Publications by authors named "Georg Bjarnason"
Objective: To evaluate and compare the outcomes of patients with localised renal cell carcinoma (RCC) with and without sarcomatoid features and the impact of this on cancer recurrence and survival.
Material And Methods: The Canadian Kidney Cancer information system database was used to identify patients diagnosed with localised RCC between January 2011 and December 2022. Patients with pT1-T3, n Nx-N0N1, M0 stage and documented sarcomatoid status were included.
Purpose: Postoperative prognostic tools allow for improved prediction of future recurrence risk, patient counseling, and assessment of eligibility for adjuvant treatments and ensure appropriate follow-up surveillance. The purpose of this analysis was to validate existing prognostic models for patients with kidney cancer.
Materials And Methods: The Canadian Kidney Cancer information system is a prospective cohort of patients managed at 14 institutions since January 1, 2011, to present.
JCO Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC.
View Article and Find Full Text PDFImmunotherapy-based systemic treatment (ST) is the standard of care for most patients diagnosed with metastatic renal cell carcinoma (mRCC). Cytoreductive nephrectomy (CN) has historically shown benefit for select patients with mRCC, but its role and timing are not well understood in the era of immunotherapy. The primary objective of this study is to assess outcomes in patients who received ST only, CN followed by ST (CN-ST), and ST followed by CN (ST-CN).
View Article and Find Full Text PDFIn the phase 3 CLEAR trial, lenvatinib plus pembrolizumab (L + P) showed superior efficacy versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (aRCC). The combination treatment was associated with a robust objective response rate of 71%. Here we report tumor responses for patients in the L + P arm in CLEAR, with median follow-up of ∼4 yr at the final prespecified overall survival (OS) analysis.
View Article and Find Full Text PDFBackground: Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI), has demonstrated efficacy in metastatic renal cell carcinoma (mRCC). The association between toxicity and therapeutic effectiveness has been established with other TKIs. We investigated whether cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, were associated with improved clinical outcomes in mRCC.
View Article and Find Full Text PDFRecent studies have established that the circadian clock influences onset, progression and therapeutic outcomes in a number of diseases including cancer and heart diseases. Therefore, there is a need for tools to measure the functional state of the molecular circadian clock and its downstream targets in patients. Moreover, the clock is a multi-dimensional stochastic oscillator and there are few tools for analysing it as a noisy multigene dynamical system.
View Article and Find Full Text PDFReal-world Assessment of Clinical Outcomes in Patients with Metastatic Renal Cell Carcinoma with or Without Sarcomatoid Features Treated with First-line Systemic Therapies.
Eur Urol Oncol
June 2024
Article Synopsis
- Metastatic renal cell carcinoma (mRCC) patients treated with immunotherapies (IO) show better overall survival outcomes compared to those treated with targeted therapies (TT), particularly in those with or without sarcomatoid features.
- A study involving 1,202 patients assessed the impact of different first-line systemic therapies, revealing that IO treatment led to a significantly longer median survival than TT for both nonsarcomatoid (72 vs. 48 months) and sarcomatoid (48 vs. 18 months) patients.
- The study utilized real-world data from the IMDC database and applied statistical models to ensure balanced comparisons, ultimately highlighting the effectiveness of IO in metastatic RCC treatment.
Article Synopsis
- The study examines the integration and use of systemic therapies for metastatic renal cell carcinoma (mRCC) in Canada between 2011 and 2021, highlighting significant advancements in treatment options over the years.
- Data was collected from the Canadian Kidney Cancer Information System, involving 4,107 patients, with a focus on treatment trends and patient demographics across two separate time cohorts.
- The findings indicate a rise in the use of immune checkpoint inhibitors and a shift towards vascular endothelial growth factor-tyrosine kinase inhibitors as subsequent treatments, with about 18-24% of patients participating in clinical trials based on their treatment line.
Article Synopsis
- - The CLEAR trial demonstrated that lenvatinib plus pembrolizumab was more effective than sunitinib in treating advanced renal cell carcinoma, particularly in the East Asian patient subset, which showed a median progression-free survival of 22.1 months versus 11.1 months with sunitinib.
- - In the East Asian group (213 patients), the objective response rate was also higher for the lenvatinib plus pembrolizumab combo at 65.3% compared to 49.2% for sunitinib.
- - Treatment-related side effects were common, with hand-foot syndrome appearing in 66.7% of those on lenvatinib plus pembrolizumab, indicating
Introduction: Several recent randomized trials evaluated the impact of adjuvant immune checkpoint inhibitor (ICI)-based therapy on post-surgical outcomes in renal cell carcinoma (RCC), with disparate results. The objective of this consensus statement is to provide data-driven guidance regarding the use of ICIs after complete resection of clear-cell RCC in a Canadian context.
Methods: An expert panel of genitourinary medical oncologists, urologic oncologists, and radiation oncologists with expertise in RCC management was convened in a dedicated session during the 2022 Canadian Kidney Cancer Forum in Toronto, Canada.
Purpose: A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-α) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported.
Patients And Methods: Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-α 9 MU subcutaneously thrice weekly.
Article Synopsis
- - 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
Background: The combination of immuno-oncology (IO) agents ipilimumab and nivolumab (IPI-NIVO) and vascular endothelial growth factor targeted therapies (VEGF-TT) combined with IO (IO-VEGF) are current standard of care first-line treatments for metastatic renal cell carcinoma (mRCC).
Objective: To establish real-world clinical benchmarks for IO combination therapies based on the International mRCC Database Consortium (IMDC) criteria.
Design, Setting, And Participants: Patients with mRCC who received first-line IPI-NIVO, IO-VEGF, or VEGF-TT from 2002 to 2021 were identified using the IMDC database and stratified according to IMDC risk groups.
Background: Brain metastases (BM) in metastatic renal cell carcinoma (mRCC) have been reported to be present in up to 25% of patients diagnosed with mRCC. There is limited published literature evaluating the role of routine intra-cranial imaging for the screening of asymptomatic BM in mRCC.
Aims: To evaluate the potential utility of routine intra-cranial imaging, a retrospective cohort study was conducted to characterize the outcomes of mRCC patients who presented with asymptomatic BM, as compared to symptomatic BM.
Introduction: We conducted a systematic literature review to identify evidence for cabozantinib activity in patients with solid tumors after prior checkpoint inhibitor (CPI) therapy.
Methods: The review was conducted according to PRISMA guidelines and registered with PROSPERO (CRD42021259873). MEDLINE®, Embase, and the Cochrane Library were searched on 19 May 2021 to identify publications reporting the efficacy/effectiveness and safety/tolerability of cabozantinib in patients with solid tumors who had received prior CPI-based therapy.
Purpose: With the integration of immunotherapy (IO) agents in the management of metastatic renal cell carcinoma (mRCC), there has been interest in the combined use with radiation therapy (RT). However, real world data are limited. The purpose of this study was to evaluate outcomes in patients with mRCC receiving both RT and IO compared with IO alone.
View Article and Find Full Text PDFBackground: Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options for patients with advanced disease. Data supporting the effectiveness of ICI-based therapy in advanced non-clear cell RCC (nccRCC) is more limited.
Methods: We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC) to evaluate the outcomes of patients with advanced nccRCC.
Introduction: Ipilimumab plus nivolumab was associated with a survival benefit in a phase III clinical trial of first-line treatment for metastatic renal cell carcinoma (mRCC). In this study, mRCC patients from the Canadian Kidney Cancer Information System (CKCis) database who received first-line ipilimumab plus nivolumab were analyzed to determine the safety and outcomes in a real-world setting.
Patients And Methods: Patients who received ipilimumab plus nivolumab as first-line therapy for mRCC in CKCis, were identified, and the amount of treatment received, discontinuation rates, and reasons for discontinuing treatment were determined.
With sunitinib treatment of metastatic renal cell carcinoma, most patients end up developing resistance over time. Recent clinical trials have shown that individualizing treatment protocols could delay resistance and result in better outcomes. We developed an in vivo xenograft tumor model and compared tumor growth rate, morphological, and transcriptomic differences between alternative and traditional treatment schedules.
View Article and Find Full Text PDFPapillary renal cell carcinoma (PRCC) classification has traditionally been divided into two histologic types, type 1 and type 2. A new biological stratification system has recently been proposed based on comprehensive morphologic and genomic analysis. The predominant molecular marker in this 4-tiered stratification is the renal drug transporter ABCC2.
View Article and Find Full Text PDFBackground: Treatment options for metastatic renal cell carcinoma (mRCC) include cytoreductive nephrectomy (CN) and systemic therapy (ST). Results from the CARMENA and SURTIME trials suggest that CN before ST may not be the optimal treatment strategy for mRCC.
Objective: To use real-world data to evaluate and compare outcomes for patients with mRCC who underwent CN before, after, or without ST to those patients who only received ST.