Publications by authors named "Roy Elias"

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 of dual IO combinations versus IO plus VEGF-TKI combinations remains unclear.

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Objective: To evaluate the association between tumour size and the growth rate (GR) of small renal masses (SRMs) in patients managed by active surveillance (AS).

Materials And Methods: We queried the prospective, multi-institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry for patients on AS with an imaging interval of ≥6 months, identifying 456 patients. We tracked tumour size over time; a GR >0.

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  • * A study compared 17 desmoplastic melanomas (including 5 NFLDM cases) with 53 neurofibromas to identify distinguishing features and the role of molecular testing in diagnosis.
  • * Key differences include the presence of lymphoid aggregates and specific vascular structures in neurofibromas that are absent in NFLDM, along with molecular testing revealing genetic abnormalities linked to melanoma.
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  • - The study aimed to analyze survival rates and genetic factors in testis cancer specifically among Hispanic men, using data from a national cancer registry between 2000 and 2020.
  • - Results showed that Hispanic patients were younger at diagnosis but had more advanced disease, leading to poorer cancer-specific survival for non-seminomatous germ cell tumors compared to Non-Hispanic Whites, while survival rates for seminomas were similar.
  • - Genetic analysis indicated that while there were no significant differences in mutation frequencies between ethnic groups, there was diverse ancestral background among Hispanic patients, highlighting variations in genetic heritage.
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Chromophobe renal cell carcinoma (ChRCC) is the third most common subtype of renal cell carcinoma and typically exhibits indolent behavior, though a rare subset can exhibit high-grade morphologic features and is associated with a poor prognosis. Although there are limited data on the molecular characteristics of metastatic and sarcomatoid ChRCC, the molecular features of high-grade, nonsarcomatoid ChRCC remain unexplored. Herein, we characterize 22 cases of ChRCC with high-grade, nonsarcomatoid components.

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This report highlights key research from the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, with a focus on clear cell renal cell carcinoma (ccRCC) and non-clear cell RCC (nccRCC) across clinical trials and translational studies. Essential updates in the metastatic ccRCC clinical space encompass results from the CONTACT-03 study, which evaluated an immunotherapy containing regimen for patients who progressed on an initial immunotherapy containing regimen, alongside updated results from the KEYNOTE-426 and CLEAR trials. In the metastatic nccRCC domain, we review clinical trials of combination immunotherapies and tyrosine kinase inhibitors (TKIs).

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Purpose: Racially driven outcomes in cancer are challenging to study. Studies evaluating the impact of race in renal cell carcinoma (RCC) outcomes are inconsistent and unable to disentangle socioeconomic disparities from inherent biological differences. We therefore seek to investigate socioeconomic determinants of racial disparities with respect to overall survival (OS) when comparing Black and White patients with RCC.

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Background: Metastatic renal cell carcinoma (mRCC) is a heterogenous disease with poor 5-year overall survival (OS) at 14%. Patients with mRCC to endocrine organs historically have prolonged OS. Pancreatic metastases are uncommon overall, with mRCC being the most common etiology of pancreatic metastases.

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Hemoptysis is a complication of intrathoracic tumors, both primary and metastatic, and the risk may be increased by procedural interventions as well as Stereotactic Ablative Radiation (SAbR). The risk of hemoptysis with SAbR for lung cancer is well characterized, but there is a paucity of data about intrathoracic metastases. Here, we sought to evaluate the incidence of life-threatening/fatal hemoptysis (LTH) in patients with renal cell carcinoma (RCC) chest metastases with a focus on SAbR.

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  • - Cabozantinib is a powerful treatment for metastatic renal cell carcinoma (mRCC), but options are limited after patients progress on standard doses; some studies suggest that increasing dosages of tyrosine kinase inhibitors (TKIs) might help control the disease better.
  • - The study evaluated the effects of escalating cabozantinib doses from 60 mg to 80 mg (or more) in patients who had previously shown responsiveness to the drug but had progressed, finding that this approach led to additional disease control lasting an average of 14 months for some patients.
  • - Results from six patients showed no severe side effects from increased dosing, and pharmacokinetic data indicated that the exposure levels from 80 mg tablets are comparable
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Purpose: Immune checkpoint inhibitors (ICI) targeting the programmed cell death protein 1 and its ligand (PD-1/PD-L1) have transformed the treatment paradigm for metastatic renal cell carcinoma (RCC). However, response rates to ICIs as single agents or in combination vary widely and predictive biomarkers are lacking. Possibly related to the heterogeneity and dynamic nature of PD-L1 expression, tissue-based methods have shown limited value.

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Characterized by intracellular lipid droplet accumulation, clear cell renal cell carcinoma (ccRCC) is resistant to cytotoxic chemotherapy and is a lethal disease. Through an unbiased siRNA screen of 2-oxoglutarate (2-OG)-dependent enzymes, which play a critical role in tumorigenesis, we identified Jumonji domain-containing 6 (JMJD6) as an essential gene for ccRCC tumor development. The downregulation of JMJD6 abolished ccRCC colony formation in vitro and inhibited orthotopic tumor growth in vivo.

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  • Immune checkpoint inhibitors (ICIs) are key treatments for metastatic renal cell carcinoma (mRCC) but can lead to immune-related adverse events, including ICI colitis, particularly in patients using proton pump inhibitors (PPIs).
  • A study at the University of Texas Southwestern examined the relationship between PPI use and ICI colitis in 176 mRCC patients treated with ICIs from 2015 to 2018, finding that 9.1% developed ICI colitis.
  • Results indicated that chronic PPI use for over 8 weeks and exposure to the drug ipilimumab were significantly associated with an increased risk of developing ICI colitis in these patients.
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Active surveillance (AS) may be used in the management of metastatic renal cell carcinoma (mRCC), but consensus regarding its application is lacking. We report an exploratory analysis of prospectively collected specimens prespecified in the only modern clinical trial evaluating AS in mRCC. Whole-exome and RNA sequencing were performed for patients providing consent to identify putative biomarkers associated with time on AS (TAS), the primary endpoint.

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Renal cell carcinoma (RCC) encompasses a heterogenous group of tumors, but representative preclinical models are lacking. We previously showed that patient-derived tumorgraft (TG) models recapitulate the biology and treatment responsiveness. Through systematic orthotopic implantation of tumor samples from 926 ethnically diverse individuals into non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice, we generate a resource comprising 172 independently derived, stably engrafted TG lines from 148 individuals.

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Purpose: Intratumoral heterogeneity (ITH) challenges the molecular characterization of clear cell renal cell carcinoma (ccRCC) and is a confounding factor for therapy selection. Most approaches to evaluate ITH are limited by two-dimensional tissue analyses. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can noninvasively assess the spatial landscape of entire tumors in their natural milieu.

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Preclinical studies demonstrated that complement promotes tumor growth. Therefore, we sought to determine the best target for complement-based therapy among common human malignancies. High expression of 11 complement genes was linked to unfavorable prognosis in renal cell carcinoma.

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Immune checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab have improved outcomes in metastatic renal cell carcinoma (mRCC) patients, but they are also associated with immune-related adverse events (irAEs). As observed in melanoma, we hypothesized that patients experiencing an autoimmune reaction directed against the tissue of origin may be more likely to benefit from ICI. Specifically, we asked whether patients with immune-related acute interstitial nephritis (irAIN) exhibited improved outcomes.

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The discovery of the von Hippel-Lindau (VHL) gene marked a milestone in our understanding of clear cell renal cell carcinoma (ccRCC) pathogenesis. VHL inactivation is not only a defining feature of ccRCC, but also the initiating event. Herein, we discuss canonical and noncanonical pVHL functions, as well as breakthroughs shaping our understanding of ccRCC evolution and evolutionary subtypes.

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Objective: To evaluate the pathologic response, safety, and feasibility of nephrectomy following receipt of immune checkpoint inhibition (ICI) for renal cell carcinoma (RCC).

Methods: Patients who underwent nephrectomy for RCC after exposure to nivolumab monotherapy or combination ipilimumab/nivolumab were reviewed. Primary surgical outcomes included operative time (OT), estimated blood loss (EBL), length of stay (LOS), readmission rates, and complication rates.

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