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Ashworth A.,Queen's University | Kong W.,Queen's University | Chow E.,Sunnybrook Regional Cancer Center | MacKillop W.J.,Queen's University
International Journal of Radiation Oncology Biology Physics | Year: 2016

Purpose To evaluate the effect of a provincial practice guideline on the fractionation of palliative radiation therapy for bone metastases (PRT.B) in Ontario. Methods and Materials The present retrospective study used electronic treatment records linked to Ontario's population-based cancer registry. Hierarchical multivariable regression analysis was used to evaluate temporal trends in the use of single fractions (SFs), controlling for patient-related factors associated with the use of SFs. Results From 1984 to 2012, 43.9% of 161,835 courses of PRT.B were administered as SFs. The percentage of SF courses was greater for older patients (age <50 years, 39.8% vs age >80 years, 52.5%), those with a shorter life expectancy (survival >12 months, 36.9% vs < 1 month, 53.6%), and those who lived farther from a radiation therapy center (<10 km, 42.1% vs > 50 km, 47.3%). The percentage of SFs to spinal fields was lower than that to other skeletal sites (31.5% vs 57.1%). The percentage of SFs varied among the cancer centers (range, 26.0%-67.8%). These differences were all highly significant in the multivariable analysis (P<.0001). In 2004, Cancer Care Ontario released a practice guideline endorsing the use of SFs for uncomplicated bone metastases. The rate of use of SFs increased from 42.3% in the pre-guideline period (1999-2003) to 52.6% in the immediate post-guideline period (2004-2007). However, it subsequently decreased again to 44.0% (2009-2012). These temporal trends were significant after controlling for patient-related factors in the multivariable analysis (P<.0001). Large intercenter variations in the use of SFs persisted after publication of the guideline. Conclusions The publication of an Ontario practice guideline endorsing the use of SF PRT.B was associated with only a transient increase in the use of SFs in Ontario and did little to reduce intercenter variations in fractionation. © 2016 Elsevier Inc.


Kupets R.,Sunnybrook Regional Cancer Center | Fernandes K.,Institute for Clinical Evaluative science | Miroshnichenko G.,University of Toronto | Paszat L.,Institute for Clinical Evaluative science
Journal of Obstetrics and Gynaecology Canada | Year: 2013

Objective: To evaluate the patterns of radiologic imaging requested by family physicians and gynaecologists in the work-up of women found to have an adnexal mass on pelvic ultrasound, and to evaluate whether advanced imaging tests are associated with more appropriate referral of women with a high-risk adnexal mass to gynaecologic oncologists. Methods: Centralized provincial databases of health care usage were used to identify women aged 45 and older who had a pelvic ultrasound examination between 2006 and 2008 Subsequent imaging tests ordered were identified according to physician specialty For women who proceeded to laparotomy, logistic regression was performed to determine which imaging tests enabled primary physicians to make appropriate referrals of women with high risk adnexal tumours to a gynaecologic oncologist. Results: We identified 193 261 women aged 45 and older who had a pelvic ultrasound Of these, 19 949 (10 3%) had a subsequent laparotomy; 2223 women were categorized as having a benign adnexal mass, 627 were categorized as having a malignant adnexal mass, and the remainder had another diagnosis such as uterine fibroid. Up to 12% of women had a pelvic MRI, and 58% of women had a CT scan after a pelvic ultrasound Family physicians referred 95% of women with a high-risk ovarian mass to a gynaecologic surgeon rather than to a gynaecologic oncologist, and gynaecologists referred 47% of such women to a gynaecologic oncologist after imaging Gynaecologic oncologists operated on 55% of women with a malignant adnexal mass On multivariate analysis, a preoperative CT scan (OR 3.58; P < 0.001) and a CT scan and MRI (OR 7.78; P < 0.001) were associated with surgery performed by a gynaecologic oncologist, but a preoperative MRI alone was not significantly associated (OR 1. 86; P = 0.09). After ultrasound alone the mean time to surgery was 100 days; this increased significantly when further imaging tests were performed (with additional CT to 131 days, with MRI to 170 days, and with CT and MRI to 179 days; P = 0.002). Conclusion: Performing a pelvic MRI after a pelvic ultrasound does not increase the rate of referral of women with a high-risk adnexal mass to a gynaecologic oncologist. A consensus on appropriate imaging and triage is needed when an adnexal mass is identified on ultrasound. © 2013 Society of Obstetricians and Gynaecologists of Canada.


PubMed | Familial Breast Cancer Research, Juravinksi Cancer Center, H. Lee Moffitt Cancer Center and Research Institute, Fondazione IRCSS Instituto Nazionale dei Tumori and 4 more.
Type: Journal Article | Journal: British journal of cancer | Year: 2016

Germline mutations in BRCA1 and BRCA2 increase the susceptibility to develop breast and ovarian cancers as well as increase the risk of some other cancers. Primary objective was to estimate the risk of leukaemia in BRCA1 and BRCA2 mutation carriers.We followed 7243 women with a BRCA1 or a BRCA2 mutation for incident cases of leukaemia. We used the standardised incidence ratio (SIR) to estimate the relative risk of leukaemia, according to mutation and history of breast cancer.We identified five incident cases of leukaemia (two BRCA1, three BRCA2). All five women had a prior history of breast cancer and four had received chemotherapy. The mean time from breast cancer diagnosis to the development of leukaemia was 10.2 years (range 3-18 years). The SIR for BRCA1 carriers was 0.66 (95% CI: 0.11-2.19, P=0.61) and the SIR for BRCA2 carriers was 2.42 (95% CI: 0.61-6.58, P=0.17). The SIR was significantly higher than expected for women with a BRCA2 mutation and breast cancer (SIR=4.76, 95% CI:1.21-12.96, P=0.03), in particular for women who received chemotherapy (SIR=8.11, 2.06-22.07, P=0.007).We observed an increased risk of leukaemia in women with a BRCA2 mutation who receive chemotherapy for breast cancer.


Mackay H.J.,Princess Margaret Phase II Consortium | Hirte H.,Princess Margaret Phase II Consortium | Colgan T.,Sunnybrook Regional Cancer Center | Covens A.,Princess Margaret Phase II Consortium | And 9 more authors.
European Journal of Cancer | Year: 2010

Aim: Micropapillary/borderline (LMP) ovarian tumours are rarely included in clinical trials and are intrinsically resistant to radiation and chemotherapy. Platinum resistant epithelial ovarian cancer (EOC) has a poor prognosis. The histone deacetylase inhibitor belinostat demonstrated antitumour activity in pre-clinical ovarian cancer models. Methods: A phase II study was performed to evaluate the activity of belinostat in two patient populations: women with metastatic or recurrent platinum resistant (progression within 6 months) EOC and LMP ovarian tumours, both groups had received no more than 3 prior lines of chemotherapy. Belinostat 1000 mg/m2/d was administered iv days 1-5 of a 21 d cycle. Peripheral blood mononuclear cells (PBMCs) and tumour biopsies, where possible, for correlative studies were obtained prior to and following treatment. Results: Eighteen patients with EOC and 14 patients with LMP tumours were enrolled on study. Belinostat was well tolerated with no grade four toxicity (179 cycles). Grade 3 toxicity consisted of thrombosis (3 patients), hypersensitivity (1) and elevated ALP (1). One patient with LMP tumour had a partial response (unconfirmed) and 10 had stable disease (SD), 3 were non-evaluable. Median progression-free survival (PFS) was 13.4 months (95% confidence interval (CI), 5.6 - not reached). Best response in patients with EOC was SD (nine patients) and median PFS was 2.3 months (95% CI, 1.2-5.7 months). An accumulation of acetylated histones H3 and H4 was noted in PBMCs and in tumour tissue. Conclusions: Belinostat is well tolerated in both patient groups and shows some activity in patients with micropapillary (LMP) disease. © 2010 Elsevier Ltd.


Phelan C.M.,Moffitt Cancer Center | Iqbal J.,Familial Breast Cancer Research | Lynch H.T.,Creighton University | Lubinski J.,Pomeranian Medical University | And 16 more authors.
British Journal of Cancer | Year: 2014

Background:The BRCA1 and BRCA2 genes confer increased susceptibility to breast and ovarian cancer and to a spectrum of other cancers. There is controversy regarding the risk of colorectal cancer conferred by germline mutations in these two genes.Methods:We followed 7015 women with a BRCA mutation for new cases of colorectal cancer. Incidence rates in carriers were compared with population-specific incidence rates, and standardised incidence ratios (SIRs) were estimated. The expected numbers of cancers were computed by multiplying person-years at risk by the appropriate age-, sex-and country-specific incidence rates from the five countries.Results:Twenty-one incident colorectal cancer cases were observed among all mutation carriers, compared with 23.6 cases expected. The SIR for BRCA1 carriers was 0.92 (95% confidence interval (CI), 0.54-1.40, P=0.7) and for BRCA2 carriers was 0.82 (95% CI, 0.30-1.81, P=0.7). The SIR for colon cancer was 3.81 (95% CI 1.77-7.23) for women below the age of 50 years (both genes combined) and was 0.60 (95% CI 0.33-1.00) for women aged 50 years and above.Conclusion:The risk of colorectal cancer is increased in female carriers of BRCA1 mutations below the age of 50 years but not in women with BRCA2 mutations or in older women. © 2014 Cancer Research UK.


Metcalfe K.A.,University of Toronto | Metcalfe K.A.,Womens College Research Institute | Semple J.,Womens College Research Institute | Quan M.-L.,Foothills Medical Center | And 6 more authors.
Annals of Surgical Oncology | Year: 2012

Background: In this study, we report on the changes in psychosocial functioning over 1 year following breast cancer surgery in 3 groups of women, including those with mastectomy alone, those with mastectomy and immediate reconstruction, and those with delayed reconstruction. Methods: Women with breast cancer at 2 teaching hospitals in Ontario who were undergoing mastectomy alone, mastectomy with immediate reconstruction, or delayed reconstruction were asked to complete a battery of psychosocial questionnaires at their preoperative appointment and 1 year following surgery. Results: A total of 190 women consented to participate in the study and completed the presurgical questionnaires. There were no presurgical differences between the 3 groups in quality of life, anxiety, depression, or sexual functioning. However, women who were undergoing delayed breast reconstruction (i.e., already had a mastectomy) had higher levels of body stigma (P = 0.01), body concerns (P = 0.002), and transparency (P = 0.002) than women who were undergoing mastectomy alone or mastectomy with immediate reconstruction. Of these women, 158 (83.2%) completed the 1-year follow-up. There were no significant differences in any of the psychosocial functioning scores between the 3 groups. Discussion: Contrary to the assumed psychological benefits of breast reconstruction, psychological distress was evident among women regardless of reconstruction or timing of reconstruction. Further, psychosocial functioning (including quality of life, sexual functioning, cancer-related distress, body image, depression, and anxiety) was not different at 1-year postsurgery between women with mastectomy alone, mastectomy with immediate reconstruction, and delayed reconstruction. These results suggest that women need psychosocial support after breast cancer diagnosis, even if they have breast reconstruction. © 2011 Society of Surgical Oncology.


Iqbal J.,Familial Breast Cancer Research | Ragone A.,Pomeranian Medical University | Lubinski J.,Creighton University | Lynch H.T.,Norwegian Radium Hospital | And 15 more authors.
British Journal of Cancer | Year: 2012

Background:Germline mutations in BRCA1 and BRCA2 predispose to pancreatic cancer. We estimated the incidence of pancreatic cancer in a cohort of female carriers of BRCA1 and BRCA2 mutation. We also estimated survival rates in pancreatic cancer cases from families with a BRCA mutation.Methods:We followed 5149 women with a mutation for new cases of pancreatic cancer. The standardised incidence ratios (SIR) for pancreatic cancer were calculated based on age group and country of residence. We also reviewed the pedigrees of 8140 pedigrees with a BRCA1 or a BRCA2 mutation for those with a case of pancreatic cancer. We recorded the year of diagnosis and the year of death for 351 identified cases.Results:Eight incident pancreatic cancer cases were identified among all mutation carriers. The SIR for BRCA1 carriers was 2.55 (95% CI=1.03-5.31, P=0.04) and for BRCA2 carriers was 2.13 (95% CI=0.36-7.03, P=0.3). The 5-year survival rate was 5% for cases from a BRCA1 family and 4% for cases from a BRCA2 family.Conclusion:The risk of pancreatic cancer is approximately doubled in female BRCA carriers. The poor survival in familial pancreatic cancer underscores the need for novel anti-tumoural strategies. © 2012 Cancer Research UK All rights reserved.


MacFadden D.,University of Toronto | Zhang B.,University of Toronto | Brock K.K.,University of Toronto | Hodaie M.,Toronto Western Hospital | And 8 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: Increasing the magnetic resonance imaging (MRI) field strength can improve image resolution and quality, but concerns remain regarding the influence on geometric fidelity. The objectives of the present study were to spatially investigate the effect of 3-Tesla (3T) MRI on clinical target localization for stereotactic radiosurgery. Methods and Materials: A total of 39 patients were enrolled in a research ethics board-approved prospective clinical trial. Imaging (1.5T and 3T MRI and computed tomography) was performed after stereotactic frame placement. Stereotactic target localization at 1.5T vs. 3T was retrospectively analyzed in a representative cohort of patients with tumor (n = 4) and functional (n = 5) radiosurgical targets. The spatial congruency of the tumor gross target volumes was determined by the mean discrepancy between the average gross target volume surfaces at 1.5T and 3T. Reproducibility was assessed by the displacement from an averaged surface and volume congruency. Spatial congruency and the reproducibility of functional radiosurgical targets was determined by comparing the mean and standard deviation of the isocenter coordinates. Results: Overall, the mean absolute discrepancy across all patients was 0.67 mm (95% confidence interval, 0.51-0.83), significantly <1 mm (p < .010). No differences were found in the overall interuser target volume congruence (mean, 84% for 1.5T vs. 84% for 3T, p > .4), and the gross target volume surface mean displacements were similar within and between users. The overall average isocenter coordinate discrepancy for the functional targets at 1.5T and 3T was 0.33 mm (95% confidence interval, 0.20-0.48), with no patient-specific differences between the mean values (p >.2) or standard deviations (p >.1). Conclusion: Our results have provided clinically relevant evidence supporting the spatial validity of 3T MRI for use in stereotactic radiosurgery under the imaging conditions used. Crown Copyright © 2010.


Metcalfe K.,Womens College Research Institute | Metcalfe K.,University of Toronto | Lubinski J.,Pomeranian Medical University | Lynch H.T.,Creighton University | And 12 more authors.
Journal of the National Cancer Institute | Year: 2010

Women who carry a deleterious mutation in BRCA1 or BRCA2 have high lifetime risks of breast and ovarian cancers. However, the influence of a family history of these cancers on these risks in women with BRCA mutations is unclear. We calculated cancer incidence rates for a multinational cohort comprising 3011 women with BRCA1 or BRCA2 mutations who were followed up for a mean of 3.9 years, during which time 243 incident breast or ovarian cancers were recorded. The 10-year cumulative risks of breast cancer were 18.1% (95% confidence interval [CI] = 13.3% to 22.8%) for women with a BRCA1 mutation and 15.2% (95% CI = 9.1% to 21.2%) for women with a BRCA2 mutation. Among women with a BRCA1 mutation, the risk of breast cancer increased by 1.2-fold for each first-degree relative with breast cancer before age 50 years (hazard ratio [HR] = 1.21; 95% confidence interval [CI] = 0.94 to 1.57) and the risk of ovarian cancer increased by 1.6 fold for each first- or second-degree relative with ovarian cancer (HR = 1.61; 95% CI = 1.21 to 2.14). Among women with a BRCA2 mutation, the risk of breast cancer increased by 1.7-fold for each first-degree relative younger than 50 years with breast cancer (HR = 1.67; 95% CI = 1.04 to 2.07). © 2010 The Author.


PubMed | Sunnybrook Regional Cancer Center and Queen's University
Type: Journal Article | Journal: International journal of radiation oncology, biology, physics | Year: 2015

To evaluate the effect of a provincial practice guideline on the fractionation of palliative radiation therapy for bone metastases (PRT.B) in Ontario.The present retrospective study used electronic treatment records linked to Ontarios population-based cancer registry. Hierarchical multivariable regression analysis was used to evaluate temporal trends in the use of single fractions (SFs), controlling for patient-related factors associated with the use of SFs.From 1984 to 2012, 43.9% of 161,835 courses of PRT.B were administered as SFs. The percentage of SF courses was greater for older patients (age <50 years, 39.8% vs age >80 years, 52.5%), those with a shorter life expectancy (survival >12 months, 36.9% vs < 1 month, 53.6%), and those who lived farther from a radiation therapy center (<10 km, 42.1% vs > 50 km, 47.3%). The percentage of SFs to spinal fields was lower than that to other skeletal sites (31.5% vs 57.1%). The percentage of SFs varied among the cancer centers (range, 26.0%-67.8%). These differences were all highly significant in the multivariable analysis (P<.0001). In 2004, Cancer Care Ontario released a practice guideline endorsing the use of SFs for uncomplicated bone metastases. The rate of use of SFs increased from 42.3% in the pre-guideline period (1999-2003) to 52.6% in the immediate post-guideline period (2004-2007). However, it subsequently decreased again to 44.0% (2009-2012). These temporal trends were significant after controlling for patient-related factors in the multivariable analysis (P<.0001). Large intercenter variations in the use of SFs persisted after publication of the guideline.The publication of an Ontario practice guideline endorsing the use of SF PRT.B was associated with only a transient increase in the use of SFs in Ontario and did little to reduce intercenter variations in fractionation.

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