis
2020
Purpose The availability of immune checkpoint inhibitors has deeply changed the therapeutic scenario of patients with advanced non-small cell lung cancer (NSCLC). Up until now, chemotherapy still represents the first-line treatment for patients with advanced NSCLC not harbouring genetic mutations or lacking high expression of programmed death ligand even if the addition of immunotherapy to first-line chemotherapy has recently been shown to improve clinical outcome. We carried out a multi-institutional retrospective analysis on third-line chemotherapy with metronomic oral vinorelbine (VNR) in a series of patients with metastatic NSCLC pre-treated with first-line chemotherapy and second-line …
Immune checkpoint inhibition therapy for advanced skin cancer in patients with concomitant hematological malignancy: a retrospective multicenter DeCO…
2020
BackgroundSkin cancers are known for their strong immunogenicity, which may contribute to a high treatment efficacy of immune checkpoint inhibition (ICI). However, a considerable proportion of patients with skin cancer is immuno-compromised by concomitant diseases. Due to their previous exclusion from clinical trials, the ICI treatment efficacy is poorly investigated in these patients. The present study analyzed the ICI treatment outcome in advanced patients with skin cancer with a concomitant hematological malignancy.MethodsThis retrospective multicenter study included patients who were treated with ICI for locally advanced or metastatic melanoma (MM), cutaneous squamous cell carcinoma (cS…
Immune-checkpoint inhibitors in non-small cell lung cancer: A tool to improve patients’ selection
2018
The identification of reliable predictive biomarkers of efficacy or resistance to immune-oncology (I–O) agents is a major issue for translational research and clinical practice. However, along with PDL1 and molecular features other clinical, radiological and laboratory factors can be considered for the selection of those patients who would not be the best candidate for immune-checkpoint inhibitors (ICPIs). We examined these factors, emerging from the results of currently available studies in non-small cell lung cancer (NSCLC), aiming to provide a useful and manageable tool which can help Oncologists in their everyday clinical practice. A thorough patient evaluation and close clinical monito…
PML risk stratification using anti-JCV antibody index and L-selectin
2015
Background: Natalizumab treatment is associated with progressive multifocal leukoencephalopathy (PML) development. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for risk stratification, but PML incidence stays high. Anti-JCV antibody index and L-selectin (CD62L) have been proposed as additional risk stratification parameters. Objective: This study aimed at verifying and integrating both parameters into one algorithm for risk stratification. Methods: Multicentric, international cohorts of natalizumab-treated MS patients were assessed for JCV index (1921 control patients and nine pre-PML patients) and CD62L (1410 control patients and 17 pre-PML patient…
Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset.
2017
Genetic variants in the adenosine triphosphate-binding cassette subfamily B member 4 (ABCB4) gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such as progressive familial intrahepatic cholestasis (PFIC) type 3, low phospholipid-associated cholelithiasis, and intrahepatic cholestasis of pregnancy. The aim of this multicenter project was to collect information on onset and progression of this entity in different age groups and to assess the relevance of this disease for the differential diagnosis of chronic liver disease. Clinical and laboratory data of 38 patients (17 males, 21 females, from 29 families) with homozygous or (compound) heter…
Secondary Progression in Multiple Sclerosis: Neuronal Exhaustion or Distinct Pathology?
2016
Prevention of progression in neurological diseases, particularly in multiple sclerosis (MS) but also in neurodegenerative diseases, remains a significant challenge. MS patients switch from a relapsing-remitting to a progressive disease course, but it is not understood why and how this conversion occurs and why some patients never experience disease progression. Do aging and accumulation of neuronal damage induce progression, or do cognitive symptoms and accelerated grey matter (GM) atrophy point to distinct processes affecting networks? This review weighs accepted dogma against real data on the secondary progressive phase of the disease, highlighting current challenges in this important fie…
Hypothesis: Etiologic and Molecular Mechanistic Leads for Sporadic Neurodegenerative Diseases Based on Experience With Western Pacific ALS/PDC
2019
Seventy years of research on Western Pacific amyotrophic lateral sclerosis and Parkinsonism-dementia Complex (ALS/PDC) have provided invaluable data on the etiology, molecular pathogenesis and latency of this disappearing, largely environmental neurodegenerative disease. ALS/PDC is linked to genotoxic chemicals (notably methylazoxymethanol, MAM) derived from seed of the cycad plant (Cycas spp.) that were used as a traditional food and/or medicine in all three disease-affected Western Pacific populations. MAM, nitrosamines and hydrazines generate methyl free radicals that damage DNA (in the form of O6-methylguanine lesions) that can induce mutations in cycling cells and degenerative changes …
Plasma polyunsaturated fatty acids are directly associated with cognition in overweight children but not in normal weight children
2016
Aim Polyunsaturated fatty acids are essential nutrients for the normal development of the brain. We investigated the associations between plasma polyunsaturated fatty acids and cognition in normal weight and overweight children. Methods The study recruited 386 normal weight children and 58 overweight children aged six to eight years and blood samples were drawn after a 12-hour fast. We assessed plasma polyunsaturated fatty acids using gas chromatography, cognition using Raven's Coloured Progressive Matrices, and overweight and obesity using the age-specific and sex-specific cut-offs from the International Obesity Task Force. The data were analysed by linear regression analyses adjusted for …
The still under-investigated role of cognitive deficits in PML diagnosis
2017
Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asy…