Search results for "Heck"
showing 10 items of 682 documents
Antibody–Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non–small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade
2019
Abstract Purpose: Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinicopathologic features nor biological mechanisms associated with HP have been identified. Experimental Design: Among 187 patients with non–small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP were identified according to clinical and radiologic criteria. Baseline histologic samples from patients treated with ICI were evaluated by IHC for myeloid and lymphoid markers. T-cell–deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDX) belonging to specific mutat…
Outcome of melanoma patients with elevated LDH treated with first-line targeted therapy or PD-1-based immune checkpoint inhibition.
2020
Abstract Background Elevated lactate dehydrogenase (LDH) is a known predictive and prognostic factor for a poor outcome in patients with metastatic melanoma. It is unclear whether first-line targeted therapy (TT) or immune checkpoint inhibition (ICI) is more beneficial in melanoma patients with elevated LDH because prospective studies in this area are lacking. Methods This multicentre retrospective cohort study was conducted at 25 melanoma centres worldwide to analyse progression-free survival (PFS) and overall survival (OS) among melanoma patients with elevated LDH. The role of confounders was addressed by using inverse probability of treatment weighting. Results Among 173 BRAFV600-mutant …
Intratumoral immunosuppression profiles in 11q-deleted neuroblastomas provide new potential therapeutic targets
2021
In this issue, Coronado et al. attempt to improve our understanding of the factors affecting the response to immunotherapy in a large subset of high‐risk neuroblastoma with hemizygous deletion of chromosome 11q. By using several computational approaches, the authors study potential transcriptional and post‐transcriptional pathways that may affect the response to immunotherapy and further be leveraged therapeutically in a biomarker‐directed fashion.
Hereditary prostate cancer – Primetime for genetic testing?
2019
Prostate cancer (PCa) remains the most common cancer in men. The proportion of all PCa attributable to high-risk hereditary factors has been estimated to 5-15%. Recent landmark discoveries in PCa genetics led to the identification of germline mutations/alterations (eg. BRCA1, BRCA2, ATM or HOXB13), single nucleotide polymorphisms or copy number variations associated with PCa incidence and progression. However, offering germline testing to men with an assumed hereditary component is currently controversial. In the present review article, we provide an overview about the epidemiology and the genetic basis of PCa predisposition and critically discuss the significance and consequence in the cli…
Retrospective Analysis of Checkpoint Inhibitor Therapy-Associated Cases of Bullous Pemphigoid From Six German Dermatology Centers
2021
Immune-related adverse events (irAEs) are a class-effect of checkpoint inhibitors (CIs). The development of a Bullous pemphigoid (BP)-like blistering disease, driven by autoantibodies against the hemidesmosomal protein BP180, is a potentially serious irAE whose incidence seems to be increasing. We therefore set out to characterize the clinical and (immuno)histopathological features and treatment responses of cases of BP which developed during or after CI therapy collated in six German tertiary referral centers between 2014 and 2018. We identified twelve cases of BP which emerged during and/or after CI therapy. The time interval between the initiation of CI therapy and the diagnosis of BP wa…
Prognostic clinical factors in patients affected by non-small-cell lung cancer receiving Nivolumab
2020
Background: Immune-checkpoint inhibitors have radically changed the treatment landscape of Non-Small-Cell Lung Cancer (NSCLC). It is still unclear whether specific clinical characteristics might identify those patients benefiting from immunotherapy more than others. The aim of this study was to identify clinical characteristics associated with disease-specific survival (DSS), time-to-treatment failure (TTF), objective responses (OR) and progressive disease (PD) in NSCLC patients treated with Nivolumab. Methods: This was a multicenter retrospective study conducted on 294 patients treated with Nivolumab for advanced NSCLC. Results: Of the more than 50 variables analyzed, five showed a signifi…
SOLTI-1503 PROMETEO TRIAL: combination of talimogene laherparepvec with atezolizumab in early breast cancer
2020
New treatment strategies such as immune checkpoint inhibitors and oncolytic viruses are opening new possibilities in cancer therapy. Preliminary results in melanoma and other tumors showed that the combination of talimogene laherparepvec with an anti-PD-1/PD-L1 or anti-CTLA4 has greater efficacy than either therapy alone, without additional safety concerns beyond those expected for each agent. The presence of residual cancer after neoadjuvant chemotherapy in early breast cancer patients is an unmet medical need. SOLTI-1503 PROMETEO is a window of opportunity trial, which evaluates the combination of talimogene laherparepvec in combination with atezolizumab in women with operable HER2-negati…
The Current Landscape of Clinical Trials for Systemic Treatment of HCC
2021
Simple Summary Liver cancer is a life-threatening disease. Apart from surgery and catheter-guided therapies, drugs are a central pillar for its treatment. Clinical trials are research studies that are designed to evaluate the treatment effect of a given drug. Therefore, they are the driving force behind innovation and medical progress. One such innovation in the past years has been immunotherapy, which has become increasingly important for treating cancer. Recently, the first such therapy has been approved for the treatment of liver cancer. Current clinical trials are exploring the benefit of immunotherapy and other therapies for this disease. This article gives an overview of such trials p…
Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants i…
2020
Simple Summary Many bilateral breast cancer patients with increased hereditary susceptibility to breast cancer result negative for BRCA1 or BRCA2 pathogenic variants and, thus, need a further genetic testing through a broader gene panel. Some patients with negative test result for BRCA1/2 pathogenic variants may harbor pathogenic variants in other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, PTEN, TP53. Of course, the use of a multi-gene panel provides clinicians more information through a single test. Therefore, we focused on potential clinical impact of a NGS-based multi-gene panel testing in bilateral breast cancer patients, in order to evaluate the utility of perform…
2021
Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patie…