Mason W.P.,University of Toronto |
Belanger K.,Hopital Notre Dame |
Nicholas G.,Ottawa Hospital Regional Cancer Center |
Vallieres I.,Hotel Dieu de Quebec |
And 5 more authors.
Journal of Neuro-Oncology | Year: 2012
This phase II trial was undertaken to evaluate the efficacy of TLN-4601 in patients with glioblastoma (GBM) at first progression. TLN-4601 inhibits the RasMAPK signaling pathway, and in animal models crosses the blood-brain barrier and accumulates in implanted gliomas, possibly by binding specifically to the peripheral benzodiazepine receptor. A maximum of 40 patients with recurrent GBM were to be enrolled in this study. TLN4601 was administered at a dose of 480 mg/m2/day by continuous intravenous (CIV) administration. Each 21-day cycle consisted of a 14-day CIV administration and a 7-day recovery period. Samples were obtained from all patients for pharmacokinetic evaluations (PK) and for Raf1 and pERK biomarker assessment using immunohistochemistry and flow cytometry. Following enrollment of 20 patients, this study was terminated due to a lack of efficacy. Of 17 evaluable patients, 14 had MR scans performed after two cycles of TLN-4601. Of these 14 patients, three had stable disease and 11 had disease progression. Only three patients had MR scans performed after four cycles and all had evidence of radiographic progression. Serum PKs confirmed that patients were exposed to TLN-4601 at targeted drug levels. TLN-4601 was generally well tolerated although two patients discontinued treatment due to adverse events. Biomarker analysis did not show consistent changes. TLN-4601 infused via CIV at 480 mg/m2/day for 14 of 21 days is well tolerated by patients with progressive GBM. However, this agent is ineffective in progressive GBM when administered as monotherapy in this schedule. © Springer Science+Business Media, LLC. 2011.
Werier J.,Ottawa Hospital Regional Cancer Center |
Yao X.,McMaster University |
Caudrelier J.-M.,Ottawa Hospital Regional Cancer Center |
Di Primio G.,St Josephs Healthcare Hamilton |
And 4 more authors.
Surgical Oncology | Year: 2016
Objective To perform a systematic review to investigate the optimal treatment strategy among the options of surgery alone, radiotherapy (RT) alone, and the combination of RT plus surgery in the management of localized Ewing's sarcoma of bone following neo-adjuvant chemotherapy. Methods MEDLINE and EMBASE (1999 to February 2015), the Cochrane Library, and relevant conferences were searched. Results Two systematic reviews and eight full texts met the pre-planned study selection criteria. When RT was compared with surgery, a meta-analysis combining two papers showed that surgery resulted in a higher event-free survival (EFS) than RT in any location (HR = 1.50, 95% CI 1.12-2.00; p = 0.007). However another paper did not find a statistically significant difference in patients with pelvic disease, and no papers identified a significant difference in overall survival. When surgery plus RT was compared with surgery alone, a meta-analysis did not demonstrate a statistically significant difference for EFS between the two groups (HR = 1.21, 95% CI 0.90-1.63). Both surgical morbidities and radiation toxicities were reported. Conclusions The existing evidence is based on very low aggregate quality as assessed by the GRADE approach. In patients with localized Ewing's sarcoma, either surgery alone (if complete surgical excision with clear margin can be achieved) or RT alone may be a reasonable treatment option. The optimal local treatment for an individual patient should be decided through consideration of patient characteristics, the potential benefit and harm of the treatment options, and patient preference. Copyright © 2015 Published by Elsevier Ltd. All rights reserved.
Courneya K.S.,University of Alberta |
Segal R.J.,Ottawa Hospital Regional Cancer Center |
McKenzie D.C.,University of British Columbia |
Dong H.,University of Alberta |
And 8 more authors.
Medicine and Science in Sports and Exercise | Year: 2014
Observational studies suggest that physical activity after a breast cancer diagnosis is associated with improved cancer outcomes; however, no randomized data are available. Here, we report an exploratory follow-up of cancer outcomes from the Supervised Trial of Aerobic versus Resistance Training (START). METHODS: The START was a Canadian multicenter trial that randomized 242 breast cancer patients between 2003 and 2005 to usual care (n = 82), supervised aerobic (n = 78), or resistance (n = 82) exercise during chemotherapy. The primary end point for this exploratory analysis was disease-free survival (DFS). Secondary end points were overall survival, distant DFS, and recurrence-free interval. The two exercise arms were combined for analysis (n = 160), and selected subgroups were explored. RESULTS: After a median follow-up of 89 months, there were 25/160 (15.6%) DFS events in the exercise groups and 18/82 (22.0%) in the control group. Eight-year DFS was 82.7% for the exercise groups compared with 75.6% for the control group (HR, 0.68; 95% confidence interval (CI), 0.37-1.24; log-rank, P = 0.21). Slightly stronger effects were observed for overall survival (HR, 0.60; 95% CI, 0.27-1.33; log-rank, P = 0.21), distant DFS (HR, 0.62; 95% CI, 0.32-1.19; log-rank, P = 0.15), and recurrence-free interval (HR, 0.58; 95% CI, 0.30-1.11; Gray test, P = 0.095). Subgroup analyses suggested potentially stronger exercise effects on DFS for women who were overweight/obese (HR, 0.59; 95% CI, 0.27-1.27), had stage II/III cancer (HR, 0.61; 95% CI, 0.31-1.20), estrogen receptor-positive tumors (HR, 0.58; 95% CI, 0.26-1.29), human epidermal growth factor receptor 2-positive tumors (HR, 0.21; 95% CI, 0.04-1.02), received taxane-based chemotherapies (HR, 0.46; 95% CI, 0.19-1.15), and â‰1 85% of their planned chemotherapy (HR, 0.50; 95% CI, 0.25-1.01). CONCLUSIONS: This exploratory follow-up of the START provides the first randomized data to suggest that adding exercise to standard chemotherapy may improve breast cancer outcomes. A definitive phase III trial is warranted. © 2014 by the American College of Sports Medicine.
Duval K.,Royal Canadian Mounted Police |
Aubin R.A.,Biologics |
Elliott J.,Royal Canadian Mounted Police |
Gorn-Hondermann I.,Ottawa Hospital Regional Cancer Center |
And 4 more authors.
Forensic Science International: Genetics | Year: 2010
Archival tissue preserved in fixative constitutes an invaluable resource for histological examination, molecular diagnostic procedures and for DNA typing analysis in forensic investigations. However, available material is often limited in size and quantity. Moreover, recovery of DNA is often severely compromised by the presence of covalent DNA-protein cross-links generated by formalin, the most prevalent fixative. We describe the evaluation of buffer formulations, sample lysis regimens and DNA recovery strategies and define optimized manual and automated procedures for the extraction of high quality DNA suitable for molecular diagnostics and genotyping. Using a 3-step enzymatic digestion protocol carried out in the absence of dithiothreitol, we demonstrate that DNA can be efficiently released from cells or tissues preserved in buffered formalin or the alcohol-based fixative GenoFix™. This preparatory procedure can then be integrated to traditional phenol/chloroform extraction, a modified manual DNA IQ™ or automated DNA IQ™/Te-Shake™-based extraction in order to recover DNA for downstream applications. Quantitative recovery of high quality DNA was best achieved from specimens archived in GenoFix™ and extracted using magnetic bead capture. Crown Copyright © 2009.
Attard C.L.,Cornerstone Research Group, Inc. |
Maroun J.A.,Ottawa Hospital Regional Cancer Center |
Alloul K.,Sanofi S.A. |
Grima D.T.,Cornerstone Research Group, Inc. |
Bernard L.M.,Cornerstone Research Group, Inc.
Current Oncology | Year: 2010
Objective: The cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5FU/LV)-the FOLFOX regimen-was compared with that of 5FU/LV alone as adjuvant therapy for patients with stage III colon cancer, from the perspective of the Cancer Care Ontario New Drug Funding Program. In the mosaic (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) trial, the FOLFOX regimen significantly improved disease-free survival. The MOSAIC trial formed the basis of the present analysis. Methodology: Extrapolated patient-level data from the MOSAIC trial were used to model patient outcomes from treatment until death. Utilities were obtained from the literature. Resource utilization data were derived from the MOSAIC trial and supplemented with data from the literature. Unit costs were obtained from the Ontario Ministry of Health and Long-Term Care, the London Health Sciences Centre, and the literature. Results: Lifetime incremental cost-effectiveness ratios for folfox compared with 5FU/LV were CA$14,266 per disease-free year, CA$23,598 per life-year saved, and CA$24,104 per quality adjusted life-year (QALY) gained, discounting costs and outcomes at 5% per annum. These results were stable for a wide range of inputs; only utility values associated with relapse seemed to influence the cost-effectiveness ratios observed. Conclusions: With an incremental cost of CA$24,104 per QALY gained, FOLFOX is a cost-effective adjuvant treatment for stage III colon cancer. Compared with 5FU/LV alone, this regimen offers better clinical outcomes and provides good value for money. Copyright © 2010 Multimed Inc.
Lemay K.,University of Ottawa |
Wilson K.G.,Ottawa Hospital Rehabilitation Center |
Buenger U.,Ottawa Hospital Rehabilitation Center |
Jarvis V.,Ottawa Hospital Regional Cancer Center |
And 3 more authors.
Clinical Journal of Pain | Year: 2011
Objectives: Pain is one of the most prevalent symptoms in patients with advanced cancer and, according to anecdotal reports, perhaps the most feared. Surprisingly, fear of pain has been the subject of little research within cancer care. The literature on chronic noncancer pain, however, suggests that fear of pain contributes to limitations in function in populations with diverse chronic illness. Little is known about the extent to which such findings might generalize from patients with chronic noncancer pain to those with chronic cancer pain. Therefore, this research examined the extent to which fear of pain is associated with limitations in function in patients with advanced cancer and also compared patients with chronic cancer and noncancer pain. Methods: We recruited 117 patients with advanced cancer who received a referral for pain management and 118 patients with a primary complaint of chronic noncancer pain. Participants completed self-report questionnaires. Results: Findings revealed similarities between the groups for fear of pain and limitations in function, but they differed on level of depression and pain severity (patients with noncancer pain were more depressed and reported higher pain severity). Fear of pain independently predicted limitations in function in both groups controlling for demographic variables and pain severity. When depression and physical symptoms were controlled, fear of pain predicted limitations in function only in patients with advanced cancer. Discussion: The findings emphasize the importance of psychological dimensions of pain in patients with advanced cancer, as well as the similarities and differences between the 2 groups of patients suffering from chronic pain. © 2011 by Lippincott Williams & Wilkins.
Gupta A.A.,University of Toronto |
Yao X.,McMaster University |
Verma S.,Ottawa Hospital Regional Cancer Center |
Mackay H.,University of Toronto |
Hopkins L.,Ottawa Hospital
Clinical Oncology | Year: 2013
The goal of this systematic review was to investigate and compare the treatment effects of systemic chemotherapy (i.e. doxorubicin, gemcitabine, gemcitabine plus docetaxel, or trabectedin) in women with inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma. A 2005 systematic review (searching the literature from 1980 to June 2004) on systemic therapy in advanced uterine sarcoma was used as the basis for this updated review. MEDLINE and EMBASE (from January 2004 to June 2011), the Cochrane Library, some main guideline websites and the American Society of Clinical Oncology and the Connective Tissue Oncology Society annual meeting abstracts were searched. One arm from a randomised controlled trial (RCT), four single-arm phase II trials and one abstract were included in this systematic review. The studies of gemcitabine plus docetaxel have reported numerically longer median overall survival (14.7-17.9 months versus 12.1 months) and numerically higher objective response rates (27-53% versus 25%) than those reported in the study of doxorubicin alone. The combination of gemcitabine plus docetaxel resulted in more toxicity than doxorubicin alone. The available study for single-agent gemcitabine reported a tumour response rate of 21%, which is not superior to the 25% response rate with doxorubicin alone. One abstract (pooling data from two RCTs) failed to show the superiority of gemcitabine plus docetaxel over gemcitabine alone for tumour response rate (23% versus 18%) and progression-free survival (6 versus 4.9 months). To date, there is insufficient evidence to support or refute the use of trabectedin in the target patients. Doxorubicin, gemcitabine, and gemcitabine plus docetaxel are treatment options in women with inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma as first- or second-line therapy. Well-designed and good-quality RCTs are required to investigate the efficacy of chemotherapy and quality of life in target patients with uterine leiomyosarcoma. © 2012 The Royal College of Radiologists.
Jonker D.J.,Ottawa Hospital Regional Cancer Center |
Spithoff K.,McMaster University |
Maroun J.,Ottawa Hospital Regional Cancer Center
Clinical Oncology | Year: 2011
Aims: The standard adjuvant therapy for resected stage III colon cancer has been intravenous 5-fluorouracil. However, newer chemotherapy agents, such as capecitabine, oxaliplatin and irinotecan, have been investigated in clinical trials since the publication of the original guidelines. The Gastrointestinal Cancer Disease Site Group (DSG) conducted a systematic review of the evidence for the use of adjuvant systemic chemotherapy for patients with resected stage II and III colon cancer and developed an updated practice guideline based on that evidence and expert consensus. The following research questions were addressed: Should patients with stage II or III colon cancer receive adjuvant systemic chemotherapy? What are the preferred adjuvant systemic chemotherapy options for patients with completely resected stage II or III colon cancer? Outcomes of interest were disease-free survival, overall survival, adverse effects and quality of life. Materials and methods: A systematic search of published studies was conducted for the time period following the publication of the original guidelines to identify relevant randomised trials and syntheses of evidence in the form of meta-analyses. Recommendations were based on that evidence, evidence contained in the original guidelines and consensus of the Gastrointestinal Cancer DSG. The systematic review and practice guideline were externally reviewed through a mailed survey of practitioners in Ontario, Canada. Results: Recommendations were drafted based on the available evidence and expert consensus. Conclusions: The routine use of adjuvant chemotherapy for all patients with stage II colon cancer is not recommended. However, a subset of patients with high-risk stage II disease should be considered for adjuvant therapy. Patients with completely resected stage III colon cancer should be offered adjuvant chemotherapy. Treatment should depend on factors such as patient suitability and preference, and patients and clinicians must work together to determine the optimal course of treatment. © 2011 The Royal College of Radiologists.
Jarvis V.,Ottawa Hospital Regional Cancer Center |
Walker-Dilks C.,McMaster University
Supportive Care in Cancer | Year: 2010
Purpose This systematic review outlines current evidence regarding the effectiveness of intraspinal techniques for cancer pain and addresses practical implementation issues. Methods A search of electronic databases identified systematic reviews and randomized controlled trials (RCTs) evaluating the effectiveness of intraspinal techniques in the setting of cancer pain. An environmental scan was completed via the internet to identify practice guidelines and resource documents addressing organizational and implementation issues in the delivery of intraspinal analgesia. Elements reviewed included patient selection, contraindications, monitoring, aftercare, follow-up, hospital discharge equipment, health personnel, patient education, and safety. Main results Three systematic reviews, three consensus conferences, and 12 RCTs met the inclusion criteria for evidence of effectiveness. No single systematic review or consensus conference included all relevant RCTs or specifically addressed the use of intraspinal techniques for cancer pain. Six RCTs compared intraspinal techniques alone or combined with other interventions alone or in combination, four compared different intraspinal medications, and two compared different intraspinal techniques. In general, the evidence supported the use of intraspinal techniques for cancer pain management. The two main indications consistently identified were intractable pain not controlled by other conventional medical routes and/or side effects from conventional pain management strategies preventing dose escalation. Reports indicate intraspinal analgesia is equally or more effective than conventional medical management and often associated with fewer side effects. Thirteen resource documents addressed issues surrounding the delivery of intraspinal analgesia and program implementation. Conclusions Intraspinal techniques monitored by an interprofessional health care team should be included as part of a comprehensive cancer pain management program. © Springer-Verlag 2009.
PubMed | Ottawa Hospital Regional Cancer Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
11086 Background: Several authors have noted aggressive tumour characteristics and poor outcomes in women diagnosed with BC under the age of 35. To provide further insight, we have undertaken a comprehensive multi-decade review of the demographics, tumour features and outcomes in very young women at our institution.Of 238 women 30 years (yrs) with BC seen at our institution between 1962 -2005, 204 were eligible for this study. Charts were reviewed for risk and genetic factors, presenting symptoms, tumour characteristics and therapy. Where possible, tumour blocks were retrieved for review and estrogen receptor (ER) and HER-2 profiles. Outcomes included recurrence rates, time to recurrence (TTR) and survival (OS).201 patients (pts) with invasive BC were included in this analysis. Median age was 28 (r: 19-30). Median tumour size was 2.5 cm (r: 0.3-11.1). 10%, 36% and 54% were grade 1, 2 and 3, respectively. 46% had axillary node involvement. Overall stage distribution was: I-31%, II-42%, III-24% and IV-3%. Lympho-vascular invasion was present in 67%. 48% of 124 cases were ER+ and HER-2 over-expression was noted in 26% of 34 cases tested. 24% were triple negative. 44% of those tested for BRCA mutations (18 cases) were positive. Overall, 50% of stage I-III pts experienced recurrences: 22% local-regional, 47% systemic and 31% had both. TTR and OS for the entire group and for ER + and ER- subsets were analyzed and compared for 3 time periods: 1962-1985, 1986-1995 and 1996-2005. A trend towards improvement was noted over time.This >40-year retrospective study represents one of the largest reviews of very young women with BC. When compared to historical subsets (>35 or >50 yrs of age), very young patients appear to present more frequently with poor prognostic markers. We have observed higher recurrence rates and lower 5-year OS compared to older subsets but an important evolving impact of adjuvant therapy over time. Although a rare group, young women with BC merit further study to optimize outcomes. No significant financial relationships to disclose.