Queens Cancer Research Institute
Queens Cancer Research Institute
Stuckless T.,Cancer Care Program |
Milosevic M.,University of Toronto |
Parliament M.,University of Alberta |
Tompkins B.,Cancer Care Program |
Brundage M.,Queens Cancer Research Institute
Radiotherapy and Oncology | Year: 2012
Purpose: The specialty of radiation oncology has experienced significant workforce planning challenges in many countries. Our purpose was to develop and validate a workforce-planning model that would forecast the balance between supply of, and demand for, radiation oncologists in Canada over a minimum 10-year time frame, to identify the model parameters that most influenced this balance, and to suggest how this model may be applicable to other countries. Methods: A forward calculation model was created and populated with data obtained from national sources. Validation was confirmed using a historical prospective approach. Results: Under baseline assumptions, the model predicts a short-term surplus of RO trainees followed by a projected deficit in 2020. Sensitivity analyses showed that access to radiotherapy (proportion of incident cases referred), individual RO workload, average age of retirement and resident training intake most influenced balance of supply and demand. Within plausible ranges of these parameters, substantial shortages or excess of graduates is possible, underscoring the need for ongoing monitoring. Conclusions: Workforce planning in radiation oncology is possible using a projection calculation model based on current system characteristics and modifiable parameters that influence projections. The workload projections should inform policy decision making regarding growth of the specialty and training program resident intake required to meet oncology health services needs. The methods used are applicable to workforce planning for radiation oncology in other countries and for other comparable medical specialties. © 2012 Elsevier Ireland Ltd. All rights reserved.
Marks L.B.,University of North Carolina at Chapel Hill |
Adams R.D.,University of North Carolina at Chapel Hill |
Pawlicki T.,University of California at San Diego |
Blumberg A.L.,Greater Baltimore Medical Center |
And 3 more authors.
Practical Radiation Oncology | Year: 2013
This report is part of a series of white papers commissioned for the American Society for Radiation Oncology (ASTRO) Board of Directors as part of ASTRO's Target Safely Campaign, focusing on the role of peer review as an important component of a broad safety/quality assurance (QA) program. Peer review is one of the most effective means for assuring the quality of qualitative, and potentially controversial, patient-specific decisions in radiation oncology. This report summarizes many of the areas throughout radiation therapy that may benefit from the application of peer review. Each radiation oncology facility should evaluate the issues raised and develop improved ways to apply the concept of peer review to its individual process and workflow. This might consist of a daily multidisciplinary (eg, physicians, dosimetrists, physicists, therapists) meeting to review patients being considered for, or undergoing planning for, radiation therapy (eg, intention to treat and target delineation), as well as meetings to review patients already under treatment (eg, adequacy of image guidance). This report is intended to clarify and broaden the understanding of radiation oncology professionals regarding the meaning, roles, benefits, and targets for peer review as a routine quality assurance tool. It is hoped that this work will be a catalyst for further investigation, development, and study of the efficacy of peer review techniques and how these efforts can help improve the safety and quality of our treatments. © 2013 American Society for Radiation Oncology.
Kong W.,Queens Cancer Research Institute |
Jarvis C.,Queens Cancer Research Institute |
Mackillop W.J.,Queens Cancer Research Institute |
Mackillop W.J.,Queen's University
Clinical Oncology | Year: 2015
Palliative radiotherapy (PRT) is useful in the management of many patients with brain metastases, but the need for this treatment in the general cancer population is unknown. The objective of this study was to estimate the appropriate rate of use of PRT for brain metastases (PRT.Br). Ontario's population-based cancer registry was used to identify patients who died of cancer. Radiotherapy records from all the province's radiotherapy centres were linked to Ontario's cancer registry to identify patients who received PRT.Br in the last 2 years of life. Multivariate analysis was used to identify social and health system-related barriers to the use of PRT.Br and to identify a subpopulation of patients with unimpeded access to PRT.Br. The rate of use of PRT.Br was measured in this benchmark subpopulation. The benchmark rate was standardised to the case mix of the overall cancer population. The study population included 231397 patients who died of cancer in Ontario between 1998 and 2007. Overall, 13944 patients received at least one course of PRT.Br in the last 2 years of life (6.0%). Multivariate analysis showed that the use of PRT.Br was strongly associated with: the availability of radiotherapy at the diagnosing hospital; the socioeconomic status of the community where the patient lived; and the distance from his/her home to the nearest radiotherapy centre. The benchmark subpopulation was defined as patients diagnosed in a hospital with radiotherapy facilities on site and who resided in a high income community, within 50km of the nearest radiotherapy centre. The standardised benchmark rate of PRT.Br was 8.0% (95% confidence interval 7.5%, 8.5%). The overall shortfall between the actual rate and the benchmark was 25%, but varied by primary cancer site: lung, 27.6%; melanoma, 19.4%; breast, 13.9%. The magnitude of the shortfall in the use of PRT.Br varied widely across the province. At least 8.0% of patients who die of cancer require PRT.Br at least once in the last 2 years of life, but PRT.Br is widely underutilised in Ontario. The 25% shortfall in the use of PRT.Br reported here is much greater than the previously reported 7.8% shortfall in the overall lifetime rate of use of any radiotherapy in Ontario. © 2014 The Royal College of Radiologists.
Peng Y.,Queen's University |
Peng Y.,Queens Cancer Research Institute |
Xu J.,Queen's University
Lifetime Data Analysis | Year: 2012
We propose a novel interpretation for a recently proposed Box-Cox transformation cure model, which leads to a natural extension of the cure model. Based on the extended model, we consider an important issue of model selection between the mixture cure model and the bounded cumulative hazard cure model via the likelihood ratio test, score test and Akaike's Information Criterion (AIC). Our empirical study shows that AIC is informative and both the score test and the likelihood ratio test have adequate power to differentiate between the mixture cure model and the bounded cumulative hazard cure model when the sample size is large. We apply the tests and AIC methods to leukemia and colon cancer data to examine the appropriateness of the cure models considered for them in the literature. © 2012 Springer Science+Business Media, LLC.
Chander H.,Queens Cancer Research Institute |
Truesdell P.,Queens Cancer Research Institute |
Meens J.,Queens Cancer Research Institute |
Craig A.W.B.,Queens Cancer Research Institute |
Craig A.W.B.,Queen's University
Oncogene | Year: 2013
Metastatic breast adenocarcinomas display activation signatures for signaling pathways that trigger cell motility and tissue invasion. Here, we report that the adaptor protein transducer of Cdc42-dependent actin assembly-1 (Toca-1) is expressed in highly invasive breast cancers and regulates their metastatic phenotypes. We show that Toca-1 localizes to the filamentous actin-rich core of invadopodial protrusions actively degrading the extracellular matrix (ECM). Toca-1 colocalizes with Cortactin, and we show that this interaction is mediated by the SH3 domain of Toca-1. Stable knockdown (KD) of Toca-1 expression in MDA-MB-231 cells led to a significant defect in epidermal growth factor (EGF)-induced cell migration and invasion. Toca-1 KD cells also showed significant defects in EGF-and Src-induced ECM digestion and formation of invadopodial membrane protrusions. To test the role of Toca-1 in metastasis, we achieved stable Toca-1 KD in both human and rat metastatic breast adenocarcinoma cell lines. Orthotopic tumor xenografting of control and Toca-1 KD cells in natural-killer/B-/T-cell-deficient mice revealed a significant defect in spontaneous lung metastases with Toca-1 silencing in vivo. In contrast, no defects in primary tumor growth or lung seeding following tail vein injection of Toca-1 KD cells was observed, suggesting that Toca-1 functions at an early step in the dissemination of metastatic breast tumor cells. Taken together, our results identify Toca-1 as a proinvasive protein in breast adenocarcinoma and a potential therapeutic target to limit tumor metastasis. © 2013 Macmillan Publishers Limited. All rights reserved.
Sharma N.,Queen's University |
Sharma N.,Queens Cancer Research Institute |
Everingham S.,Queen's University |
Everingham S.,Queens Cancer Research Institute |
And 5 more authors.
Oncotarget | Year: 2014
Acquired mutations in KIT are driver mutations in systemic mastocytosis (SM). Here, we tested the role of SHP2/PTPN11 phosphatase in oncogenic KIT signaling using an aggressive SM mouse model. Stable knock-down (KD) of SHP2 led to impaired growth, colony formation, and increased rates of apoptosis in P815 cells. This correlated with defects in signaling to ERK/Bim, Btk, Lyn, and Stat5 pathways in P815-KD cells compared to non-targeting (NT). Retro-orbital injections of P815 NT cells in syngeneic DBA/2 mice resulted in rapid development of aggressive SM within 13-16 days characterized by splenomegaly, extramedullary hematopoiesis, and multifocal liver tumors. In contrast, mice injected with P815 SHP2 KD cells showed less disease burden, including normal spleen weight and cellularity, and significant reductions in mastocytoma cells in spleen, bone marrow, peripheral blood and liver compared to NT controls. Treatment of human mast cell leukemia HMC-1 cells or P815 cells with SHP2 inhibitor II-B08, resulted in reduced colony formation and cell viability. Combining II-B08 with multi-kinase inhibitor Dasatinib showed enhanced efficacy than either inhibitor alone in blocking cell growth pathways and cell viability. Taken together, these results identify SHP2 as a key effector of oncogenic KIT and a therapeutic target in aggressive SM.
Peng Y.,Queen's University |
Peng Y.,Queens Cancer Research Institute |
Taylor J.M.G.,University of Michigan
Statistics in Medicine | Year: 2011
Cure models for clustered survival data have the potential for broad applicability. In this paper, we consider the mixture cure model with random effects and propose several estimation methods based on Gaussian quadrature, rejection sampling, and importance sampling to obtain the maximum likelihood estimates of the model for clustered survival data with a cure fraction. The methods are flexible to accommodate various correlation structures. A simulation study demonstrates that the maximum likelihood estimates of parameters in the model tend to have smaller biases and variances than the estimates obtained from the existing methods. We apply the model to a study of tonsil cancer patients clustered by treatment centers to investigate the effect of covariates on the cure rate and on the failure time distribution of the uncured patients. The maximum likelihood estimates of the parameters demonstrate strong correlation among the failure times of the uncured patients and weak correlation among cure statuses in the same center. Copyright © 2010 John Wiley & Sons, Ltd.
Badham H.J.,Queens Cancer Research Institute |
LeBrun D.P.,Queens Cancer Research Institute |
Rutter A.,Queen's University |
Winn L.M.,Queens Cancer Research Institute |
Winn L.M.,Queen's University
Carcinogenesis | Year: 2010
Childhood cancer is the leading cause of disease-related death in children aged 1-14 years in Canada and the USA and it has been hypothesized that transplacental exposure to environmental carcinogens such as benzene may contribute to the etiology of these cancers. Our objectives were to determine if transplacental benzene exposure increased tumor incidence in mouse offspring and assess fetal benzene metabolism capability. Pregnant CD-1 and C57Bl/6N mice were given intraperitoneal injections of corn oil, 200 mg/kg, or 400 mg/kg benzene on gestational days 8, 10, 12 and 14. A significant increase in tumor incidence was observed in CD-1, but not C57BL/6N, 1-year-old offspring exposed transplacentally to 200 mg/kg benzene. Hepatic and hematopoietic tumors were predominantly observed in male and female CD-1 offspring, respectively. Female CD-1 offspring exposed transplacentally to 200 mg/kg benzene had significantly suppressed bone marrow CD11b+ cells 1 year after birth, correlating with reduced colonyforming unit granulocyte/macrophage numbers in 2-day-old pups. CD-1 and C57Bl/6N maternal blood benzene levels and fetal liver benzene, t, t-muconic acid, hydroquinone and catechol levels were analyzed by gas chromatography/mass spectrometry. Significant strain-, gender- and dose-related differences were observed. Male CD-1 fetuses had high hydroquinone levels, whereas females had high catechol levels after maternal exposure to 200 mg/kg benzene. This is the first demonstration that transplacental benzene exposure can induce hepatic and hematopoietic tumors in mice, which may be dependent on fetal benzene metabolism capability. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Withrow D.R.,Queens Cancer Research Institute |
Degroot J.M.,Queens Cancer Research Institute |
Siemens D.R.,Queen's University |
Groome P.A.,Queens Cancer Research Institute
BJU International | Year: 2011
OBJECTIVE To examine the association between the number of lymph nodes removed in pelvic lymphadenectomy and the risk of prostate cancer death, particularly in low to intermediate risk prostate cancer patients. PATIENTS AND METHODS Data on a subset of patients from a population-based case-cohort study was used to assess the effect of lymph node removal on prostate cancer-specific mortality. The subset included in this report were those 281 patients from the parent study who were treated with prostatectomy and had a pelvic lymph node dissection and for whom we had a record of the number of nodes removed (the sub-cohort) and 41 patients fitting the same criteria who died of their prostate cancer within 10 years (the cases). Study variables included number of lymph nodes removed, lymph node status, age, pre-treatment PSA, T category, Gleason score and use of hormonal therapy. We ran a Cox proportional hazards regression analysis that accounted for the study design and allowed us to consider these patient and disease characteristics as potential confounders of the association of interest. In a secondary analysis, the results were stratified by nodal status. RESULTS The crude hazard ratio (HR), which is a measure of relative risk, was not statistically significantly associated with a reduction in the risk of prostate cancer mortality as the number of lymph nodes removed at PLND increased (HR: 0.97, 95% CI: 0.91-1.03). None of the variables considered as potential confounders had an impact on the crude HR. Using two cut points to categorize the number of lymph nodes removed, one at 4 or more removed and the other at 10 or more removed resulted in HRs indicating a risk reduction of 25% in both cases, although these results were not statistically significant. When we analyzed the association by pathological nodal status, we observed a possible increase in risk in the node-positive group (HR: 1.10, 95% CI: 0.86, 1.42), while those with negative lymph nodes may have benefited from increasing numbers removed (HR 0.95, 95% CI: 0.89,1.02). CONCLUSION The results of this study indicate a possible therapeutic benefit of lymph node removal in node negative patients. Future research should focus on gaining a better understanding of the biologic mechanisms of a possible therapeutic benefit of PLND, particularly for those lower risk patients with histologically negative lymph nodes. © 2010 BJU INTERNATIONAL.
Grundy A.,Queen's University |
Grundy A.,Queens Cancer Research Institute |
Tranmer J.,Queen's University |
Richardson H.,Queen's University |
And 4 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2011
Background: Shift work has been identified as a risk factor for several cancer sites in recent years, with melatonin as a potential intermediate on the proposed causal pathway. This study examined the influence of nighttime light exposure on melatonin levels among 123 rotating shift nurses. Methods: Nurses working a rotating shift schedule (two 12-hour days, two 12-hour nights, and five days off) were recruited and participated on a day and night shift in both the summer and winter seasons. Over each 48-hour study period, nurses wore a light data logger and provided two urine and four saliva samples. Results: Saliva measurements showed that the pattern of melatonin production did not differ between day and night shifts. Mean light exposure was significantly higher (P < 0.0001) when nurses were working at night, although peak melatonin levels (P = 0.65) and the daily change in melatonin levels (P = 0.80) were similar across day/night shifts. Multivariate analysis did not show an association between light exposure and melatonin levels when data from both shifts was combined; however, when data from the night shift was considered alone, a statistically significant inverse relationship between light and change in melatonin was observed (P = 0.04). Conclusion: These results show that light exposure does not seem to be strongly related to reduced melatonin production among nurses on this rapidly rotating shift schedule. Impact: Future research considering more extreme shift patterns or brighter lighting conditions could further clarify the relationship between light exposure and melatonin production in observational settings. ©2011 AACR.