Publications by authors named "Lori A Wood"

33 Publications

Outcomes of patients with solid tumour malignancies treated with first-line immuno-oncology agents who do not meet eligibility criteria for clinical trials.

Eur J Cancer 2021 Jul 8;151:115-125. Epub 2021 May 8.

Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada. Electronic address:

Background: Immuno-oncology (IO)-based therapies have been approved based on randomised clinical trials, yet a significant proportion of real-world patients are not represented in these trials. We sought to compare the outcomes of trial-ineligible vs. -eligible patients with advanced solid tumours treated with first-line (1L) IO therapy.

Patients And Methods: Using the International Metastatic Renal Cell Carcinoma (RCC) Database Consortium and the Alberta Immunotherapy Database, patients with advanced RCC, non-small-cell lung cancer (NSCLC) or melanoma treated with 1L PD-(L)1 inhibition-based therapy were included. Trial eligibility was retrospectively determined as per commonly used exclusion criteria. The outcomes of interest were overall survival (OS), overall response rate (ORR), treatment duration (TD) and time to next treatment (TTNT).

Results: A total of 395 of 1241 (32%) patients were deemed trial-ineligible. The main reasons for ineligibility based on preselected exclusion criteria were Karnofsky performance status <70%/Eastern Cooperative Oncology Group performance status >1 (40%, 158 of 395), brain metastases (32%, 126 of 395), haemoglobin < 9 g/dL (16%, 63 of 395) and estimated glomerular filtration rate <40 mL/min (15%, 61 of 395). Between the ineligible vs. eligible groups, the median OS, ORR, median TD and median TTNT were 10.2 vs. 39.7 months (p < 0.01), 36% vs. 47% (p < 0.01), 2.7 vs. 6.9 months (p < 0.01) and 6.0 vs. 16.8 months (p < 0.01), respectively. Subgroup analyses showed statistically significant inferior OS, TD and TTNT for trial-ineligible vs. -eligible patients across all tumour types. Adjusted hazard ratios for death in RCC, NSCLC and melanoma were 1.84 (95% confidence interval [CI] 1.22-2.77), 2.21 (95% CI 1.58-3.11) and 1.82 (95% CI 1.21-2.74), respectively..

Conclusions: Thirty-two percent of real-world patients treated with contemporary 1L IO-based therapies were ineligible for clinical trials. Although one-third of the trial-ineligible patients responded to treatment, the overall trial-ineligible population had inferior outcomes than trial-eligible patients. These data may guide patient counselling and temper expectations of benefit.
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http://dx.doi.org/10.1016/j.ejca.2021.04.004DOI Listing
July 2021

Determining generalizability of the Canadian Kidney Cancer information system (CKCis) to the entire Canadian kidney cancer population.

Can Urol Assoc J 2020 Oct;14(10):E499-E506

Department of Medicine and Urology, Dalhousie University, Halifax, NS, Canada.

Introduction: The Canadian Kidney Cancer information system (CKCis) has prospectively collected data on patients with renal tumors since January 1, 2011 from 16 sites within 14 academic centers in six provinces. Canadian kidney cancer experts have used CKCis data to address several research questions. The goal of this study was to determine if the CKCis cohort is representative of the entire Canadian kidney cancer population, specifically regarding demographic and geographic distributions.

Methods: The CKCis prospective cohort was analyzed up to December 31, 2018. Baseline demographics and tumor characteristics were analyzed, including location of patients' residence at the time of CKCis entry. Geographic data is presented by province, rural vs. urban via postal code information (2 digit=0) and by Canadian urban boundary files. To determine the proportion of renal cell carcinoma (RCC) patients that CKCis captures, CKCis accruals were compared to projected Canadian Cancer Society RCC incidence in 2016-2017 and the incidence from the 2016 Canadian Cancer Registry. To determine if the CKCis baseline data is representative, it was compared to registry data and other published data when registry data was not available.

Results: This CKCis cohort includes 10 298 eligible patients: 66.6% male, median age 62.6 years; 14.6% had metastatic disease at the time of diagnosis and 70.4% had clear-cell carcinomas. The CKCis cohort captures about 1250 patients per year, which represents approximately 20% of the total kidney cancer incidence. The proportion of patients captured per province did vary from 13-43%. Rural patients make up 17% of patients, with some baseline differences between rural and urban patients. There appears to be no major differences between CKCis patient demographics and disease characteristics compared to national data sources. Canadian heat maps detailing patient location are presented.

Conclusions: CKCis contains prospective data on >10 000 Canadian kidney cancer patients, making it a valuable resource for kidney cancer research. The baseline demographic and geographic data do appear to include a broad cross-section of patients and seem to be highly representative of the Canadian kidney cancer population. Moving forward, future projects will include determining if CKCis cancer outcomes are also representative of the entire Canadian kidney cancer population and studying variations across provinces and within rural vs. urban areas.
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http://dx.doi.org/10.5489/cuaj.6716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716824PMC
October 2020

Prognostic impact of paraneoplastic syndromes on patients with non-metastatic renal cell carcinoma undergoing surgery: Results from Canadian Kidney Cancer information system.

Can Urol Assoc J 2021 Apr;15(4):132-137

Department of Surgery, University of Manitoba, Winnipeg, MB, Canada.

Introduction: The impact of paraneoplastic syndromes (PNS) on survival in patients with renal cell carcinoma (RCC) is uncertain. This study was conducted to analyze the association of PNS with recurrence and survival of patients with non-metastatic RCC undergoing nephrectomy.

Methods: The Canadian Kidney Cancer information system is a multi-institutional cohort of patients started in January 2011. Patients with nephrectomy for non-metastatic RCC were identified. PNS included anemia, polycythemia, hypercalcemia, and weight loss. Associations between PNS and recurrence or death were assessed using Kaplan-Meier curves and multivariable analysis.

Results: Of 4337 patients, 1314 (30.3%) had evidence of one or more PNS. Patients with PNS were older, had higher comorbidity, and had more advanced clinical and pathological tumor characteristics as compared to patients without PNS (all p<0.05). Kaplan-Meier five-year estimated recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were significantly worse in patients with PNS (63.7%, 84.3%, and 79.6%, respectively, for patients with PNS vs. 73.9%, 90.8%, and 90.1%, respectively, for patients without PNS, all p<0.005). On univariable analysis, presence of PNS increased risk of recurrence (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.48-1.90, p<0.0001) and cancer-related death (HR 1.85, 95% CI 1.34-2.54, p=0.0002). Adjusting for known prognostic factors, PNS was not associated with recurrence or survival.

Conclusions: In non-metastatic RCC patients undergoing surgery, presence of PNS is associated with older age, higher Charlson comorbidity index score, advanced tumor stage, and aggressive tumor histology. Following surgery, baseline PNS is not strongly independently associated with recurrence or death.
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http://dx.doi.org/10.5489/cuaj.6833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021432PMC
April 2021

Outcomes of complete metastasectomy in metastatic renal cell carcinoma patients: The Canadian Kidney Cancer information system experience.

Urol Oncol 2020 10 7;38(10):799.e1-799.e10. Epub 2020 Aug 7.

Faculty of Medicine, McGill University, Montreal, QC, Canada.

Background: Surgical resection of metastasis can be integrated in the management of metastatic renal cell carcinoma (mRCC) as it can contribute to delay disease progression and improve survival.

Objective: This study assessed the impact of complete metastasectomy in mRCC patients using real-world pan-Canadian data.

Design, Setting And Participants: The Canadian Kidney Cancer information system (CKCis) database was used to select patients who were diagnosed with mRCC between January 2011 and April 2019. To minimize selection bias, each patient having received a complete metastasectomy was matched with up to 4 patients not treated with metastasectomy.

Outcome Measurements And Statistical Analysis: Overall survival (OS) was calculated from the date of metastasectomy or selection, to death from any cause. A Cox proportional hazards model was used to assess the impact of the metastasectomy while adjusting for potential confounding variables.

Results: A total of 229 patients undergoing complete metastasectomy were matched with 803 patients not treated with metastasectomy. After matching, baseline characteristics were well balanced between groups. After 12 months, the proportion of patients that were still alive was 96.0% and 89.8% in the complete metastasectomy and its matched group, respectively; the 5-year OS were 63.2% and 51.4%, respectively. Multivariate analysis performed in the matched cohort revealed that patients who underwent complete metastasectomy had a lower risk of mortality compared to patients who did not undergo metastasectomy (hazard ratio: 0.41, 95% confidence interval:0.27-0.63).

Conclusion: Our study found that patients who underwent complete metastasectomy have a longer overall survival and a longer time to initiation of targeted therapy compared to patients not receiving metastasectomy. These findings should support aggressive resection of metastasis in selected patients.
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http://dx.doi.org/10.1016/j.urolonc.2020.07.021DOI Listing
October 2020

A Canadian approach to the regionalization of testis cancer: A review.

Can Urol Assoc J 2020 Oct;14(10):346-351

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada.

At the Canadian Testis Cancer Workshop, the rationale and feasibility of regionalization of testis cancer care were discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents and fellows, and nurses, as well as patients and patient advocacy groups.This review summarizes the discussion and recommendations of one of the central topics of the workshop - the centralization of testis cancer in Canada. It was acknowledged that non-guideline-concordant care in testis cancer occurs frequently, in the range of 18-30%. The National Health Service in the U.K. stipulates various testis cancer care modalities be delivered through supra-regional network. All cases are reviewed at a multidisciplinary team meeting and aspects of care can be delivered locally through the network. In Germany, no such network exists, but an insurance-supported online second opinion network was developed that currently achieves expert case review in over 30% of cases. There are clear benefits to regionalization in terms of survival, treatment morbidity, and cost. There was agreement at the workshop that a structured pathway for diagnosis and treatment of testis cancer patients is required.Regionalization may be challenging in Canada because of geography; independent administration of healthcare by each province; physicians fearing loss of autonomy and revenue; patient unwillingness to travel long distances from home; and the inability of the larger centers to handle the ensuing increase in volume. We feel the first step is to identify the key performance indicators and quality metrics to track the quality of care received. After identifying these metrics, implementation of a "networks of excellence" model, similar to that seen in sarcoma care in Ontario, could be effective, coupled with increased use of health technology, such as virtual clinics and telemedicine.
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http://dx.doi.org/10.5489/cuaj.6268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716843PMC
October 2020

First-line Immuno-Oncology Combination Therapies in Metastatic Renal-cell Carcinoma: Results from the International Metastatic Renal-cell Carcinoma Database Consortium.

Eur Urol 2019 12 22;76(6):861-867. Epub 2019 Aug 22.

Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada. Electronic address:

Background: In metastatic renal-cell carcinoma (mRCC), recent data have shown efficacy of first-line ipilimumab and nivolumab (ipi-nivo) as well as immuno-oncology (IO)/vascular endothelial growth factor (VEGF) inhibitor combinations. Comparative data between these strategies are limited.

Objective: To compare the efficacy of ipi-nivo versus IO-VEGF (IOVE) combinations in mRCC, and describe practice patterns and effectiveness of second-line therapies.

Design, Setting, And Participants: Using the International Metastatic Renal-cell Carcinoma Database Consortium (IMDC) dataset, patients treated with any first-line IOVE combination were compared with those treated with ipi-nivo.

Intervention: All patients received first-line IO combination therapies.

Outcome Measurements And Statistical Analysis: First- and second-line response rates, time to treatment failure (TTF), time to next treatment (TNT), and overall survival (OS) were analysed. Hazard ratios were adjusted for IMDC risk factors.

Results And Limitations: In total, 113 patients received IOVE combinations and 75 received ipi-nivo. For IOVE combinations versus ipi-nivo, first-line response rates were 33% versus 40% (between-group difference 7%, 95% confidence interval [CI] -8% to 22%, p =  0.4), TTF was 14.3 versus 10.2 mo (p =  0.2), TNT was 19.7 versus 17.9 mo (p =  0.4), and median OS was immature but not statistically different (p = 0.17). Adjusted hazard ratios for TTF, TNT, and OS were 0.71 (95% CI 0.46-1.12, p =  0.14), 0.65 (95% CI 0.38-1.11, p =  0.11), and 1.74 (95% CI 0.82-3.68, p =  0.14), respectively. Sixty-four (34%) patients received second-line treatment. In patients receiving subsequent VEGF-based therapy, second-line response rates were lower in the IOVE cohort than in the ipi-nivo cohort (15% vs 45%; between-group difference 30%, 95% CI 3-57%, p =  0.04; n = 40), though second-line TTF was not significantly different (3.7 vs 5.4 mo; p =  0.4; n = 55). Limitations include the study's retrospective design and sample size.

Conclusions: There were no significant differences in first-line outcomes between IOVE combinations and ipi-nivo. Most patients received VEGF-based therapy in the second line. In this group, second-line response rate was greater in patients who received ipi-nivo initially.

Patient Summary: There were no significant differences in key first-line outcomes for patients with metastatic renal-cell carcinoma receiving immuno-oncology/vascular endothelial growth factor inhibitor combinations versus ipilimumab and nivolumab.
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http://dx.doi.org/10.1016/j.eururo.2019.07.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858928PMC
December 2019

Cytoreductive Nephrectomy in Metastatic Papillary Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Eur Urol Oncol 2019 Nov 5;2(6):643-648. Epub 2019 Apr 5.

Tom Baker Cancer Centre, University of Calgary, Calgary, Canada. Electronic address:

Background: There is evidence that cytoreductive nephrectomy (CN) may be beneficial in metastatic renal cell carcinoma (mRCC). This has been studied predominantly in clear-cell RCC, with more limited data on the role of CN in patients with papillary histology.

Objective: To determine the benefit of CN in synchronous metastatic papillary RCC.

Design, Setting, And Participants: Using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) database, a retrospective analysis was performed for patients with papillary mRCC treated with or without CN.

Outcome Measurements And Statistical Analysis: Median overall survival (OS) and progression-free survival (PFS) were determined for both patient groups. Cox regression analysis was performed to control for imbalances in individual IMDC risk factors.

Results And Limitations: In total, 647 patients with papillary mRCC were identified, of whom 353 had synchronous metastatic disease. Of these, 109 patients were treated with CN and 244 were not. The median follow-up was 57.1mo (95% confidence interval [CI] 32.9-77.8) and the OS from the start of first-line targeted therapy for the entire cohort was 13.2mo (95% CI 12.0-16.1). Median OS for patients with CN was 16.3mo, compared to 8.6mo (p<0.0001) in the no-CN group. When adjusted for individual IMDC risk factors, the hazard ratio (HR) of death for CN was 0.62 (95% CI 0.45-0.85; p=0.0031). Limitations include the retrospective nature of the analysis.

Conclusions: The use of CN in patients with mRCC and papillary histology appears to be associated with better survival compared to no CN after adjustment for risk criteria. Selection of appropriate candidates for CN is crucial. A clinical trial in this rare population may not be possible.

Patient Summary: In a population of patients with advanced papillary kidney cancer, we found that surgical removal of the primary kidney tumor was associated with better overall survival.
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http://dx.doi.org/10.1016/j.euo.2019.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886238PMC
November 2019

Followup imaging studies in metastatic castration-resistant prostate cancer: An individualized approach.

Can Urol Assoc J 2019 Jun;13(6):201-202

Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.

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http://dx.doi.org/10.5489/cuaj.6033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570598PMC
June 2019

Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Cancer 2018 09 11;124(18):3677-3683. Epub 2018 Oct 11.

Department of Medical Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.

Background: To the authors' knowledge, outcomes and prognostic tools have yet to be clearly defined in patients with metastatic renal cell carcinoma (mRCC) who are treated with immuno-oncology (IO) checkpoint inhibitors (programmed death-ligand 1 [PD-L1] inhibitors). In the current study, the authors aimed to establish IO efficacy benchmarks in patients with mRCC and update patient outcomes in each International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class.

Methods: A retrospective analysis was performed using the IMDC database with data from 38 centers. It included patients with mRCC who were treated with ≥1 line of IO. Overall response rates (ORRs), duration of treatment (DOT), and overall survival (OS) were calculated. Patients were stratified using IMDC prognostic factors.

Results: A total of 687 patients (90% with clear cell and 10% with non-clear cell) were included. The ORR was 27% in evaluable patients (461 patients). In patients treated with first-line nivolumab and ipilimumab (49 patients), the combination of PD-L1 inhibitor and vascular endothelial growth factor inhibitor (72 patients), and PD-L1 inhibitor (51 patients), the ORR was 31%, 39%, and 40%, respectively, and the median DOT was 8.3 months, 14.7 months, and 8.3 months, respectively. The ORR for second-line, third-line, and fourth-line nivolumab was 22%, 24%, and 26%, respectively. The median DOT was 5.7 months, 6.2 months, and 8.3 months, respectively, in the second-line, third-line, and fourth-line settings. When segregated into IMDC favorable-risk, intermediate-risk, and poor-risk groups, the median OS rates for the first-line, second-line, third-line, and fourth-line treatment settings were not reached (NR), NR, and NR, respectively (P = .163); NR, 26.7 months, and 7.4 months, respectively (P < 0. 0001); 36.1 months, 28.2 months, and 11.1 months, respectively (P = .016); and NR, NR, and 6.7 months, respectively (P = .047).

Conclusions: The ORR was not found to deteriorate from the first-line to the fourth-line of IO therapy. In the second line through fourth line, the IMDC criteria appropriately stratified patients into favorable-risk, intermediate-risk, and poor-risk groups for OS.
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http://dx.doi.org/10.1002/cncr.31595DOI Listing
September 2018

Accuracy of kidney cancer diagnosis and histological subtype within Canadian cancer registry data.

Can Urol Assoc J 2017 Sep;11(9):E326-E329

Department of Urology, Dalhousie University, Halifax, NS; Canada.

Introduction: Provincial/territorial cancer registries (PTCRs) are the mainstay for Canadian population-based cancer statistics. Each jurisdiction captures this data in a population-based registry, including the Nova Scotia Cancer Registry (NSCR). The goal of this study was to describe data from the NSCR regarding renal cell carcinoma (RCC) pathology subtype and method of diagnosis and compare it to the actual pathology reports to determine the accuracy of diagnosis and histological subtype assignment.

Methods: This retrospective analysis included patients diagnosed with RCC in the NSCR from 2006-2010 with an ICD-O-3 code C64.9 seen or treated in the largest NS health district. From the NSCR, method of diagnosis and pathological diagnosis was recorded. All diagnoses of non-clear-cell RCC (nonccRCC) from NSCR were compared to the actual pathology report for descriptive comparison and reasons for discordance.

Results: 723 patients make up the study cohort. 81.3% of patients were diagnosed by nephrectomy, 11.1% radiography, 6.9 % biopsy, and 0.7% autopsy. By NSCR data, 52.8% had clear-cell (ccRCC), 20.5% RCC not otherwise specified (NOS), 12.7% papillary, 4% chromophobe, and the rest had other nonccRCC subtypes. By pathology reports, 69.5% had clear-cell, 15% papillary, 5% chromophobe, only 2.7% RCC NOS. There was a discordance rate of 15.4% between NSCR data and diagnosis from pathology report. Reasons for discordance were not enough information by the pathologist in 45.5%, misinterpretation of report by data coder in 22.2%, and true coding error in 32.3%.

Conclusions: When using PTCR for RCC incidence data, it is important to understand how the diagnosis is made, as not all are based on pathological confirmation; in this cohort 11% were based on radiology. One must also be aware that clear-cell and non-clear-cell subtypes may differ between the PTCR data and pathology reports. In this study, ccRCC made up 52.8% of the registry diagnoses, but increased to 69.6% on pathology report review. Use of synoptic reporting and ongoing education may improve accuracy of registry data.
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http://dx.doi.org/10.5489/cuaj.4269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798435PMC
September 2017

Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma.

J Clin Oncol 2017 Dec 13;35(35):3916-3923. Epub 2017 Sep 13.

Robert J. Motzer and Paul Russo, Memorial Sloan Kettering Cancer Center, New York, NY; Naomi B. Haas, University of Pennsylvania, Philadelphia, PA; Frede Donskov, Aarhus University Hospital, Aarhus, Denmark; Marine Gross-Goupil, Bordeaux University Hospital, Bordeaux, France; Sergei Varlamov, Altai Regional Cancer Center, Barnaul; Evgeny Kopyltsov, State Institution of Healthcare Regional Clinical Oncology Dispensary, Omsk, Russia; Jae Lyun Lee, University of Ulsan College of Medicine; Ho Yeong Lim, Sungkyunkwan University, Seoul, Republic of Korea; Bohuslav Melichar, Palacky University Medical School and Teaching Hospital, Olomouc; Milada Zemanova, Charles University and General University Hospital, Prague, Czech Republic; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; Lori A. Wood, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia; M. Neil Reaume, Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada; Arnulf Stenzl, University Hospital Tübingen, Tübingen; Christian Doehn, University of Lübeck Medical School and Urologikum Lübeck, Lübeck, Germany; Simon Chowdhury, Guy's and St Thomas' National Health Service Foundation/St Thomas' Hospital, London; Ray McDermott, Tallaght University Hospital and Cancer Trials Ireland, Dublin; Agnieszka Michael, University of Surrey, Guildford, United Kingdom; Weichao Bao, Marlene J. Carrasco-Alfonso, and Maurizio Voi, Novartis Oncology, East Hanover, NJ; Paola Aimone, Novartis Pharma AG, Basel, Switzerland; and Cora N. Sternberg, San Camillo Forlanini Hospital, Rome, Italy.

Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intent-to-treat (ITT) pazopanib 600 mg group (ITT), and DFS follow-up analysis was performed 12 months later. Secondary end point analyses included DFS with ITT pazopanib 800 mg (ITT) and safety. Results The primary analysis results of DFS ITT favored pazopanib but did not show a significant improvement over placebo (hazard ratio [HR], 0.86; 95% CI, 0.70 to 1.06; P = .165). The secondary analysis of DFS in ITT (n = 403) yielded an HR of 0.69 (95% CI, 0.51 to 0.94). Follow-up analysis in ITT yielded an HR of 0.94 (95% CI, 0.77 to 1.14). Increased ALT and AST were common adverse events leading to treatment discontinuation in the pazopanib 600 mg (ALT, 16%; AST, 5%) and 800 mg (ALT, 18%; AST, 7%) groups. Conclusion The results of the primary DFS analysis of pazopanib 600 mg showed no benefit over placebo in the adjuvant setting.
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http://dx.doi.org/10.1200/JCO.2017.73.5324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018511PMC
December 2017

Development and Implementation of a Continuing Medical Education Program in Canada: Knowledge Translation for Renal Cell Carcinoma (KT4RCC).

J Cancer Educ 2019 02;34(1):14-18

Division of Urology, Department of Surgery, The Ottawa Hospital, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada.

An in-person multidisciplinary continuing medical education (CME) program was designed to address previously identified knowledge gaps regarding quality indicators of care in kidney cancer. The objective of this study was to develop a CME program and determine if the program was effective for improving participant knowledge. CME programs for clinicians were delivered by local experts (uro-oncologist and medical oncologist) in four Canadian cities. Participants completed knowledge assessment tests pre-CME, immediately post-CME, and 3-month post-CME. Test questions were related to topics covered in the CME program including prognostic factors for advanced disease, surgery for advanced disease, indications for hereditary screening, systemic therapy, and management of small renal masses. Fifty-two participants attended the CME program and completed the pre- and immediate post-CME tests. Participants attended in Ottawa (14; 27%), Toronto (13; 25%), Québec City (18; 35%), and Montréal (7; 13%) and were staff urologists (21; 40%), staff medical oncologists (9; 17%), fellows (5; 10%), residents (16; 31%), and oncology nurses (1; 2%). The mean pre-CME test score was 61% and the mean post-CME test score was 70% (p = 0.003). Twenty-one participants (40%) completed the 3-month post-CME test. Of those that completed the post-test, scores remained 10% higher than the pre-test (p value 0.01). Variability in test scores was observed across sites and between French and English test versions. Urologists had the largest specialty-specific increase in knowledge at 13.8% (SD 24.2, p value 0.02). The kidney cancer CME program was moderately effective in improving provider knowledge regarding quality indicators of kidney cancer care. These findings support continued use of this CME program at other sites.
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http://dx.doi.org/10.1007/s13187-017-1259-7DOI Listing
February 2019

Spermatocytic Tumor With Sarcoma: A Rare Testicular Neoplasm.

Int J Surg Pathol 2017 Sep 25;25(6):559-562. Epub 2017 Apr 25.

1 Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.

Spermatocytic tumor, formerly known as spermatocytic seminoma, is an uncommon testicular neoplasm which is a distinct clinicopathologic entity from classic seminoma. These tumors are not associated with germ cell neoplasia in situ, other germ cell tumors, or isochromosome 12p. Although typically, these tumors have an excellent prognosis occasional cases are associated with sarcoma and have a very poor prognosis. We present a case of spermatocytic tumor with sarcoma showing a chondrosarcomatous component, discuss the pathologic findings and differential diagnosis and provide follow-up information.
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http://dx.doi.org/10.1177/1066896917706156DOI Listing
September 2017

Characterizing the outcomes of metastatic papillary renal cell carcinoma.

Cancer Med 2017 May 16;6(5):902-909. Epub 2017 Apr 16.

Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.

Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer in ccRCC patients and the hazard ratio of death was 0.71 for ccRCC patients. No differences in PFS or ORR were detected between type I and II PRCC in this limited dataset. The median OS for type I pRCC was 20.0 months while the median OS for type II was 12.6 months (P = 0.096). The IMDC prognostic model was able to stratify pRCC patients into favorable risk (OS = 34.1 months), intermediate risk (OS = 17.0 months), and poor-risk groups (OS = 6.0 months). pRCC patient outcomes were inferior to ccRCC, even after controlling for IMDC prognostic factors. The IMDC prognostic model was able to effectively stratify pRCC patients.
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http://dx.doi.org/10.1002/cam4.1048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430092PMC
May 2017

Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma.

Clin Genitourin Cancer 2017 06 12;15(3):403-410.e2. Epub 2017 Jan 12.

Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA. Electronic address:

Background: A significant subgroup of metastatic renal cell carcinoma (mRCC) patients discontinue vascular endothelial growth factor-targeted therapies (VEGF-TT) because of toxicity. Whether clinical outcomes differ in patients who receive second-line (2L) targeted therapy on the basis of reason for discontinuation of first-line (1L) therapy is unknown.

Patients And Methods: Patients from 15 International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) centers who started 2L targeted therapy were included and the reason for discontinuation of 1L therapy retrospectively collected. Treatment outcomes of 2L, including response, time to treatment failure, and overall survival (OS) were assessed.

Results: In total, 1124 patients were identified: 866 patients (77%) discontinued 1L VEGF-TT because of disease progression, and 208 patients (19%) because of toxicity. The reason for discontinuation of 1L therapy did not differ according to IMDC risk group. Compared with patients who stopped 1L VEGF-TT because of disease progression, patients who stopped because of toxicity had greater clinical benefit (nonprogressive disease as best response) in 2L treatment (68% vs. 56%; adjusted odds ratio, 1.58; 95% confidence interval [CI], 1.07-2.35; P = .023) and longer OS (17.4 vs. 11.2 months; adjusted hazard ratio, 0.69; 95% CI, 0.56-0.84; P = .0002) adjusted for type of therapy, time to initiation of 2L treatment, IMDC risk group, and number of metastases at initiation of 2L treatment.

Conclusion: mRCC patients who discontinue 1L VEGF-TT because of toxicity have better outcomes with 2L therapy than patients who stop therapy because of disease progression. These findings should be taken into consideration when designing clinical trials for 2L therapies in mRCC.
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http://dx.doi.org/10.1016/j.clgc.2017.01.005DOI Listing
June 2017

Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category.

Eur Urol 2017 06 19;71(6):970-978. Epub 2016 Oct 19.

Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada.

Background: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response.

Objective: To assess outcomes of 2L according to type of therapy and change in IMDC prognostic category.

Design, Setting, And Participants: We performed a retrospective review of the IMDC database for mRCC patients who received first-line (1L) VEGF inhibitors (VEGFi) and then 2L with VEGFi or mTOR inhibitors (mTORi). IMDC prognostic categories were defined before each line of therapy (favorable, F; intermediate, I; poor, P). Data were analyzed for 1516 patients, of whom 89% had clear cell histology.

Intervention: All included patients received targeted therapy for mRCC.

Outcome Measurements And Statistical Analysis: Overall survival (OS), time to treatment failure, and response to 2L were analyzed using Cox or logistic regression.

Results And Limitations: At start of 2L, 60% of patients remained in the same prognostic category; 9.0% improved (3% I → F; 6% P → I); 31% deteriorated (15% F → I or P; 16% I → P). Patients with the same or better IMDC prognostic category had a longer time to treatment failure if they remained on VEGFi compared to those who switched to mTORi (adjusted hazard ratio [AHR] ranging from 0.33 to 0.78, adjusted p<0.05). Patients who deteriorated from F to I appeared more likely to benefit from switching to mTORi (median OS 16.5 mo, 95% confidence interval [CI] 12.0-19.0 for VEGFi; 20.2 mo, 95% CI 14.3-26.1 for mTORi; AHR 1.53, 95% CI 1.04-2.24; adjusted p=0.03).

Conclusions: Changes in IMDC prognostic category predict the subsequent clinical course for patients with mRCC and provide a rational basis for selection of subsequent therapy.

Patient Summary: The pattern of treatment failure might help to predict what the next treatment should be for patients with metastatic renal cell carcinoma.
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http://dx.doi.org/10.1016/j.eururo.2016.09.047DOI Listing
June 2017

Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations.

J Clin Oncol 2016 Oct;34(30):3655-3663

Laurence Albiges, Wanling Xie, Rana R. McKay, Andre P. Fay, Guillermo de Velasco, Sabina Signoretti, and Toni K. Choueiri, Dana-Farber Cancer Institute; Wanling Xie, Rana R. McKay, Mark A. Preston, Eunyoung Cho, Sabina Signoretti, and Toni K. Choueiri, Brigham and Women's Hospital; Laurence Albiges, Wanling Xie, Rana R. McKay, Andre P. Fay, Guillermo de Velasco, Eunyoung Cho, David F. McDermott, Sabina Signoretti, and Toni K. Choueiri, Harvard Medical School; Mark A. Preston and Kathryn M. Wilson, Harvard School of Public Health; David F. McDermott, Beth Israel Deaconess Medical Center, Boston, MA; Laurence Albiges, Gustave Roussy, Université Paris-Saclay, Villejuif, France; A. Ari Hakimi, Emily C. Zabor, Anders J. Skanderup, and Helena Furberg, Memorial Sloan Kettering Cancer Center, New York; Ronit Simantov and Xun Lin, Pfizer Oncology, New York, NY; Jae-Lyun Lee, University of Ulsan College of Medicine, Asan; Sun-Young Rha, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Sandy Srinivas, Stanford Cancer Institute, Stanford; Sumanta K. Pal, City of Hope Comprehensive Cancer Center, Duarte, CA; Georg A. Bjarnason, Sunnybrook Odette Cancer Center, Toronto; Scott Ernst, London Health Sciences Center, London, Ontario; Lori A. Wood, Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia; Daniel Y.C. Heng, Tom Baker Cancer Center; University of Calgary, Calgary, Alberta, Canada; Ulka N. Vaishamayan, Karmanos Cancer Center, Detroit, MI; Neeraj Agarwal, University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Takeshi Yuasa, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; Aristotelis Bamias, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; and Eunyoung Cho, The Warren Alpert Medical School of Brown University; Brown University School of Public Health, Providence, RI.

Purpose: Obesity is an established risk factor for clear cell renal cell carcinoma (RCC); however, some reports suggest that RCC developing in obese patients may be more indolent. We investigated the clinical and biologic effect of body mass index (BMI) on treatment outcomes in patients with metastatic RCC.

Methods: The impact of BMI (high BMI: ≥ 25 kg/m v low BMI: < 25 kg/m) on overall survival (OS) and treatment outcome with targeted therapy was investigated in 1,975 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and in an external validation cohort of 4,657 patients. Gene expression profiling focusing on fatty acid metabolism pathway, in The Cancer Genome Atlas data set, and immunohistochemistry staining for fatty acid synthase (FASN) were also investigated. Cox regression was undertaken to estimate the association of BMI with OS, adjusted for the IMDC prognostic factors.

Results: In the IMDC cohort, median OS was 25.6 months (95% CI, 23.2 to 28.6) in patients with high BMI versus 17.1 months (95% CI, 15.5 to 18.5) in patients with low BMI (adjusted hazard ratio, 0.84; 95% CI, 0.73 to 0.95). In the validation cohort, high BMI was associated with improved OS (adjusted hazard ratio, 0.83; 95% CI, 0.74 to 0.93; medians: 23.4 months [95% CI, 21.9 to 25.3 months] v 14.5 months [95% CI, 13.8 to 15.9 months], respectively). In The Cancer Genome Atlas data set (n = 61), FASN gene expression inversely correlated with BMI (P = .034), and OS was longer in the low FASN expression group (medians: 36.8 v 15.0 months; P = .002). FASN immunohistochemistry positivity was more frequently detected in IMDC poor (48%) and intermediate (34%) risk groups than in the favorable risk group (17%; P-trend = .015).

Conclusion: High BMI is a prognostic factor for improved survival and progression-free survival in patients with metastatic RCC treated with targeted therapy. Underlying biology suggests a role for the FASN pathway.
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http://dx.doi.org/10.1200/JCO.2016.66.7311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065111PMC
October 2016

First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Eur J Cancer 2016 09 31;65:102-8. Epub 2016 Jul 31.

Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada. Electronic address:

Background: Sunitinib (SU) and pazopanib (PZ) are standards of care for first-line treatment of metastatic renal cell carcinoma (mRCC). However, how the efficacy of these drugs translates into effectiveness on a population-based level is unknown.

Patients And Methods: We used the International mRCC Database Consortium (IMDC) to assess overall survival (OS), progression-free survival (PFS), response rate (RR) and performed proportional hazard regression adjusting for IMDC prognostic groups. Second-line OS (OS2) and second-line PFS (PFS2) were also evaluated.

Results: We obtained data from 7438 patients with mRCC treated with either first-line SU (n = 6519) or PZ (n = 919) with an overall median follow-up of 40.4 months (95% confidence interval [CI] 39.2-42.1). There were no significant differences in IMDC prognostic groups (p = 0.36). There was no OS difference between SU and PZ (22.3 versus 22.6 months, respectively, p = 0.65). When adjusted for IMDC criteria, the hazard ratio (HR) of death for PZ versus SU was 1.03 (95% CI 0.92-1.17, p = 0.58). There was no PFS difference between SU and PZ (8.4 versus 8.3 months, respectively, p = 0.17). When adjusted for IMDC criteria, the HR for PFS for PZ versus SU was 1.08 (95% CI 0.981-1.19, p = 0.12). There was no difference in RR between SU and PZ (30% versus 28%, respectively, p = 0.15). We also found no difference in any second-line treatment between either post-SU or post-PZ groups for OS2 (13.1 versus 11 months, p = 0.27) and PFS2 (3.7 versus 5.0 months, p = 0.07).

Conclusions: We confirmed in real-world practice that SU and PZ have similar efficacy in the first-line setting for mRCC and do not affect outcomes with subsequent second-line treatment.
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http://dx.doi.org/10.1016/j.ejca.2016.06.016DOI Listing
September 2016

Third-line Targeted Therapy in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Eur Urol 2017 02 16;71(2):204-209. Epub 2016 Jun 16.

Tom Baker Cancer Center, Calgary, AB, Canada. Electronic address:

Background: The use of third-line targeted therapy (TTT) in metastatic renal cell carcinoma (mRCC) is not well characterized and varies due to the lack of robust data to guide treatment decisions. This study examined the use of third-line therapy in a large international population.

Objective: To evaluate the use and efficacy of targeted therapy in a third-line setting.

Design, Setting, And Participants: Twenty-five international cancer centers provided consecutive data on 4824 mRCC patients who were treated with an approved targeted therapy. One thousand and twelve patients (21%) received TTT and were included in the analysis.

Outcome Measurements And Statistical Analysis: Patients were analyzed for overall survival (OS) and progression-free survival using Kaplan-Meier curves, and were evaluated for overall response. Cox regression analyses were used to determine the statistical association between OS and the six factors included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. Subgroup analysis was performed on patients stratified by their IMDC prognostic risk status.

Results And Limitations: Everolimus was the most prevalent third-line therapy (27.5%), but sunitinib, sorafenib, pazopanib, temsirolimus, and axitinib were all utilized in over ≥9% of patients. Patients receiving any TTT had an OS of 12.4 mo, a progression-free survival of 3.9 mo, and 61.1% of patients experienced an overall response of stable disease or better. Patients not receiving TTT had an OS of 2.1 mo. Patients with favorable- (7.2%) or intermediate-risk (65.3%) disease had the highest OS with TTT, 29.9 mo and 15.5 mo, respectively, while poor-risk (27.5%) patients survived 5.5 mo. Results are limited by the retrospective nature of the study.

Conclusions: TTT remains highly heterogeneous. The IMDC prognostic criteria can be used to stratify third-line patients. TTT use in favorable- and intermediate-risk patients was associated with the greatest OS.

Patient Summary: Patients with favorable- and intermediate-prognostic criteria disease treated with third-line targeted therapy have an associated longer overall survival compared with those with poor risk disease.
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http://dx.doi.org/10.1016/j.eururo.2016.05.049DOI Listing
February 2017

Characterizing the impact of lymph node metastases on the survival outcome for metastatic renal cell carcinoma patients treated with targeted therapies.

Eur Urol 2015 Sep 15;68(3):506-15. Epub 2014 Dec 15.

Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada. Electronic address:

Background: It is unknown whether lymph node metastases (LNM) and their localization negatively affect clinical outcome in metastatic renal cell carcinoma (mRCC) patients.

Objective: To evaluate the clinicopathological features, survival outcome, and treatment response in mRCC patients with LNM versus those without LNM after treatment with targeted therapies (TT).

Design, Setting, And Participants: Patients (n=2996) were first analyzed without consideration of lymph node (LN) localization or histologic subtype. Additional analyses (n=1536) were performed in subgroups of patients with supradiaphragmatic (SPD) LNM, subdiaphragmatic (SBD) LNM, and patients with LNM in both locations (SPD+/SBD+) without histologic considerations, and then separately in clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC) patients, respectively.

Outcome Measurements And Statistical Analysis: The primary outcome was overall survival (OS) and the secondary outcome was progression-free survival (PFS).

Results And Limitations: All patients with LNM had worse PFS (p=0.001) and OS (p<0.001) compared to those without LNM. Compared to patients without LNM (PFS 8.8 mo; OS 25.1 mo), any SBD LNM involvement was associated with worse PFS (SBD, 6.8 mo; p=0.003; SPD+/SBD+, 5.5 mo; p<0.001) and OS (SBD, 16.2 mo; p<0.001; SPD+/SBD+, 11.5 mo; p<0.001). Both SBD and SPD+/SBD+ LNM were retained as independent prognostic factors in multivariate analyses (MVA) for PFS (p=0.006 and p=0.022, respectively) and OS (both p<0.001), while SPD LNM was not an independent risk factor. Likewise, in ccRCC, SBD LNM (19.8 mo) and SPD+/SBD+ LNM (12.85 mo) patients had the worst OS. SPD+/SBD+ LNM (p=0.006) and SBD LNM (p=0.028) were independent prognostic factors for OS in MVA, while SPD LNM was not significant (p=0.301). The study is limited by its retrospective design and the lack of pathologic evaluation of LNM in all cases.

Conclusions: The metastatic spread of RCC to SBD lymph nodes is associated with poor prognosis in mRCC patients treated with TT.

Patient Summary: The presence of lymph node metastases below the diaphragm is associated with shorter survival outcome when metastatic renal cell carcinoma (mRCC) patients are treated with targeted therapies. Clinical trials should evaluate whether surgical removal of regional lymph nodes at the time of nephrectomy may improve outcomes in high-risk RCC patients.
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http://dx.doi.org/10.1016/j.eururo.2014.11.054DOI Listing
September 2015

Outcome of patients with metastatic sarcomatoid renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Clin Genitourin Cancer 2015 Apr 23;13(2):e79-85. Epub 2014 Sep 23.

Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.

Background: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking.

Patients And Methods: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed.

Results: Two thousand two hundred eighty-six patients were identified (sRCC: n = 230 and non-sRCC: n = 2056). sRCC patients had significantly worse IMDC prognostic criteria compared with non-sRCC (11% vs. 19% favorable risk; 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; P < .0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; P < .0001). There was no significant difference in the incidence of central nervous system metastases (6%-8%) or underlying clear cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as first-line therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P < .0001, for both). sRCC patients had significantly less use of second- (P = .018) and third-line (P < .0001) systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P < .0001 for both). Sarcomatoid histology was associated with a significantly worse PFS and OS after adjusting for individual IMDC risk factors in multivariable analysis (hazard ratio, 1.5; P < .0001 for both).

Conclusion: Patients with sRCC have a shorter time to relapse, worse baseline prognostic criteria, and worse clinical outcome with targeted therapy. Additional insight into the biology of sRCC is needed to develop alternative therapeutics.
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http://dx.doi.org/10.1016/j.clgc.2014.08.011DOI Listing
April 2015

Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Eur Urol 2014 Oct 13;66(4):704-10. Epub 2014 Jun 13.

Dana-Farber Cancer Institute, Boston, MA, USA.

Background: The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic renal cell carcinoma (mRCC) in the era of targeted therapy.

Objective: To determine OS benefit of CN compared with no CN in mRCC patients treated with targeted therapies.

Design, Setting, And Participants: Retrospective data from patients with synchronous mRCC (n=1658) from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676 mRCC patients who did not.

Outcome Measurements And Statistical Analysis: OS was compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria.

Results And Limitations: Patients who had CN had better IMDC prognostic profiles versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%, 45%, and 54%, respectively). The median OS of patients with CN versus without CN was 20.6 versus 9.5 mo (p<0.0001). When adjusted for IMDC criteria to correct for imbalances, the HR of death was 0.60 (95% confidence interval, 0.52-0.69; p<0.0001). Patients estimated to survive <12 mo may receive marginal benefit from CN. Patients who have four or more of the IMDC prognostic criteria did not benefit from CN. Data were collected retrospectively.

Conclusions: CN is beneficial in synchronous mRCC patients treated with targeted therapy, even after adjusting for prognostic factors. Patients with estimated survival times <12 mo or four or more IMDC prognostic factors may not benefit from CN. This information may aid in patient selection as we await results from randomized controlled trials.

Patient Summary: We looked at the survival outcomes of metastatic renal cell carcinoma patients who did or did not have the primary tumor removed. We found that most patients benefited from tumor removal, except for those with four or more IMDC risk factors.
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http://dx.doi.org/10.1016/j.eururo.2014.05.034DOI Listing
October 2014

The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Cancer Database Consortium.

Eur Urol 2014 Apr 26;65(4):723-30. Epub 2013 Oct 26.

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Background: Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients treated with immunotherapy.

Objective: To investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium.

Design, Setting, And Participants: Data on 1661 patients treated with first-line vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy for mRCC were available from 18 cancer centers to study the impact of hyponatremia (serum sodium level <135 mmol/l) on clinical outcomes.

Outcome Measurements And Statistical Analysis: The primary objective was overall survival (OS) and secondary end points included time to treatment failure (TTF) and the disease control rate (DCR). The chi-square test was used to compare the DCR in patients with and without hyponatremia. OS and TTF were estimated with the Kaplan-Meier method and differences between groups were examined by the log-rank test. Multivariable logistic regression (for DCR) and Cox regression (for OS and TTF) were undertaken adjusted for prognostic risk factors.

Results And Limitations: Median OS after treatment initiation was 18.5 mo (95% confidence interval [CI], 17.5-19.8 mo), with 552 (33.2%) of patients remaining alive on a median follow-up of 22.1 mo. Median baseline serum sodium was 138 mmol/l (range: 122-159 mmol/l), and hyponatremia was found in 14.6% of patients. On univariate analysis, hyponatremia was associated with shorter OS (7.0 vs 20.9 mo), shorter TTF (2.9 vs 7.4 mo), and lower DCR rate (54.9% vs 78.8%) (p<0.0001 for all comparisons). In multivariate analysis, these effects remain significant (hazard ratios: 1.51 [95% CI, 1.26-1.80] for OS, and 1.57 [95% CI, 1.34-1.83] for TTF; odds ratio: 0.50 [95% CI, 34-0.72] for DCR; adjusted p<0.001). Results were similar if sodium was analyzed as a continuous variable (adjusted p<0.0001 for OS, TTF, and DCR).

Conclusions: This is the largest multi-institutional report to show that hyponatremia is independently associated with a worse outcome in mRCC patients treated with VEGF- and mTOR-targeted agents.
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http://dx.doi.org/10.1016/j.eururo.2013.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142674PMC
April 2014

Lingual angioedema associated with everolimus.

Acta Oncol 2010 ;49(1):107-9

Dalhousie University, Halifax, Nova Scotia, Canada.

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http://dx.doi.org/10.3109/02841860903246599DOI Listing
April 2010

Renal cell carcinoma: currently the most interesting genitourinary malignancy.

Can Urol Assoc J 2007 Jun;1(2 Suppl):S74-6

Department of Medicine, Dalhousie University, Halifax, NS, and the Division of Urology, and the Departments of Surgery and Surgical Oncology, Princess Margaret Hospital and the University Health Network, and the University of Toronto, Toronto, Ont.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2422952PMC
http://dx.doi.org/10.5489/cuaj.72DOI Listing
June 2007

Summary of the first annual Genitourinary Medical Oncology Conference Renal Cell Carcinoma Forum.

Can Urol Assoc J 2007 Jun;1(2 Suppl):S6-S12

Division of Medical Oncology, Queen Elizabeth II Health Sciences Centre, Halifax, NS.

The first annual Canadian Genitourinary Medical Oncology Conference was held in June 2006 before the Canadian Urology Association Annual Meeting. This article summarizes 3 presentations that took place as part of the Renal Cell Carcinoma Forum: "Treatment of Metastatic Renal Cell Carcinoma: 2006 and Beyond" was presented by Dr. Bernard Escudier; "Practical Experience with Targeted Therapy," by Dr. Lori Wood; and "Sarcomatoid Renal Cell Carcinoma," by Dr. Neil Reaume.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2422956PMC
http://dx.doi.org/10.5489/cuaj.62DOI Listing
June 2007