Purpose: Clinical trials enable renal cell carcinoma (RCC) patients to receive promising investigational agents, yet access may be limited. Telemedicine (TM) is an increasingly utilized platform that can expand access, but perspectives on its use in clinical trial care are unknown.
Patients And Methods: A prospective study was conducted between Jan 2023 - Oct 2023 at Memorial Sloan Kettering Cancer Center.
Background: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS).
Objective: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort.
Aims: Virus infection triggers inflammation and, may impose nutrient shortage to the heart. Supported by type I interferon (IFN) signalling, cardiomyocytes counteract infection by various effector processes, with the IFN-stimulated gene of 15 kDa (ISG15) system being intensively regulated and protein modification with ISG15 protecting mice Coxsackievirus B3 (CVB3) infection. The underlying molecular aspects how the ISG15 system affects the functional properties of respective protein substrates in the heart are unknown.
View Article and Find Full Text PDFBackground: Although different kidney cancers represent a heterogeneous group of malignancies, multiple subtypes including Von Hippel-Lindau (VHL)-altered clear cell renal cell carcinoma (ccRCC), fumarate hydratase (FH)- and succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC), and renal medullary carcinoma (RMC) are affected by genomic instability. Synthetic lethality with poly ADP-ribose polymerase inhibitors (PARPis) has been suggested in preclinical models of these subtypes, and paired PARPis with immune checkpoint blockade (ICB) may achieve additive and/or synergistic effects in patients with previously treated advanced kidney cancers.
Objective: To evaluate combined PARPi + ICB in treatment-refractory metastatic kidney cancer.
Combination treatment with immunotherapy agents and/or vascular endothelial growth factor tyrosine kinase inhibitors are a standard of care for patients with advanced clear cell renal cell carcinoma (ccRCC). Novel therapeutic combinations that include the hypoxia-inducible factor 2α inhibitor belzutifan and the cytotoxic T-lymphocyte-associated protein 4 inhibitor quavonlimab are being investigated for their potential to further improve patient outcomes. This protocol describes the rationale and design of the randomized, phase III LITESPARK-012 study, which will evaluate the efficacy and safety of pembrolizumab plus lenvatinib with or without belzutifan or quavonlimab as first-line treatment for advanced ccRCC.
View Article and Find Full Text PDFTumor cell phenotypes and anti-tumor immune responses are shaped by local metabolite availability, but intratumoral metabolite heterogeneity (IMH) and its phenotypic consequences remain poorly understood. To study IMH, we profiled tumor/normal regions from clear cell renal cell carcinoma (ccRCC) patients. A common pattern of IMH transcended all patients, characterized by correlated fluctuations in the abundance of metabolites and processes associated with ferroptosis.
View Article and Find Full Text PDFPurpose: The clinical course of patients being placed on surveillance in a cohort of systemic therapy-naïve patients who undergo cytoreductive nephrectomy is not well documented. Thus, we evaluated the clinical course of patients placed on surveillance following cytoreductive nephrectomy and identified predictors of survival.
Materials And Methods: In this large single-institution study, we retrospectively analyzed metastatic renal cell carcinoma patients who underwent cytoreductive nephrectomy followed by surveillance.
Enhanced Disease Susceptibility 1 (EDS1), a key component of microbe-triggered immunity and effector-triggered immunity in most higher plants, forms functional heterodimeric complexes with its homologs Phytoalexin Deficient 4 (PAD4) or Senescence-associated Gene 101 (SAG101). Here, the crystal structure of VvEDS1 , the N-terminal domain of EDS1 from Vitis vinifera, is reported, representing the first structure of an EDS1 entity beyond the model plant Arabidopsis thaliana. VvEDS1 has an α/β-hydrolase fold, is similar to the N-terminal domain of A.
View Article and Find Full Text PDFBackground: Renal cell carcinoma (RCC) with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is a highly aggressive tumor with a poor prognosis. Immune checkpoint therapy (ICT) has shown significant treatment efficacy in this subtype. There remains uncertainly regarding the role of cytoreductive nephrectomy (CN) for patients with metastatic RCC (mRCC) with S/R who received ICT.
View Article and Find Full Text PDFThe severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has changed the clinical day-to-day practice. The aim of this study was to evaluate the impact of the pandemic on patients with high-grade glioma (HGG) as well as to derive best practice recommendations. We compared a multi-institutional cohort with HGG (n = 251) from 03/2020 to 05/2020 (n = 119) to a historical cohort from 03/2019 to 05/2019 (n = 132).
View Article and Find Full Text PDFBackground: Opsoclonus-myoclonus syndrome (OMS) is a rare, immune-mediated neurological disorder. In adults, the pathogenesis can be idiopathic, post-infectious or paraneoplastic, the latter etiology belonging to the ever-expanding group of defined paraneoplastic neurological syndromes (PNS). In contrast to other phenotypes of PNS, OMS cannot be ascribed to a single pathogenic autoantibody.
View Article and Find Full Text PDFBackground: Intratumoral heterogeneity (ITH) is a hallmark of clear cell renal cell carcinoma (ccRCC) that reflects the trajectory of evolution and influences clinical prognosis. Here, we seek to elucidate how ITH and tumor evolution during immune checkpoint inhibitor (ICI) treatment can lead to therapy resistance.
Methods: Here, we completed a single-arm pilot study to examine the safety and feasibility of neoadjuvant nivolumab in patients with localized RCC.
Purpose: With increasing patient self-empowerment and participation in decision making, we hypothesized that patients with adult-type diffuse gliomas, CNS WHO grade 4 who change sites of treatment differ from patients being entirely treated in one neuro-oncological center.
Methods: Prospectively collected data from all diffuse glioma grade 4 patients who underwent treatment in our neuro-oncological center between 2012 and 2018 were retrospectively examined for differences between patients having initially been diagnosed and/or treated elsewhere (External Group) and patients having entirely been treated in our neuro-oncological center (Internal Group). Additionally, a matched-pair analysis was performed to adjust for possible confounders.
Immunotherapy (IO)-based combinations used to treat metastatic clear cell renal cell carcinoma (ccRCC) include dual immune checkpoint inhibition with ipilimumab and nivolumab (IO/IO) and several combinations of vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors (TKIs) with an immune checkpoint inhibitor (TKI/IO). IO/IO and TKI/IO approaches have not been compared directly, and it is unknown whether patients who do not respond to first-line IO/IO can salvage long-term survival by receiving a second-line TKI. Progression-free survival after second-line therapy (PFS-2) evaluates the ability to be salvaged by second-line therapy.
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