A spatial architecture-embedding HLA signature to predict clinical response to immunotherapy in renal cell carcinoma.

An important challenge in the real-world management of patients with advanced clear-cell renal cell carcinoma (aRCC) is determining who might benefit from immune checkpoint blockade (ICB). Here we performed a comprehensive multiomics mapping of aRCC in the context of ICB treatment, involving discovery analyses in a real-world data cohort followed by validation in independent cohorts. We cross-connected bulk-tumor transcriptomes across >1,000 patients with validations at single-cell and spatial resolutions, revealing a patient-specific crosstalk between proinflammatory tumor-associated macrophages and (pre-)exhausted CD8 T cells that was distinguished by a human leukocyte antigen repertoire with higher preference for tumoral neoantigens.

Molecular Heterogeneity Between Paired Primary and Metastatic Lesions from Clear Cell Renal Cell Carcinoma.

Unlabelled: Highly effective systemic treatments have globally improved outcomes in metastatic clear-cell renal cell carcinoma (m-ccRCC). However, despite many efforts, reliable biomarkers predicting individual responses are currently lacking. Moreover, mixed responses are commonly observed.

Enterohormone therapy for short bowel syndrome.

Purpose Of Review: Short bowel syndrome (SBS) patients are at risk to develop intestinal failure when the decreased absorption of macronutrients, water, and electrolytes necessitates parenteral support for survival. The adverse effects of SBS and parenteral support negatively affect the quality of life (QoL) of SBS-intestinal failure patients. However, spontaneous intestinal adaptation along with disease-modifying therapies allow reducing parenteral support, thereby improving QoL.

Molecular underpinnings of glandular tropism in metastatic clear cell renal cell carcinoma: therapeutic implications.

Background: Glandular metastases (GM) have been associated with improved survival in metastatic clear cell renal cell carcinoma (m-ccRCC). We aimed to molecularly characterize m-ccRCC with GM.

Material And Methods: We performed a retrospective cohort study on all m-ccRCC patients with available tissue at our institution, diagnosed with metastatic disease from 2000 to 2019.

Molecular Subtypes and Gene Expression Signatures as Prognostic Features in Fully Resected Clear Cell Renal Cell Carcinoma: A Tailored Approach to Adjuvant Trials.

Background: Trials with adjuvant vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) failed to demonstrate meaningful benefit in clinically high-risk, fully resected clear cell renal cell carcinoma (ccRCC). We evaluated whether the ccrcc1-4 molecular subtypes and gene expression signatures (GES) are associated with outcomes in this setting.

Materials And Methods: We determined molecular subtypes as well as angiogenesis- and immune-related GES through RNA sequencing of 75 fresh frozen (FF) and 62 formalin-fixed, paraffin-embedded (FFPE) tumor samples.

MicroRNAs Targeting HIF-2α, VEGFR1 and/or VEGFR2 as Potential Predictive Biomarkers for VEGFR Tyrosine Kinase and HIF-2α Inhibitors in Metastatic Clear-Cell Renal Cell Carcinoma.

Metastatic clear-cell renal cell carcinoma (m-ccRCC) is characterized by increased hypoxia-induced factor (HIF)-2α and vascular endothelial growth factor receptor (VEGFR)-dependent angiogenesis through loss of function of the von Hippel-Lindau protein. VEGFR tyrosine kinase inhibitors (VEGFR-TKIs) are a cornerstone of m-ccRCC treatment, and new treatments targeting HIF-2α are currently under investigation. However, predictive biomarkers for these treatments are lacking.

MicroRNAs Possibly Involved in the Development of Bone Metastasis in Clear-Cell Renal Cell Carcinoma.

Bone metastasis in clear-cell renal cell carcinoma (ccRCC) leads to substantial morbidity through skeletal related adverse events and implicates worse clinical outcomes. MicroRNAs (miRNA) are small non-protein coding RNA molecules with important regulatory functions in cancer development and metastasis. In this retrospective analysis we present dysregulated miRNA in ccRCC, which are associated with bone metastasis.

Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma.

Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance.

C-reactive protein and neutrophil-lymphocyte ratio are prognostic in metastatic clear-cell renal cell carcinoma patients treated with nivolumab.

Objective: To evaluate the impact of markers of systemic inflammation such as C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) on outcomes of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with nivolumab.

Patients And Methods: We retrospectively evaluated m-ccRCC patients treated with nivolumab and collected known prognostic factors and survival data. We used Kaplan-Meier survival analysis and cox proportional hazards regression analysis to study prognostic factors for overall survival (OS) and progression-free survival (PFS) since start of nivolumab.

Too good for CARMENA: criteria associated with long systemic therapy free intervals post cytoreductive nephrectomy for metastatic clear cell renal cell carcinoma.

Purpose: The prospective CARMENA trial surprisingly suggested that patients with upfront metastatic clear-cell renal cell carcinoma (m-ccRCC) would not benefit from cytoreductive nephrectomy (CN). We aimed to identify the m-ccRCC patient subpopulation who would benefit from the continued use of CN.

Methods: We performed a retrospective cohort study on upfront m-ccRCC patients and identified three subgroups: patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) only without CN (TKI ONLY), patients undergoing CN immediately followed within 6 months by VEGFR-TKIs (CN > TKI) and patients undergoing CN followed by a considerable therapy-free interval of at least 6 months (CN > AS).

Pushing the limits of metastasis-directed treatment in metastatic renal cell carcinoma in the era of targeted therapy.

Objective: To assess the role of metastasis directed therapy and in particular surgical metastasectomy (MxT) in metastatic renal cell carcinoma (mRCC) in the era of targeted therapy.

Method: The files of all patients who underwent MxT for treatment of mRCC in University Hospitals Leuven between 1989 and 2015 were reviewed.

Results: One hundred and thirty eight patients met the inclusion criteria.

Bone metastasis is associated with poor prognosis in metastatic papillary renal cell carcinoma patients treated with first agent angiogenesis inhibitors.

Objective: Papillary renal cell carcinoma (papRCC) is a rare (10%-15%) subtype of renal cancer. Few prognostic biomarkers have been described in metastatic papRCC (m-papRCC) patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). We aimed to study the prognostic impact of bone metastases (BM) on response rate, progression-free and overall survival (PFS and OS) in patients with m-papRCC treated with first agent VEGFR-TKIs.

Rates and Predictors of Perioperative Complications in Cytoreductive Nephrectomy: Analysis of the Registry for Metastatic Renal Cell Carcinoma.

Background: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients.

Objective: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes.

Design, Setting, And Participants: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC).

Whole-body diffusion-weighted magnetic resonance imaging for the detection of bone metastases and their prognostic impact in metastatic renal cell carcinoma patients treated with angiogenesis inhibitors.

Metastatic renal cell carcinoma (mRCC) patients with bone metastases (BM) are at high risk for skeletal related events and have a poorer outcome when treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs). Computed tomography (CT) lacks sensitivity to detect BM in mRCC. We aimed to determine the added value of whole body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) to CT for the detection of BM in mRCC and to estimate the prognostic impact of the number of BM in mRCC patients treated with VEGFR-TKIs.

Clear-cell Renal Cell Carcinoma: Molecular Characterization of IMDC Risk Groups and Sarcomatoid Tumors.

Introduction: Recent trials have suggested predictive biomarkers in advanced clear-cell renal cell carcinoma (accRCC): International Metastatic RCC Database Consortium (IMDC) good risk or angiogenic gene signature for sunitinib and IMDC intermediate/poor risk for ipilimumab-nivolumab and T-effector cell signature or sarcomatoid dedifferentiation for atezolizumab-bevacizumab. We hypothesized that earlier described molecular subtypes, ccrcc1 to ccrcc4, could provide similar information as a single generic biomarker and molecularly characterize the heterogeneous intermediate-risk group.

Patients And Methods: Patients with accRCC treated with systemic therapies were included.

Fibroblast Growth Factor Receptor-2 Polymorphism rs2981582 is Correlated With Progression-free Survival and Overall Survival in Patients With Metastatic Clear-cell Renal Cell Carcinoma Treated With Sunitinib.

Background: There are no validated markers that predict response or resistance in patients with metastatic clear-cell renal cell carcinoma (mccRCC) treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors such as sunitinib and pazopanib. Recently, single nucleotide polymorphism (SNP) rs2981582 in Fibroblast Growth Factor Receptor 2 (FGFR2) was found to be associated with clinical outcome in patients with mccRCC treated with pazopanib and sunitinib. We aimed to validate these findings in patients treated with sunitinib.

Bone metastases and age are associated with earlier dose reductions in metastatic clear-cell renal cell carcinoma patients treated with angiogenesis inhibitors.

: Metastatic clear-cell renal cell carcinoma (m-ccRCC) patients with bone metastases (BM) treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) have a poorer outcome compared to patients without BM. We aimed to investigate whether an increased incidence of VEGFR-TKI treatment interruptions and/or dose reductions in patients with BM could explain this difference in outcome. : Retrospective study on m-ccRCC patients treated in first-line with VEGFR-TKI.

ABCG2 Polymorphism rs2231142 and hypothyroidism in metastatic renal cell carcinoma patients treated with sunitinib.

Background And Aim: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) cause significant adverse events including thyroid dysfunction, mainly hypothyroidism, in a considerable proportion of patients. In a series of metastatic renal cell carcinoma (mRCC) patients treated with sunitinib, we aimed to study the correlation between hypothyroidism and single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics and pharmacodynamics.

Patients And Methods: We included 79 mRCC patients who started sunitinib between November 2005 and March 2016.

Prospective evaluation of hypogonadism in male metastatic renal cell carcinoma patients treated with targeted therapies.

Objectives: To study the prevalence of hypogonadism in male patients with metastatic renal cell carcinoma (mRCC) starting with targeted therapies and the impact of the vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) sunitinib and pazopanib on the luteinizing hormone (LH)/testosterone (TT)-axis.

Methods: Male mRCC patients starting with targeted therapies were prospectively included in this study. TT- and LH-levels were sampled at start as well as during systemic therapy.

Polymorphisms in the Von Hippel-Lindau Gene Are Associated With Overall Survival in Metastatic Clear-Cell Renal-Cell Carcinoma Patients Treated With VEGFR Tyrosine Kinase Inhibitors.

Background: Clear-cell renal-cell carcinoma (ccRCC) is characterized by loss of a functional Von Hippel-Lindau (VHL) protein. We investigated the potential of 3 single nucleotide polymorphisms (SNPs) in VHL as biomarkers in metastatic ccRCC (m-ccRCC) patients treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).

Patients And Methods: We genotyped 3 VHL SNPs in 199 m-ccRCC patients: rs1642742 T > C, rs1642743 A > G, and rs1678607 C > A.