56 results on '"David E. Dawe"'
Search Results
2. The Role of Immunotherapy in the Treatment of Malignant Pleural Mesothelioma
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Shantanu Banerji, David E. Dawe, Daniel E. Meyers, and Craig Harlos
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Oncology ,medicine.medical_specialty ,Pleural Neoplasms ,medicine.medical_treatment ,Ipilimumab ,Review ,Pembrolizumab ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Mesothelioma ,ipilimumab ,RC254-282 ,nivolumab ,business.industry ,Mesothelioma, Malignant ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer ,Immunotherapy ,medicine.disease ,Immune checkpoint ,Serous fluid ,mesothelioma ,immunotherapy ,pembrolizumab ,cell therapy ,Nivolumab ,business ,medicine.drug - Abstract
Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward.
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- 2021
3. Never too old to learn new tricks: Surveying Canadian healthcare professionals about learning needs in caring for older adults with cancer
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David E. Dawe, Tamas Fulop, Fay J. Strohschein, Ewa Szumacher, Shabbir M.H. Alibhai, Martine Puts, Jennifer M. Jones, Tina Hsu, and Margaret I. Fitch
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Canada ,medicine.medical_specialty ,Medical Oncology ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Surveys and Questionnaires ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Polypharmacy ,Descriptive statistics ,business.industry ,Cancer ,Special Interest Group ,medicine.disease ,Mental health ,Oncology ,Geriatric oncology ,030220 oncology & carcinogenesis ,Family medicine ,Respondent ,Needs assessment ,Geriatrics and Gerontology ,business ,Delivery of Health Care - Abstract
The number of older adults with cancer is growing but little is known about healthcare professionals' (HCPs) perceptions of their readiness to care for older adults with cancer. The Canadian Network on Aging and Cancer together with the Canadian Association of Nurses in Oncology, Oncology and Aging Special Interest Group, conducted a survey to assess geriatric oncology learning needs of Canadian HCPs and explore any differences in needs between nurses and physicians.An online survey was distributed to Canadian HCP, which assessed respondent confidence and desire to learn about domains related to geriatric oncology, current clinical practice and sociodemographic information. Descriptive statistics and chi-square tests were used to characterize participant characteristics, learning needs and compare learning needs of physicians vs. nurses.Respondents (n = 154) were mostly physicians (n = 78, 51%) or nurses (n = 56, 36%). Respondents reported not being confident addressing mental health issues (75%), polypharmacy (71%), geriatric oncology care models (69%), and return to baseline function post-treatment (67%). Physicians reported more confidence than nurses in managing comorbidities (72% vs. 49%, p 0.05), having difficult conversations (90% vs. 68%, p 0.001), and addressing ageism (76% vs. 58%, p 0.05), while nurses reported more confidence with managing mobility limitations (64% vs 42%, p 0.05), fall prevention (72% vs. 26%, p 0.01) and supporting caregivers (74% vs 52%, p 0.05). Nurses wanted to learn more about geriatric oncology than physicians for 10 domains (p 0.05).There is a need for interprofessional educational initiatives that address differences between nurses and physicians in clinical areas of confidence and learning needs.
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- 2021
4. Elevated expression of interleukin 16 in chronic lymphocytic leukemia is associated with disease burden and abnormal immune microenvironment
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Xun Wu, Jordan Thisdelle, Sen Hou, J Ernesto Fajardo-Despaigne, Spencer B Gibson, James B Johnston, David E Dawe, Versha Banerji, and Aaron J Marshall
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Cancer Research ,Oncology ,Hematology - Published
- 2023
5. Population-based Assessment of Intermittent Androgen Deprivation Therapy Utilization for Relapsed, Nonmetastatic, Hormone-sensitive Adenocarcinoma of the Prostate
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Bryan Janzen, Rashmi Koul, Bashir Bashir, Makoy Penner, Amitava Chowdhury, Aldrich Ong, Julian O. Kim, Arbind Dubey, David E. Dawe, Jasmir G. Nayak, and Shahida Ahmed
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Male ,Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,Population ,Adenocarcinoma ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,education ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,Marital Status ,business.industry ,Radiation Oncologists ,Prostatic Neoplasms ,Androgen Antagonists ,Manitoba ,Retrospective cohort study ,Odds ratio ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,Survival Analysis ,Prostatic Neoplasms, Castration-Resistant ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Kallikreins ,Neoplasm Recurrence, Local ,business ,Cohort study - Abstract
OBJECTIVES Androgen deprivation therapy (ADT) is the standard of care for men with nonmetastatic hormone-sensitive prostate cancer (nmHSPC) after treatment failure. Although intermittent ADT (iADT) is noninferior to continuous ADT for prostate cancer outcomes, with superior quality of life and cost-to-benefit ratio, little is known regarding its real-world utilization. The authors aimed to determine the utilization of iADT in a Canadian Provincial Cancer Program for relapsed nmHSPC and identified risk factors associated with the nonreceipt of iADT. MATERIALS AND METHODS This retrospective population-based cohort study used linked administrative databases to identify all patients with relapsed nmHSPC from 2012 to 2016 and quantified ADT prescription history. Patients were defined as iADT eligible if prostate-specific antigen (PSA) was
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- 2020
6. Effect of Hospitalization During First Chemotherapy and Performance Status on Small-cell Lung Cancer Outcomes
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Oliver Bucher, Shantanu Banerji, David E. Dawe, Rebekah Rittberg, Susan Green, and Trevor Aquin
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Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Neutropenia ,Carboplatin ,Nephrotoxicity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Progression-free survival ,Lung cancer ,Aged ,Etoposide ,Retrospective Studies ,Chemotherapy ,Performance status ,business.industry ,Retrospective cohort study ,Prognosis ,medicine.disease ,Small Cell Lung Carcinoma ,Hospitalization ,Survival Rate ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Follow-Up Studies - Abstract
Small-cell lung cancer (SCLC) is highly responsive to chemotherapy (CT) and one of the few malignancies treated in hospitalized patients with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS). Because of the little current information available on the outcomes experienced by hospitalized patients with SCLC receiving CT, we explored the outcomes for these patients to improve the evidence base for practice.We conducted a retrospective cohort study to evaluate patients with a diagnosis of SCLC and treated with CT during a 10-year period. Progression-free survival (PFS) and overall survival (OS) were evaluated according to site of first CT (inpatient vs. outpatient) and PS. Multivariable analysis was completed to assess for independent survival predictors.A total of 530 patients with SCLC were treated, with 82 (15%) receiving their first CT in hospital. Inpatients had a greater burden of disease and poorer PS. Neutropenia, thrombocytopenia, nephrotoxicity, and fatigue were all experienced less often by the inpatient cohort (P .001, P .001, P .001, and P = .007, respectively). For inpatients and outpatients, the OS rate at 12, 24, and 60 months was 22%, 9%, and 7% and 43%, 20%, and 9%, respectively (P .001 for all). The median PFS and OS were longer for outpatients and highly functional patients. On multivariable analysis, ECOG PS was an independent predictor of the outcome and the site of first CT was not (P = .04 and P = .49, respectively).Patients with SCLC initially treated as inpatients and those with poor functional status had shorter PFS and OS; however, some experienced long-term survival, including 5-year survival of 7% for the inpatient cohort and 5% for the ECOG PS 3-4 cohort. CT toxicities were less common in the inpatient cohort, validating that administration of CT in hospital should be considered for these patients because they could experience a meaningful long-term response to therapy.
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- 2020
7. Real world risk of infusion reactions and effectiveness of front-line obinutuzumab plus chlorambucil compared with other frontline treatments for chronic lymphocytic leukemia
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Nicole Bourrier, Ivan Landego, Oliver Bucher, Mandy Squires, Erin Streu, Irena Hibbert, Theresa Whiteside, Spencer B. Gibson, Marc Geirnaert, James B. Johnston, David E. Dawe, Versha Banerji, and University of Manitoba
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Retrospective cohort study ,Aged, 80 and over ,Male ,Cancer Research ,Research ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Manitoba ,Middle Aged ,Antibodies, Monoclonal, Humanized ,Leukemia, Lymphocytic, Chronic, B-Cell ,Injection Site Reaction ,Treatment Outcome ,Oncology ,Antineoplastic Combined Chemotherapy Protocols ,Obinutuzumab ,Genetics ,Humans ,Chronic lymphocytic leukemia ,Chlorambucil ,Female ,RC254-282 ,CLL ,Front-line therapy ,Aged ,Retrospective Studies - Abstract
Background Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB). Methods A retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan–Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy. Results Forty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil. Conclusions In summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.
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- 2022
8. Treatment Patterns, Toxicity, and Outcomes of Older Adults With Advanced Pancreatic Cancer Receiving First-line Palliative Chemotherapy
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Erin N. McAndrew, Hanbo Zhang, Pascal Lambert, Rebekah Rittberg, David E. Dawe, and Christina A. Kim
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Male ,Cancer Research ,Paclitaxel ,Vomiting ,Palliative Care ,Leucovorin ,Nausea ,Kaplan-Meier Estimate ,Irinotecan ,Deoxycytidine ,Gemcitabine ,Oxaliplatin ,Pancreatic Neoplasms ,Treatment Outcome ,Oncology ,Albumins ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Fluorouracil ,Aged - Abstract
Advanced pancreatic cancer (APC) disproportionately impacts older adults. Randomized trials demonstrate improved overall survival (OS) with combination chemotherapy including 5-fluorouracil, irinotecan, leucovorin, and oxaliplatin (FOLFIRINOX) or nab-paclitaxel and gemcitabine compared with gemcitabine alone, but with increased toxicity. Older adults are at increased risk of side effects from chemotherapy. The aim of this study was to assess the efficacy and toxicity of chemotherapy in older adults with APC.Patients diagnosed with APC from 2011 to 2016 were identified using the Manitoba Cancer Registry. Patient and treatment characteristics, toxicity, and outcomes of patients 65 years of age and above treated with palliative chemotherapy were compared by treatment regimen. OS was assessed using the Kaplan-Meier method. A Cox regression was used to identify independent predictors of OS.A total of 87 patients aged 65 years and above received palliative chemotherapy: 52 (59.7%) FOLFIRINOX, 21 (24.1%) nab-paclitaxel and gemcitabine, and 14 (16.1%) gemcitabine, with a median age of 69 (65 to 84), 75 (65 to 88), and 73 (67 to 82), Eastern Cooperative Oncology Group (ECOG) performance status difference in hematologic toxicity between regimens (P=0.807). An increase in nonhematologic toxicity was seen with FOLFIRINOX (P0.001), specifically neuropathy (P=0.008), fatigue (P0.001), and nausea/vomiting (P=0.008). FOLFIRINOX was associated with improved radiologic response (P=0.05) and OS (P=0.035). PS, baseline carbohydrate antigen 19-9 level, and chemotherapy regimen were independent predictors of survival.FOLFIRINOX is associated with improved response and OS in older adults with APC. FOLFIRINOX has a manageable safety profile in this population and should be considered in fit older adults with APC.
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- 2022
9. Treatment and Prevention of Brain Metastases in Small Cell Lung Cancer
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Shantanu Banerji, Julian O. Kim, Rebekah Rittberg, Shrinivas Rathod, and David E. Dawe
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Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Central nervous system ,Disease ,Radiosurgery ,Metastasis ,Internal medicine ,medicine ,Humans ,Extensive stage ,Limited Stage ,Chemotherapy ,business.industry ,Brain Neoplasms ,medicine.disease ,Small Cell Lung Carcinoma ,respiratory tract diseases ,medicine.anatomical_structure ,Conventional PCI ,Prophylactic cranial irradiation ,Cranial Irradiation ,business - Abstract
Central nervous system (CNS) metastasis will develop in 50% of small cell lung cancer (SCLC) patients throughout disease course. Development of CNS metastasis poses a particular treatment dilemma due to the accompanied cognitive changes, poor permeability of the blood-brain barrier to systemic therapy and relatively advanced state of disease. Survival of patients with untreated SCLC brain metastases is generally
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- 2021
10. Data Driven Identification of Plasma Metabolite Clusters and Metabolites of Interest for Potential Detection of Early Stage Non-Small Cell Lung Cancer Cases Versus Cancer-Free Controls
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Biniam Kidane, Gefei Qing, Shantanu Banerji, Lawrence Tan, Sadeesh Srinathan, Michael Domaratzki, Robert Balshaw, David E. Dawe, Leigh C. Murphy, Michel Aliani, Connel Trevena, Julian Oliver Kim, and Gordon Buduhan
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chemistry.chemical_compound ,Chemistry ,Metabolite ,Cancer-Free ,medicine ,Cancer research ,Identification (biology) ,Non small cell ,Stage (cooking) ,Lung cancer ,medicine.disease - Abstract
Objectives: Metabolomics is a potential means for biofluid-based lung cancer detection. We conducted a non-targeted, data-driven, assessment of plasma from early-stage non-small cell lung cancer (ES-NSCLC) cases versus cancer-free controls (CFC) to explore and identify classes of metabolites for further targeted metabolomics biomarker development. Materials and Methods: Plasma from 250 ES-NSCLC cases and 250 CFCs underwent Ultra High-Performance Liquid Chromatography/Quadrupole Time-Of-Flight Mass Spectrometry (UHPLC-QTOF-MS) in positive and negative electrospray ionization (ESI) modes. Molecular feature extraction, formula generation, and find-by-ion tools annotated metabolic entities. Analysis was restricted to endogenous metabolites present in ≥80% of samples. Unsupervised hierarchical cluster analysis identified clusters of metabolites. The metabolites with the strongest correlation with the principal component of each cluster were included in logistic regression modeling to assess discriminatory performance with and without adjustment for clinical covariates. Results: 1,900 UHPLC-QTOF-MS assessments identified 1,667 and 2,032 endogenous metabolites in the ESI positive and ESI negative modes, respectively. After data filtration, 676 metabolites remained, and 12 clusters of metabolites were identified from each ESI mode. Multivariable logistic regression using the representative metabolite from each cluster revealed effective classification of cases from controls with overall diagnostic accuracy of 91% (ESI positive) and 94% (ESI negative). Metabolites of interest identified for further targeted analysis include: 1b, 3a, 12a-trihydroxy-5b-cholanoic acid, pyridoxamine 5’-phosphate, sphinganine 1-phosphate, gamma-CEHC, 20-carboxy-leukotriene B4, isodesmosine, and 18-hydroxycortisol.Conclusions: Plasma-based metabolomic detection of early-stage NSCLC appears feasible. Further metabolomics studies targeting phospholipid, steroid, and fatty acid metabolism are warranted to further develop non-invasive metabolomics-based detection of early-stage NSCLC.
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- 2021
11. The impact of the modified frailty index on clinical outcomes for patients with stage IV non-small cell lung cancer receiving chemotherapy
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Shivani Mathur, Laura Prince, Oliver Bucher, Lin Xue, Shantanu Banerji, and David E. Dawe
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Male ,Lung Neoplasms ,Oncology ,Frailty ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Geriatrics and Gerontology ,Proportional Hazards Models ,Retrospective Studies - Abstract
Frailty impacts outcomes for patients with lung cancer, but no brief tools have been assessed in patients with metastatic disease. We evaluated the impact of the Modified Frailty Index (mFI) on clinical outcomes for patients with metastatic non-small cell lung cancer (NSCLC).We conducted a retrospective cohort study of all patients with Stage IV NSCLC diagnosed in Manitoba between 2011 and 2016 who then received first-line cytotoxic chemotherapy. We assigned mFI scores based on documented comorbidities and collected data on toxicity, progression, and survival. Descriptive statistics characterized the cohort and toxicity experienced. Kaplan-Meier methods were used to evaluate progression-free survival (PFS) and overall survival (OS), followed by multivariable Cox proportional hazards models.Our cohort of 426 (mFI 0/1-2/3+ = 175/196/55) patients, showed no significant association between higher mFI score and incidence of overall chemotherapy toxicity. Patients with mFI 0 experienced more frequent thromboses (p=0.022) and a trend towards less nausea or vomiting (p = 0.059). There was no significant difference in PFS or OS among frailty groups. Poorer performance status, number of metastatic sites, and the absence of a driver mutation were independently associated with poorer PFS and OS. Male sex and not completing chemotherapy were also associated with worse OS.This study is the first to investigate the use of the mFI as a frailty tool in patients with metastatic NSCLC receiving cytotoxic chemotherapy. The mFI does not appear to be strongly associated with treatment-related toxicities, PFS, or OS in patients with metastatic NSCLC receiving first-line cytotoxic chemotherapy.
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- 2021
12. Descriptive Analysis of Dosing and Outcomes for Patients with Ibrutinib-Treated Relapsed or Refractory Chronic Lymphocytic Leukemia in a Canadian Centre
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K. Uminski, David E. Dawe, I. Hibbert, O. Bucher, James B. Johnston, Versha Banerji, K. Brown, M. Geirnaert, and Dhali H.S. Dhaliwal
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Male ,Canada ,medicine.medical_specialty ,Population ,small lymphocytic lymphoma ,Antineoplastic Agents ,clinical response ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,hemic and lymphatic diseases ,Internal medicine ,Agammaglobulinaemia Tyrosine Kinase ,medicine ,Humans ,030212 general & internal medicine ,education ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Adenine ,Ibrutinib ,toxicity ,Retrospective cohort study ,Middle Aged ,Leukemia, Lymphocytic, Chronic, B-Cell ,Hematologic Response ,Discontinuation ,Pyrimidines ,Treatment Outcome ,chemistry ,030220 oncology & carcinogenesis ,Cohort ,chronic lymphocytic leukemia ,Pyrazoles ,Female ,Original Article ,Refractory Chronic Lymphocytic Leukemia ,business ,IGHV@ - Abstract
Ibrutinib is an approved treatment for relapsed or refractory chronic lymphocytic leukemia (cll) and small lymphocytic lymphoma (sll). The effect of ibrutinib dose reduction compared with discontinuation in a population-based setting is unclear. To examine the patterns of ibrutinib use in a Canadian population-based setting, we analyzed a retrospective cohort of patients with relapsed or refractory cll or sll treated with ibrutinib. The 64 patients diagnosed with cll or sll had a median age of 76.5 years. Most had unmutated ighv (immunoglobulin variable heavy chain). A hematologic response occurred in 39 patients regardless of the ibrutinib dose. The most common toxicities were infection, bruising or bleeding, and musculoskeletal problems, with a median time to first toxicity of 14 days. More than half the cohort experienced a dose reduction, with musculoskeletal problems, cytopenias, and infection being the leading causes, surgery was the most frequent indication for holding treatment. Only 26 of the 64 patients (40.6%) stayed on the recommended maximal dose of ibrutinib. No differences in reported toxicities or hematologic response rates were evident between the patients receiving maximal and submaximal therapy. At the end of the study period, 53 patients from the initial cohort remained on ibrutinib. More than half the study patients received ibrutinib therapy at a submaximal dose without evidence of increased frequency of toxicities or disease progression. The rate of ibrutinib discontinuation was lower in our cohort than has been reported in other settings. Submaximal ibrutinib dosing will have to be further systematically evaluated.
- Published
- 2019
13. A scoping review documenting cancer outcomes and inequities for adults living with intellectual and/or developmental disabilities
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David E. Dawe, Christine Kelly, Mark Kristjanson, Alexandrea Anderson, Kathleen Decker, Julie Hallet, Morgan Stirling, Alyson L. Mahar, Hélène Ouellette-Kuntz, and Shahin Shooshtari
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Gerontology ,Adult ,Databases, Factual ,Oncology (nursing) ,business.industry ,Developmental Disabilities ,Cancer ,General Medicine ,medicine.disease ,Health equity ,Intellectual Disability ,Neoplasms ,Cancer screening ,medicine ,Humans ,Program planning ,Social determinants of health ,business ,Child ,Delivery of Health Care ,Healthcare system - Abstract
Introduction Emerging evidence suggests adults with intellectual and/or developmental disabilities (IDD) may be at risk of inequities in cancer experiences and outcomes. Individuals with IDD may experience multiple barriers that could worsen outcomes and experience. These barriers may be connected to features of IDD or the healthcare system overall. Future research and program planning to support adults with IDD and cancer must be informed by evidence that acknowledges potential disparities , underlying determinants, and knowledge deficits. Objective We conducted a scoping review to systematically map the evidence describing and comparing cancer-related outcomes along the cancer continuum from risk to mortality for adults with IDD. We identified specific factors observed to influence those outcomes. Methods We followed the expanded Arksey & O'Malley framework for conducting the scoping review. We searched for literature in PubMed and Embase databases. We abstracted cancer-related data, IDD-related data, and data related to physical and social determinants of health . Results Of the 2796 studies retrieved, 38 were included for review. Most studies focused on screening outcomes and experiences. Studies reported that adults with IDD experienced inequities at various points along the cancer continuum. Numerous social and physical determinants of health influenced the experiences and outcomes of adults with IDD. Conclusion This scoping review identified significant gaps in the literature. Of note was the focus on cancer screening and lack of attention to larger systems of oppression that may influence poor cancer experiences and outcomes for adults with IDD. There is strong need to improve both quality and quantity of research in this area.
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- 2021
14. Active Surveillance in Metastatic Renal Cell Carcinoma: Results From the Canadian Kidney Cancer Information System
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Igal Kushnir, Daniel Y.C. Heng, Aly-Khan A. Lalani, Denis Soulières, Rodney H. Breau, Aaron R. Hansen, David E. Dawe, Georg A. Bjarnason, Naveen S. Basappa, Jeffrey Graham, Lori Wood, Anil Kapoor, Christian Kollmannsberger, Sunita Ghosh, M. Neil Reaume, Frédéric Pouliot, and Simon Tanguay
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medicine.medical_specialty ,Canada ,Databases, Factual ,Urology ,030232 urology & nephrology ,Disease ,Treatment results ,urologic and male genital diseases ,Systemic therapy ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,medicine ,Humans ,In patient ,Watchful Waiting ,Carcinoma, Renal Cell ,Retrospective Studies ,business.industry ,medicine.disease ,Kidney Neoplasms ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Toxicity ,business ,Kidney cancer - Abstract
Active surveillance (AS) is a commonly used strategy in patients with slow-growing disease. We aimed to assess the outcomes and safety of AS in patients with metastatic renal cell carcinoma (mRCC).We used the Canadian Kidney Cancer information system (CKCis) to identify patients with mRCC diagnosed between January 1, 2011, and December 31, 2016. The AS strategy was defined as (1) the start of systemic therapy ≥ 6 months after diagnosis of mRCC, or (2) never receiving systemic therapy for mRCC with an overall survival (OS) of ≥1 year. Patients starting systemic treatment6 months after diagnosis of mRCC were defined as receiving immediate systemic treatment. OS and time until first-line treatment failure (TTF) were compared between the two cohorts.A total of 853 patients met the criteria for AS (cohort A). Of these, 364 started treatment6 months after their initial diagnosis (cohort A1) and 489 never started systemic therapy (cohort A2); 827 patients received immediate systemic treatment (cohort B). The 5-year OS probability was significantly greater for cohort A than for cohort B (70% vs. 33.6%; P.0001). After adjusting for International Metastatic RCC Database Consortium risk criteria and age, both OS (hazard ratio [HR] = 0.58; 95% confidence interval [CI], 0.47-0.70; P.0001) and TTF (HR = 0.72; 95% CI, 0.60-0.85; P = .0002) were greater in cohort A1 compared with B. For cohort A1, the median time on AS was 14.2 months (range, 6-71).Based on the largest analysis of AS in mRCC to date, our data suggest that a subset of patients may be safely observed without immediate initiation of systemic therapy.
- Published
- 2021
15. Immunotherapy Benefit in a Patient With Non-Small Cell Lung Cancer and a Rare BRAF Mutation
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Rebekah Rittberg, Gefei Qing, David E. Dawe, Susan Green, and Shantanu Banerji
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Pulmonology ,medicine.medical_treatment ,immune checkpoint inhibitor ,Disease ,030204 cardiovascular system & hematology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Pathology ,medicine ,Anaplastic lymphoma kinase ,Epidermal growth factor receptor ,Lung cancer ,neoplasms ,non-small cell lung cancer ,nivolumab ,Mutation ,biology ,business.industry ,driver mutation ,General Engineering ,Immunotherapy ,medicine.disease ,digestive system diseases ,respiratory tract diseases ,Oncology ,Cancer research ,biology.protein ,Nivolumab ,business ,braf ,030217 neurology & neurosurgery ,V600E - Abstract
Immunotherapy is less effective in non-small cell lung cancer (NSCLC) with driver mutations in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) and some may extrapolate this trend to other driver mutations. Up to 4% of NSCLC cases contain a BRAF mutation. Most BRAF mutations are V600E, and little is known about the impact of treatment in rare BRAF G469A mutations. We present a case of a patient found to have BRAF G469A mutated NSCLC. She was diagnosed with Stage IIIB NSCLC and treated with concurrent chemotherapy and radiation. Post-treatment imaging demonstrated disease progression and she was started on nivolumab, resulting in a dramatic and prolonged response which is ongoing after 76 cycles. Her substantial response and prolonged benefit suggest that BRAF-mutated NSCLC may respond better than EGFR- or ALK-driven disease to immunotherapy. Due to the rarity of specific mutations, this case adds to the limited current published literature on NSCLC harbouring a BRAF G469A mutation and suggests that immunotherapy is a reasonable treatment option.
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- 2020
16. Integration of geriatric assessment into clinical oncology practice: A scoping review
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Tina Hsu, Morgan Stirling, Florentin Racovitan, Ahmed M Abou-Setta, David E. Dawe, Otto L T Lam, Leslie Copstein, Viraj K Reddy, and George N. Okoli
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0301 basic medicine ,Male ,Cancer Research ,Open science ,medicine.medical_specialty ,Best practice ,Medical Oncology ,Older population ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,medicine ,Humans ,Geriatric Assessment ,Aged ,Protocol (science) ,Clinical Oncology ,Aged, 80 and over ,business.industry ,Geriatric assessment ,Grey literature ,Guideline ,Professional-Patient Relations ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Family medicine ,Quality of Life ,Female ,business - Abstract
Sixty percent of newly diagnosed cancers occur in older adults and more complex planning is required to sustain quality care for older populations. Individualized care incorporating geriatric assessment can predict early mortality and treatment toxicity for older cancer patients. We mapped and summarized the available evidence on the integration of geriatric assessment into clinical oncology practice, and ascertained which domains have been implemented. We systematically searched bibliographic databases and trial registries for reports of clinical studies, clinical practice guidelines, systematic and non-systematic reviews, and grey literature published in English. We gathered data on study characteristics, geriatric domains and strategies evaluated, and relevant study objectives and findings. From a total of 10,124 identified citations, 38 articles met our eligibility criteria, 3 of which were clinical practice guidelines. Nearly half of these articles came from the United States. Domains of the geriatric assessment implemented in studies ranged from 1 to 12, with varied combinations. We identified 27 studies on strategies for implementing geriatric assessment and 24 studies on feasibility of implementing geriatric assessment, into clinical oncology practice. We also identified 3 main geriatric assessment models: 2 from the United States and 1 from Australia. Furthermore, we identified 2 reviews that reported varied components of geriatric assessment models. There is increasingly robust evidence to implement formal geriatric assessment in oncology practice. There remains a great deal of variation in the tools recommended to address each of the domains in a geriatric assessment, with only 1 guideline (American Society of Clinical Oncology guideline) settling on a specific best practice. Protocol registration: Open Science Framework osf.io/mec93.
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- 2020
17. Immuno-oncology-the new paradigm of lung cancer treatment
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Rosalyn A. Juergens, Craig Harlos, and David E. Dawe
- Subjects
Oncology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Treatment of lung cancer ,Review Article ,Systemic therapy ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,PD-L1 ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Lung cancer ,biology ,business.industry ,Immunotherapy ,medicine.disease ,respiratory tract diseases ,030220 oncology & carcinogenesis ,biology.protein ,business ,Chemoradiotherapy - Abstract
Systemic therapy is an essential part of treatment for all patients with small-cell lung cancer (sclc) and for most patients with non-small-cell lung cancer (nsclc). Standards of care have evolved dramatically since 2009, especially in the setting of incurable or advanced nsclc. Part of that evolution has been the incorporation of immuno-oncology drugs, especially immune checkpoint inhibitors (icis) into multiple therapeutic scenarios. In the present review, we discuss the role of the immune system in lung cancer and the previous failures of immunotherapy for patients with lung cancer. We then provide an overview of the existing evidence for the use of icis in patients with advanced nsclc that is either treatment-naïve or pretreated, for consolidative treatment after chemoradiotherapy in stage iii nsclc, and for palliative therapy in patients with sclc. Finally, we discuss duration of treatment, special populations, and the future of immuno-oncology for patients with lung cancer. Overall, we provide an evidence-based snapshot of immuno-oncology agents in the treatment of lung cancer up to early 2019.
- Published
- 2020
18. Utility of the modified frailty index in predicting toxicity and cancer outcomes for older adults with advanced pancreatic cancer receiving first-line palliative chemotherapy
- Author
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Rebekah Rittberg, Christina Kim, Robert Kudlovich, Hanbo Zhang, Pascal Lambert, and David E. Dawe
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Pancreatic cancer ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,education ,Geriatric Assessment ,Aged ,Retrospective Studies ,Chemotherapy ,education.field_of_study ,Frailty ,business.industry ,Cancer ,Retrospective cohort study ,medicine.disease ,Oxaliplatin ,Irinotecan ,Pancreatic Neoplasms ,Oncology ,030220 oncology & carcinogenesis ,Toxicity ,Female ,Geriatrics and Gerontology ,business ,medicine.drug - Abstract
Background Pancreatic cancer primarily affects older adults and is associated with a high morbidity and mortality. Identifying frail patients with advanced pancreatic cancer (APC) helps to mitigate the risks of chemotherapy (CT). The modified Frailty Index (mFI) is an 11-point deficit measure used to identify frail patients. Although validated in surgical fields, it has not been assessed in an APC population. Methods A retrospective cohort study evaluated consecutive patients, aged ≥65 years, diagnosed with APC from 2011 to 2016 and treated with first line palliative-intent CT. mFI was categorized as: 0, 1, 2 and ≥ 3. Descriptive analysis was completed comparing patient characteristics, CT toxicity, response to treatment, and overall survival (OS) by mFI score. Results 87 patients with APC received palliative CT. Median age was 71 (65–88), 54% male. A mFI score of 0, 1, 2, and ≥ 3 occurred for 20 (23%), 28 (32.2%), 25 (28.7%) and 14 (16.1%) patients respectively. Patients with mFI scores of 0–1 were more likely to receive: 5-fluorouracil, irinotecan and oxaliplatin. CT toxicity, emergency room (ED) and urgent cancer clinic (UCC) presentation, and hospitalization length did not differ by mFI. Longer OS was associated with better ECOG and receipt of combination CT. Conclusion This is the first assessment of the mFI in an APC population receiving CT. The mFI score did not correlate with toxicity, ED/UCC visits, hospitalization length or OS. Ongoing assessment of tools that accurately identify frailty in patients with APC is critical to help better select candidates for aggressive CT.
- Published
- 2020
19. Methods to improve the estimation of time-to-event outcomes when data is de-identified
- Author
-
Samantha-Jo Caetano, Peter M. Ellis, Craig C. Earle, David E. Dawe, and Gregory R. Pond
- Subjects
Statistics and Probability ,Data set ,Estimation ,Patient confidentiality ,Epidemiology ,Computer science ,Small number ,Statistics ,De-identification ,Event (probability theory) - Abstract
Technological advancements in recent years have sparked the use of large databases for research. The availability of these large databases has administered a need for anonymization and de-identification techniques, prior to publishing the data. This de-identification alters the data, which in turn can impact the results derived post de-identification and potentially lead to false conclusions. The objective of this study is to investigate if alterations to a de-identified time-to-event data set may improve the accuracy of the estimates. In this data set, a missing time bias was present among censored patients as a means to preserve patient confidentiality. This study investigates five methods intended to reduce the bias of time-to-event estimates. A simulation study was conducted to evaluate the effectiveness of each method in reducing bias. In situations where there was a large number of censored patients, the results of the simulation showed that Method 4 yielded the most accurate estimates. This method adjusted the survival times of censored patients by adding a random uniform component such that the modified survival time would occur within the final year of the study. Alternatively, when there was only a small number of censored patients, the method that did not alter the de-identified data set (Method 1) provided the most accurate estimates.
- Published
- 2018
20. Androgen Receptor and Ki67 Expression and Survival Outcomes in Non-small Cell Lung Cancer
- Author
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Laurel Grant, Gefei Qing, David E. Dawe, Shantanu Banerji, Anne Blanchard, Marshall Pitz, Leigh C. Murphy, Carla Penner, Yvonne Myal, Zoann Nugent, and Craig Harlos
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Biomarkers, Tumor ,medicine ,Overall survival ,Humans ,Lung cancer ,Aged ,Endocrine and Autonomic Systems ,business.industry ,Hazard ratio ,Middle Aged ,Prognosis ,medicine.disease ,Androgen receptor ,Ki-67 Antigen ,030104 developmental biology ,Receptors, Androgen ,Estrogen ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Immunohistochemistry ,Female ,Non small cell ,business - Abstract
Lung cancer is the most common cause of cancer-related deaths worldwide with non-small cell lung cancer (NSCLC) making up most of these cases. Males have poorer overall survival compared to women following a lung cancer diagnosis. Many studies have focused on the effects of estrogen to explain higher survival rates among women, but few have looked at the effects of androgens. We describe the expression of the androgen receptor (AR) and Ki67 in lung cancer specimens in the Manitoba Tumor Bank (MTB) and correlate these factors with patient outcome. Using the MTB, we performed immunohistochemistry on lung cancer tissue to determine expression of the AR and Ki67. These were then correlated with patient outcome. Of the 136 cases, 55% were female and 55% were adenocarcinoma. AR expression was not independently associated with outcome. Ki67 was associated with a significantly higher hazard ratio for death and recurrence (HR 2.19, 95% CI 1.30-3.70; HR 1.92, 95% CI 1.07-3.46, respectively). AR expression modified the effect of Ki67 on outcome, such that when both were expressed, there was no association with recurrence or survival (HR 2.39, 95% CI 1.31-4.36 for AR- Ki67+ vs HR 1.54, 95% CI 0.44-5.37 for AR+ Ki67+). Ki67 was associated with poorer outcomes alone. AR status alone was not associated with outcome. Although the mechanism remains unclear, AR status seems to negate the association of a high Ki67 and poor outcome.
- Published
- 2018
21. The effect of statin use on the incidence of prostate cancer: A population-based nested case-control study
- Author
-
David Skarsgard, Armen Aprikian, David E. Dawe, Salaheddin M. Mahmud, Piotr Czaykowski, Xibiao Ye, Harminder Singh, and Davinder S. Jassal
- Subjects
Cancer Research ,medicine.medical_specialty ,education.field_of_study ,Prescription drug ,Statin ,business.industry ,medicine.drug_class ,Incidence (epidemiology) ,Population ,Pharmacoepidemiology ,medicine.disease ,3. Good health ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Internal medicine ,Epidemiology ,Nested case-control study ,medicine ,030212 general & internal medicine ,business ,education - Abstract
Preclinical studies suggest statins may help prevent prostate cancer (PC), but epidemiologic results are mixed. Many epidemiological studies have relatively short prediagnosis drug exposure data, which may miss some statin use. We completed a nested case-control study investigating the impact of statin use on PC diagnosis and clinically significant PC using data from men aged ≥40 years in the Canadian province of Saskatchewan between 1990 and 2010. Drug exposure histories were derived from a population-based prescription drug database. We used conditional logistic regression to model use of statins as a class and stratified analyses for groups defined by lipophilicity. Clinically significant PC was defined as Gleason score 8-10 OR stage C or D or III or IV at diagnosis. 12,745 cases of PC were risk-set matched on age and geographic location to 50,979 controls. Greater than 90% of subjects had prediagnosis drug exposure histories >15 years. 2,064 (16.2%) cases and 7,956 (15.6%) controls were dispensed one or more statin prescriptions. In multivariable models, ever prescription of statins was not associated with PC diagnosis (OR 0.97; 95% CI 0.90-1.05). Neither lipophilic statins (OR 0.96, 95% CI 0.88-1.04) nor hydrophilic statins (OR 1.06, 95% CI 0.95-1.20) impacted PC diagnosis. There was no effect of the dose or duration of statin use. Diagnosis of clinically significant PC decreased with statin use (OR 0.84, 95% CI 0.73-0.97). Statin use is not associated with overall PC risk, regardless of duration or dose of statin exposure. Statin use is associated with a decreased risk of clinically significant PC.
- Published
- 2018
22. P63.07 Real World Predictors for Long Term Survival in Stage IV Small Cell Lung Cancer Treated With Standard of Care Chemotherapy
- Author
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David E. Dawe, D. Moldaver, O. Bucher, I. Syed, and Rebekah Rittberg
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Chemotherapy ,Standard of care ,business.industry ,medicine.medical_treatment ,Internal medicine ,Long term survival ,medicine ,Non small cell ,Stage iv ,business - Published
- 2021
23. 1843P Impact of age, comorbidities and polypharmacy on receipt of systemic therapy in advanced cancers
- Author
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Rebekah Rittberg, Piotr Czaykowski, P. St. John, David E. Dawe, Pascal Lambert, Donna Turner, Kathleen Decker, and J. Bravo
- Subjects
Polypharmacy ,Receipt ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Hematology ,Intensive care medicine ,business ,Systemic therapy - Published
- 2021
24. 1840P Impact of age, comorbidities and polypharmacy on survival in advanced cancers
- Author
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J. Bravo, Pascal Lambert, Rebekah Rittberg, David E. Dawe, Donna Turner, Kathleen Decker, Piotr Czaykowski, and P. St. John
- Subjects
Polypharmacy ,medicine.medical_specialty ,Oncology ,business.industry ,Internal medicine ,medicine ,Hematology ,business - Published
- 2021
25. Impact of Age, Comorbidity, and Polypharmacy on Treatment and Survival for Aggressive Non-Hodgkin Lymphoma
- Author
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Pascal Lambert, Laura Tapley, David E. Dawe, Phil St. John, Kathleen Decker, Jenniebie Bravo, Donna Turner, Pamela Skrabek, and Piotr Czaykowski
- Subjects
Polypharmacy ,education.field_of_study ,medicine.medical_specialty ,Multivariate analysis ,business.industry ,Immunology ,Population ,Cell Biology ,Hematology ,medicine.disease ,Logistic regression ,Biochemistry ,Comorbidity ,Cancer registry ,Internal medicine ,Cohort ,Medicine ,business ,education ,Cohort study - Abstract
Introduction: Non-Hodgkin's lymphoma (NHL) is the most prevalent hematologic malignancy, with most people diagnosed aged over 65 years (Alexander et. al. Int.J.Cancer 2007). Older populations have more comorbid health conditions, frailty, polypharmacy, and health resource use (Ogle et. al. Cancer 2000). The complex interplay of these factors may influence the prescription of curative therapy and prognosis. In trials evaluating NHL therapies, elderly patients are underrepresented, particularly those with frailty or comorbidity, resulting in knowledge gaps. We report a retrospective, population-based cohort study of aggressive NHL patients and examine the impact of age and its interaction with comorbidity and polypharmacy on treatment patterns and survival. Methods: Using the Manitoba Cancer Registry we identified patients aged over 18 years with NHL diagnosed from 2004-2015. We limited the cohort to aggressive NHL types using morphology codes. Data on demographics, stage, NHL type, comorbidities, polypharmacy, and chemotherapy were obtained from population-based provincial databases. Comorbidity was measured using Johns Hopkins ACG System software, which factored in all measured hospital-based and outpatient medical services utilized and collapsed them into one of six Resource Utilization Band (RUB) categories, from no use to very high user. Overall survival (OS) was calculated using Kaplan-Meier curves. Cox proportional hazards regression models were constructed to determine the interaction of age with a variety of factors. Multi-variable logistic regression was also used to examine the receipt of chemotherapy and the interaction with age. Results: In our cohort of 1,073 patients with aggressive NHL, 704 were treated with systemic chemotherapy. Treatment rates decreased with increasing age and medication count, while stage and comorbidity had little impact (Table 1). Median OS decreased with age among treated patients and was very short without chemotherapy (Table 1). Multivariate analyses found that individuals with increasing age, stage III, unknown stage, histology other than DLBCL, and higher medication counts were less likely to receive chemotherapy. For the receipt of chemotherapy, no age interactions were found. In addition, in patients who received chemotherapy, increased age and stage were associated with poorer survival, while more recent year of diagnosis improved survival. No age interactions with a substantial impact on survival were found. Conclusions: OS in aggressive NHL diminishes with increasing age, but is longer in those receiving chemotherapy across all age groups. Comorbidity and medication count influenced the receipt of chemotherapy and OS. Higher medication count was only independently associated with less likelihood of receiving chemotherapy, while comorbidity was not independent of other factors for either receipt of chemotherapy or OS. Disclosures Dawe: AstraZeneca Canada: Research Funding; AstraZeneca Canada: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Honoraria; Merck Canada: Membership on an entity's Board of Directors or advisory committees.
- Published
- 2020
26. Never too old to learn new tricks: surveying Canadian health care professionals about learning needs in caring for older adults with cancer
- Author
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M. Fitch, David E. Dawe, Tamas Fulop, Ewa Szumacher, Jennifer M. Jones, Martine Puts, S. Alibhai, Fay J. Strohschein, and Tina Hsu
- Subjects
medicine.medical_specialty ,Canada ,Terminal Care ,business.industry ,Health Services for the Aged ,Health Personnel ,Cancer ,medicine.disease ,Editorial ,Geriatric oncology ,Oncology ,Cancer Survivors ,Family medicine ,Neoplasms ,Surveys and Questionnaires ,Health care ,Medicine ,Humans ,Learning ,Geriatrics and Gerontology ,business - Abstract
Cancer is the leading cause of death in Canada [...]
- Published
- 2019
27. Chemoradiotherapy versus radiotherapy alone in elderly patients with stage III non-small cell lung cancer: A systematic review and meta-analysis
- Author
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Janet Rothney, Ahmed M Abou-Setta, David E. Dawe, Peter M. Ellis, Rasheda Rabbani, Ryan Zarychanski, Anand Swaminath, Salaheddin M. Mahmud, and David Christiansen
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Blinding ,medicine.medical_treatment ,MEDLINE ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Odds Ratio ,medicine ,Humans ,Stage (cooking) ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Pneumonitis ,Aged, 80 and over ,Radiotherapy ,business.industry ,Age Factors ,Chemoradiotherapy ,medicine.disease ,Surgery ,Radiation therapy ,Treatment Outcome ,030104 developmental biology ,030220 oncology & carcinogenesis ,Meta-analysis ,business - Abstract
In stage III non-small cell lung cancer (NSCLC), the standard of care in young patients is chemoradiotherapy, but this standard is not as clearly established for older patients. We aimed to determine the efficacy and harm associated with chemoradiotherapy versus radiotherapy alone in elderly (≥70 years), stage III NSCLC patients through a systematic review. We conducted a systematic search of MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science and conference proceedings. Two reviewers independently identified randomized trials (RCT) and extracted trial-level data. Risk of bias was assessed and meta-analysis was conducted looking at survival and safety outcomes. We included three trials and subgroup data from one systematic review. The three RCTs had high risk of bias due primarily to lack of blinding and the systematic review scored 4/11 using the AMSTAR tool. Overall survival (HR 0.66, 95% CI 0.53-0.82; I2 0%; 3 trials; 407 patients) and progression-free survival (HR 0.67, 95% CI 0.53-0.85; I2 0%; 2 trials; 327 patients) both favored chemoradiotherapy. Risk of treatment-related death and grade 3+ pneumonitis were not significantly different between groups. In conclusion, treatment of stage III NSCLC patients 70 years or older with chemotherapy and radiotherapy is associated with improved overall survival compared to radiotherapy alone. With the exception of increased hematological toxicity, CRT appears to be tolerable in fit elderly patients and represents a reasonable standard of clinical care.
- Published
- 2016
28. Immune Signatures of Non–Small Cell Lung Cancer
- Author
-
David E. Dawe, Shantanu Banerji, and Susan Green
- Subjects
Pulmonary and Respiratory Medicine ,business.industry ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,030212 general & internal medicine ,Non small cell ,business ,Lung cancer - Published
- 2017
29. Assessing the learning needs of the multidisciplinary team on geriatric oncology and frailty
- Author
-
David E. Dawe, Morgan Stirling, Rebekah Rittberg, Elizabeth Huynh, Allison Wiens, Susan Green, and Jill Sutherland
- Subjects
Health Services for the Aged ,Psycho-Oncology ,MEDLINE ,Nurses ,Multidisciplinary team ,Medical Oncology ,Nursing ,Multidisciplinary approach ,Physicians ,Surveys and Questionnaires ,Medicine ,Humans ,Pain Management ,Cognitive Dysfunction ,Geriatric Assessment ,Referral and Consultation ,Aged ,Aged, 80 and over ,Patient Care Team ,Frailty ,business.industry ,Oncology Nursing ,Oncology ,Geriatric oncology ,Geriatrics ,Needs assessment ,Polypharmacy ,Clinical Competence ,Geriatrics and Gerontology ,business ,Needs Assessment - Published
- 2018
30. The use of chemotherapy in older patients with stage II and III colon cancer: Variation by age and era of diagnosis
- Author
-
Winson Y. Cheung, Susan Green, Zoann Nugent, Piotr Czaykowski, and David E. Dawe
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Antineoplastic Agents ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Risk of mortality ,Humans ,030212 general & internal medicine ,Stage (cooking) ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Aged, 80 and over ,Chemotherapy ,business.industry ,Proportional hazards model ,Age Factors ,medicine.disease ,Survival Analysis ,Logistic Models ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Cohort ,Colonic Neoplasms ,Female ,Geriatrics and Gerontology ,business ,Adjuvant ,SEER Program - Abstract
Objective We aim to examine the use and outcomes of adjuvant chemotherapy in older patients with stage II and III colon cancer. Material and Methods Using data from the SEER-Medicare database, we analyzed patients aged 66 or greater, diagnosed with stage II or III colon cancer between 1991 and 2007 who received surgery. Using Medicare claims, receipt of adjuvant chemotherapy was identified, and compared between age bands. Logistic regression modeling was performed to assess predictors of receipt of adjuvant chemotherapy, and Cox proportional hazards modeling was performed to assess predictors of mortality. Results A total of 31,990 patients were identified: 4371 aged 66–69, 6922 (70–74), 7673 (75–79), 6807 (80–84), 4266 (85–89), and 1951 (90+). The percent starting adjuvant chemotherapy decreased by age cohort: 57% in the 66–69 age cohort, 48% (70–74), 37% (75–79), 20% (80–84), 8% (85–89), and 1% (90+). Multivariable analysis showed that stage III disease was the strongest positive predictor of chemotherapy receipt. Multivariable analysis for mortality risk showed that adjuvant chemotherapy was associated with an increased risk of mortality in stage II patients. Adjuvant chemotherapy was associated with a decreased risk of mortality in stage III patients, consistent across all age cohorts, with the exception of the 90+ cohort, in whom adjuvant chemotherapy appeared to increase mortality. Conclusion Administration of adjuvant chemotherapy for stage II/III colon cancer decreases with advancing age, but improved outcomes are seen in stage III patients under 90 years of age.
- Published
- 2018
31. P2.11-10 Discovery of Potential Biomarkers That Discriminate Early Stage NSCLC from Controls by Non-Targeted Metabolomics Profiling
- Author
-
David E. Dawe, R. Balshaw, Biniam Kidane, C. Trevena, Michel Aliani, Sadeesh Srinathan, Julian Kim, Gordon Buduhan, Gefei Qing, L. Tan, Michael Domaratzki, Shantanu Banerji, and Leigh C. Murphy
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Non targeted metabolomics ,business.industry ,Potential biomarkers ,Medicine ,Profiling (information science) ,Computational biology ,business - Published
- 2019
32. Nivolumab-Induced Secondary Sclerosing Cholangitis with Deterioration Despite Immunosuppression
- Author
-
Brady Anderson and David E. Dawe
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,MEDLINE ,Immunosuppression ,medicine.disease ,Gastroenterology ,Oncology ,Internal medicine ,medicine ,Secondary sclerosing cholangitis ,Neoplasm staging ,Nivolumab ,business - Published
- 2019
33. Biologic and epidemiologic evidence assessing if statins prevent prostate cancer
- Author
-
David E, Dawe and Salaheddin, Mahmud
- Subjects
Male ,Neovascularization, Pathologic ,Incidence ,Androgens ,Animals ,Humans ,Prostatic Neoplasms ,Apoptosis ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cell Proliferation ,Signal Transduction - Abstract
During their lives, 1 in 8 men will be diagnosed with prostate cancer. Several drugs have been shown to decrease prostate cancer risk, but have not been widely used in prostate cancer prevention because of concerns about side-effects and cost-effectiveness. Statins are indicated for prevention of cardiovascular disease, have an excellent benefit to risk profile, and some studies suggest that statins may reduce the risk of prostate cancer.We performed a systematic search of Medline (Ovid), EMBASE (Ovid), and PubMed. This search informed a narrative review of the biological rationale for why statins may reduce prostate cancer risk and an evaluation of the existing epidemiological evidence to determine whether further studies are needed to assess the true impact of statins on prostate cancer risk.Statins may help prevent the development of prostate cancer through inhibition of sustained proliferative signals (androgen and Ras/Rho), sensitizing potentially malignant cells to programmed cell death, minimizing inflammation, reducing angiogenesis, and impeding invasiveness by blocking adhesion molecules. The epidemiologic literature examining the effect of statin use on overall prostate cancer diagnosis is highly heterogeneous, with relative risks of 0.26 to 2.94. Out of 33 published studies, 5 show an increased risk of prostate cancer with statin use, 10 demonstrate a decreased risk, and 18 suggest no effect.There is a compelling pre-clinical rationale for statins as potential chemopreventive agents. However, large, population-based studies with long pre-diagnosis drug exposure data are needed to investigate the impact of statin exposure on prostate cancer incidence.
- Published
- 2017
34. The effect of statin use on the incidence of prostate cancer: A population-based nested case-control study
- Author
-
David E, Dawe, Xibiao, Ye, Piotr, Czaykowski, Davinder, Jassal, Harminder, Singh, David, Skarsgard, Armen, Aprikian, and Salaheddin M, Mahmud
- Subjects
Adult ,Aged, 80 and over ,Male ,Canada ,Logistic Models ,Case-Control Studies ,Incidence ,Humans ,Prostatic Neoplasms ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Middle Aged ,Neoplasm Grading ,Aged - Abstract
Preclinical studies suggest statins may help prevent prostate cancer (PC), but epidemiologic results are mixed. Many epidemiological studies have relatively short prediagnosis drug exposure data, which may miss some statin use. We completed a nested case-control study investigating the impact of statin use on PC diagnosis and clinically significant PC using data from men aged ≥40 years in the Canadian province of Saskatchewan between 1990 and 2010. Drug exposure histories were derived from a population-based prescription drug database. We used conditional logistic regression to model use of statins as a class and stratified analyses for groups defined by lipophilicity. Clinically significant PC was defined as Gleason score 8-10 OR stage C or D or III or IV at diagnosis. 12,745 cases of PC were risk-set matched on age and geographic location to 50,979 controls. Greater than 90% of subjects had prediagnosis drug exposure histories15 years. 2,064 (16.2%) cases and 7,956 (15.6%) controls were dispensed one or more statin prescriptions. In multivariable models, ever prescription of statins was not associated with PC diagnosis (OR 0.97; 95% CI 0.90-1.05). Neither lipophilic statins (OR 0.96, 95% CI 0.88-1.04) nor hydrophilic statins (OR 1.06, 95% CI 0.95-1.20) impacted PC diagnosis. There was no effect of the dose or duration of statin use. Diagnosis of clinically significant PC decreased with statin use (OR 0.84, 95% CI 0.73-0.97). Statin use is not associated with overall PC risk, regardless of duration or dose of statin exposure. Statin use is associated with a decreased risk of clinically significant PC.
- Published
- 2017
35. Benefit of crizotinib in a lung cancer patient with discordant ALK testing results
- Author
-
Shantanu Banerji, Steven Grocholski, David E. Dawe, and Gefei Qing
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Pleural effusion ,medicine.medical_treatment ,Population ,Antineoplastic Agents ,Adenocarcinoma ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Crizotinib ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Anaplastic lymphoma kinase ,Humans ,Anaplastic Lymphoma Kinase ,Lung cancer ,education ,In Situ Hybridization, Fluorescence ,Neoplasm Staging ,education.field_of_study ,Performance status ,business.industry ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Progression-Free Survival ,030104 developmental biology ,Dyspnea ,030220 oncology & carcinogenesis ,Lymph Nodes ,business ,medicine.drug - Abstract
Crizotinib is a first line treatment for patients with non-small cell lung cancer (NSCLC) harboring translocations in anaplastic lymphoma kinase (ALK). The current gold standard for determining ALK status is fluorescence in-situ hybridisation (FISH), but immunohistochemistry (IHC) is becoming increasingly popular due to lower cost. There are currently few reports on clinical outcomes with crizotinib therapy in patients who have tested negative by FISH and positive by IHC. A 53 year old lifelong non-smoking, physically active male with newly diagnosed Stage IV NSCLC presented with shortness of breath on exertion one month prior to referral. Staging CT scan failed to show a discreet lung lesion, but the left lower lobe was collapsed due to pleural effusion. Pleural fluid showed adenocarcinoma and IHC was positive for an ALK mutation, while FISH was negative. Pre-treatment PET-CT showed hypermetabolic, enlarged lymph nodes in the mediastinum and retroperitoneum. Partially due to patient concerns about cytotoxic chemotherapy toxicity, crizotinib therapy was instituted. Repeat CT conducted two months after crizotinib initiation showed a decrease in lymphadenopathy at all sites compared to the PET-CT. Furthermore, the patient showed clinical improvement, with less drainage through his PleurX catheter and stability of his excellent performance status. After 12 months on crizotinib CT showed ongoing improvement in lymphadenopathy. His bloodwork has been stable, and he denies significant drug toxicity. This case illustrates a sustained response to crizotinib therapy in a patient with an ALK translocation identified by IHC, but with negative FISH testing. The literature suggests that the population with these discordant results could be up to 19% of ALK positive NSCLC. Patients in this subgroup who are receiving crizotinib should be identified and outcome data pooled. However, in the interim, oncologists may wish to consider targeted therapy for these discordant patients.
- Published
- 2017
36. Brain Metastases in Non–Small-Cell Lung Cancer
- Author
-
Peter M. Ellis, David E. Dawe, and Jeffrey Greenspoon
- Subjects
Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,Biomedical Research ,Lung Neoplasms ,Standard of care ,medicine.medical_treatment ,Radiosurgery ,Pharmacotherapy ,Drug Therapy ,Carcinoma, Non-Small-Cell Lung ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,Intensive care medicine ,Lung cancer ,Chemotherapy ,Brain Neoplasms ,business.industry ,Standard of Care ,medicine.disease ,Surgery ,Radiation therapy ,Oncology ,Non small cell ,business - Abstract
Up to 50% of patients with advanced non-small-cell lung cancer will develop brain metastases at some point during their illness. These metastases cause a substantial burden in morbidity and mortality, which has motivated research and technological innovation over the past 2 decades. Surgery, radiotherapy, and systemic therapies have each played a role in management, with the greatest changes associated with the popularization of stereotactic radiosurgery. In this review, the evidence behind each modality used in the management of brain metastases for non-small-cell lung cancer patients is examined, and recommendations regarding the current standards of care and areas of future research focus are provided.
- Published
- 2014
37. Assessment of Referral and Chemotherapy Treatment Patterns for Elderly Patients With Non-small-Cell Lung Cancer
- Author
-
Peter M. Ellis, David E. Dawe, and Gregory R. Pond
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Canada ,Lung Neoplasms ,Population ,Adenocarcinoma ,Malignancy ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Practice Patterns, Physicians' ,Lung cancer ,education ,Referral and Consultation ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Prognosis ,Comorbidity ,Surgery ,Survival Rate ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Female ,Outcomes research ,business ,Cohort study ,Follow-Up Studies - Abstract
Physiologic changes of aging in combination with greater comorbidity could lead to treatment nihilism for elderly patients (≥ 70 years old) with non-small-cell lung cancer (NSCLC). Randomized trials have shown improved survival with chemotherapy since 1999, but it remains unclear whether these data have translated into practice.We conducted a retrospective, population-based cohort study of NSCLC cases diagnosed in Ontario, Canada from 2000 to 2010. We compared referral and treatment patterns among patients aged 70 versus ≥ 70 years. Multivariable analyses evaluated predictors of referral to medical oncology or treatment with chemotherapy.Of 61,646 patients with NSCLC, 32,131 (52.1%) were ≥ 70 years. Fewer adenocarcinomas were diagnosed in the elderly (29.8% vs. 44%), and more elderly patients lacked microscopic confirmation of malignancy (20.1% vs. 6.2%). Charlson co-morbidity scores ≥ 2 (14.0% vs. 7.4%) were higher in the elderly. Only 59.5% of elderly patients with NSCLC were referred to a medical oncologist, versus 78.5% of younger patients. Elderly patients were less likely to receive chemotherapy (18.3% vs. 46.7%), even among those referred to a medical oncologist (30.1% vs. 58.6%). Neither referral nor treatment changed substantially over time. The elderly also had a shorter median survival (5.8 vs. 9.6 months); however, there was less difference in median survival (13.6 vs. 14.9 months) among patients receiving chemotherapy.Elderly patients are less likely to be considered for systemic therapy for NSCLC, and evidence of benefit has had minimal impact on practice. We believe this disparity could be improved through systematically using tools to comprehensively assess elderly patients.
- Published
- 2016
38. Challenges in Implementing Personalized Medicine for Lung Cancer within a National Healthcare System
- Author
-
Peter M. Ellis and David E. Dawe
- Subjects
erlotinib ,medicine.medical_specialty ,molecular targeted therapy ,gefitinib ,lcsh:Medicine ,Medicine (miscellaneous) ,Review ,Bioinformatics ,Gefitinib ,Health care ,medicine ,Epidermal growth factor receptor ,Intensive care medicine ,Lung cancer ,non-small cell lung cancer ,crizotinib ,Crizotinib ,biology ,business.industry ,lcsh:R ,personalized medicine ,medicine.disease ,biology.protein ,delivery of healthcare ,Biomarker (medicine) ,Personalized medicine ,Erlotinib ,epidermal growth factor receptor ,business ,medicine.drug - Abstract
The traditional approach to the treatment of advanced non-small cell lung cancer (NSCLC) relied on the uniform use of cytotoxic chemotherapy. Over the last eight years, this paradigm of care has been shifting towards the use of molecularly targeted agents. Epidermal growth factor receptor (EGFR) mutations have emerged as an important biomarker for these targeted agents and multiple studies have shown that tyrosine kinase inhibitors (TKI) that inhibit EGFR are superior to traditional chemotherapy in patients possessing an EGFR mutation. Nationally funded health care systems face a number of challenges in implementing these targeted therapies, most related to the need to test for biomarkers that predict likelihood of benefiting from the drug. These obstacles include the challenge of getting a large enough tissue sample, workload of involved specialists, reliability of subtyping in NSCLC, differences in biomarker tests, and the disconnect between the funding of drugs and the related biomarker test. In order to improve patient outcomes, in a national healthcare system, there is a need for governments to accept the changing paradigm, invest in technology and build capacity for molecular testing to facilitate the implementation of improved patient care.
- Published
- 2012
39. P2.01-038 Discrimination of NSCLC Cases from Cancer-Free Controls and Adenocarcinoma from Squamous Cell Carcinoma Using Plasma Metabolomics Profiles
- Author
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Julian Kim, Gefei Qing, David E. Dawe, Michael Abdalmassih, Shantanu Banerji, and Michel Aliani
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Cancer-Free ,medicine.disease ,Proteomics ,Metabolomics ,Internal medicine ,Medicine ,Adenocarcinoma ,Basal cell ,business ,Lung cancer - Published
- 2017
40. A Descriptive Analysis of Obinutuzumab Usage in a Single Canadian Centre
- Author
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Spencer B. Gibson, James B. Johnston, Oliver Bucher, Nicole Bourrier, Mandy Squires, Versha Banerji, David E. Dawe, Ivan Landego, Zeb Aurangzeb, Marc Geirnaert, Irena Hibbert, Theresa L. Whiteside, and Erin Streu
- Subjects
education.field_of_study ,medicine.medical_specialty ,Chlorambucil ,business.industry ,Incidence (epidemiology) ,Immunology ,Population ,Cell Biology ,Hematology ,Gene mutation ,Biochemistry ,chemistry.chemical_compound ,Tolerability ,chemistry ,Obinutuzumab ,Internal medicine ,Cohort ,Medicine ,Progression-free survival ,education ,business ,medicine.drug - Abstract
Background:Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in North America with the majority of patients being over the age of 70 (Goede et al, 2014). CLL is a heterogeneous disease with some patients undergoing treatment at time of diagnosis, while others follow along a more indolent, asymptomatic course. When indicated, the choice of treatment is based on the patient's functional status, renal function and other comorbidities (Shanafelt, 2013). Previous studies have shown that unfit patients treated with Obinutuzumab plus Chlorambucil have shown prolongation of progression free survival and higher rates of complete response compared to other monoclonal based regimens (Goede et al, 2014). The aim of this study is to investigate the clinical use and uptake of Obinutuzumab in combination with Chlorambucil in a Canadian based population. Methods:All patients receiving Obinutuzumab were identified using the CLL CAISIS database. Then a retrospective chart review was conducted for patients approved for first-line antibody treatment with Obinutuzumab from January 1, 2014 to December 31, 2017. Data including patient characteristics, patterns of treatment, reported toxicities, response rates and survival data were collected and analyzed. This data was used to determine the overall safety and efficacy of this treatment regimen. Results: There were a total of 66 patients that met the inclusion criteria for this study. This cohort consisted of 54.5% males and 45.5% females, with a median age at diagnosis of 68 years (range: 46-94). Within this population 47 patients underwent florescence in situ hybridization testing, which identified 32 patients with chromosomal abnormalities. The immunoglobulin heavy chain variable region gene mutation was also tested in 41 patients, and identified 22 patients that were unmutated. At the time of treatment the median age was 73 (range: 55-98) with a median Cumulative Illness Rating Scale (CIRS) score of 8 (range: 3-15). Of the 66 patients who started treatment with Obinutuzumab, 50 patients (76%) achieved a partial response and 5 patients (8%) had no response. Of note, 21 patients (31.8%) discontinued treatment prior to completion of all six cycles due to cytopenias (4), other comorbidities (4), progression of CLL (2), decline in functional/mental status (2), patient request (2) and other (7). In regards to their treatment there was a high incidence of infusion related reactions (IRRs) on the first day of treatment, with 30 patients (45.5%) requiring intervention. There was a subset of 15 patients that had received low dose Chlorambucil prior to treatment with Obinutuzumab which resulted in a lower average lymphocyte count (38.1) and lower rate of IRRs (33%) compared to those with no prior Chlorambucil (average lymphocyte count: 66.5, rate of IRR: 42%). Due to toxicity and tolerability of Chlorambucil, dose reduction was observed in 37 patients (56%) throughout all six cycles of treatment. In the end, only 18 patients (27.3%) received all doses of Obinutuzumab and Chlorambucil while 37 patients (56%) received all doses of Obinutuzumab. Within the entire cohort, 12 patients have relapsed and 9 of these patients have required additional therapy. This relapse rate can be attributed to lack of response to Obinutuzumab (3), a 17p del (1), poor prognostic markers (5), and inadequate Obinutuzumab (1). Conclusion:In this current study, our results demonstrate that the majority of patients in this cohort were able to complete treatment with Obinutuzumab. Although our demographics were similar to previous studies, we found higher partial response rates (76%) likely due to differences in standards of practice, such as imaging studies after treatment. Disclosures Whiteside: Roche: Membership on an entity's Board of Directors or advisory committees, Other: teaching sessions. Dawe:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees. Johnston:Roche: Other: unrestricted grant received in the past; Abbvie: Other: unrestricted grant received in the past; Teva: Other: unrestricted grant received in the past; Gilead: Other: unrestricted grant received in the past; Janssen: Other: unrestricted grant received in the past. Banerji:Roche: Other: Unrestricted grant received in the past; Janssen: Other: Unrestricted grant received in the past; Abbvie: Other: Unrestricted grant received in the past; Gilead: Other: Unrestricted grant received in the past; Teva: Other: Unrestricted grant received in the past.
- Published
- 2018
41. Treatment patterns, toxicity, and outcomes of elderly patients with advanced pancreatic cancer receiving first-line chemotherapy
- Author
-
David E. Dawe, Hanbo Zhang, Robert Kudlovich, and Christina Kim
- Subjects
Oncology ,Cancer Research ,Poor prognosis ,medicine.medical_specialty ,business.industry ,Palliative chemotherapy ,medicine.disease ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Pancreatic cancer ,Internal medicine ,Toxicity ,Overall survival ,medicine ,First line chemotherapy ,business ,030215 immunology - Abstract
71 Background: Advanced pancreatic cancer (APC) has a poor prognosis despite treatment with palliative chemotherapy. Randomized trials have demonstrated improved overall survival (OS) with combination chemotherapy including 5-fluorouracil, irinotecan, leucovorin, and oxaliplatin (FOLFIRINOX) or nab-plaxictaxel and Gemcitabine (NG) compared to Gemcitabine (GEM) alone, however, combination therapy is associated with higher rates of toxicity. There is limited data regarding the efficacy and toxicity of FOLFIRINOX, NG, and GEM in elderly patients with APC. Objective: Describe the treatment patterns, toxicity, and outcomes of patients ≥ 65 years of age treated with first-line palliative FOLFIRINOX, NG, or GEM. Methods: Patients ≥ 65 diagnosed with APC from 2012-2016 and treated with palliative chemotherapy in Manitoba were identified from the Manitoba Cancer Registry. Retrospective review identified patients who received first line FOLFIRINOX, NG, or GEM. Patient and treatment characteristics including hematologic and non-hematologic toxicities, dose reductions or delays, tumour response and survival were recorded. Results: 87 patients aged ≥ 65 received palliative chemotherapy: 52 (60%) FOLFIRINOX, 21 (24%) NG, and 14 (16%) GEM, with median ages of 69 (65-84), 75 (65-88), and 73 (67-82), respectively. More patients treated with FOLFIRINOX had an ECOG 0-1 compared to other treatments (p = < 0.001). There was no difference in hematologic toxicity according to treatment group (p = 0.807). There was more non-hematologic toxicity with FOLFIRINOX (p = < 0.001), particularly neuropathy (p = 0.008), fatigue (p = < 0.001), and nausea/vomiting (p = 0.008). Tumour response was highest with FOLFIRINOX (p = 0.005), with a trend towards improved survival compared to NG and GEM (median OS 267 vs 232 and 126 days, respectively, p = 0.057). Conclusions: Many older patients with APC received FOLFIRINOX, with more toxicity, but also greater tumour response and a trend toward improved survival. This suggests that selected elderly patients can tolerate first-line FOLFIRINOX. This may be also due to effective patient evaluation and appropriate assignment to different treatments.
- Published
- 2018
42. P1.12-08 The Effect of Cisplatin Versus Carboplatin on Cancer Outcomes for Small Cell Lung Cancer Patients in a Population-Based Cohort
- Author
-
Shantanu Banerji, O. Bucher, T. Aquin, and David E. Dawe
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Cisplatin ,medicine.medical_specialty ,business.industry ,Cancer ,medicine.disease ,Carboplatin ,Population based cohort ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Non small cell ,business ,medicine.drug - Published
- 2018
43. P1.12-09 The Effect of Site of First Chemotherapy on Small Cell Lung Cancer Patient Outcomes
- Author
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David E. Dawe, Susan Green, O. Bucher, Rebekah Rittberg, Shantanu Banerji, and T. Aquin
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Internal medicine ,medicine ,Non small cell ,business - Published
- 2018
44. P3.12-01 Targeting Mitochondrial Metabolism as a Selective Therapeutic Approach in Small Cell Lung Cancer (SCLC)
- Author
-
S. Roy Chowdhury, Cheryl Peltier, Shantanu Banerji, David E. Dawe, Versha Banerji, C. Girard, D. Desautels, and Ryan Saleh
- Subjects
Pulmonary and Respiratory Medicine ,Therapeutic approach ,Oncology ,business.industry ,Cancer research ,Medicine ,Non small cell ,Metabolism ,business - Published
- 2018
45. Is There a Role for Statins in Atrial Fibrillation?
- Author
-
Vignendra Ariyarajah, David E. Dawe, and Aliasghar Khadem
- Subjects
medicine.medical_specialty ,business.industry ,Psychological intervention ,Rate control ,Atrial fibrillation ,Rhythm control ,General Medicine ,medicine.disease ,Clinical Practice ,Internal medicine ,Cardiology ,Medicine ,Lipid modification ,Cardiology and Cardiovascular Medicine ,business ,Intensive care medicine ,Prescribed drugs - Abstract
3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are some of the most commonly prescribed drugs in the world. While lipid modification remains the primary function of statins, there has been increasing interest in its potential pleiotropic effects, particularly as an anti-inflammatory agent in its role as an antiarrhythmic. Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and carries with it a significant burden in both morbidity and mortality. Treatment for AF currently involves either rate or rhythm control where both have demonstrable associated risks. Rate control necessitates anticoagulation, which can cause life-threatening bleeding, while rhythm control has a poor side-effect profile that may lead to greater mortality and may not completely eliminate the need for anticoagulation. Considering this pressing need for novel therapeutic interventions in AF, this long overdue systematic review explores the potential role of statins in the treatment and prevention of AF. Physicians, especially cardiologists, need to be aware of the host of currently available literature and, more importantly, need to be stimulated to generate discussion and formulate studies that will help debate the issues under the most erudite standards.
- Published
- 2009
46. Cigarette Smoke Decreases Pulmonary Dendritic Cells and Impacts Antiviral Immune Responsiveness
- Author
-
David E. Dawe, Clinton S. Robbins, Filip K. Swirski, Susanna Goncharova, Gerard Cox, Anna G. Drannik, Mahmoud A. Pouladi, and Martin R. Stämpfli
- Subjects
Pulmonary and Respiratory Medicine ,T-Lymphocytes ,Clinical Biochemistry ,Spleen ,Lymphocyte Activation ,medicine.disease_cause ,Tobacco smoke ,Adenoviridae ,Mice ,Immune system ,Antigens, CD ,T-Lymphocyte Subsets ,Immunity ,Smoke ,Tobacco ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Respiratory system ,Lung ,Molecular Biology ,Cells, Cultured ,business.industry ,Smoking ,Dendritic Cells ,Cell Biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Immunology ,Leukocytes, Mononuclear ,Cytokines ,Female ,business - Abstract
We investigated the impact of cigarette smoke exposure on respiratory immune defense mechanisms. Mice were exposed to two cigarettes daily, 5 d/wk, for 2-4 mo. Tobacco smoke decreased the number of dendritic cells (DCs) in the lung tissue. Furthermore, smoke exposure dramatically reduced the percentage of B7.1-expressing DCs. Because DCs are believed to be indispensable to the initiation of adaptive immune responses, we investigated the impact of cigarette smoke on immune responsiveness toward adenovirus. Mice were exposed to two cigarettes for 2-4 mo and inoculated with 2 x 10(8) pfu of a replication-deficient adenovirus on three occasions, 2 wk apart, during the last month of tobacco smoke exposure. Smoke exposure specifically prevented the expansion and maximal activation of CD4 T cells and reduced the number of both activated CD4 and CD8 T cells. Consequently, smoke exposure shifted the activated CD4:CD8 T cell ratio from 3 to 1.5 when compared with sham exposure. Significant decreases were also observed in serum adenovirus-specific pan IgG, IgG1, and IgG2a immunoglobulin levels, which was associated with diminished viral neutralization capacity. We demonstrate that chronic tobacco smoke exposure impairs the immune response against adenovirus. This may, in part, explain the increased prevalence of viral infections in chronic obstructive pulmonary disease.
- Published
- 2004
47. Is there a role for statins in atrial fibrillation?
- Author
-
David E, Dawe, Vignendra, Ariyarajah, and Aliasghar, Khadem
- Subjects
Survival Rate ,Treatment Outcome ,Atrial Fibrillation ,Prevalence ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Anti-Arrhythmia Agents ,Survival Analysis - Abstract
3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are some of the most commonly prescribed drugs in the world. While lipid modification remains the primary function of statins, there has been increasing interest in its potential pleiotropic effects, particularly as an anti-inflammatory agent in its role as an antiarrhythmic. Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and carries with it a significant burden in both morbidity and mortality. Treatment for AF currently involves either rate or rhythm control where both have demonstrable associated risks. Rate control necessitates anticoagulation, which can cause life-threatening bleeding, while rhythm control has a poor side-effect profile that may lead to greater mortality and may not completely eliminate the need for anticoagulation. Considering this pressing need for novel therapeutic interventions in AF, this long overdue systematic review explores the potential role of statins in the treatment and prevention of AF. Physicians, especially cardiologists, need to be aware of the host of currently available literature and, more importantly, need to be stimulated to generate discussion and formulate studies that will help debate the issues under the most erudite standards.
- Published
- 2009
48. Mainstream cigarette smoke exposure attenuates airway immune inflammatory responses to surrogate and common environmental allergens in mice, despite evidence of increased systemic sensitization
- Author
-
Manel Jordana, Ramzi Fattouh, Neda Vujicic, Clinton S. Robbins, Mahmoud A. Pouladi, David E. Dawe, Martin R. Stämpfli, Mark D. Inman, and Carl D. Richards
- Subjects
Ragweed ,Ovalbumin ,Immunology ,Inflammation ,Immunoglobulin E ,Allergic sensitization ,Mice ,Immune system ,Smoke ,Tobacco ,Hypersensitivity ,Immunology and Allergy ,Medicine ,Animals ,Lung ,Sensitization ,Mice, Inbred BALB C ,biology ,business.industry ,CD69 ,respiratory system ,Allergens ,biology.organism_classification ,Flow Cytometry ,medicine.anatomical_structure ,Antibody Formation ,biology.protein ,Cytokines ,Female ,Tobacco Smoke Pollution ,medicine.symptom ,Ambrosia ,Bronchial Hyperreactivity ,business - Abstract
The purpose of this study was to investigate the impact of mainstream cigarette smoke exposure (MTS) on allergic sensitization and the development of allergic inflammatory processes. Using two different experimental murine models of allergic airways inflammation, we present evidence that MTS increased cytokine production by splenocytes in response to OVA and ragweed challenge. Paradoxically, MTS exposure resulted in an overall attenuation of the immune inflammatory response, including a dramatic reduction in the number of eosinophils and activated (CD69+) and Th2-associated (T1ST2+) CD4 T lymphocytes in the lung. Although MTS did not impact circulating levels of OVA-specific IgE and IgG1, we observed a striking reduction in OVA-specific IgG2a production and significantly diminished airway hyperresponsiveness. MTS, therefore, plays a disparate role in the development of allergic responses, inducing a heightened state of allergen-specific sensitization, but dampening local immune inflammatory processes in the lung.
- Published
- 2005
49. Health-related quality of life following operative treatment of unstable ankle fractures: a prospective observational study
- Author
-
Gordon H. Guyatt, Mohit Bhandari, Sheila Sprague, Beate Hanson, David E. Dawe, Jason W. Busse, and Jaydeep Moro
- Subjects
Adult ,Joint Instability ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Health Status ,MEDLINE ,Traumatology ,Cohort Studies ,Quality of life ,Predictive Value of Tests ,Medicine ,Humans ,Orthopedics and Sports Medicine ,Ankle Injuries ,Aged ,Aged, 80 and over ,business.industry ,General Medicine ,Recovery of Function ,Middle Aged ,Tibial Fractures ,medicine.anatomical_structure ,Treatment Outcome ,Fibula ,Predictive value of tests ,Orthopedic surgery ,Physical therapy ,Quality of Life ,Surgery ,Observational study ,Female ,Ankle ,business ,Ankle Joint ,Cohort study - Abstract
Although Weber type B ankle fractures are often considered benign with a good prognosis, evidence from observational studies suggests that 17% to 24% of such patients may have less satisfactory outcomes. Although the explanation for variability in outcomes remains unclear, previous studies of other surgical procedures have suggested nonsurgery-related causes account for much of the variability in outcomes.We conducted a prospective observational cohort study to evaluate health-related quality of life in 30 patients with unstable ankle fractures who were otherwise healthy. Only patients from 2 university-affiliated hospitals sustaining unstable type B Weber injury patterns requiring surgery were eligible. Patients provided detailed baseline information regarding alcohol consumption, smoking habits, and educational level. Patients completed the short form 36 questionnaire and a visual analogue pain scale at regular follow-up intervals.The average patient age was 51.6 years (SD 15.2 years), and 57% (17 out of 30) were male. The majority of fractures were the result of a fall (67%, 20 out of 30), and all were closed injuries. Almost half of all patients were smokers (47%, 14 out of 30), whereas 43% consumed alcohol on a weekly basis (13 out of 30). Forty-three percent of patients (13 out of 30) had obtained an elementary or high school level of education. Patients experienced significant improvements in all domains of the SF-36 questionnaire (P0.001), except general health, which remained essentially normal over the 24-month period. Study patients achieved scores similar to age-matched U.S. normative data across 6 of the 8 domains (Role Emotional, Social Function, Mental Health, Bodily Pain, Vitality, and General Health). However, patients' physical function and role physical scores remained significantly lower than US norms at 24 months (21.8 and 20.7 points lower on a 100-point scale, respectively; P0.001). Smoking history (P = 0.02), presence of a medial malleolar fracture (P = 0.02), and lower levels of education (P = 0.01) were significant independent predictors of lower physical function up to 3 months postoperation. Lower mental health domain scores were significantly associated with alcohol use (P = 0.02) and increasing age (P = 0.04).As is the case in many other areas, social factors may be important determinants of outcome in patients with traumatic fractures. Optimal orthopedic care may involve attention to modifiable risk factors, including smoking and alcohol consumption.
- Published
- 2004
50. Do patients with small cell lung cancer (SCLC) who have chemotherapy initiated during a hospital admission benefit from therapy?
- Author
-
David E. Dawe, Peter M. Ellis, and Gregory R. Pond
- Subjects
Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,macromolecular substances ,medicine.disease ,respiratory tract diseases ,carbohydrates (lipids) ,Oncology ,Hospital admission ,Emergency medicine ,otorhinolaryngologic diseases ,Medicine ,Poor performance status ,Non small cell ,business ,Lung cancer ,Intensive care medicine ,neoplasms - Abstract
e17661 Background: Lung cancer patients (pts) admitted to hospital in Canada generally have a poor performance status (ECOG 3 or 4). This often precludes treatment for pts with NSCLC, although many...
- Published
- 2014
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