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Whelan T.J.,McMaster University | Pignol J.-P.,Odette Cancer Center | Levine M.N.,McMaster University | Julian J.A.,McMaster University | And 10 more authors.
New England Journal of Medicine | Year: 2010

BACKGROUND: The optimal fractionation schedule for whole-breast irradiation after breast-conserving surgery is unknown. METHODS: We conducted a study to determine whether a hypofractionated 3-week schedule of whole-breast irradiation is as effective as a 5-week schedule. Women with invasive breast cancer who had undergone breast-conserving surgery and in whom resection margins were clear and axillary lymph nodes were negative were randomly assigned to receive whole-breast irradiation either at a standard dose of 50.0 Gy in 25 fractions over a period of 35 days (the control group) or at a dose of 42.5 Gy in 16 fractions over a period of 22 days (the hypofractionated-radiation group). RESULTS: The risk of local recurrence at 10 years was 6.7% among the 612 women assigned to standard irradiation as compared with 6.2% among the 622 women assigned to the hypofractionated regimen (absolute difference, 0.5 percentage points; 95% confidence interval [CI], -2.5 to 3.5). At 10 years, 71.3% of women in the control group as compared with 69.8% of the women in the hypofractionated-radiation group had a good or excellent cosmetic outcome (absolute difference, 1.5 percentage points; 95% CI, -6.9 to 9.8). CONCLUSIONS: Ten years after treatment, accelerated, hypofractionated whole-breast irradiation was not inferior to standard radiation treatment in women who had undergone breast-conserving surgery for invasive breast cancer with clear surgical margins and negative axillary nodes. (ClinicalTrials.gov number, NCT00156052.) Copyright © 2010 Massachusetts Medical Society.


Ko Y.-J.,Sunnybrook Odette Cancer Center | Canil C.M.,Ottawa Regional Cancer Center | Mukherjee S.D.,Juravinski Cancer Center | Winquist E.,London Health Sciences Center | And 5 more authors.
The Lancet Oncology | Year: 2013

Background: No standard treatment exists for patients with platinum-refractory urothelial cancer. Taxanes and vinflunine are commonly used, but response is less than 20% with no survival benefit. In this phase 2 study, we assessed efficacy and tolerability of nanoparticle albumin-bound (nab) paclitaxel in platinum-refractory urothelial cancer. Methods: We did an open-label, single-group, two-stage study at five centres in Canada. We enrolled patients aged at least 18 years with histologically confirmed, locally advanced, or metastatic measurable urothelial cancer, with documented progression on or within 12 months of treatment with one previous platinum-containing regimen. Patients received nab-paclitaxel at 260 mg/m2 intravenously every 3 weeks. Treatment continued until disease progression or occurrence of unacceptable toxic effects. The primary endpoint was objective tumour response, defined by a complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (version 1.0) criteria. Tumour response and safety were assessed in all patients who received at least one cycle of nab-paclitaxel. This study is registered with ClinicalTrials.gov, number NCT00683059. Findings: We enrolled 48 patients between Oct 16, 2008, and June 23, 2010. Patients received a median of six cycles (range one to 15). 47 patients were evaluable; one (2·1%) had a CR and 12 (25·5%) had PRs, resulting in an overall response of 27·7% (95% CI 17·3-44·4). The most frequently recorded adverse events of any grade were fatigue (38 of 48; 79%), pain (37 of 48; 77%), alopecia (34 of 48; 71%), and neuropathy (30 of 48; 77%). The most frequently recorded adverse events of grade 3 or higher were pain (11 of 48; 23%), fatigue (five of 48; 23%), hypertension (three of 48; 6%), neuropathy (three of 48, 6%), and joint stiffness or pain (two of 48; 4%). Interpretation: Nab-paclitaxel was well tolerated in this population of patients with pretreated advanced urothelial cancer with an encouraging tumour response. These results warrant further study of nab-paclitaxel in second-line treatment of urothelial cancer. Funding: Abraxis Bioscience, Celgene. © 2013 Elsevier Ltd.


Alexander A.,British Columbia Cancer Agency | Crook J.,Princess Margaret Hospital | Jones S.,British Columbia Cancer Agency | Malone S.,Ottawa Regional Cancer Center | And 4 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: To ascertain whether biochemical response to neoadjuvant androgen-deprivation therapy (ADT) before radiotherapy (RT), rather than duration, is the critical determinant of benefit in the multimodal treatment of localized prostate cancer, by comparing outcomes of subjects from the Canadian multicenter 3- vs 8-month trial with a pre-RT, post-hormone PSA (PRPH-PSA) ≤0.1 ng/ml vs those >0.1 ng/ml. Methods and Materials: From 1995 to 2001, 378 men with localized prostate cancer were randomized to 3 or 8 months of neoadjuvant ADT before RT. On univariate analysis, survival indices were compared between those with a PRPH-PSA ≤0.1 ng/ml vs >0.1 ng/ml, for all patients and subgroups, including treatment arm, risk group, and gleason Score. Multivariate analysis identified independent predictors of outcome. Results: Biochemical disease-free survival (bDFS) was significantly higher for those with a PRPH-PSA ≤0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (55.3% vs 49.4%, p = 0.014). No difference in survival indices was observed between treatment arms. There was no difference in bDFS between patients in the 3- and 8-month arms with a PRPH-PSA ≤0.1 ng/ml nor those with PRPH-PSA >0.1 ng/ml. bDFS was significantly higher for high-risk patients with PRPH-PSA ≤0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (57.0% vs 29.4%, p = 0.017). Multivariate analysis identified PRPH-PSA (p = 0.041), Gleason score (p = 0.001), initial PSA (p = 0.025), and T-stage (p = 0.003), not ADT duration, as independent predictors of outcome. Conclusion: Biochemical response to neoadjuvant ADT before RT, not duration, appears to be the critical determinant of benefit in the setting of combined therapy. Individually tailored ADT duration based on PRPH-PSA would maximize therapeutic gain, while minimizing the duration of ADT and its related toxicities. © 2010 Elsevier Inc. All rights reserved.


Mittmann N.,Research Center | Verma S.,Ottawa Regional Cancer Center | Koo M.,Research Center | Alloul K.,Sanofi S.A. | Trudeau M.,Odette Cancer Center
Current Oncology | Year: 2010

Background: This economic analysis aimed to determine, from the perspective of a Canadian provincial government payer, the cost-effectiveness of docetaxel (Taxotere: Sanofi-Aventis, Laval, QC) in combination with doxorubicin and cyclophosphamide (TAC) compared with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) following primary surgery for breast cancer in women with operable, axillary lymph node-positive breast cancer. Methods: A Markov model looking at two time phases-5-year treatment and long-term follow-up-was constructed. Clinical events included clinical response (based on disease-free survival and overall survival) and rates of febrile neutropenia, stomatitis, diarrhea, and infections. Health states were "no recurrence," "locoregional recurrence," "distant recurrence," and "death." Costs were based on published sources and are presented in 2006 Canadian dollars. Model inputs included chemotherapy drug acquisition costs, chemotherapy administration costs, relapse and followup costs, costs for management of adverse events, and costs for granulocyte colony-stimulating factor (G-CSF) prophylaxis. A 5% discount rate was applied to costs and outcomes alike. Health utilities were obtained from published sources. Results: For TAC as compared with fac, the incremental cost was $6921 per life-year (LY) gained and $6,848 per quality-adjusted life-year (QALY) gained. The model was robust to changes in input variables (for example, febrile neutropenia rate, utility). When G-CSF and antibiotics were given prophylactically before every cycle, the incremental ratios increased to $13,183 and $13,044 respectively. Conclusions: Compared with FAC, TAC offered improved response at a higher cost. The cost-effectiveness ratios were low, indicating good economic value in the adjuvant setting of node-positive breast cancer patients. Copyright © 2010 Multimed Inc.


PubMed | University of Tampere, Chania General Hospital, Amgen Inc., Brust Zentrum Zurich and 5 more.
Type: | Journal: Breast (Edinburgh, Scotland) | Year: 2016

To investigate the use and impact of granulocyte colony-stimulating factors (G-CSF) on chemotherapy delivery and neutropenia management in breast cancer in a clinical practice setting.IMPACT Solid was an international, prospective observational study in patients with a physician-assessed febrile neutropenia (FN) risk of 20%. This analysis focused on stages I-III breast cancer patients who received a standard chemotherapy regimen for which the FN risk was published. Chemotherapy delivery and neutropenia-related outcomes were reported according to the FN risk of the regimen and intent of G-CSF use.690 patients received a standard chemotherapy regimen; 483 received the textbook dose/schedule with a majority of these regimens (84%) having a FN risk 10%. Patients receiving a regimen with a FN risk 10% were younger with better performance status than those receiving a regimen with a FN risk <10%. Patients who received higher-risk regimens were more likely to receive G-CSF primary prophylaxis (48% vs 22%), complete their planned chemotherapy (97% vs 88%) and achieve relative dose intensity 85% (93% vs 86%) than those receiving lower-risk regimens. Most first FN events (56%) occurred in cycles not supported with G-CSF primary prophylaxis.Physicians generally recommend standard adjuvant chemotherapy regimens and were more likely to follow G-CSF guidelines for younger, good performance status patients in the curative setting, and often modify standard regimens in more compromised patients. However, G-CSF support is not optimal, indicated by G-CSF primary prophylaxis use in <50% of high-risk patients and observation of FN without G-CSF support.


Palma D.A.,90 Commissioners Rd E | Haasbeek C.J.A.,VU University Amsterdam | Rodrigues G.B.,90 Commissioners Rd E | Dahele M.,VU University Amsterdam | And 9 more authors.
BMC Cancer | Year: 2012

Background: Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control. Survival outcomes for patients with oligometastatic disease treated with SABR appear promising, but conclusions are limited by patient selection, and the lack of adequate controls in most studies. The goal of this multicenter randomized phase II trial is to assess the impact of a comprehensive oligometastatic SABR treatment program on overall survival and quality of life in patients with up to 5 metastatic cancer lesions, compared to patients who receive standard of care treatment alone.Methods: After stratification by the number of metastases (1-3 vs. 4-5), patients will be randomized between Arm 1: current standard of care treatment, and Arm 2: standard of care treatment + SABR to all sites of known disease. Patients will be randomized in a 1:2 ratio to Arm 1:Arm 2, respectively. For patients receiving SABR, radiotherapy dose and fractionation depends on the site of metastasis and the proximity to critical normal structures. This study aims to accrue a total of 99 patients within four years. The primary endpoint is overall survival, and secondary endpoints include quality of life, toxicity, progression-free survival, lesion control rate, and number of cycles of further chemotherapy/systemic therapy.Discussion: This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with oligometastatic disease, and will inform the design of a possible phase III study.Trial registration: Clinicaltrials.gov identifier: NCT01446744. © 2012 Palma et al.; licensee BioMed Central Ltd.


PubMed | McMaster University, Ottawa Hospital Research Institute and Ottawa Regional Cancer Center
Type: Journal Article | Journal: Journal of bone oncology | Year: 2016

Bone-targeted agents are usually administered to breast cancer patients with bone metastases every 3-4 weeks. Less frequent (de-escalated) treatment may provide similar benefits with improved safety and reduced cost.To systematically review randomised trials comparing de-escalated treatment with bone-targeted agents (i.e. every 12-16 weeks) to standard treatment (i.e. every 3-4 weeks), a formal systematic review of the literature was performed. Two individuals independently screened citations and full text articles. Random effects meta-analyses of clinically important outcomes were planned provided homogeneous studies were identified.Five relevant studies (n=1287 patients) were identified. Sample size ranged from 38 to 425. Information on outcomes including occurrence of SREs, bone pain, urinary N-telopeptide concentrations, serum C-telopeptide concentrations, pain medication use and safety outcomes was not consistently available. Two trials were non-inferiority studies, two dose-response evaluations and one was a pilot study. Bone-targeted agents use varied between studies, as did duration of prior therapy. Patient populations were considered heterogeneous in several ways, and thus no meta-analyses were performed. Observations from the included studies suggest there is potential that 3 month de-escalated treatment may provide similar benefits compared to 3-4 weekly treatment and that lower doses of zoledronic acid and denosumab might be equally effective.Studies comparing standard and de-escalated treatment with bone-targeted agents in breast cancer are rare. The benefits of standard treatment compared to de-escalated therapy on important clinical outcomes remain unclear. Future pragmatic studies must be conducted to determine the merits of this approach.


Tran T.,The Ottawa Hospital | Burt D.,Riverside Court Medical Clinic | Eapen L.,Ottawa Regional Cancer Center | Keller O.R.,Ottawa Regional Cancer Center
Current Oncology | Year: 2013

Spontaneous regression of metastatic melanoma is an exceedingly rare event, with only 76 well-documented cases in the literature since 1866. Here, we present the case of a patient who developed metastatic melanoma despite interferon therapy and who then achieved spontaneous regression shortly after a reaction to tetanus-diphtheria-pertussis vaccination. A common theme among these cases is the development of febrile illness before remission of the malignant disease. A brief overview of proposed mechanisms for these miraculous recoveries is presented, including a highlight on the potential role of the HERV-K-MEL viral marker, a nona- or decapeptide that appears in most melanomas, with homologies to peptides in pathogenic microorganisms. © 2013 Multimed Inc.


PubMed | Ottawa Regional Cancer Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

6087 Background: Considerable cancer supportive care research has been devoted to febrile neutropenia, emesis and anemia. In contrast, diarrhea as a side effect of chemotherapy has received less attention. However, CID is common with many types of chemotherapy and can have a major impact on maintaining dose intensity, treatment effectiveness and on overall health care resources. In this study, a cost of illness analysis was conducted to estimate the overall economic impact of grade III/IV diarrhea in patients with colorectal cancer receiving chemotherapy.This was a retrospective cohort study consisting of patients with colorectal cancer that had received chemotherapy and had developed grade III or IV diarrhea. Data collection included patient demographics, disease related information and healthcare resource utilization to manage the grade III/IV CID event. Multivariable logistic regression analysis was then used to identify factors associated with hospitalization for uncontrolled CID.Patients (n=96) had a mean age of 60.3 years and 49% of the sample was receiving adjuvant chemotherapy with a curative intent. The severe CID developed after the first cycle of chemotherapy in 54.2% of patients and was responsible for a median dose reduction and delay of 20% and 7 days respectively. Overall, 30 of 96 patients (31%) with severe CID required a hospital admission for supportive care with an 8-day median length of stay (range = 2 to 28 days). There were 2 deaths with 1 possibly being related to the diarrhea. When the economic impact of the grade III/IV CID was quantified, the mean cost was $2,559 per patient (95%CI: $1,665 to $3,453). The logistic regression analysis identified grade IV diarrhea (OR=9.9; P < 0.001) and severe CID developing after the first chemotherapy cycle (OR=3.6; P = 0.026) as significant predictors of patient hospitalization.Grade III/IV diarrhea is a debilitating and costly complication of chemotherapy in colorectal cancer. Effective interventions that prevent the development of severe CID need to be identified to save health care costs and reduce patient morbidity. [Table: see text].


PubMed | Ottawa Regional Cancer Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

706 Background: Phase II studies of T with D have demonstrated encouraging response rates in women with HER2/neu overexpressing (HER2+) MBC. Because there are no studies comparing this combination to the efficacy of the well-studied combination of Paclitaxel (P) and T, we undertook a MA to obtain a summary estimate of the response rate and toxicity, and to derive aggregate measures of other efficacy parameters.The project was designed in 2 phases: An LBMA and an IPDMA. Studies were included in the LBMA if they were prospective clinical trials of D + T in women with HER2+ MBC containing 10 patients. Studies were identified by an electronic literature search of 8 medical databases (Medline and Premedline, Embase, Cancerlit, CINAHL, Biological Abstracts, HealthStar, ACP Journal Club, and Cochrane Database of Systematic Reviews) for the years 1966-2002 using the following criteria; trastuzuamab, herceptin, docetaxel and taxotere. This was supplemented by hand searches of abstracts from proceedings of the European Society of Medical Oncology, American Society for Clinical Oncology and San Antonio Breast Cancer meetings for the years 1995 - 2002. Summary estimates of the objective response rates (OR) (intent to treat) were obtained using methods described by Laird and Mosteller (Int J Technol Assess in Health Care 6:5-30, 1990) for random effects adjustment.7 phase II trials with a total of 165 patients were identified. The overall estimated response rate was 60% (95% CI 52%-68%). Major grade 3/4 toxicities are presented. The IPDMA is currently underway and is to be completed in the spring of 2004.Results of the LBMA and IPDMA will be presented and their clinical implication discussed in light of known outcome with P + T and subsequent clinical implications. [Figure: see text] [Table: see text].

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