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1.  Progression-Free Survival as a Predictor of Overall Survival in Metastatic Renal Cell Carcinoma Treated With Contemporary Targeted Therapy 
Cancer  2010;117(12):10.1002/cncr.25750.
BACKGROUND
The majority of metastatic renal cell carcinoma (mRCC) clinical trials that examined targeted agents used progression-free survival (PFS) as the primary endpoint. Whether PFS can be used as a predictor of overall survival (OS) is unknown.
METHODS
Patients from 12 cancer centers who received targeted therapy for mRCC were identified. Landmark analyses for progression at 3 months and 6 months after drug initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS.
RESULTS
In total, 1158 patients were included. The median follow-up was 30.6 months, the median age was 60 years, and the median Karnofsky performance status was 80%. For the entire cohort, the median PFS was 7.6 months, and the median OS was 19.7 months. In the landmark analysis, the median OS for patients who progressed at 3 months was 7.8 months compared with 23.6 months for patients who did not progress (log-rank test; P < .0001). Similarly, for patients who progressed at 6 months, the median OS was 8.6 months compared with 26 months for patients who did not progress (P < .0001). Compared with those who did not progress, for the patients who progressed at 3 months and at 6 months, the hazard ratios for death adjusted for adverse prognostic factors were 3.05 (95% confidence interval, 2.42-3.84) and 2.96 (95% confidence interval, 2.39-3.67), respectively. Similar results were demonstrated with landmark analyses at 9 months and at 12 months and in the bootstrap validation. Kendall tau rank correlation and a Fleischer model demonstrated a statistically significant dependent correlation.
CONCLUSIONS
PFS at 3 months and at 6 months predicted OS, and the current results indicated that PFS may be a meaningful intermediate endpoint for OS in patients with mRCC who receive treatment with novel agents.
doi:10.1002/cncr.25750
PMCID: PMC3856357  PMID: 21656741
progression-free survival; overall survival; surrogate endpoints; vascular endothelial growth factor; metastatic renal cell carcinoma
2.  Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: a population-based study 
The lancet oncology  2012;13(9):10.1016/S1470-2045(12)70285-1.
Summary
Background
The advent of targeted therapies in the past 7 years has extended median survival for metastatic renal-cell carcinoma. This improvement in clinical outcome has created a need for new, more accurate prognostic measures. We assessed the use of conditional survival—a measure that accounts for elapsed time since treatment initiation—for prognostication in patients with metastatic renal-cell carcinoma treated with first-line VEGF-targeted therapies.
Methods
We obtained data for patients with metastatic renal-cell carcinoma who were treated with a first-line VEGF-targeted therapy between April 7, 2003, and Oct 12, 2010, from our large multi-institutional International mRCC Database Consortium (centres in Canada, the USA, Singapore, Denmark, and South Korea). All histologies, performance statuses, and prognostic risk groups were included. The primary outcome was 2-year conditional survival, defined as the probability of surviving an additional 2 years from a given timepoint since the start of targeted therapy. Secondary analyses included 1-year and 3-year conditional survival, along with stratification of patients by Heng prognostic risk criteria and Karnofsky performance score, and conditional survival based on length of time on therapy. We used the Kaplan-Meier method and a landmark analysis to calculate conditional survival.
Findings
In the 1673 patients analysed, median follow-up for alive patients was 20·1 months (IQR 9·0–34·4). We recorded an increase in the 2-year conditional survival probability from 44% (95% CI 41–47) at 0 months to 51% (46–55) at 18 months since beginning targeted therapy. When stratified by the Heng prognostic risk criteria defined at therapy initiation, 2-year conditional survival changed little in the favourable and intermediate groups, but in the poor-risk group, 2-year conditional survival improved from 11% (8–15) at 0 months to 33% (18–48) after 18 months. When conditioned on time on targeted therapy from 0 months to 18 months, 2-year conditional survival improved from 44% (41–47) to 68% (60–75) in the overall population and from 74% (68–79) to 90% (77–96) in the favourable group, 49% (45–53) to 57% (45–67) in the intermediate group, and 11% (8–15) to 73% (43–89) in the poor risk group.
Interpretation
Conditional survival is a clinically useful prediction measure that adjusts prognosis of patients with metastatic renal-cell carcinoma on the basis of survival since treatment initiation or therapy duration. Conditional survival might be especially relevant to adjust prognosis for poor-risk patients.
Funding
The Trust Family Fund for Kidney Cancer Research.
doi:10.1016/S1470-2045(12)70285-1
PMCID: PMC3856362  PMID: 22877847
4.  Neoadjuvant chemotherapy should be administered to fit patients with newly diagnosed, potentially resectable muscle-invasive urothelial cancer of the bladder (MIBC): A 2013 CAGMO Consensus Statement and Call for a Streamlined Referral Process 
Neoadjuvant chemotherapy (NC) improves overall survival in patients with resectable muscle-invasive urothelial cancer of the bladder (MIBC). However uptake of NC in Canada is dis-appointingly low. Following a detailed literature review and in consultation with urologic oncology, the Canadian Association of Genitourinary Medical Oncologists (CAGMO) has developed a consensus statement for the use of NC in MIBC. Our primary goal is to increase the uptake of NC for MIBC in Canada and improve patient outcomes.
doi:10.5489/cuaj.1506
PMCID: PMC3854467  PMID: 24319508
5.  Canadian guideline on genetic screening for hereditary renal cell cancers 
Background:
Hereditary renal cell cancer (RCC) is an ideal model for germline genetic testing. We propose a guideline of hereditary RCC specific criteria to suggest referral for genetic assessment.
Methods:
A review of the literature and stakeholder resources for existing guidelines or consensus statements was performed. Referral criteria were developed by expert consensus.
Results:
The criteria included characteristics for patients with RCC (age ≤45 years, bilateral or multifocal tumours, associated medical conditions and non-clear cell histologies with unusual features) and for patients with or without RCC, but a family history of specific clinical or genetic diagnoses.
Conclusions:
This guideline represents a practical RCC-specific reference to allow healthcare providers to identify patients who may have a hereditary RCC syndrome, without extensive knowledge of each syndrome. RCC survivors and their families can also use the document to guide their discussions with healthcare providers about their need for referral. The criteria refer to the most common hereditary renal tumour syndromes and do not represent a comprehensive or exclusive list. Prospective validation of the criteria is warranted.
doi:10.5489/cuaj.1496
PMCID: PMC3854468  PMID: 24319509
9.  A case of metastatic adenocarcinoma of the prostate arising in a meningioma 
We present the case of a 70-year-old man who had a prostate adenocarcinoma that metastatized to a previously unknown cranial meningioma. Central nervous system (CNS) metastases are very uncommon in patients with prostate cancer, and metastases to pre-existing primary CNS tumours are even more uncommon. Rare events like this can cause diagnostic uncertainty, as shown by this case. This case is a reminder for clinicians to consider prostate metastases in patients with known prostate carcinoma and focal neurological symptoms.
PMCID: PMC2692142  PMID: 19543455
10.  Application of the International Germ Cell Consensus Classification to the Nova Scotia population of patients with germ cell tumours 
Background
The International Germ Cell Consensus Classification (IGCCC) is the internationally accepted, clinically based prognostic classification used to assist in the management and research of metastatic germ cell tumours (GCTs). The goal of this study was to determine whether the IGCCC is applicable to a population-based cohort.
Methods
We completed a retrospective chart review of patients who received diagnoses of GCT in Nova Scotia between 1984 and 2004 and who received treatment with platin-based chemotherapy for metastatic disease. We assigned the IGCCC to each patient based on the site of the primary lesion, the presence or absence of nonpulmonary visceral metastases and prechemotherapy tumour marker values. We calculated Kaplan–Meier estimates of 5-year progression-free survival (PFS) and overall survival for each IGCCC group.
Results
The study cohort comprised 129 patients. The distribution and outcomes in each group of patients in Nova Scotia was similar to that published in the IGCCC. Among patients with nonseminoma GCTs (NSGCT) 61% had good, 22% had intermediate and 17% had poor prognoses. Among those with seminomas, 85% had good and 15% had intermediate prognoses. Among patients with NSGCTs, the 5-year PFS was 90%, 69% and 55%, and the 5-year overall survival was 94%, 84%, 61% in the good, intermediate, and poor prognostic categories respectively. Among patients with seminomas, the 5-year PFS was 95% and 50% and the 5-year overall survival was 94% and 50% in the good and intermediate prognostic categories, respectively.
Conclusion
The IGCCC seems applicable to a population-based cohort, with similar distribution of categories and clear prognostic ability.
PMCID: PMC2666903  PMID: 19424465
11.  Hereditary renal cell carcinoma associated with von Hippel–Lindau disease: a description of a Nova Scotia cohort 
Abstract
Background
von Hippel–Lindau (VHL) disease is an autosomal dominant condition characterized by the development of benign and malignant tumours, including cases of renal cell carcinoma (RCC). Early detection of RCC through routine surveillance can lead to decreased morbidity and mortality. Data on the number of patients in Nova Scotia (NS) who have VHL disease, disease manifestations and the frequency and mode of the surveillance have not previously been collected or reported. This project was designed to obtain that information.
Methods
The number and management of patients with VHL disease was determined by multiple sources: the Maritime Medical Genetics Service, patient charts, and pathology, radiology and laboratory data. The actual surveillance being performed was compared with that recommended in the literature.
Results
Twenty-one patients from 11 families in NS were identified. Manifestations included cases of RCC (31.6%), central nervous system (CNS) hemangioblastoma (73.7%), retinal hemangioma (47.4%), renal cyst (47.4%) and pheochromocytoma (10.5%). Of the 6 patients with RCC, 4 had bilateral tumours, 2 required kidney transplants and 1 developed metastatic disease. Routine surveillance was being done for the CNS in 62.5% of patients, retina in 47.4%, abdomen in 43.8% and urine catecholamines in only 10.5%. Only 1 of the 6 patients who developed RCC was undergoing routine abdominal imaging. Surveillance investigations were ordered by a number of different specialists.
Conclusion
Patients with VHL disease in NS have a number of manifestations associated with their disease, including RCC, in a similar frequency to that reported in the literature. The surveillance of these patients is suboptimal in frequency and coordination. von Hippel–Lindau disease is a complex condition that requires a coordinated approach to care to ensure proper surveillance and treatment. Our study highlights current deficiencies and offers an enormous opportunity for improvement.
PMCID: PMC2645893  PMID: 19293973
12.  Summary of the first annual Genitourinary Medical Oncology Conference Renal Cell Carcinoma Forum 
Canadian Urological Association Journal  2007;1(2 Suppl):S6-S12.
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.
PMCID: PMC2422956  PMID: 18542786
15.  Skeletal cryptococcosis: Case report and review of the literature 
A case of isolated cryptococcal skull infection is presented in a patient with unexplained CD4 lymphopenia and chronic hepatitis B. All cases of this disease reported in the English literature from 1956 to the present are reviewed. The literature suggests that skeletal cryptococcosis is manifested in only 5% to 10% of recognized cases of disseminated cryptococcosis and that isolated skeletal disease without evidence of other tissue involvement is even less common. When isolated bony disease does occur it tends to occur in immunocompromised hosts, particularly those with defects of cell mediated immunity. Any bony site can be involved, most commonly the vertebrae, with the presentation often being a soft tissue swelling and pain in the affected area. Systemic constitutional symptoms occur in a minority of patients. Radiographic investigations are nonspecific and the gold standard of diagnosis remains culture isolation from bone tissue. The most commonly employed therapy for isolated bone disease is amphotericin alone or combined with surgical debridement. The new azoles may have a role in future therapy.
PMCID: PMC3327391  PMID: 22514429
Bone infection; Cryptococcus; Fluconazole; Osteomyelitis; Skeletal infection

Results 1-15 (15)