Publications by authors named "Brandon Manley"

Article Synopsis
  • Immunotherapy has enhanced survival rates for patients with advanced clear cell renal cell carcinoma (ccRCC), but many patients still develop resistance to treatment.
  • A study examined tumor samples from patients with both treatment-naïve and treatment-exposed ccRCC, revealing that tumors exposed to immunotherapy contained more immune cells (like CD8+ T cells and neutrophils) and showed significant changes in cellular markers.
  • Key findings included increased expression of COL4A1 and ITGAV in the stroma of treated tumors, suggesting a need for further investigation into how these changes impact the tumor immune environment and potential new therapies.
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  • Integrative analysis of expression data is tough due to varying factors like sample processing and RNA quality, making it hard to remove unwanted batch effects effectively.
  • The BatchFLEX Shiny app helps visualize and correct these batch effects using different methods, illustrating their impact on gene expression in immune cells.
  • The tool is accessible on GitHub and Shiny.io, with additional supplementary data available online for further reference.
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  • Neuroendocrine carcinoma of the bladder (NEC-bladder) is a rare and aggressive cancer, and the study focused on patients treated between 2001-2021 to assess treatment outcomes.
  • The research found that most patients received neoadjuvant chemotherapy (NAC), and higher rates of pathologic complete response (pCR) and downstaging were associated with improved progression-free and overall survival (PFS and OS).
  • Key findings indicated that achieving ypN0 status (negative nodes post-treatment) correlated with better long-term survival, while the presence of nodal involvement (pN+) was linked to poorer outcomes.
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Prostate cancer is the most commonly diagnosed cancer in men worldwide. Early diagnosis of the disease provides better treatment options for these patients. Magnetic resonance imaging (MRI) provides an overall assessment of prostate disease.

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New spatial molecular technologies are poised to transform our understanding and treatment of urological cancers. By mapping the spatial molecular architecture of tumours, these platforms uncover the complex heterogeneity within and around individual malignancies, offering novel insights into disease development, progression, diagnosis, and treatment. They enable tracking of clonal phylogenetics in situ and immune-cell interactions in the tumour microenvironment.

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  • There is limited data on how often testicular germ cell tumors (TGCT) occur alongside venous tumor thrombus (VTT), and the study aims to provide insights on this rare condition and its management.
  • Researchers analyzed records from the IBM Marketscan database, identifying a small prevalence of TGCT with VTT and gathered expert insights from surgeons on the patient management practices at multiple centers.
  • Findings showed that approximately 0.3% to 3.1% of TGCT cases involved VTT, with surgical options being the primary treatment, emphasizing the complexity of managing this combination and the need for a multidisciplinary approach.
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Purpose: Patients with advanced renal cell carcinoma (RCC) face significant challenges, stemming both from the complexities of the disease itself and the adverse effects of treatments. This study evaluated the feasibility and acceptability of a mobile health (mHealth) application tailored for education and symptom management of patients with advanced RCC receiving combined immune checkpoint inhibitor and tyrosine kinase inhibitor (ICI-TKI) therapy.

Methods: The primary end points were acceptability and feasibility.

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Background: Patients with advanced chronic kidney disease (ACKD) are at an increased risk of developing renal cell carcinoma (RCC), but molecular alterations in RCC specimens arising from ACKD and overall survival (OS) in affected patients are not well defined.

Patients And Methods: Using the Oncology Research Information Exchange Network (ORIEN) Total Cancer Care protocol, 296 consented adult patients with RCC and somatic tumor whole exome sequencing were included. Patients with ACKD were defined as those with serum creatinine ≥1.

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Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.

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A specific splicing isoform of RNASET2 is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). However, the interplay between wild-type RNASET2 and its splice variant and how this might contribute to the pathogenesis of ccRCC remains poorly understood. We sought to better understand the relationship of RNASET2 in the pathogenesis of ccRCC and the interplay with a pathogenic splicing isoform (RNASET2-SV) and the tumor immune microenvironment.

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The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

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Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis.

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Background: Standardized, high-quality PRO data reporting is crucial for patient centered care in the field of oncology, especially in clinical trials that establish standard of care. This study evaluated PRO endpoint design, conduct and reporting methods in FDA approved drugs for GU malignancies.

Methods: A systematic review of the FDA archives identified GU cancer drug approvals from Feb 2007 to July 2022.

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Article Synopsis
  • Multifocal partial nephrectomy (MPN) is crucial for removing multiple kidney masses, but its effects on kidney function over time are not well understood.* -
  • A study involving 1,307 partial nephrectomies compared the changes in kidney function (measured by glomerular filtration rate) between MPN and standard partial nephrectomy (SPN) across different time points after surgery.* -
  • Results showed that MPN leads to a greater initial decline in kidney function within the first year compared to SPN, but long-term kidney function outcomes were found to be similar for both procedures after 24 months.*
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Background: Immunotherapy (IO) has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with IO naïve and IO exposed primary ccRCC tumors to better understand IO resistance. Spatial molecular imaging (SMI) was obtained for tumor and adjacent stroma samples.

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  • * Researchers analyzed plasma samples from 55 prostate cancer patients over time, identifying significant 5hmC differences in genes associated with disease progression, particularly noting enrichment in androgen response genes.
  • * Findings suggest that 5hmC profiles can help predict which patients may develop resistance to ADT, revealing important insights into cancer progression and potential therapeutic approaches.
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  • Immunotherapy (IO) has revolutionized the treatment of advanced genitourinary cancers, showing benefits in both metastatic and localized cases.
  • Recent trials, such as KEYNOTE-057 and Checkmate274, have highlighted the positive effects of drugs like pembrolizumab and nivolumab for various bladder and kidney cancers, leading to FDA approvals.
  • The integration of IO into treatment plans for aggressive localized genitourinary cancers is becoming increasingly important, with oncologists urged to stay updated on emerging trials and practices.
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Background: Immunogenomics approaches to the characterization of renal cell carcinoma (RCC) have helped to better our understanding of the features of RCC immune dysfunction. However, much is still unknown with regard to specific immune interactions and their impact in the tumor microenvironment.

Objective: This study applied chemical complementarity scoring for the TRB complementarity determining region-3 (CDR3) amino acid sequences and cancer testis antigens (CTAs) to determine whether such complementarity correlated with survival and the expression of immune marker genes.

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Introduction: In clear cell renal cell carcinoma (ccRCC), tumor-associated macrophage (TAM) induction of CD8+T cells into a terminally exhausted state has been implicated as a major mechanism of immunotherapy resistance, but a deeper biological understanding is necessary.

Methods: Primary ccRCC tumor samples were obtained from 97 patients between 2004 and 2018. Multiplex immunofluorescence using lymphoid and myeloid markers was performed in seven regions of interest per patient across three predefined zones, and geospatial analysis was performed using Ripley's K analysis, a methodology adapted from ecology.

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Clinical trials play a critical role in evidence-based medicine, when rigorous scientific methodology is utilized to discover and test the effectiveness and safety of new drugs to prevent or cure diseases, including cancer. Participation in clinical trials thus becomes key to successful completion of these trials. Although it is estimated that >70% of Americans are inclined to participate in clinical trials, less than 5% of adult cancer patients participate in clinical trials.

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Background: The treatment landscape for metastatic renal cell carcinoma (mRCC) has significantly evolved in recent years. Without direct comparator trials, factors such as cost effectiveness (CE) are important to guide decision-making.

Objective: To assess the CE of guideline-recommended approved first- and second-line treatment regimens.

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Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment.

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Cancer-specific alternatively spliced events (ASE) play a role in cancer pathogenesis and can be targeted by immunotherapy, oligonucleotide therapy, and small molecule inhibition. However, identifying actionable ASE targets remains challenging due to the uncertainty of its protein product, structure impact, and proteoform (protein isoform) function. Here we argue that an integrated multi-omics profiling strategy can overcome these challenges, allowing us to mine this untapped source of targets for therapeutic development.

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Renal cell carcinoma is a diverse group of diseases that can be distinguished by distinct histopathologic and genomic features. In this comprehensive review, we highlight recent advancements in our understanding of the genetic and microenvironmental hallmarks of kidney cancer. We begin with clear cell renal cell carcinoma (ccRCC), the most common subtype of this disease.

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Objectives: To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC) with the aim of decreasing morbidity associated with therapy.

Patients And Methods: Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centres between 2020 and 2022. The primary outcome was safety profile, as graded by Common Terminology Criteria for Adverse Events (v5.

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