A5070461373- Renal cell carcinoma treatment
- Cancer Genomics and Diagnostics
- Renal and related cancers
- Cancer, Hypoxia, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Cancer Immunotherapy and Biomarkers
- Diabetes Treatment and Management
- Bladder and Urothelial Cancer Treatments
- Multiple and Secondary Primary Cancers
- Economic and Financial Impacts of Cancer
- Prostate Cancer Treatment and Research
- Cancer Diagnosis and Treatment
- Radiopharmaceutical Chemistry and Applications
- Genetic and Kidney Cyst Diseases
- Ferroptosis and cancer prognosis
- Brain Metastases and Treatment
- Glioma Diagnosis and Treatment
- Cancer Research and Treatments
- Testicular diseases and treatments
- Dialysis and Renal Disease Management
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
- Global Cancer Incidence and Screening
- CAR-T cell therapy research
Johns Hopkins Medicine
2020-2025
Johns Hopkins University
2020-2025
Sidney Kimmel Comprehensive Cancer Center
2022-2025
University Hospital Waterford
2016-2024
Johns Hopkins Hospital
2021-2024
Memorial Sloan Kettering Cancer Center
2018-2023
St. Vincent's University Hospital
2015-2017
St. James's Hospital
2016
The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or stage IV RCC typically undergo surgery and/or receive systemic therapy. Tumor histology risk stratification patients is important in therapy selection. stratify treatment recommendations by histology; first-line ccRCC are also stratified group. To further guide advanced RCC, Panel has categorized all kidney cancer regimens as...
The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These Insights focus on the systemic therapy options advanced RCC summarize new clinical data evaluated by panel recommended therapies in Version 2.2024 Cancer.
Abstract Purpose: Fumarate hydratase–deficient renal cell carcinoma (FH-RCC) is a rare, aggressive form of RCC associated with hereditary leiomyomatosis and syndrome. Evidence for systemic therapy efficacy lacking. Experimental Design: We studied clinical genomic characteristics FH-RCC, including response [objective rate (ORR)] to therapies next-generation sequencing (NGS). Patients metastatic defined by presence pathogenic germline or somatic FH mutation plus IHC evidence loss, were...
Metastatic translocation renal cell carcinomas (mtRCCs) are rare and aggressive tumors with limited treatment options. Recent studies demonstrated promising activity of immune-oncology (IO) combinations in mtRCC. However, the effectiveness dual IO versus plus VEGF-TKI remains unclear. We conducted a retrospective analysis mtRCC patients at 4 institutions. Eligible had confirmed by genitourinary pathologist received combination therapy (IO+IO or IO+VEGF-TKI). Clinical data outcomes were...
Abstract There is conflicting data regarding the role of PBAF complex mutations and response to immune checkpoint blockade (ICB) therapy in clear cell renal carcinoma (ccRCC) other solid tumors. We assess prevalence from two large cohorts including pan-cancer TCGA project ( n = 10,359) MSK-IMPACT immunotherapy cohort 3700). Across both cohorts, mutations, predominantly PBRM1 are most common ccRCC. In multivariate models ccRCC patients treated with ICB 189), loss-of-function (LOF) not...
With a rapidly developing immunotherapeutic landscape for patients with metastatic clear cell renal carcinoma, biomarkers of efficacy are highly desirable to guide treatment strategy. Hematoxylin and eosin (H&E)-stained slides inexpensive widely available in pathology laboratories, including resource-poor settings. Here, H&E scoring tumor-infiltrating immune cells (TILplus) pre-treatment tumor specimens using light microscopy is associated improved overall survival (OS) three independent...
BACKGROUNDImmune-related adverse events (irAEs) and their associated morbidity/mortality are a key concern for patients receiving immune checkpoint inhibitors (ICIs). Prospective evaluation of the drivers irAEs in diverse pan-tumor cohort is needed to identify at greatest risk develop rational treatment interception strategies.METHODSIn an observational study, we prospectively collected blood samples performed regular clinical evaluations ICI therapy as standard care solid tumors. We...
Background Loss-of-function alterations in DNA damage repair (DDR) genes are associated with human tumorigenesis and may determine benefit from immune-oncology (I/O) agents as shown colon cancer. However, biologic significance relevance to I/O metastatic clear cell RCC (ccRCC) unknown. Methods Genomic data treatment outcomes were retrospectively collected for patients ccRCC. Tumor germline subject targeted next generation sequencing across >400 of interest, including 34 DDR genes....
TPST-1120 is a first-in-class oral inhibitor of peroxisome proliferator-activated receptor α (PPARα), fatty acid ligand-activated transcription factor that regulates genes involved in oxidation, angiogenesis, and inflammation, novel target for cancer therapy. displayed antitumor activity xenograft models synergistic tumor reduction syngeneic when combined with anti-PD-1 agents.
We previously reported on a phase 2 study of everolimus plus bevacizumab across various nonclear cell renal carcinoma (nccRCC) histologies and observed encouraging activity among patients with papillary RCC (pRCC) unclassified (uRCC) major component. subsequently expanded the to enroll additional pRCC variants.Everolimus was administered at standard doses until disease progression or intolerance therapy. The primary endpoint 6-month progression-free survival (PFS) rate; secondary endpoints...
Abstract Purpose: High body mass index (BMI) may lead to improved immune-checkpoint blockade (ICB) outcomes in metastatic clear cell renal carcinoma (mccRCC). However, BMI is a crude size measure. We investigated and radiographically assessed composition (BC) parameters association with mccRCC ICB outcomes. Experimental Design: Retrospective study of ICB-treated patients mccRCC. BC variables [skeletal muscle (SMI) multiple adiposity indexes] were determined using pretreatment CT scans....
Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior 15 evaluable with ccRCC. leveraged tissue from that cohort elucidate the effects PD-1 inhibition on immune populations ccRCC and correlate evolving milieu anti-PD-1 response. found durably induces pro-inflammatory state within primary tumor, baseline...
445 Background: The treatment landscape of mRCC has evolved in recent years with the advent immune-checkpoint inhibitors (ICIs). Area Deprivation Index (ADI) measures social determinants health geographically, ranking neighborhoods by socioeconomic disadvantage. However, there are limited data on ICIs outcomes relation to ADI. We investigated association between ADI and clinical ICI mRCC. Methods: conducted a retrospective analysis 560 patients (pts) treated at our institution from 2013...
503 Background: LDTs, including surgical resection, radiation treatment and ablation/embolization, can be employed to achieve a disease-free state in indolent oligometastatic RCC irrespective of subtype. However, the efficacy LDTs chRCC, rare subtype, has not been investigated. We utilized multi-institutional chRCC dataset examine LDT use patterns associated duration disease control. Methods: Clinical characteristics patients with metachronous metastases were retrospectively collected from...
548 Background: Combination tyrosine kinase inhibitors (TKIs) and immune checkpoint (IO) are an established standard of care for patients with metastatic renal cell carcinoma (mRCC). We report updated analysis a multi-center, investigator-initiated (IIT), phase I/II study axitinib (axi) nivolumab (nivo) in the previously treated patient cohort. Methods: The investigated combination axi/nivo initial dose finding I portion II including 2 parallel arms: treatment naïve mRCC TKIs or IO/IO...
Abstract Self-reported Black (B) individuals remain underrepresented in molecular studies of clear cell renal carcinoma (ccRCC) relative to White (W) individuals. We performed whole-exome and transcriptome sequencing on paired tumor normal samples from 59 matched B W patients undergoing nephrectomy for localized ccRCC, comparing differences by estimated genetic similarity African (AFR) European (EUR) 1000 Genomes groups. validated our findings with a propensity-matched subset TCGA, yielding...
<p>AFR and EUR groups drive somatic alterations in ccRCC independent of AFR genetic similarity percentage. <b>A,</b> Density plot by self-reported race demonstrating a bimodal distribution. Frequency mutations (<b>B</b>) cytoband gains/losses (<b>C</b>). <i>P</i> values were determined Fisher’s exact test corrected for FDR. <b>D,</b> Logistic regression percentage among B individuals (<i>n</i> = 69) vs....
<p>Differential expression analysis and hallmark gene set enrichment of AFR vs. EUR groups. <b>A,</b> Wald statistic DEGs comparing T (<i>x</i>-axis) N (<i>y</i>-axis). Colored points depict significant genes with an FDR-adjusted <i>P</i> < 0.05, green representing genetic similarity–associated in tumor comparisons (<i>n</i> = 73), blue normal 74), red that are both 1). <b>B,</b> Volcano plot depicting the TCGA...
<p><i>VHL</i> mutation status is associated with both molecular subtype and genetic similarity. <b>A,</b> OncoPrint of ccRCC driver mutations split by IMm151 subtype. <i>P</i> values were calculated using Fisher’s exact test. <b>B,</b> Frequency <i>VHL</i> in patients AFR/EUR grouping. Mut, mutant; SNV, single nucleotide variant; wt, wild-type.</p>