Showing papers by "Maureen E. Trudeau published in 2016"
TL;DR: A Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer including adjUvant targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancers was identified for adaptation.
Abstract: PurposeA Cancer Care Ontario (CCO) guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer including adjuvant targeted therapy for human epidermal growth factor receptor 2 (HER2)–positive breast cancers was identified for adaptation.MethodsThe American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The CCO guideline was reviewed for developmental rigor and content applicability.ResultsOn the basis of the content review of the CCO guideline, the ASCO Panel agreed that, in general, the recommendations were clear and thorough and were based on the most relevant scientific evidence, and they presented options that will be acceptable to patients. However, for some topics addressed in the CCO guideline, the ASCO Panel formulated a set of adapted recommendations on the basis of local context and practice beliefs of the Panel members.RecommendationsDecisions regarding adjuvant c...
111 citations
TL;DR: Bedtime melatonin was associated with a significant improvement in a marker of objective sleep quality, sleep fragmentation and quantity, subjective sleep, fatigue severity, global quality of life, and social and cognitive functioning scales.
Abstract: Fatigue and sleep problems are prevalent in cancer patients and can be associated with disruption of circadian rhythmicity. In this prospective phase II trial, we sought to assess the effect of melatonin on circadian biomarkers, sleep, and quality of life in breast cancer patients. Thirty-two patients with metastatic breast cancer, receiving hormonal or trastuzumab therapy, took 5 mg of melatonin at bedtime for 2 months. Before starting and after 2 months on melatonin therapy, sleep and circadian rhythmicity were assessed by actigraphy, diurnal patterns of serum cortisol, and the expression of the core clock genes PER2 and BMAL1 in peripheral blood mononuclear cells. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was completed for subjective parameters. Bedtime melatonin was associated with a significant improvement in a marker of objective sleep quality, sleep fragmentation and quantity, subjective sleep, fatigue severity, global quality of life, and social and cognitive functioning scales. Morning clock gene expression was increased following bedtime melatonin intake. Melatonin did not affect actigraphy measure of circadian rhythmicity, or the diurnal cortisol pattern. These results invite further investigation of melatonin as a potentially useful therapeutic agent for improving sleep and quality of life in cancer patients.
80 citations
TL;DR: Adjuvant trastuzumab was associated with increased risk of new incidence of HF in breast cancer survivors during the period of adjuvant treatment but not thereafter, and Routine intensive monitoring may not be necessary after completing adjUvant therapy.
Abstract: Background: The late cardiac effect of adjuvant trastuzumab and its potential interaction with anthracycline have not been well-studied on a population level. Methods: In this retrospective population-based cohort study, female breast cancer patients in Ontario, diagnosed between 2003 and 2009, were identified by the Ontario Cancer Registry and linked to administrative databases to ascertain demographics, cardiac risk factors, comorbidities, and use of adjuvant trastuzumab and other chemotherapy. Patients with pre-existing heart failure (HF) were excluded. The main endpoint was new diagnosis of HF. Analyses included KaplanMeier (KM) survival analysis, multivariable piecewise Cox regression, and competing risk and propensity score analyses. All statistical tests were two-sided. Results: Nineteen thousand seventy-four women with breast cancer treated with adjuvant chemotherapy were identified, of whom 3371 (17.7%) also received adjuvant trastuzumab. Anthracycline use was 84.9% overall. After a median followup of 5.9 years, patients treated with trastuzumab and chemotherapy were more likely to develop HF than patients on chemotherapy alone (5-year cumulative incidences of 5.2% vs 2.5%; log-rank P < .001). After adjusting for confounders, adjuvant trastuzumab remained independently associated with incident HF in the first 1.5 years (HR = 5.77, 95% CI = 4.38 to 7.62, P < .001), but not thereafter (HR = 0.87, 95% CI = 0.57 to 1.33, P = .53). Anthracycline use did not increase the risk of HF with trastuzumab synergistically, neither within ( P interaction = .92) nor beyond 1.5 years ( interaction = .23). Conclusion: Adjuvant trastuzumab was associated with increased risk of new incidence of HF in breast cancer survivors during the period of adjuvant treatment but not thereafter. Routine intensive monitoring may not be necessary after completing adjuvant therapy.
68 citations
TL;DR: The RS substantially influenced both oncologists' recommendations and patients' preferences for chemotherapy, and the major effect was avoidance of chemotherapy when AOL indicated high or intermediate risk.
Abstract: PurposeTo evaluate the 21-gene recurrence score (RS) on decision-making in a population-based cohort.Patients and MethodsPatients with axillary node-negative or nodal micrometastases, estrogen receptor–positive, and human epidermal growth factor receptor 2–negative breast cancer being considered for chemotherapy were eligible. All cancer treatment centers in Ontario, Canada, participated. Oncologists made a preliminary recommendation for endocrine therapy with or without chemotherapy on the basis of Adjuvant! Online (AOL) risk estimation. Patients were asked for their preference regarding chemotherapy. After RSs were available, patients returned for final decision-making. Patient satisfaction was measured by using the decisional conflict scale.ResultsBetween January 2012 and July 2013, 1,000 patients were recruited. RSs were available for 979 patients. In 58% of patients, risk was categorized as low (RS, 0 to 18); in 33%, intermediate (RS, 19 to 30); and in 9%, high (RS, ≥ 31). Oncologists' recommendation...
65 citations
TL;DR: The authors investigated whether patients with breast cancer who had different socioeconomic status (SES) received different care and had different overall survival in Ontario, Canada.
Abstract: BACKGROUND
The Canadian health care system provides equitable access to equivalent standards of care. The authors investigated to determine whether patients with breast cancer who had different socioeconomic status (SES) received different care and had different overall survival (OS) in Ontario, Canada.
METHODS
Women who were diagnosed with breast cancer between 2004 and 2009 were identified from the Ontario Cancer Registry and linked to provincial databases to ascertain patient demographics, screening, diagnosis, treatment patterns, and survival. SES was defined as neighborhood income by postal code and was divided into income quintiles (Q1-Q5; with Q5 the highest SES quintile). Univariable and multivariable analyses were used to examine the associations between: 1) SES and mammogram screening and breast cancer treatments, and 2) SES and OS.
RESULTS
In total, 34,776 patients with breast cancer who had information on disease stage available at diagnosis were identified. Seventy-six percent of women were aged >50 years. Patients with higher SES were more likely to be diagnosed at an earlier stage (Q5 [44.3%] vs Q1 [37.7%]; odds ratio [OR], 1.31; 95% confidence interval [CI], 1.23-1.41; P < .0001) and also were more likely to receive adjuvant chemotherapy (Q5 vs Q1: OR, 1.18; 95% CI, 1.10-1.26; P < .0001) and radiotherapy (Q5 vs Q1: OR, 1.24; 95% CI, 1.15-1.33; P < .0001). The 5-year OS rates for Q1 through Q5 were 80%, 81%, 82.2%, 83.9%, and 85.7%, respectively (P < .0001). After adjusting for patient demographics, cancer stage at diagnosis, adjuvant chemotherapy, trastuzumab, radiotherapy and surgery types, higher SES remained associated with better OS (P = .0017).
CONCLUSIONS
In a universal health care system, higher SES is associated with greater screening and treatments and with better OS after adjusting for screening, cancer stage at diagnosis, and treatments. Cancer 2015. © 2015 American Cancer Society.
50 citations
TL;DR: Recommendations for primary prophylaxis with granulocyte-colony-stimulating factors for patients above a febrile neutropenia (FN) risk threshold are clarified and guidelines should clarify how FN rates from RCTs should be applied in clinical practice.
40 citations
TL;DR: It is demonstrated for the first time, using new parameters tested on relatively large patient cohort and leave-one-out classifier evaluation, that a hybrid QUS biomarker including MBF, SS, and SAS could detect the response of LABC tumors to NAC as early as after 4 weeks of therapy.
Abstract: // Hadi Tadayyon 1, 2 , Lakshmanan Sannachi 1, 2, 3, 4 , Mehrdad Gangeh 1, 2, 3, 4 , Ali Sadeghi-Naini 1, 2, 3, 4 , William Tran 3 , Maureen E. Trudeau 5 , Kathleen Pritchard 5 , Sonal Ghandi 5 , Sunil Verma 5 , Gregory J. Czarnota 1, 2, 3, 4 1 Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada 2 Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada 3 Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada 4 Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada 5 Division of Medical Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada Correspondence to: Gregory J. Czarnota, email: Gregory.czarnota@sunnybrook.ca Keywords: quantitative ultrasound, tissue characterization, breast cancer, breast cancer chemotherapy, tumor response assessment Received: September 18, 2015 Accepted: March 28, 2016 Published: April 20, 2016 ABSTRACT Purpose: This study demonstrated the ability of quantitative ultrasound (QUS) parameters in providing an early prediction of tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC). Methods: Using a 6-MHz array transducer, ultrasound radiofrequency (RF) data were collected from 58 LABC patients prior to NAC treatment and at weeks 1, 4, and 8 of their treatment, and prior to surgery. QUS parameters including midband fit (MBF), spectral slope (SS), spectral intercept (SI), spacing among scatterers (SAS), attenuation coefficient estimate (ACE), average scatterer diameter (ASD), and average acoustic concentration (AAC) were determined from the tumor region of interest. Ultrasound data were compared with the ultimate clinical and pathological response of the patient’s tumor to treatment and patient recurrence-free survival. Results: Multi-parameter discriminant analysis using the κ -nearest-neighbor classifier demonstrated that the best response classification could be achieved using the combination of MBF, SS, and SAS, with an accuracy of 60 ± 10% at week 1, 77 ± 8% at week 4 and 75 ± 6% at week 8. Furthermore, when the QUS measurements at each time (week) were combined with pre-treatment (week 0) QUS values, the classification accuracies improved (70 ± 9% at week 1, 80 ± 5% at week 4, and 81 ± 6% at week 8). Finally, the multi-parameter QUS model demonstrated a significant difference in survival rates of responding and non-responding patients at weeks 1 and 4 (p=0.035, and 0.027, respectively). Conclusion: This study demonstrated for the first time, using new parameters tested on relatively large patient cohort and leave-one-out classifier evaluation, that a hybrid QUS biomarker including MBF, SS, and SAS could, with relatively high sensitivity and specificity, detect the response of LABC tumors to NAC as early as after 4 weeks of therapy. The findings of this study also suggested that incorporating pre-treatment QUS parameters of a tumor improved the classification results. This work demonstrated the potential of QUS and machine learning methods for the early assessment of breast tumor response to NAC and providing personalized medicine with regards to the treatment planning of refractory patients.
36 citations
TL;DR: GEP testing information influences chemotherapy treatment decisions in early-stage breast cancer and varies depending on clinical risk, so clinicians should be aware of these differences and tailor the use of GEP testing accordingly.
Abstract: Objectives Gene expression profiling (GEP) of tumours informs baseline risk prediction, potentially affecting adjuvant chemotherapy decisions for women with early-stage breast cancer. Since only 15% will experience a recurrence, concerns have been raised about potential harms from overtreatment and high GEP costs in publicly funded healthcare systems. We aimed to estimate preferences and personal utility of GEP testing information and benefit–risk trade-offs in chemotherapy treatment decisions. Design, setting and intervention Based on literature review and findings from our qualitative research (focus groups, interviews with patients with breast cancer and medical oncologists), we developed a discrete choice experiment (DCE) survey and administered it via an internet panel. The DCE included 12 choice tasks with 5 attributes and 3 alternatives considering orthogonality, D-efficiency and level balance. Participants The DCE survey was administered to 1004 Canadian women from the general population. Main outcome measures Preferences were analysed using conditional logit and hierarchical Bayes and evaluated for goodness of fit. We conducted simulation analyses for alternative scenarios. Results GEP test score indicating likely benefit from chemotherapy was the most important attribute. Doctor9s clinical estimate of the risk of cancer returning, trust in your cancer doctor and side effects of chemotherapy (temporary and permanent) were relatively less important but showed significant differences among levels. In the scenario analyses, 78% were likely to choose chemotherapy in a high-risk scenario, 55% in a moderate-risk scenario and 33% in a low-risk scenario, with the other attributes held constant. A high GEP score was more important in influencing the choice of chemotherapy for those at intermediate clinical risk. Conclusions GEP testing information influences chemotherapy treatment decisions in early-stage breast cancer and varies depending on clinical risk. Clinicians should be aware of these differences and tailor the use of GEP testing accordingly.
28 citations
TL;DR: Early trastuzumab discontinuation is a powerful independent predictor of cardiac events and clinically significant relapse, and both may contribute to poor survival; both adequate cancer control and optimal CV management are required to improve long-term outcomes.
Abstract: We critically examined long-term cardiovascular (CV) outcomes and overall survival (OS) of breast cancer (BC) patients who had cardiotoxicity during adjuvant trastuzumab treatment requiring discontinuation in a population-based sample. This was a retrospective cohort of early-stage BC patients diagnosed before 2010 and treated with trastuzumab in Ontario. Patients were stratified based on trastuzumab doses received: 1-8, 9-15, ≥16 (therapy completion). Time-dependent multivariable Cox models were used to analyze primary endpoint OS, and the following composite endpoints: hospitalization/emergency room visit for heart failure (HF) or death; non-HF CV (myocardial infarction, stroke) or death; and clinically significant relapse (palliative systemic therapy initiation >90 days after last trastuzumab dose) or death. Of the 3134 women, 6, 10, and 85 % received 1-8, 9-15, and ≥16 doses, respectively. Over 5-year median follow-up, early trastuzumab discontinuation was associated with more HF/death [1-8 doses hazard ratio (HR) 4.0, 95 % confidence interval (CI) 2.7-6.0; 9-15 doses HR 2.97, 95 % CI 2.1-4.3], non-HF/death (1-8 doses HR 4.3, 95 % CI 3.0-6.1; 9-15 doses HR 3.1, 95 % CI 2.2-4.4), clinically significant relapse/death (1-8 doses HR 3.1, 95 % CI 2.2-4.4; 9-15 doses HR 2.4, 95 % CI 1.8-3.3), and importantly lower OS (77, 80, 93 %; P < 0.001). Early discontinuation (1-8 doses HR 2.41, 95 % CI 1.5-3.8; 9-15 doses HR 2.9, 95 % CI 2.0-4.1) and clinically significant relapse (HR 34.0, 95 % CI 24.9-46.6) were both independent predictors of mortality. Of note, early discontinuation remained a critical independent predictor of OS even after adjusting for incident HF. Early trastuzumab discontinuation is a powerful independent predictor of cardiac events and clinically significant relapse, and both may contribute to poor survival. Both adequate cancer control and optimal CV management are required to improve long-term outcomes.
23 citations
18 Feb 2016
TL;DR: Greater hospital and physician case volumes are associated with reduced rates of trastuzumab-related cardiotoxicity, most likely because of better cardiac monitoring at higher volume centres.
Abstract: Background: Adjuvant trastuzumab is the standard of care for patients with HER2 overexpressing breast cancer, but use of trastuzumab may lead to cardiotoxicity. Our goal was to evaluate the relationship between hospital and physician case volume and cardiac outcomes in this population. Methods: In this retrospective cohort study, we identified all female patients in Ontario with a breast cancer diagnosis in 2003–2009 who underwent treatment with trastuzumab through a provincial drug-funding program and linked these patients to administrative databases to ascertain patient demographics, treating hospital and physician characteristics, admissions to hospital, cardiac risk factors, cardiac imaging and comorbidities. Insufficient cardiac monitoring was defined as per the Canadian Trastuzumab Working Group guideline. Cardiotoxicity was defined as receiving fewer than 16 of 18 doses of trastuzumab because of heart failure admission, heart failure diagnosis or discontinuation of the drug after cardiac imaging. We constructed hierarchical multivariable logistic regression models to evaluate the effect of annual hospital volume, cumulative physician volume and treatment period on cardiac monitoring and cardiotoxicity. Results: Of 3777 women treated by 214 oncologists at 68 hospitals, 918 (24.3%) had insufficient cardiac monitoring and cardiotoxicity developed in 640 (16.9%). Cardiotoxicity occurred in 389 (42.4%) and 251 (8.8%) patients in the insufficient- and sufficient-monitoring groups, respectively. Higher annual hospital and cumulative physician volumes, and more recent calendar period, were all independent predictors for decreased cardiotoxicity. Adjustment for rates of cardiac monitoring annulled the relationships between case volume and cardiotoxicity. Interpretation: Greater hospital and physician case volumes are associated with reduced rates of trastuzumab-related cardiotoxicity, most likely because of better cardiac monitoring at higher volume centres.
11 citations
TL;DR: GEP testing adds value for women initially unsure about chemotherapy treatment with a decrease in decisional conflict, but for women who are confident about their treatment decisions, GEP testing may not add value.
TL;DR: A need for more target-matched agent development, maintenance of a value-based focus in research and a need for the clinical development of agents to treat TN/BRCA-positive and HR-positive BC are suggested.
Abstract: We undertake an analysis of ongoing BC targeted therapy trials registered to CT.gov to describe patterns of ongoing clinical research, highlight gaps in current research programs and identify ways of optimizing ongoing initiatives. A search of clinicaltrials.gov was conducted on September 4, 2013 to identify ongoing randomized phase II and III trials of targeted therapies in BC. A total of 280 trials were analyzed, the majority conducted in either human epidermal growth factor receptor 2 (HER2)-positive (n = 79, 28.2 %) or hormone receptor (HR)-positive (n = 104, 37.1 %) populations. Less than half of all trials were conducted in populations selected to match the agent under investigation (n = 126, 45 %). HER2-directed therapy is the single most investigated class of targeted agents (n = 73, 26.1 %), but trials investigating anti-angiogenic agents are also common (n = 49, 17.5 %). The most common new classes of agents under investigation in HR-positive and triple negative (TN)/BRCA-positive disease, are non-receptor protein kinase-inhibitors (n = 12; 11.5 %) and poly (ADP-ribose) polymerase inhibitors (n = 6; 30 %), respectively. The majority of regimens combine new targeted agents with either chemotherapy (n = 164, 58.6 %) or endocrine therapy (n = 113, 40.4 %); a total of 8 trials (2.8 %) investigated peptide-drug conjugates. The most frequently utilized end-points were pathological complete response in the neo-adjuvant setting (n = 36, 52.9 %) and time-to-event end-points in the adjuvant and advanced settings (77.3 and 72.6 %, respectively). Our findings suggest a need for more target-matched agent development, maintenance of a value-based focus in research and a need for the clinical development of agents to treat TN/BRCA-positive and HR-positive BC.
TL;DR: This prospective study evaluates recommendations for adjuvant therapy for 70 patients with ER+, HER2-negative EBC and 1-3 positive lymph nodes by evaluating how the results of the RS assay impact the decision making processes of medical oncologists in an academic centre in Ontario.
Abstract: e12026Background: The 21-gene Recurrence Score (RS) assay has been shown to be both prognostic and predictive of chemotherapy (CT) benefit in patients with node negative and node positive (N+), est...