439 results on '"Kelvin K. W. Chan"'
Search Results
202. PCN439 DEVELOPING A DISCRETE-EVENT SIMULATION TO STUDY THE INFLUENCE OF WAITING TIMES ON THE EFFECTIVENESS AND COST-EFFECTIVENESS OF CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY IN LARGE B-CELL LYMPHOMA
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Kelvin K. W. Chan, Zeny Feng, William Wong, K. Grindrod, S. Tully, and T. McFarlane
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Waiting time ,business.industry ,Cost effectiveness ,Health Policy ,Public Health, Environmental and Occupational Health ,medicine ,Cancer research ,CAR T-cell therapy ,Discrete event simulation ,B-cell lymphoma ,medicine.disease ,business ,Chimeric antigen receptor - Published
- 2019
203. Cost-effectiveness of Pembrolizumab in Second-line Advanced Bladder Cancer
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Peter Hall, Noa Gordon, Assaf Moore, Daniel A. Goldstein, Michal Sarfaty, Moshe Leshno, Kelvin K. W. Chan, Kiran Virik, Victoria Neiman, and Eli Rosenbaum
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Oncology ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Canada ,Cost effectiveness ,medicine.medical_treatment ,Urology ,Cost-Benefit Analysis ,Pembrolizumab ,Health outcomes ,Antibodies, Monoclonal, Humanized ,Drug Costs ,03 medical and health sciences ,0302 clinical medicine ,Second line ,Antineoplastic Agents, Immunological ,Internal medicine ,Overall survival ,medicine ,Journal Article ,Humans ,Statistical analysis ,Sensitivity analyses ,health care economics and organizations ,Bladder cancer ,business.industry ,Australia ,Immunotherapy ,medicine.disease ,Markov Chains ,United Kingdom ,United States ,Metastatic bladder cancer ,030104 developmental biology ,Transitional cell carcinoma ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Emergency medicine ,Advanced bladder cancer ,Quality-Adjusted Life Years ,business - Abstract
BACKGROUND: Immune-modulating drugs have recently been introduced to the second-line setting of advanced bladder cancer. Pembrolizumab increases overall survival and is associated with less toxicity compared with chemotherapy in this setting based on the Keynote 045 study. The high cost of immunotherapy necessitates an assessment of its value by considering both efficacy and cost.OBJECTIVE: To estimate the cost-effectiveness of pembrolizumab for the second-line treatment of advanced bladder cancer from the perspective of payers in multiple countries.DESIGN, SETTING, AND PARTICIPANTS: We developed a Markov model to compare the cost and effectiveness of pembrolizumab with those of chemotherapy in the second-line treatment of advanced bladder cancer based on the Keynote 045 study. Drug costs were acquired for the United States (US), United Kingdom (UK), Canada, and Australia. All costs were converted from local currency to US dollars at the exchange rates in September 2017.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Health outcomes were measured in quality-adjusted life-years (QALYs).RESULTS AND LIMITATIONS: Pembrolizumab generated a gain of 0.36-0.37 QALYs compared with chemotherapy. Our analysis established the following incremental cost-effectiveness ratios (ICERs) for pembrolizumab versus chemotherapy in second-line advanced bladder cancer treatment: US $122 557/QALY; UK $91 995/QALY; Canada $90 099/QALY; and Australia $99 966/QALY. The willingness-to-pay (WTP) thresholds per QALY are considered to be around 100 000-150 000 US dollars for the US, 20 000-50 000 pounds for the UK (US$25 000-65 000), 20 000 -100 000 CAD for Canada (US$16 000-80 000), and 40 000-75 000 AUD for Australia (US$32 000-60 000).CONCLUSIONS: Cost-effectiveness and WTP thresholds vary between countries. Compared with the other countries examined, US drug prices were found to be the highest, leading to the highest ICER. With standard WTP thresholds, pembrolizumab may be considered cost-effective in the US but not in the other countries examined.PATIENT SUMMARY: This article assessed the cost-effectiveness of pembrolizumab for the treatment of patients with metastatic bladder cancer who had previously failed one treatment regimen. It would cost $122 557 in the United States, $91 995 in the United Kingdom, $90 099 in Canada, and $99 966 in Australia to gain one quality-adjusted life-year with pembrolizumab versus chemotherapy in these patients, which may be considered cost-effective only in the United States because of the differences in willingness-to-pay thresholds.
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- 2018
204. Estimates and predictors of health care costs of esophageal adenocarcinoma: a population-based cohort study
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Craig C. Earle, Nathaniel Jembere, Chin Hur, Kelvin K. W. Chan, Hla-Hla Thein, Claire de Oliveira, Kednapa Thavorn, and Peter C. Coyte
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Esophageal Neoplasms ,Population ,Adenocarcinoma ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Health care ,Genetics ,Humans ,Medicine ,education ,Generalized estimating equation ,Survival rate ,Aged ,Neoplasm Staging ,Retrospective Studies ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Retrospective cohort study ,Stage at diagnosis ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Comorbidity ,Treatment ,Oncology ,030220 oncology & carcinogenesis ,Emergency medicine ,Economic evaluation ,Female ,Costs and cost analysis ,030211 gastroenterology & hepatology ,Esophageal adenocarcinoma ,Health care costs ,business ,Research Article - Abstract
Background Esophageal adenocarcinoma (EAC) incidence is increasing rapidly. Esophageal cancer has the second lowest 5-year survival rate of people diagnosed with cancer in Canada. Given the poor survival and the potential for further increases in incidence, phase-specific cost estimates constitute an important input for economic evaluation of prevention, screening, and treatment interventions. The study aims to estimate phase-specific net direct medical costs of care attributable to EAC, costs stratified by cancer stage and treatment, and predictors of total net costs of care for EAC. Methods A population-based retrospective cohort study was conducted using Ontario Cancer Registry-linked administrative health data from 2003 to 2011. The mean net costs of EAC care per 30 patient-days (2016 CAD) were estimated from the payer perspective using phase of care approach and generalized estimating equations. Predictors of net cost by phase of care were based on a generalized estimating equations model with a logarithmic link and gamma distribution adjusting for sociodemographic and clinical factors. Results The mean net costs of EAC care per 30 patient-days were $1016 (95% CI, $955–$1078) in the initial phase, $669 (95% CI, $594–$743) in the continuing care phase, and $8678 (95% CI, $8217–$9139) in the terminal phase. Overall, stage IV at diagnosis and surgery plus radiotherapy for EAC incurred the highest cost, particularly in the terminal phase. Strong predictors of higher net costs were receipt of chemotherapy plus radiotherapy, surgery plus chemotherapy, radiotherapy alone, surgery alone, and chemotherapy alone in the initial and continuing care phases, stage III-IV disease and patients diagnosed with EAC later in a calendar year (2007–2011) in the initial and terminal phases, comorbidity in the continuing care phase, and older age at diagnosis (70–74 years), and geographic region in the terminal phase. Conclusions Costs of care vary by phase of care, stage at diagnosis, and type of treatment for EAC. These cost estimates provide information to guide future resource allocation decisions, and clinical and policy interventions to reduce the burden of EAC. Electronic supplementary material The online version of this article (10.1186/s12885-018-4620-2) contains supplementary material, which is available to authorized users.
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- 2018
205. Early diastolic strain rate measurements by cardiac MRI in breast cancer patients treated with trastuzumab: a longitudinal study
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Chi-Ming Chow, John J. Graham, Inna Y. Gong, Paaladinesh Thavendiranathan, Kim A. Connelly, Joseph Barfett, Kelvin K. W. Chan, Djeven P. Deva, Ming-Yen Ng, Geraldine Ong, Andrew T. Yan, Vinita Dhir, Christine Brezden-Masley, and Day Dai
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Adult ,medicine.medical_specialty ,Longitudinal study ,Time Factors ,Diastole ,Breast Neoplasms ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,03 medical and health sciences ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,cardiovascular diseases ,Longitudinal Studies ,Prospective Studies ,Subclinical infection ,Ontario ,Cardiotoxicity ,Ejection fraction ,medicine.diagnostic_test ,Strain (chemistry) ,business.industry ,Magnetic resonance imaging ,Stroke Volume ,Strain rate ,Middle Aged ,Trastuzumab ,Magnetic Resonance Imaging ,3. Good health ,Early Diagnosis ,Treatment Outcome ,030220 oncology & carcinogenesis ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
We evaluated temporal changes in early diastolic strain rates by cardiovascular magnetic resonance (CMR) as an early detector of trastuzumab-induced ventricular dysfunction. We conducted a prospective, multi-centre, longitudinal observational study of 41 trastuzumab-treated breast cancer women who underwent serial CMR (baseline, 6, 12, and 18 months). Two blinded readers independently measured left ventricular ejection fraction (LVEF), peak systolic strain parameters (global longitudinal strain [GLS] and global circumferential strain [GCS]), and early diastolic strain rate parameters (global longitudinal diastolic strain rate [GLSR-E], global circumferential diastolic strain rate [GCSR-E], and global radial diastolic strain rate [GRSR-E]), by feature tracking (FT-CMR) using CMR42. There was a significant decline in peak systolic strain GLS and GCS at 6 months (p = 0.024 and p 0.001, respectively) and 12 months (p = 0.002 and p 0.001, respectively), followed by recovery at 18 months, which paralleled decline in LVEF at 6 months (p = 0.034) and 12 months (p = 0.012). Conversely, early diastolic strain rates GLSR-E and GCSR-E did not significantly change over 18 months (p 0.10), while GRSR-E was marginally significant at 12 months (p = 0.021). There was no significant correlation between changes at 6 months in LVEF and GLSR-E or GRSR-E (p 0.10), and a marginally significant weak correlation between LVEF and GCSR-E (p = 0.046). Among trastuzumab-treated patients without overt cardiotoxicity, there was no consistent temporal change in FT-CMR-derived diastolic strain rate parameters up to 18 months, in contrast to decline in systolic strain and LVEF. Systolic strains by FT-CMR are likely more useful than diastolic strain rates for monitoring subclinical trastuzumab-related myocardial dysfunction.ClinicalTrials.gov identifier NCT01022086.
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- 2018
206. What does meaningful look like? A qualitative study of patient engagement at the Pan-Canadian Oncology Drug Review: perspectives of reviewers and payers
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Kelvin K. W. Chan, Linda Rozmovits, Helen Mai, and Alexandra Chambers
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Canada ,Technology Assessment, Biomedical ,Cost-Benefit Analysis ,Advisory Committees ,Antineoplastic Agents ,Patient advocacy ,Interviews as Topic ,03 medical and health sciences ,0302 clinical medicine ,Residence Characteristics ,Humans ,030212 general & internal medicine ,Qualitative Research ,Medical education ,030503 health policy & services ,Health Policy ,Public Health, Environmental and Occupational Health ,Stakeholder ,Health technology ,Patient Preference ,Transparency (behavior) ,Clinical trial ,Appeal to emotion ,Research Design ,Thematic analysis ,Patient Participation ,0305 other medical science ,Psychology ,Qualitative research - Abstract
Objectives While there is wide support for patient engagement in health technology assessment, determining what constitutes meaningful (as opposed to tokenistic) engagement is complex. This paper explores reviewer and payer perceptions of what constitutes meaningful patient engagement in the Pan-Canadian Oncology Drug Review process. Methods Qualitative interview study comprising 24 semi-structured telephone interviews. A qualitative descriptive approach, employing the technique of constant comparison, was used to produce a thematic analysis. Results Submissions from patient advocacy groups were seen as meaningful when they provided information unavailable from other sources. This included information not collected in clinical trials, information relevant to clinical trade-offs and information about aspects of lived experience such as geographic differences and patient and carer priorities. In contrast, patient submissions that relied on emotional appeals or lacked transparency about their own methods were seen as detracting from the meaningfulness of patient engagement by conflating health technology assessment with other functions of patient advocacy groups such as fundraising or public awareness campaigns, and by failing to provide credible information relevant to deliberations. Conclusions This study suggests that misalignment of stakeholder expectations remains an issue even for a well-regarded health technology assessment process that has promoted patient engagement since its inception. Support for the technical capacity of patient groups to participate in health technology assessment is necessary but not sufficient to address this issue fully. There is a fundamental tension between the evidence-based nature of health technology assessment and the experientially oriented culture of patient advocacy. Divergent notions of what constitutes evidence and how it should be used must also be addressed.
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- 2018
207. Examining Trends in Cost and Clinical Benefit of Novel Anticancer Drugs Over Time
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Erica McDonald, Matthew C. Cheung, Sierra Cheng, Kelvin K. W. Chan, Ronak Saluja, Vanessa Sarah Arciero, and William Wong
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Drug ,medicine.medical_specialty ,media_common.quotation_subject ,Cost-Benefit Analysis ,MEDLINE ,Antineoplastic Agents ,Medical Oncology ,History, 21st Century ,Drug Costs ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Neoplasms ,medicine ,Drug approval ,Humans ,030212 general & internal medicine ,Clinical efficacy ,Intensive care medicine ,media_common ,Randomized Controlled Trials as Topic ,Cost–benefit analysis ,Oncology (nursing) ,business.industry ,Health Policy ,History, 20th Century ,Anticancer drug ,Clinical trial ,Oncology ,Clinical Trials, Phase III as Topic ,030220 oncology & carcinogenesis ,Linear Models ,business - Abstract
Purpose: The purpose of this study was to determine if clinical benefits of novel anticancer drugs, measured by the ASCO Value Framework and European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale, have increased over time in parallel with increasing costs. Methods: Anticancer drugs from phase III randomized controlled trials cited for clinical efficacy evidence in drug approvals between January 2006 to December 2015 were identified and scored using both frameworks. For each drug, the monthly price and incremental anticancer drug costs were calculated. Relationships between cost and year of approval were examined using generalized linear regressions models. Ordinary least square models were used to evaluate relationships between ASCO and ESMO scores and year of approval. Spearman correlation coefficients between costs and clinical benefit scores were calculated. Results: In total, 42 randomized controlled trials were included. Both monthly prices and incremental anticancer drug costs were significantly associated with year of approval and showed an average annual increase of 9% and 21%, respectively. The predicted mean incremental anticancer drug cost increased from $30,447 in 2006 to $161,141 in 2015 (greater than five-fold increase). Both ASCO and ESMO scores were not statistically associated with year of approval or correlated with monthly prices or incremental anticancer drug costs. Conclusion: Over the past decade, costs of novel oncology drugs have increased, while clinical benefits of these medications have not experienced a proportional positive change. The incremental anticancer drug costs have increased at a much greater rate than monthly prices, indicating that the increase in anticancer drug costs may be higher than commonly reported.
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- 2018
208. The economic burden of cancer care in Canada: a population-based cost study
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Jagadish Rangrej, Stuart Peacock, Kelvin K. W. Chan, Nicole Mittmann, Claire de Oliveira, Jeffrey S Hoch, Murray Krahn, and Sharada Weir
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0301 basic medicine ,Comparative Effectiveness Research ,Cost estimate ,MEDLINE ,Population based ,Burden of care ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Environmental health ,Health care ,medicine ,health care economics and organizations ,Cancer ,business.industry ,Research ,General Medicine ,Health Services ,medicine.disease ,Good Health and Well Being ,030104 developmental biology ,Burden of Illness ,Work (electrical) ,030220 oncology & carcinogenesis ,Business ,8.2 Health and welfare economics ,Health and social care services research ,Cost study - Abstract
Author(s): de Oliveira, Claire; Weir, Sharada; Rangrej, Jagadish; Krahn, Murray D; Mittmann, Nicole; Hoch, Jeffrey S; Chan, Kelvin KW; Peacock, Stuart | Abstract: BackgroundResource and cost issues are a growing concern in health care. Thus, it is important to have an accurate estimate of the economic burden of care. Previous work has estimated the economic burden of cancer care for Canada; however, there is some concern this estimate is too low. The objective of this analysis was to provide a comprehensive revised estimate of this burden.MethodsWe used a case-control prevalence-based approach to estimate direct annual cancer costs from 2005 to 2012. We used patient-level administrative health care data from Ontario to correctly attribute health care costs to cancer. We employed the net cost method (cost difference between patients with cancer and control subjects without cancer) to account for costs directly and indirectly related to cancer and its sequelae. Using average patient-level cost estimates from Ontario, we applied proportions from national health expenditures data to obtain the economic burden of cancer care for Canada. All costs were adjusted to 2015 Canadian dollars.ResultsCosts of cancer care rose steadily over our analysis period, from $2.9 billion in 2005 to $7.5 billion in 2012, mostly owing to the increase in costs of hospital-based care. Most expenditures for health care services increased over time, with chemotherapy and radiation therapy expenditures accounting for the largest increases over the study period. Our cost estimates were larger than those in the Economic Burden of Illness in Canada 2005-2008 report for every year except 2005 and 2006.InterpretationThe economic burden of cancer care in Canada is substantial. Further research is needed to understand how the economic burden of cancer compares to that of other diseases.
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- 2018
209. PCN42 THE HEALTH UTILITY BOOK (HUB): TOWARD A CENTRALIZED, SYSTEMATIC APPROACH TO THE IDENTIFICATION, APPRAISAL, AND USE OF HEALTH STATE UTILITY VALUES FOR REIMBURSEMENT DECISION MAKING
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Michael J. Zoratti, Oren Levine, Don Husereau, Murray Krahn, Holger J. Schünemann, Kelvin K. W. Chan, Feng Xie, Gordon H. Guyatt, and Tammy Clifford
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Identification (information) ,Risk analysis (engineering) ,Health utility ,Health Policy ,Public Health, Environmental and Occupational Health ,Business ,State (computer science) ,Reimbursement - Published
- 2019
210. Quality of life changes after stereotactic ablative radiotherapy for liver metastases: A prospective cohort analysis
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Darby Erler, Isabelle Thibault, Renee Korol, William Chu, M. Davidson, Kelvin K. W. Chan, Hans T. Chung, Pablo Munoz-Schuffenegger, Joelle Helou, Andrew Warner, Edward Chow, and George Rodrigues
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Oncology ,Male ,medicine.medical_specialty ,Palliative care ,Constipation ,Nausea ,medicine.medical_treatment ,Health Status ,SABR volatility model ,Radiosurgery ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,Surveys and Questionnaires ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Neoplasm Metastasis ,Prospective cohort study ,Fatigue ,Aged ,business.industry ,Liver Neoplasms ,Palliative Care ,Cancer ,Hematology ,Middle Aged ,medicine.disease ,humanities ,Radiation therapy ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,medicine.symptom ,business ,Colorectal Neoplasms - Abstract
To report the changes in quality of life (QoL) after stereotactic ablative radiotherapy (SABR) in patients with liver metastases (LM).A prospective cohort study was undertaken to measure the acute changes in QoL after SABR. Patients with 1-3 treated LM were eligible. Doses of 30-60 Gy in 3-5 fractions were delivered. Prospective QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, Core 15 for Palliative Care (EORTC QLQ-C15-PAL) and liver metastases (LM21), at baseline, 1st week and last day of treatment, then 1, 6 and 12 weeks after SABR. The functional living index-emesis (FLIE) was collected at baseline, 1st week, last day and 1 week after treatment. Univariable and multivariable linear mixed modeling were performed as appropriate to assess changes in QoL over time.Sixty patients were included. The most common primary cancer was colorectal (42%). The global health score measured by QLQ-C15-PAL was significantly worse at treatment completion (p = 0.001), 1 week (p = 0.003) and 6 weeks (p = 0.002) after SABR but recovered by 12 weeks (p = 0.124). Nausea and constipation were worse at treatment completion (p 0.05) but recovered 1 week after while fatigue recovered 6 weeks post-SABR. The majority of patients reported stable QoL at 12 weeks for all domains in the C15-PAL and LM21 questionnaires.SABR offers a non-invasive mean of ablating LM with minimal impact on acute QoL.
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- 2017
211. Pan-Canadian Quality Indicators for Patients at End of Life Derived from interRAI Data
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Lisa E. Harman, Kim McGrail, Kelvin K. W. Chan, Rinku Sutradhar, Hsien Seow, Beverley Lawson, Lisa Barbera, Dawn M. Guthrie, Stuart Peacock, and Fred Burge
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Gerontology ,business.industry ,030503 health policy & services ,media_common.quotation_subject ,03 medical and health sciences ,0302 clinical medicine ,Anesthesiology and Pain Medicine ,Medicine ,Quality (business) ,030212 general & internal medicine ,Neurology (clinical) ,0305 other medical science ,business ,General Nursing ,media_common - Published
- 2018
212. Stereotactic Body Radiation Therapy for Metastatic Colorectal Cancer: Comprehensive Review from a Large Academic Institution
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Sten Myrehaug, Shun Wong, Yoo-Joung Ko, L. Zhang, Hany Soliman, Ian Poon, Susanna Y Cheng, Darby Erler, William Chu, Kelvin K. W. Chan, Ana Beatriz Kinupe Abrahao, Patrick Cheung, Craig C. Earle, Scott R. Berry, Robert Thompson, Hans T. Chung, Arjun Sahgal, Y.C. Ung, and Chia-Lin Tseng
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Academic institution ,Cancer Research ,medicine.medical_specialty ,Radiation ,Oncology ,Stereotactic body radiation therapy ,Colorectal cancer ,business.industry ,General surgery ,medicine ,Radiology, Nuclear Medicine and imaging ,medicine.disease ,business - Published
- 2018
213. Chemoradiotherapy regimens for locoregionally advanced nasopharyngeal carcinoma: A Bayesian network meta-analysis
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Alexander Kumachev, Lillian L. Siu, Kelvin K. W. Chan, Marie Yan, and Kelly Lien
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Oncology ,Cancer Research ,medicine.medical_specialty ,genetic structures ,Adjuvant chemotherapy ,medicine.medical_treatment ,Nasopharyngeal neoplasm ,health services administration ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,cardiovascular diseases ,Neoadjuvant therapy ,Clinical Trials as Topic ,Nasopharyngeal Carcinoma ,Relative survival ,business.industry ,Carcinoma ,Hazard ratio ,Bayes Theorem ,Nasopharyngeal Neoplasms ,Chemoradiotherapy ,medicine.disease ,Survival Analysis ,Neoadjuvant Therapy ,Surgery ,Concurrent chemoradiotherapy ,Regimen ,Nasopharyngeal carcinoma ,Chemotherapy, Adjuvant ,Meta-analysis ,cardiovascular system ,business ,circulatory and respiratory physiology - Abstract
Background Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-A) is often the regimen of choice in locoregionally advanced nasopharyngeal carcinoma (NPC). Many alternative regimens have been reported in the literature, however, it is unknown how effective these regimens are compared to each other due to the lack of direct comparisons. Our objective was to perform a network meta-analysis (NMA) to determine the relative survival benefits of these treatments for locoregionally advanced NPC. Methods We performed a systematic review following the Cochrane methodology, using MEDLINE, EMBASE and CENTRAL to identify all randomised controlled trials (RCTs) that compared different chemoradiotherapy regimens for locoregionally advanced NPC. Overall survival (OS) was the primary outcome of interest, and hazard ratios (HRs) were extracted using the Parmar method. Bayesian NMAs with random effects were conducted using WinBUGS. Results Twenty-five RCTs (5576 patients) were included in this review. All together, these trials compared seven different regimens: radiotherapy (RT), concurrent chemoradiotherapy (CRT), neoadjuvant followed by CRT (N-CRT), CRT-A, RT-A, N-RT and N-RT-A. All regimens that contained CRT performed significantly better than RT. CRT-A did not improve survival compared to CRT alone (0.98; 95% credible regions: 0.71–1.34). For N-CRT versus CRT, the HR was 1.03 (0.69–1.47). When CRT-A was compared against N-CRT, the resulting HR was 0.96 (0.64–1.48). Conclusions Adjuvant chemotherapy does not appear to improve survival following CRT. The efficacies of CRT, CRT-A and N-CRT all appeared to be similar. Further studies are warranted to determine the value of additional chemotherapy phases in specific patient subgroups.
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- 2015
214. Salivary duct carcinoma: Treatment, outcomes, and patterns of failure
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Eshetu G. Atenafu, Bernard Cummings, Patrick Gullane, Ralph W. Gilbert, Brian O'Sullivan, I. Witterick, Bayardo Perez-Ordonez, Andrew Bayley, Laura A. Dawson, John Waldron, Ilan Weinreb, Shao Hui Huang, Meredith Johnston, Jolie Ringash, Andrew Hope, Kelvin K. W. Chan, David P. Goldstein, John Kim, John Cho, and Jonathan C. Irish
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medicine.medical_specialty ,Multivariate analysis ,business.industry ,medicine.medical_treatment ,Hazard ratio ,medicine.disease ,Submandibular gland ,Facial nerve ,Parotid gland ,Salivary duct carcinoma ,Surgery ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,medicine ,Radiology ,030223 otorhinolaryngology ,business ,Duct (anatomy) - Abstract
Background Salivary duct carcinoma is rare, with distinct morphology and behavior. We reviewed our institutional experience with salivary duct carcinoma, aiming to characterize clinical behavior and treatment outcomes. Methods All salivary duct carcinomas treated curatively between 1999 and 2010 were reviewed. Overall survival (OS), locoregional control, distant control, and patterns of failure were analyzed. Multivariate analysis identified predictors of OS. Results Fifty-four patients with salivary duct carcinoma (parotid gland = 49; submandibular gland = 5) were included in the analysis. Fifty-three patients underwent primary surgery, and 48 (89%) received postoperative radiotherapy (RT; median dose = 60 Gy). Median follow-up was 5.7 years. The 5-year OS, locoregional control, and distant control were 43%, 70%, and 48%, respectively. Nine local (6 involving facial nerve), 10 regional, and 28 distant failures were identified. Multiple pathologic involved lymph nodes (pN2b/N2c) predicted reduced OS (hazard ratio [HR] = 3.6; p = .02). Conclusion Distant recurrence is common. Presence of pN2b/N2c disease is associated with reduced OS. Local recurrence frequently involves the facial nerves. © 2015 Wiley Periodicals, Inc. Head Neck, 2015
- Published
- 2015
215. Quantifying Parameter Uncertainty in EQ-5D-3L Value Sets and Its Impact on Studies That Use the EQ-5D-3L to Measure Health Utility
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Kelvin K. W. Chan, Eleanor Pullenayegum, and Feng Xie
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Health Status ,Bayesian probability ,Pain ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,Scoring algorithm ,Activities of Daily Living ,Statistics ,Linear regression ,Econometrics ,Humans ,Sensitivity analysis ,030212 general & internal medicine ,Mobility Limitation ,Uncertainty analysis ,Mathematics ,030503 health policy & services ,Health Policy ,Uncertainty ,Reproducibility of Results ,Bayes Theorem ,United States ,Mental Health ,Quality of Life ,Measurement uncertainty ,Valuation (measure theory) ,0305 other medical science ,Value (mathematics) ,Algorithms - Abstract
Background. Parameter uncertainty in EQ-5D value sets is routinely ignored. Sources of parameter uncertainty include uncertainty in the estimated regression coefficients of the scoring algorithm and uncertainty that arises from the need to use a nonsaturated functional form when creating the scoring algorithm. We hypothesize that this latter source is the major contributor to parameter uncertainty in the value sets. Methods. We used data from the United States EQ-5D-3L valuation study to assess the extent of parameter uncertainty in the value set. We refitted the US scoring algorithm to quantify contributors to the mean square prediction errors and used a Bayesian approach to estimate the predictive distribution of the mean utilities. The impact of parameter uncertainty in the value set was assessed using survey data. Results. Parameter uncertainty in the estimated regression coefficients explained 16% of the mean squared prediction error; uncertainty in the functional form explained the remaining 84%. The median width of the 95% credible intervals for the mean utilities was 0.15. In estimating mean utility in our survey population, parameter uncertainty in the value set was responsible for 93% of the total variance, with sampling variation in the survey population being responsible for the remaining 7%. Conclusion. EQ-5D-3L value sets are estimated subject to considerable parameter uncertainty; the median credible interval width is large compared with reported values of the minimum important difference for the EQ-5D-3L, which have been reported to be as small as 0.03. Other countries’ scoring algorithms are based on smaller studies and are hence subject to greater uncertainty. This uncertainty should be accounted for when using EQ-5D health utilities in economic evaluations.
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- 2015
216. ASCO Provisional Clinical Opinion for Hepatitis B Virus Screening Before Cancer Therapy: Are These the Right Tests in the Right Patients?
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Lisa K. Hicks, Kelly Lien, and Kelvin K. W. Chan
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Hepatitis B virus ,medicine.medical_specialty ,HBsAg ,medicine.disease_cause ,law.invention ,Hepatitis B, Chronic ,Randomized controlled trial ,law ,Neoplasms ,Internal medicine ,medicine ,Humans ,Overdiagnosis ,Prospective cohort study ,Gynecology ,Oncology (nursing) ,business.industry ,Health Policy ,virus diseases ,Cancer ,Hepatitis B ,medicine.disease ,digestive system diseases ,Transplantation ,Oncology ,business - Abstract
Hepatitis B virus (HBV) reactivation is a well-documented complication of cancer treatment that can cause serious morbidity and mortality. A systematic review from 2008 reported reactivation probabilities between24%and88%,withhigher ratesofHBVreactivationamong patients with hematologic malignancies. Subsequent reports have reported an especially high risk of reactivation among patients receiving anti-CD20 therapy and/or stem-cell transplantation (SCT). Small randomized controlled trials and prospective cohort studies suggest thatHBVreactivation rates canbe reduced tonear zerowith theuseof prophylacticantiviralmedication. However, studiesofHBVscreening suggest varied uptake in cancer clinics. Clear clinical guidelines are required, and the revised ASCO Provisional Clinical Opinion (PCO) on HBV screening before cancer therapy is welcomed. As outlined in Table 1, the new PCO recommends that when HBV screening is pursued, both HB surface antigen (HBsAg) and HB core antibody (anti-HBc) be tested. It also recommends against screening all patients for HBV before cancer treatment (universal screening). Instead, selective HBV screening is recommended, except for patients receiving antiCD20 therapies or SCT, in which case universal HBV screening is favored. In our view, these recommendations open the door to both overdiagnosis of so-called resolved HBV (HBsAg negative/anti-HBc positive) of uncertain clinical significance in patients with solid tumors, and underdiagnosis of clinically important HBV infection (HBsAg positive) in patients receiving cancer treatments other than anti-CD20 or SCT. Our perspective is consistent with the dissenting opinion of two authors on the ASCO PCO panel, who suggested that universal screening is preferable to the risk-adapted approach.
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- 2015
217. Adjuvant taxane-based chemotherapy for early stage breast cancer: a real-world comparison of chemotherapy regimens in Ontario
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Maureen E. Trudeau, Craig C. Earle, Sofia Torres, Kelvin K. W. Chan, and Andrea Eisen
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Adult ,Bridged-Ring Compounds ,Oncology ,Emergency Medical Services ,Cancer Research ,medicine.medical_specialty ,Databases, Factual ,Cyclophosphamide ,medicine.medical_treatment ,Breast Neoplasms ,Comorbidity ,Breast cancer ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Registries ,Mortality ,Adverse effect ,Aged ,Neoplasm Staging ,Heart Failure ,Ontario ,Gynecology ,Chemotherapy ,Taxane ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Hospitalization ,Regimen ,Chemotherapy, Adjuvant ,Population Surveillance ,Female ,Taxoids ,business ,medicine.drug ,Epirubicin - Abstract
The purpose of this study was to compare survival and risk of adverse events in women with early stage breast cancer (BC) treated with (1) doxorubicin (A), cyclophosphamide (C) + paclitaxel (P), (2) fluorouracil (F), epirubicin (E), cyclophosphamide (C) + docetaxel (D), or (3) dose-dense AC-P. Retrospective cohort study including 8462 women aged ≥18 years, with resected stage I–III BC, diagnosed between 2003 and 2009 in Ontario, identified through linkage of administrative databases. Primary outcome is overall survival (OS). Secondary outcomes are emergency room (ER) visits/hospitalizations, heart failure (HF), and leukemia. 4710 women were treated with FEC-D, 2065 with AC-P, and 1687 with dd AC-P. Adjusted 5-year OS was 92.1, 87.7, and 90.3 %, for each regimen, respectively (p = 0.0006). There was no difference in OS for FEC-D and dd AC-P in the propensity score-matched analyses (HR 1.24, 95 % CI 0.99–1.55). Five-year risk of HF was also similar (HR 1.09; 0.66–1.791.4 % for dd AC-P and 1.3 % for FEC-D and, p = 0.72). Treatment with FEC-D was significantly associated with ER visits and hospital admissions (p
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- 2015
218. Hepatitis B virus screening before adjuvant chemotherapy in patients with early-stage breast cancer: a cost-effectiveness analysis
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Hong-Anh Tu, Murray Krahn, Kathleen I. Pritchard, Jordan J. Feld, William Wong, Lisa K. Hicks, and Kelvin K. W. Chan
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Liver Cirrhosis ,Oncology ,Canada ,Hepatitis B virus ,Cancer Research ,medicine.medical_specialty ,Cost effectiveness ,Cost-Benefit Analysis ,medicine.medical_treatment ,Breast Neoplasms ,medicine.disease_cause ,Antiviral Agents ,Breast cancer ,Internal medicine ,Prevalence ,medicine ,Humans ,Mass Screening ,Aged ,Neoplasm Staging ,Chemotherapy ,Models, Statistical ,business.industry ,Liver Neoplasms ,Reproducibility of Results ,Lamivudine ,Health Care Costs ,Entecavir ,Middle Aged ,Hepatitis B ,medicine.disease ,Immunology ,Cohort ,Female ,business ,Biomarkers ,medicine.drug - Abstract
Most patients with hepatitis B virus (HBV) have no symptoms, and many are unaware of the infection. However, HBV can reactivate with immunosuppression; chemotherapy causes reactivation in 22 % of hepatitis B surface antigen-positive patients. HBV reactivation can be fatal. HBV reactivation can be prevented, provided that HBV is recognized prior to chemotherapy. The objective of this study is to estimate the health and economic effects of HBV screening strategies in patients receiving adjuvant chemotherapy for breast cancer. We developed a state-transition microsimulation model to examine the cost-effectiveness of three HBV screening strategies: (1) "No screening"; (2) "Screen-and-Treat to prevent reactivation" (screen-all) with either lamivudine/tenofovir (LAM/TDF) or entecavir (ETV); and (3) "Screen-and-Treat high-risk only" (screen-HR) and treat with either LAM/TDF or ETV. Model data were obtained from the published literature. We used a payer's perspective, a lifetime horizon, and a 5 % discount rate for the analysis. "Screen-all" would prevent at least 38 severe reactivations per 100,000 persons screened over the lifetime of the cohort. "Screen-all" was associated with an increase of 0.0034-0.0035 QALYs and an additional cost of C$164-C$266 per person, which translated into an incremental cost-effectiveness ratio of C$47,808/QALY-C$76,527/QALY gained compared with "No screening" depending on the antiviral therapy received. "Screen-all" was the most cost-effective strategy, while "Screen-HR" was inferior in all scenarios tested. HBV screening before adjuvant chemotherapy for breast cancer patients would prevent a significant number of reactivations, would likely be moderately cost-effective, and may extend the lives of breast cancer patients.
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- 2015
219. Pharmacokinetic assessment of dacomitinib (pan-HER tyrosine kinase inhibitor) in patients with locally advanced head and neck squamous cell carcinoma (LA SCCHN) following administration through a gastrostomy feeding tube (GT)
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Eric Chen, Joanne W. Chiu, Lillian L. Siu, Kelvin K. W. Chan, and Albiruni Ryan Abdul Razak
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Male ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Urology ,Cmax ,Antineoplastic Agents ,Enteral administration ,Tyrosine-kinase inhibitor ,chemistry.chemical_compound ,Enteral Nutrition ,Pharmacokinetics ,medicine ,Carcinoma ,Humans ,Pharmacology (medical) ,Protein Kinase Inhibitors ,Aged ,Quinazolinones ,Gastrostomy ,Pharmacology ,Chemotherapy ,Squamous Cell Carcinoma of Head and Neck ,business.industry ,Middle Aged ,medicine.disease ,Head and neck squamous-cell carcinoma ,Dacomitinib ,Surgery ,ErbB Receptors ,Oncology ,chemistry ,Head and Neck Neoplasms ,Carcinoma, Squamous Cell ,Female ,business - Abstract
Background Dacomitinib is an irreversible oral pan-HER tyrosine kinase inhibitor with antitumor activity demonstrated in patients with recurrent/metastatic (RM) SCCHN. A Phase I trial of dacomitinib with standard therapy in LA SCCHN is ongoing (NCT01737008). As enteral feeding is needed for many SCCHN patients, this study investigated the PK properties of dacomitinib when administered via GT (NCT01484847). Since patients with GT are difficult to recruit, this study also determined the feasibility of PK assessments using a unique design in LA SCCHN patients with GT, by giving a single dose of drug during their radiotherapy (co-administration with chemotherapy avoided). Methods Eligible patients were given a single dose of crushed dacomitinib at 45 mg in water suspension via GT. All doses were administered in fasting state and supine position. PK samples were drawn prior to dose (t = 0), 30 min and 1, 2, 3, 4, 6, 12, 24, 48, 72, 96, 144, 168, 192 and 216 hrs post-dose, and analyzed by HPLC-MS/MS. PK parameters (mean [CV%]) of this study were compared with those of dacomitinib given orally using Student t test. Results Six patients with LA SCCHN patients were enrolled. The median age of patients was 54 years. Two different types of GT were used: 14 F Cope-loop tube (n = 3), 20 F PEG/disc retention tube (n = 3). PK study showed t1/2 of 58 h, Cmax of 17 ng/ml, Tmax of 8 h, AUC0-inf of 1185 ng*hr/ml, Vd/F of 3310 L and CL/F of 41 L/hr. Conclusion Compared with oral dosing of intact immediate release (IR) tablets, GT administration resulted in 34 % reduction in Cmax and 33–44 % decrease in AUC (all p
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- 2015
220. Frontline rituximab monotherapy induction versus a watch and wait approach for asymptomatic advanced-stage follicular lymphoma: A cost-effectiveness analysis
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Kelvin K. W. Chan, Anca Prica, and Matthew C. Cheung
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Cancer Research ,medicine.medical_specialty ,Pediatrics ,business.industry ,Cost effectiveness ,Follicular lymphoma ,Cancer ,Cost-effectiveness analysis ,medicine.disease ,Asymptomatic ,Surgery ,Oncology ,Quality of life ,Medicine ,Rituximab ,medicine.symptom ,business ,medicine.drug ,Decision analysis - Abstract
BACKGROUND A watch and wait (WW) strategy is the standard of care for patients with asymptomatic advanced-stage follicular lymphoma. Recent data have demonstrated an improvement in the time to progression with rituximab induction (RI) with or without rituximab maintenance (RM) in comparison with a WW strategy wait in such patients. It remains unclear whether this is a cost-effective strategy. METHODS A Markov decision analysis model was developed to compare the clinical outcomes, costs, and cost-effectiveness of RI (4 weekly doses) plus RM (12 doses every 2 months), RI (4 weekly doses), and a WW strategy for patients newly diagnosed with low-burden, asymptomatic advanced-stage follicular lymphoma over a lifetime horizon. Baseline probabilities and utilities were derived from a systematic review of published studies, and they were evaluated on a 6-month cycle. A Canadian public health payer's perspective was adopted, and costs were presented in 2012 Canadian dollars. RESULTS RI was the cheapest strategy. It was less costly at $59,953 versus $67,489 for the RM arm and $75,895 for the WW arm. It was also associated with a slightly lower quality-adjusted life expectancy at 6.16 quality-adjusted life years (QALYs) versus 6.28 QALYs for the RM strategy but was superior to WW (5.71 QALYs). In sensitivity analyses of key variables, this effectiveness was sensitive to the probability of first and second progression in the RI arm, and this indicated relatively neutral effectiveness between the 2 rituximab arms. CONCLUSIONS RI without maintenance for asymptomatic advanced-stage follicular lymphoma is the preferred strategy: it minimizes costs per patient over a lifetime horizon. Cancer 2015;121:2637–2645. © 2015 American Cancer Society.
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- 2015
221. Cost-effectiveness of prophylactic granulocyte colony-stimulating factor for febrile neutropenia in breast cancer patients receiving FEC-D
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Kelvin K. W. Chan, Maureen E. Trudeau, William Wong, and Esther K. Lee
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Oncology ,Canada ,Cancer Research ,medicine.medical_specialty ,Cost effectiveness ,Cost-Benefit Analysis ,Premedication ,Breast Neoplasms ,Docetaxel ,Filgrastim ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Intensive care medicine ,Cyclophosphamide ,health care economics and organizations ,Epirubicin ,Febrile Neutropenia ,business.industry ,Health Care Costs ,medicine.disease ,Quality-adjusted life year ,Chemotherapy, Adjuvant ,Female ,Taxoids ,Fluorouracil ,Quality-Adjusted Life Years ,business ,Febrile neutropenia ,Pegfilgrastim ,medicine.drug - Abstract
5-fluorouracil, epirubicin, cyclophosphamide → docetaxel (FEC-D) has been associated with higher-than-expected rates of febrile neutropenia (FN) that meet the current guideline threshold of 20 % for primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF). We examined the cost-effectiveness of FEC-D with varying strategies of G-CSF prophylaxis from the perspective of the public payer in Ontario, Canada. A state-transition model was developed to compare three strategies: FEC-D with secondary prophylaxis (SP) only, PP starting with the first cycle of D, and PP starting with the first cycle of FEC. Analysis was conducted for a hypothetical cohort of 50-year-old early-stage breast cancer patients undergoing adjuvant chemotherapy, at a 10-year horizon. Results were expressed in quality-adjusted life-years (QALYs) and 2013 Canadian dollars. Costs and benefits were discounted at 5 %. Event rates, costs, and utilities were derived from the literature. One-way and probabilistic sensitivity analyses were conducted. Using filgrastim, the incremental cost-effectiveness ratios (ICERs) for starting PP with the first cycle of D and starting PP with the first cycle of FEC, compared to using SP only, were $57,886/QALY and $116,186/QALY, respectively. With pegfilgrastim, the ICERs for the same strategies were $90,735/QALY and $149,483/QALY. Compared to using filgrastim SP only, starting PP with D had a 24 % chance of being cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY, and a 99 % chance at a WTP threshold of $100,000/QALY. Results were sensitive to FN-related parameters, such as the risk of FN per cycle with D and the associated mortality, but were robust to uncertainty in parameters related to breast cancer, such as the utilities and hazard of relapse. FEC-D with PP starting with the first cycle of D is most likely to be cost-effective, especially with increased risk of FN and mortality from FN.
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- 2015
222. Strategies of Sequential Therapies in Unresectable Metastatic Colorectal Cancer: A Meta-Analysis
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Kelvin K. W. Chan, Natalie G. Coburn, Roxanne Cosby, Scott R. Berry, M. Rother, and Timothy R. Asmis
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Oncology ,medicine.medical_specialty ,chemotherapy strategies ,Colorectal cancer ,medicine.medical_treatment ,systematic reviews ,Review Article ,Neutropenia ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Chemotherapy ,Metastatic colorectal cancer ,business.industry ,Hazard ratio ,palliative treatment ,Combination chemotherapy ,medicine.disease ,digestive system diseases ,Surgery ,Regimen ,meta-analyses ,business ,Febrile neutropenia - Abstract
Before the emergence of first-line combination chemotherapy, the standard of care for unresectable metastatic colorectal cancer (mcrc) was first-line monotherapy with modulated 5-fluorouracil. Several large phase iii randomized controlled trials, now completed, have assessed whether a planned sequential chemotherapy strategy&mdash, beginning with fluoropyrimidine monotherapy until treatment failure, followed by another regimen (either monotherapy or combination chemotherapy) until treatment failure&mdash, could result in the same survival benefit produced with an upfront combination chemotherapy strategy, but with less toxicity for patients. The medline and embase databases, and abstracts from meetings of the American Society for Clinical Oncology and the European Society for Medical Oncology, were searched for reports comparing a sequential strategy of chemotherapy with an upfront combination chemotherapy in adult patients with mcrc. Publications that reported efficacy or toxicity data (or both) were included. The five eligible trials that were identified included 4532 patients. A meta-analysis of those trials demonstrates a statistically significant survival advantage for combination chemotherapy (hazard ratio: 0.92, 95% confidence interval: 0.86 to 0.99). However, the median survival advantage (3&ndash, 6 weeks in most trials) is small and of questionable clinical significance. Three trials reported first-line toxicities. Upfront combination chemotherapy results in significantly more neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, nausea, vomiting, and sensory neuropathy. Sequential chemotherapy results in significantly more hand&ndash, foot syndrome. Given the small survival advantage associated with upfront combination chemotherapy, planned sequential chemotherapy and upfront combination chemotherapy can both be considered treatment strategies. Treatment should be chosen on an individual basis considering patient and tumour characteristics, toxicity of each strategy, and patient preference.
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- 2014
223. Cost-effectiveness analysis of staging strategies in patients with regionally metastatic melanoma
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Teresa M. Petrella, Nicole J. Look Hong, and Kelvin K. W. Chan
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Cost effectiveness ,Radiography ,Physical examination ,General Medicine ,Cost-effectiveness analysis ,Regimen ,Oncology ,Positron emission tomography ,Medical imaging ,Medicine ,Surgery ,Radiology ,Medical diagnosis ,business ,Nuclear medicine ,health care economics and organizations - Abstract
Purpose Variability exists regarding optimal staging for node-positive melanoma. Options include combinations of physical examination (PE), radiography, computed tomography (CT), and positron emission tomography (PET). Cost-effectiveness of regimens has never been investigated. Methods A modeled cost-effectiveness analysis was performed to examine the cost per surgery performed and per accurate diagnosis achieved with three staging regimens (PE/chest radiography, CT, PET/CT) for node-positive melanoma. Incremental cost-effectiveness ratios were used to compare regimens. Deterministic and probabilistic sensitivity analyses were undertaken to address variation in parameters. Costs are direct from the perspective of the Canadian single-payer system and 2012 valuations. Results Staging with PE/radiography is the least cost-effective option, resulting in greater costs than CT alone, and fewer accurate diagnoses. Compared to CT alone, PET/CT incurs greater incremental cost ($902.81CAD), but results in 4% fewer lymphadenectomies and 4% more accurate diagnoses. PET/CT costs $22,570.25CAD for each additional accurate diagnosis achieved compared to CT alone. Sensitivity analyses demonstrate that the optimal staging strategy is influenced by diagnostic test characteristics and the willingness-to-pay threshold, but robust to other varied parameters. Conclusions PE/radiography appears to be the least cost-effective staging regimen. The benefit of PET/CT over CT alone depends on a health system's priorities and willingness-to-pay. J. Surg. Oncol. 2015 111:423–430. © 2014 Wiley Periodicals, Inc.
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- 2014
224. Impact of the pan-Canadian Oncology Drug Review on provincial concordance with respect to cancer drug funding decisions and time to funding
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Kelvin K. W. Chan, A. Srikanthan, Eitan Amir, Helen Mai, N. Penner, M. Sabharwal, and A. Laupacis
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Data collection ,Notice ,business.industry ,Concordance ,Cancer drugs ,drug funding ,03 medical and health sciences ,0302 clinical medicine ,Cohen's kappa ,030220 oncology & carcinogenesis ,Oncology drug ,Drug product ,Medicine ,Original Article ,030212 general & internal medicine ,Formulary ,time to drug funding ,business ,Demography - Abstract
The pan-Canadian Oncology Drug Review (pcodr) was implemented in 2011 to address uneven drug coverage and lack of transparency with respect to the various provincial cancer drug review processes in Canada. We evaluated the impact of the pcodr on provincial decision concordance and time from Notice of Compliance (noc) to drug funding. In a retrospective review, Health Canada&rsquo, s Drug Product Database was used to identify new indications for cancer drugs between January 2003 and May 2014, and provincial formulary listings for drug-funding dates and decisions between 1 January 2003 and 31 December 2014 were retrieved. Multiple linear models and quantile regressions were used to evaluate changes in time to decision-making before and after the implementation of the pcodr. Agreement of decisions between provinces was evaluated using kappa statistics. Data were available from 9 provinces (all Canadian provinces except Quebec), identifying 88 indications that represented 51 unique cancer drugs. Two provinces lacked available data for all 88 indications at the time of data collection. Interprovincial concordance in drug funding decisions significantly increased after the pcodr&rsquo, s implementation (Brennan-Prediger coefficient: 0.54 pre-pcodr vs. 0.78 post-pcodr, p = 0.002). Nationwide, the median number of days from Health Canada&rsquo, s noc date to the date of funding significantly declined (to 393 days from 522 days, p < 0.001). Exploratory analyses excluding provinces with incomplete data did not change the results. After the implementation of the pcodr, greater concordance in cancer drug funding decisions between provinces and decreased time to funding decisions were observed.
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- 2017
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225. Economic evaluation of smoking cessation in Ontario's regional cancer programs
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Wanrudee Isaranuwatchai, Alice Peter, Linda Rabeneck, Rebecca Truscott, William Howard Evans, Lisa Masucci, E. Cameron, S. Djalalov, Kelvin K. W. Chan, Jeffrey S Hoch, and Nicole Mittmann
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Male ,Cancer Research ,Time Factors ,Referral ,Cost effectiveness ,Best practice ,medicine.medical_treatment ,Cost-Benefit Analysis ,Oncology and Carcinogenesis ,Disease ,and over ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Theoretical ,Regional cancer ,Models ,Neoplasms ,Cost‐effectiveness ,medicine ,80 and over ,Humans ,Radiology, Nuclear Medicine and imaging ,Public Health Surveillance ,030212 general & internal medicine ,Aged ,Aged, 80 and over ,Ontario ,business.industry ,030503 health policy & services ,Hazard ratio ,Middle Aged ,Models, Theoretical ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,smoking cessation ,Oncology ,Economic evaluation ,oncology ,Costs and Cost Analysis ,Smoking cessation ,Cost-effectiveness ,Female ,Smoking Cessation ,Biochemistry and Cell Biology ,0305 other medical science ,business ,Demography - Abstract
Quitting smoking after a diagnosis of cancer results in greater response to treatment and decreased risk of disease recurrence and second primary cancers. The objective of this study was to evaluate the potential cost‐effectiveness of two smoking cessation approaches: the current basic smoking cessation program consisting of screening for tobacco use, advice, and referral; and a best practice smoking cessation program that includes the current basic program with the addition of pharmacological therapy, counseling, and follow‐up. A Markov model was constructed that followed 65‐year‐old smokers with cancer over a lifetime horizon. Transition probabilities and mortality estimates were obtained from the published literature. Costs were obtained from standard costing sources in Ontario and reports. Probabilistic and deterministic sensitivity analyses were conducted to address parameter uncertainties. For smokers with cancer, the best practice smoking cessation program was more effective and more costly than the basic smoking cessation program. The incremental cost‐effectiveness ratio of the best practice smoking cessation program compared to the basic smoking cessation program was $3367 per QALY gained and $5050 per LY gained for males, and $2050 per QALY gained and $4100 per LY gained for females. Results were most sensitive to the hazard ratio of mortality for former and current smokers, the probability of quitting smoking through participation in the program and smoking‐attributable costs. The study results suggested that a best practice smoking cessation program could be a cost‐effective option. These findings can support and guide implementation of smoking cessation programs.
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- 2017
226. Temporal changes in treatments and outcomes after acute myocardial infarction among cancer survivors and patients without cancer, 1995 to 2013
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Inna Y, Gong, Andrew T, Yan, Dennis T, Ko, Craig C, Earle, Winson Y, Cheung, Stuart, Peacock, Marlous, Hall, Chris P, Gale, and Kelvin K W, Chan
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Male ,Time Factors ,Adrenergic beta-Antagonists ,Myocardial Infarction ,Angiotensin-Converting Enzyme Inhibitors ,Cardiovascular Agents ,Middle Aged ,Survival Rate ,Treatment Outcome ,Cancer Survivors ,Case-Control Studies ,Neoplasms ,Acute Disease ,Humans ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Aged ,Follow-Up Studies - Abstract
There is a paucity of information about treatment and mortality trends after acute myocardial infarction (AMI) for cancer survivors (CS).In this population-based study, the authors compared temporal trends of treatments and outcomes (mortality, nonfatal cardiovascular outcomes), among CS and patients without cancer (the noncancer patient [NCP] group) with AMI in Ontario (Canada) using inverse probability treatment weight (IPTW)-adjusted modeling.Of 270,089 patients with AMI (22,907 CS, 247,182 NCP, 1995-2013; median follow-up, 10.1 and 11.0 years, respectively), the use of invasive coronary strategies and pharmacotherapies increased and mortality declined for CS and NCP (all PAmong CS and NCP with AMI in Ontario, similar improvements in mortality and receipt of treatments were observed between 1995 and 2013. However, compared with NCP, CS had a higher risk of mortality and heart failure. Cancer 2018;124:1269-78. © 2017 American Cancer Society.
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- 2017
227. Neoadjuvant treatments for locally advanced, resectable esophageal cancer: A network meta-analysis
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Kelvin K W, Chan, Ronak, Saluja, Keemo, Delos Santos, Kelly, Lien, Keya, Shah, Gemma, Cramarossa, Xiaofu, Zhu, and Rebecca K S, Wong
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Treatment Outcome ,Esophageal Neoplasms ,Chemotherapy, Adjuvant ,Network Meta-Analysis ,Humans ,Radiotherapy, Adjuvant ,Chemoradiotherapy ,Combined Modality Therapy ,Survival Analysis ,Neoadjuvant Therapy ,Randomized Controlled Trials as Topic - Abstract
The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy only, radiotherapy only or chemoradiotherapy) for esophageal cancer patients are not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, a Bayesian network meta-analysis was performed. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for publications up to May 2016. ASCO and ASTRO annual meeting abstracts were also searched up to the 2015 conferences. Randomized controlled trials that compared at least two of the following treatments for resectable esophageal cancer were included: surgery alone, surgery preceded by neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy. The primary outcome assessed from the trials was overall survival. Thirty-one randomized controlled trials involving 5496 patients were included in the quantitative analysis. The network meta-analysis showed that neoadjuvant chemoradiotherapy improved overall survival when compared to all other treatments including surgery alone (HR 0.75, 95% CR 0.67-0.85), neoadjuvant chemotherapy (HR 0.83. 95% CR 0.70-0.96) and neoadjuvant radiotherapy (HR 0.82, 95% CR 0.67-0.99). However, the risk of postoperative mortality increased when comparing neoadjuvant chemoradiotherapy to either surgery alone (RR 1.46, 95% CR 1.00-2.14) or to neoadjuvant chemotherapy (RR 1.58, 95% CR 1.00-2.49). In conclusion, neoadjuvant chemoradiotherapy improves overall survival but may also increase the risk of postoperative mortality in patients locally advanced resectable esophageal carcinoma.
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- 2017
228. Do patients with reduced or excellent performance status derive the same clinical benefit from novel systemic cancer therapies? A systematic review and meta-analysis
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Mahin Qureshi, Kelvin K. W. Chan, Sierra Cheng, Adam E. Haynes, and Eleanor Pullenayegum
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Oncology ,Drug ,Cancer Research ,medicine.medical_specialty ,media_common.quotation_subject ,medicine.medical_treatment ,chemotherapy ,Systemic therapy ,Targeted therapy ,systemic therapy ,03 medical and health sciences ,0302 clinical medicine ,systematic review ,Internal medicine ,medicine ,030212 general & internal medicine ,media_common ,Original Research ,Chemotherapy ,Performance status ,business.industry ,Cancer ,medicine.disease ,targeted therapy ,Clinical trial ,meta-analysis ,030220 oncology & carcinogenesis ,Meta-analysis ,business ,Biomedical engineering - Abstract
Background Whether patients with excellent and reduced performance status (PS) derive different net clinical benefit from novel anticancer systemic therapies on clinical trials is unclear. Materials and methods A systematic review was conducted of randomised controlled trials (RCTs) cited for drug approvals between 2006 and August 2015 by the Food and Drug Administration, the European Medicines Agency and Health Canada. Included studies had overall survival (OS) and/or progression-free survival (PFS) primary endpoints. Meta-analyses of OS/PFS based on PS dichotomised into excellent and reduced subgroups were performed using random effects. Results The systematic review identified 110 RCTs, with none reporting PS subgroup analyses for toxicity and 66 (60%) for efficacy. For these 66 RCTs involving 44 511 patients, pooled HRs for excellent and reduced groups were 0.65 (95% CI 0.61 to 0.70) and 0.67 (95% CI 0.62 to 0.72), respectively, with no difference between the two groups (p=0.68). Sensitivity analyses based on drug or cancer type and type of endpoints (OS or PFS) demonstrated similar results. Conclusions No decrease in relative efficacy from novel systemic therapy was found for patients with reduced PS when compared with patients with excellent PS for the range which were included in modern RCTs. Reporting of PS subgroup analyses of toxicities and more inclusion of patients with borderline low PS in RCTs should be considered for a more comprehensive understanding of the net clinical benefits of contemporary systemic therapies in patients across the spectrum of different PS.
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- 2017
229. Targeted metabolomics in colorectal cancer: a strategic approach using standardized laboratory tests of the blood and urine
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Kevin Zbuk, Peter A. Kavsak, Katarzyna J. Jerzak, Marissa Laureano, Radwa Elsharawi, Sukhbinder Dhesy-Thind, and Kelvin K. W. Chan
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0301 basic medicine ,medicine.medical_specialty ,Colorectal cancer ,Anion gap ,venous CO2 ,colorectal cancer ,Urine ,Pharmacology ,Gastroenterology ,03 medical and health sciences ,Internal medicine ,medicine ,Hypoxia ,Original Research ,business.industry ,hypoxia ,Cancer ,Venous blood ,medicine.disease ,metabolomics ,digestive system diseases ,030104 developmental biology ,Concomitant ,Biomarker (medicine) ,biomarker ,business ,Anaerobic exercise ,metabolism - Abstract
Katarzyna J Jerzak,1,2 Marissa Laureano,3 Radwa Elsharawi,4 Peter Kavsak,5 Kelvin KW Chan,2,6 Sukhbinder K Dhesy-Thind,7 Kevin Zbuk7 1Department of Medicine, University of Toronto, Toronto, Ontario, 2Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, 3Department of Medicine, McMaster University, Hamilton, Ontario, 4Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, 5Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, 6Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, 7Department of Oncology, McMaster University, Hamilton, Ontario, Canada Background: Glycolytic markers have been detected in colorectal cancer (CRC) using advanced analytical methods. Methods: Using commercially available assays, by-products of anaerobic metabolism were prospectively measured in the blood and urine of 20 patients with metastatic colorectal cancer (mCRC) and 20 patients with local disease. Twenty-four-hour urine citrate, plasma lactate, ketones, venous blood gas, anion gap, and osmolar gap were investigated. Results of patients with metastatic and local CRC were compared using two-sample t-tests or equivalent nonparametric tests. In addition, plasma total CO2 concentrations in our local hospital (5,931 inpatients and 1,783 outpatients) were compared retrospectively with those in our dedicated cancer center (1,825 outpatients) over 1 year. Results: The average venous pCO2 was higher in patients with mCRC (50.2 mmHg; standard deviation [SD]=9.36) compared with those with local disease (42.8 mmHg; SD=8.98), p=0.045. Calculated serum osmolarity was higher in mCRC and attributed to concomitant sodium and urea elevations. In our retrospective analysis, plasma total CO2 concentrations (median=27 mmol/L) were higher in cancer patients compared to both hospital inpatients (median=23 mmol/L) and outpatients (median=24 mmol/L), p
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- 2017
230. Pretreatment neurocognitive function and self-reported symptoms in patients with newly diagnosed head and neck cancer compared with noncancer cohort
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Kattleya Tirona, Albiruni Ryan Abdul Razak, Lori J. Bernstein, Lillian L. Siu, Kelvin K. W. Chan, John Kim, Gregory R. Pond, Eric X. Chen, Hui K Gan, and Andrew Hope
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Adult ,Male ,medicine.medical_specialty ,Disease ,Anxiety ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,medicine ,Humans ,Cognitive Dysfunction ,Fatigue ,Aged ,medicine.diagnostic_test ,business.industry ,Head and neck cancer ,Cancer ,Neuropsychological test ,Middle Aged ,medicine.disease ,3. Good health ,Otorhinolaryngology ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Case-Control Studies ,Cohort ,Female ,Self Report ,medicine.symptom ,Symptom Assessment ,business ,Neurocognitive ,030217 neurology & neurosurgery - Abstract
BACKGROUND Newly diagnosed patients with head and neck cancer may be at risk for impaired neurocognitive function (NCF) due to disease, treatment, and lifestyle factors. METHODS Eighty pretreatment patients with head and neck cancer and 40 control patients without cancer completed assessment of NCF and self-reported cognition, fatigue, and mood. Blood samples to evaluate organ reserves, hormones, and cytokines were collected. RESULTS Patients experienced worse symptoms of cognitive dysfunction, fatigue, and anxiety than controls. In contrast, NCF was equivalent for patients and controls. Using published norms as comparison, groups had similar high rates of impairment in performance (9/80 patients and 3/40 controls scored in the abnormal range). CONCLUSION Pretreatment patients with head and neck cancer reported cognitive disturbance. The frequency of impaired performance, albeit high, was consistent with the literature demonstrating false-positive "abnormal" neuropsychological test performance is not uncommon. Inclusion of a noncancer patient control cohort is essential because using solely normative data as a comparison may foster erroneous interpretation.
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- 2017
231. Longitudinal assessment of right ventricular structure and function by cardiovascular magnetic resonance in breast cancer patients treated with trastuzumab: a prospective observational study
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Kim A. Connelly, Rashida Haq, Christine Brezden-Masley, Gauri R. Karur, Vinita Dhir, Anish Kirpalani, Joseph Barfett, Djeven P. Deva, Andrew T. Yan, Ashita Barthur, Laura Jimenez-Juan, and Kelvin K. W. Chan
- Subjects
lcsh:Diseases of the circulatory (Cardiovascular) system ,Time Factors ,Ventricular Dysfunction, Right ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,030218 nuclear medicine & medical imaging ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Medicine ,Single-Blind Method ,Longitudinal Studies ,Prospective Studies ,Prospective cohort study ,Ontario ,Ejection fraction ,Radiological and Ultrasound Technology ,Stroke volume ,Middle Aged ,3. Good health ,Treatment Outcome ,medicine.anatomical_structure ,Predictive value of tests ,Cardiology ,Right ventricle ,Female ,Cardiology and Cardiovascular Medicine ,Adult ,medicine.medical_specialty ,Heart Ventricles ,Magnetic Resonance Imaging, Cine ,Breast Neoplasms ,03 medical and health sciences ,Breast cancer ,Predictive Value of Tests ,Internal medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Angiology ,Analysis of Variance ,Cardiotoxicity ,business.industry ,Research ,Stroke Volume ,Recovery of Function ,Trastuzumab ,medicine.disease ,Early Diagnosis ,lcsh:RC666-701 ,Ventricle ,Linear Models ,Ventricular Function, Right ,Cardiovascular magnetic resonance ,business - Abstract
Background There are limited data on the effects of trastuzumab on the right ventricle (RV). Therefore, we sought to evaluate the temporal changes in right ventricular (RV) structure and function as measured by cardiovascular magnetic resonance (CMR), and their relationship with left ventricular (LV) structure and function in breast cancer patients treated with trastuzumab. Methods Prospective, longitudinal, observational study involving 41 women with HER2+ breast cancer who underwent serial CMR at baseline, 6, 12, and 18 months after initiation of trastuzumab. A single blinded observer measured RV parameters on de-identified CMRs in a random order. Linear mixed models were used to investigate temporal changes in RV parameters. Results Of the 41 women (age 52 ± 11 years), only one patient experienced trastuzumab-induced cardiotoxicity. Compared to baseline, there were small but significant increases in the RV end-diastolic volume at 6 months (p = 0.002) and RV end-systolic volume at 6 and 12 months (p
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- 2017
232. Impact of a New Palliative Care Program on Health System Finances: An Analysis of the Palliative Care Program Inpatient Unit and Consultations at Johns Hopkins Medical Institutions
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Michael A Cardamone, Sarina R. Isenberg, John P McQuade, Chunhua Lu, Natasha Gill, Kelvin K. W. Chan, Rab Razzak, Terry Langbaum, Deirdre Torto, and Thomas J. Smith
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Program evaluation ,medicine.medical_specialty ,Palliative care ,Oncology (nursing) ,Financial impact ,business.industry ,Health Policy ,Hospital unit ,Original Contributions ,MEDLINE ,Variable cost ,Unit (housing) ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Family medicine ,Usual care ,Medicine ,030212 general & internal medicine ,business - Abstract
Purpose: Palliative care inpatient units (PCUs) can improve symptoms, family perception of care, and lower per-diem costs compared with usual care. In March 2013, Johns Hopkins Medical Institutions (JHMI) added a PCU to the palliative care (PC) program. We studied the financial impact of the PC program on JHMI from March 2013 to March 2014. Methods: This study considered three components of the PC program: PCU, PC consultations, and professional fees. Using 13 months of admissions data, the team calculated the per-day variable cost pre-PCU (ie, in another hospital unit) and after transfer to the PCU. These fees were multiplied by the number of patients transferred to the PCU and by the average length of stay in the PCU. Consultation savings were estimated using established methods. Professional fees assumed a collection rate of 50%. Results: The total positive financial impact of the PC program was $3,488,863.17. There were 153 transfers to the PCU, 60% with cancer, and an average length of stay of 5.11 days. The daily loss pretransfer to the PCU of $1,797.67 was reduced to $1,345.34 in the PCU (−25%). The PCU saved JHMI $353,645.17 in variable costs, or $452.33 per transfer. Cost savings for PC consultations in the hospital, 60% with cancer, were estimated at $2,765,218. $370,000 was collected in professional fees savings. Conclusion: The PCU and PC program had a favorable impact on JHMI while providing expert patient-centered care. As JHMI moves to an accountable care organization model, value-based patient-centered care and increased intensive care unit availability are desirable.
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- 2017
233. A network meta-analysis of the sequencing and types of systemic therapies with definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)☆
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Justin Lee, Kelvin K. W. Chan, Katarzyna J. Jerzak, Kelly Lien, Keemo Delos Santos, and Ronak Saluja
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Network Meta-Analysis ,Locally advanced ,MEDLINE ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Chemotherapy ,Taxane ,business.industry ,Squamous Cell Carcinoma of Head and Neck ,Chemoradiotherapy ,Radiation therapy ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Meta-analysis ,Carcinoma, Squamous Cell ,Oral Surgery ,business ,Adjuvant - Abstract
Objectives The current standard therapy for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is platinum-based chemotherapy plus concurrent radiotherapy (CRT), but several systemic therapies have been evaluated. We performed a Bayesian network meta-analysis (NMA) with random effects to enable direct and indirect comparisons of all existing treatment modalities for LASCCHN simultaneously. Material and methods A systematic review was conducted using MEDLINE, EMBASE, ASCO abstracts, ASTRO abstracts and the Cochrane Central of Registered Trials using Cochrane methodology to identify randomized controlled trials (RCTs) up to June 2016. Only abstracts that involved the same definitive radiotherapy in the arms for the RCT were included. Results Sixty-five RCTs involving 13,574 patients and 16 different treatment strategies were identified. Chemotherapy plus concurrent radiation (CRT) was superior to RT with a HR of 0.74 (95%CR 0.69–0.79) for OS in the NMA. Only 3 trials compared RT alone to concurrent therapy with an EGFR antibody (ERT), demonstrating a superior OS (HR 0.75, 95% CR 0.60–0.94), but this difference was not statistically significant when interpreted in a NMA (HR 0.84, 95%CR 0.65–1.08). ERT was not superior to CRT (HR 1.19, 95%CR 0.93–1.54), and the addition of neo-adjuvant taxane-based chemotherapy to CRT was not beneficial (HR 0.86, 95% CR 0.70–1.07). Conclusion The addition of either adjuvant or neoadjuvant chemotherapy to the CRT backbone does not confer an OS benefit in the treatment of LASCCHN. Similarly, ERT does not confer an OS benefit for patients who are eligible for CRT.
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- 2017
234. Cost-effectiveness analysis of treatment with non-curative or palliative intent for hepatocellular carcinoma in the real-world setting
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Eric M. Yoshida, Kelvin K. W. Chan, Yao Qiao, Gonzalo Sapisochin, Craig C. Earle, Ahmad Zaheen, Nathaniel Jembere, and Hla-Hla Thein
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Male ,Oncology ,Palliative care ,Economics ,Cost-Benefit Analysis ,Cancer Treatment ,Social Sciences ,lcsh:Medicine ,Kaplan-Meier Estimate ,0302 clinical medicine ,Medicine and Health Sciences ,lcsh:Science ,health care economics and organizations ,Aged, 80 and over ,Multidisciplinary ,Pharmaceutics ,Liver Diseases ,Liver Neoplasms ,Palliative Care ,HIV diagnosis and management ,Cost-effectiveness analysis ,Middle Aged ,Sorafenib ,Combined Modality Therapy ,Treatment Outcome ,Cirrhosis ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Female ,030211 gastroenterology & hepatology ,Research Article ,medicine.drug ,Niacinamide ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cost-Effectiveness Analysis ,Gastroenterology and Hepatology ,Carcinomas ,03 medical and health sciences ,Drug Therapy ,Diagnostic Medicine ,Internal medicine ,Gastrointestinal Tumors ,Cancer Detection and Diagnosis ,medicine ,Carcinoma ,Humans ,Chemotherapy ,Chemoembolization, Therapeutic ,neoplasms ,Aged ,Neoplasm Staging ,business.industry ,Phenylurea Compounds ,lcsh:R ,Cancers and Neoplasms ,Hepatocellular Carcinoma ,medicine.disease ,Comorbidity ,Economic Analysis ,digestive system diseases ,Health Care ,Propensity score matching ,lcsh:Q ,business - Abstract
Hepatocellular carcinoma (HCC) presentation is heterogeneous necessitating a variety of therapeutic interventions with varying efficacies and associated prognoses. Poor prognostic patients often undergo non-curative palliative interventions including transarterial chemoembolization (TACE), sorafenib, chemotherapy, or purely supportive care. The decision to pursue one of many palliative interventions for HCC is complex and an economic evaluation comparing these interventions has not been done. This study evaluates the cost-effectiveness of non-curative palliative treatment strategies such as TACE alone or TACE+sorafenib, sorafenib alone, and non-sorafenib chemotherapy compared with no treatment or best supportive care (BSC) among patients diagnosed with HCC between 2007 and 2010 in a Canadian setting. Using person-level data, we estimated effectiveness in life years and quality-adjusted life years (QALYs) along with total health care costs (2013 US dollars) from the health care payer’s perspective (3% annual discount). A net benefit regression approach accounting for baseline covariates with propensity score adjustment was used to calculate incremental net benefit to generate incremental cost-effectiveness ratio (ICER) and uncertainty measures. Among 1,172 identified patients diagnosed with HCC, 4.5%, 7.9%, and 5.6%, received TACE alone or TACE+sorafenib, sorafenib, and non-sorafenib chemotherapy clone, respectively. Compared with no treatment or BSC (81.9%), ICER estimates for TACE alone or TACE+sorafenib was $6,665/QALY (additional QALY: 0.47, additional cost: $3,120; 95% CI: -$18,800-$34,500/QALY). The cost-effectiveness acceptability curve demonstrated that if the relevant threshold was $50,000/QALY, TACE alone or TACE+sorafenib, non-sorafenib chemotherapy, and sorafenib alone, would have a cost-effectiveness probability of 99.7%, 46.6%, and 5.5%, respectively. Covariates associated with the incremental net benefit of treatments are age, sex, comorbidity, and cancer stage. Findings suggest that TACE with or without sorafenib is currently the most cost-effective active non-curative palliative treatment approach to HCC. Further research into new combination treatment strategies that afford the best tumor response is needed.
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- 2017
235. Phase 1 study of nab-paclitaxel, cisplatin and 5-fluorouracil as induction chemotherapy followed by concurrent chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the oropharynx
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Andrew Bayley, Nancy Read, L.L. Siu, Kelvin K. W. Chan, Soo Chin, Eric X. Chen, I. Diaz-Padilla, Eric Winquist, John Waldron, Albiruni Ryan Abdul Razak, Andrew Hope, Lisa Wang, John Kim, David A. Palma, M. Hossain, and Herbert H. Loong
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Paclitaxel ,medicine.medical_treatment ,chemistry.chemical_compound ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Humans ,Aged ,Cisplatin ,Squamous Cell Carcinoma of Head and Neck ,business.industry ,Induction chemotherapy ,Chemoradiotherapy ,Induction Chemotherapy ,Middle Aged ,Carboplatin ,Radiation therapy ,Oropharyngeal Neoplasms ,chemistry ,Docetaxel ,Head and Neck Neoplasms ,Fluorouracil ,Carcinoma, Squamous Cell ,Female ,business ,medicine.drug - Abstract
Induction chemotherapy followed by concurrent chemoradiation (CRT) (sequential therapy) has been evaluated in the treatment of locoregionally-advanced squamous cell cancer of the head and neck (LA-SCCHN), with docetaxel, cisplatin (P) and 5-flurouracil (F) shown to be superior to PF doublet. Nab-paclitaxel (A) is a novel albumin-bound paclitaxel with a superior therapeutic index to docetaxel.A phase I trial [Clinical trials.gov identifier NCT00731380] to assess the safety and efficacy of nab-paclitaxel+cisplatin+5-fluorouracil (APF) as induction chemotherapy for three cycles, followed by concurrent carboplatin (area-under-curve (AUC) 1.5 weekly) with radiation therapy (RT) (70 Gy/35 fractions), was conducted using a 3+3 design in patients with previously untreated LA-SCCHN. Dose-limiting toxicities (DLTs) included: standard haematologic and non-haematologic toxicities, treatment delays, inability to complete ⩾95% of RT and skin/mucosal toxicity related to RT assessed from day 1 of treatment to 8 weeks after completion of CRT.17 patients with oropharyngeal cancer were enrolled in three dose levels, with 15 patients evaluable for DLT. The median age was 54 years (range, 44-65 years), 14 patients were male, and 11 patients' tumours were p16 positive and four negative. Grade 3/4 adverse events during APF (%total number of cycles) were hyponatraemia (14%) neutropenia (10%), lymphopaenia (4%) and thrombocytopenia (2%) during 49 evaluable APF cycles. Febrile neutropenia occurred during one cycle of treatment.The recommended phase 2 dose of APF is nab-paclitaxel 100mg/m(2) days 1 and 8, cisplatin 75 mg/mg(2) day 1 and 5-fluorouracil 1000 mg/m(2)/day×96 h days 1-4, every 3 weeks, for three cycles prior to CRT.
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- 2014
236. Mesa
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Fan Yang, Andrey Gubarev, David Jones, Masood Siddiqi, Jamie Cameron, Sandeep Govind Dhoot, Ankur Agiwal, Abhilash Rajesh Kumar, Sanjay Bhansali, Jason Govig, Mingsheng Hong, Divyakant Agrawal, Kevin Lai, Kelvin K. W. Chan, Shivakumar Venkataraman, Jeff Shute, Shuo Wu, Adam Kirsch, and Ashish Gupta
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Database ,Computer science ,Reliability (computer networking) ,General Engineering ,Petabyte ,Fault tolerance ,computer.software_genre ,Data warehouse ,Mesa ,High availability ,Scalability ,computer ,Row ,computer.programming_language - Abstract
Mesa is a highly scalable analytic data warehousing system that stores critical measurement data related to Google's Internet advertising business. Mesa is designed to satisfy a complex and challenging set of user and systems requirements, including near real-time data ingestion and queryability, as well as high availability, reliability, fault tolerance, and scalability for large data and query volumes. Specifically, Mesa handles petabytes of data, processes millions of row updates per second, and serves billions of queries that fetch trillions of rows per day. Mesa is geo-replicated across multiple datacenters and provides consistent and repeatable query answers at low latency, even when an entire datacenter fails. This paper presents the Mesa system and reports the performance and scale that it achieves.
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- 2014
237. A systematic literature analysis of correlative studies in low-dose metronomic chemotherapy trials
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Esther K. Lee, Urban Emmenegger, Gemma Cramarossa, Soley Georgsdottir, Lavarnan Sivanathan, Kelvin K. W. Chan, Kelly Lien, and Keemo Delos Santos
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Oncology ,medicine.medical_specialty ,Chemotherapy ,End point ,Maximum Tolerated Dose ,business.industry ,MEDLINE ,medicine.medical_treatment ,Biochemistry (medical) ,Clinical Biochemistry ,Low dose ,Cancer ,Pharmacology ,medicine.disease ,Biomarkers, Pharmacological ,Low dose metronomic ,Internal medicine ,Maximum tolerated dose ,Administration, Metronomic ,Drug Discovery ,medicine ,Humans ,Biomarker (medicine) ,business - Abstract
Low-dose metronomic (LDM) chemotherapy is a beneficial and very well-tolerated form of chemotherapy utilization characterized by the frequent and uninterrupted administration of low doses of conventional chemotherapeutic agents over prolonged periods of time. While patients resistant to standard maximum tolerated dose (MTD) chemotherapy may still benefit from LDM chemotherapy, there is a lack of predictive markers of response to LDM chemotherapy. We searched the MEDLINE, EMBASE, CENTRAL and PubMed databases for correlative studies conducted as part of LDM chemotherapy trials in order to identify the most promising biomarker candidates. Given the antiangiogenic properties of LDM chemotherapy, angiogenesis-related biomarkers were most commonly studied. However, significant correlations between angiogenesis-related biomarkers and study end points were rare and variable, even so far as biomarkers correlating positively with an end point in some studies and negatively with the same end point in other studies. Pursuing biomarkers outside the angiogenesis field may be more promising.
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- 2014
238. Genomic testing in cancer: Patient knowledge, attitudes, and expectations
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Phillip Blanchette, Steve Kang, Jack Holland, Larissa Potanina, Kelvin K. W. Chan, Suzanne Kamel-Reid, Albiruni R. Razak, Andrea Eisen, Philippe L. Bedard, Jessica P. Bytautas, Anna Spreafico, Fiona A. Miller, John Douglas Mcpherson, and Lillian L. Siu
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Cancer Research ,medicine.medical_specialty ,Pathology ,business.industry ,Genetic counseling ,Phases of clinical research ,Cancer ,Context (language use) ,medicine.disease ,Oncology ,Interquartile range ,Needle biopsy ,Family medicine ,Surgical biopsy ,medicine ,Personalized medicine ,business - Abstract
BACKGROUND Genomic testing in cancer (GTC) characterizes genes that play an important role in the development and growth of a patient's cancer. This form of DNA testing is currently being studied for its ability to guide cancer therapy. The objective of the current study was to describe patients' knowledge, attitudes, and expectations toward GTC. METHODS A 42-item self-administered GTC questionnaire was developed by a multidisciplinary group and patient pretesting. The questionnaire was distributed to patients with advanced cancer who were referred to the Princess Margaret Cancer Center for a phase 1 clinical trial or GTC testing. RESULTS Results were reported from 98 patients with advanced cancer, representing 66% of the patients surveyed. Seventy-six percent of patients were interested in learning more about GTC, and 64% reported that GTC would significantly improve their cancer care. The median score on a 12-item questionnaire to assess knowledge of cancer genomics was 8 of 12 items correct (67%; interquartile range, 7-9 of 12 items correct [58%-75%]). Scores were associated significantly with patients' education level (P
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- 2014
239. Outcomes of intensity-modulated radiotherapy versus conventional radiotherapy for hypopharyngeal cancer
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Ian J. Witterick, Laura A. Dawson, Brian O'Sullivan, John Waldron, Isabelle Gauthier, Jolie Ringash, Gary Mok, Kelvin K. W. Chan, Shao Hui Huang, B.C. John Cho, John Kim, Bernard Cummings, Andrew Bayley, Andrew Hope, and Haiyan Jiang
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Urology ,Distant relapse ,Hypopharyngeal cancer ,medicine.disease ,Enteral administration ,Surgery ,Radiation therapy ,stomatognathic diseases ,Conventional radiotherapy ,Otorhinolaryngology ,Larynx preservation ,Medicine ,Intensity modulated radiotherapy ,business ,Feeding tube - Abstract
Background The purpose of this study was to discuss if the adoption of intensity-modulated radiotherapy (IMRT) for hypopharyngeal squamous cell carcinoma (SCC) has improved the outcome. Methods We compared 3-dimensional (3D) radiotherapy (RT) and IMRT in all patients with hypopharyngeal SCC treated with curative intent RT or chemoradiation therapy (CRT) from January 1, 2000, to February 28, 2010. Locoregional control, overall survival (OS), distant relapse rate, larynx preservation rate, and enteral feeding tube duration were analyzed. Results Of 181 consecutive patients, 90 received 3D-RT and 91 received IMRT. At 3 years, the IMRT group had higher locoregional control compared with the 3D-RT group (75% vs 58%; p = .003), but similar OS (50% vs 52%; p = .99), distant relapse rate (23% vs 20%; p = .79), and larynx-preservation rate (90% vs 86%; p = .16). The 2-year enteral feeding tube dependency rate was similar in both groups (19% vs 18%; p = .12). Conclusion Patients with hypopharyngeal SCC treated with IMRT showed a higher locoregional control compared with 3D-RT. However, distant-relapse rate and OS remain comparable between treatment techniques. © 2014 Wiley Periodicals, Inc. Head Neck 37: 655–661, 2015
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- 2014
240. The impact of cancer drug wastage on economic evaluations
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Judy, Truong, Matthew C, Cheung, Helen, Mai, Jessa, Letargo, Alexandra, Chambers, Mona, Sabharwal, Maureen E, Trudeau, and Kelvin K W, Chan
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Canada ,Models, Economic ,Cost-Benefit Analysis ,Neoplasms ,Humans ,Antineoplastic Agents ,Infusions, Intravenous ,Drug Costs ,Prescription Drug Misuse - Abstract
The objective of this study was to determine the impact of modeling cancer drug wastage in economic evaluations because wastage can result from single-dose vials on account of body surface area- or weight-based dosing.Intravenous chemotherapy drugs were identified from the pan-Canadian Oncology Drug Review (pCODR) program as of January 2015. Economic evaluations performed by drug manufacturers and pCODR were reviewed. Cost-effectiveness analyses and budget impact analyses were conducted for no-wastage and maximum-wastage scenarios (ie, the entire unused portion of the vial was discarded at each infusion). Sensitivity analyses were performed for a range of body surface areas and weights.Twelve drugs used for 17 indications were analyzed. Wastage was reported (ie, assumptions were explicit) in 71% of the models and was incorporated into 53% by manufacturers; this resulted in a mean incremental cost-effectiveness ratio increase of 6.1% (range, 1.3%-14.6%). pCODR reported and incorporated wastage for 59% of the models, and this resulted in a mean incremental cost-effectiveness ratio increase of 15.0% (range, 2.6%-48.2%). In the maximum-wastage scenario, there was a mean increase in the incremental cost-effectiveness ratio of 24.0% (range, 0.0%-97.2%), a mean increase in the 3-year total incremental budget costs of 26.0% (range, 0.0%-83.1%), and an increase in the 3-year total incremental drug budget cost of approximately CaD $102 million nationally. Changing the mean body surface area or body weight caused 45% of the drugs to have a change in the vial size and/or quantity, and this resulted in increased drug costs.Cancer drug wastage can increase drug costs but is not uniformly modeled in economic evaluations. Cancer 2017;123:3583-90. © 2017 American Cancer Society.
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- 2016
241. The right amount of chemotherapy in non-curable disease:insights from health economics
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Charlotte Chamberlain, Kelvin K. W. Chan, Jaclyn Beca, and Jeffrey S Hoch
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Marginal cost ,Value (ethics) ,economic evaluation ,Population ,QALYs ,Marginal ,03 medical and health sciences ,0302 clinical medicine ,Health care ,Economics ,030212 general & internal medicine ,education ,education.field_of_study ,Actuarial science ,Health economics ,Public economics ,business.industry ,Health Policy ,cost-effectiveness analysis ,Cost-effectiveness analysis ,Oncology ,030220 oncology & carcinogenesis ,Economic evaluation ,business ,Marginal utility - Abstract
This article applies concepts from health economics to address what is the "right" amount of chemotherapy in non-curable disease. A health economics perspective is beneficial because it forces a focus on objectives and constraints. We review and apply the concepts of "Choice of Comparator", "Use of QALYs" and "Equating Marginal Benefit to Marginal Cost", demonstrating their fit for purpose when considering the optimal amount of chemotherapy for non-curable disease. Many efforts underway to improve healthcare can be viewed as applications of these key economic principles. The true value is in the concepts themselves and not in the associated calculations. Given the difference between a population and a patient perspective, different "optimal" amounts of chemotherapy may exist. For many, however, best may not be most. Optimal decisions may vary depending on whether the goal of treatment is to maximize hope or health.
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- 2016
242. Cetuximab plus irinotecan versus panitumumab in patients with refractory metastatic colorectal cancer in Ontario, Canada
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Katarzyna J, Jerzak, Scott, Berry, Yoo-Joung, Ko, Craig, Earle, and Kelvin K W, Chan
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Male ,Canada ,Panitumumab ,Antibodies, Monoclonal ,Cetuximab ,Exons ,Middle Aged ,Antibodies, Monoclonal, Humanized ,Irinotecan ,Disease-Free Survival ,ErbB Receptors ,Proto-Oncogene Proteins p21(ras) ,Treatment Outcome ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Camptothecin ,Female ,Neoplasm Metastasis ,Colorectal Neoplasms ,Aged - Abstract
The addition of irinotecan to an epidermal growth factor receptor (EGFR) antibody has previously been shown to improve tumor response rate and time to progression but not overall survival (OS) for refractory metastatic colorectal cancer (mCRC). We assessed the "real-world" effectiveness and toxicity of the combination versus monotherapy. In Ontario, Canada, universal public funding is available for either cetuximab plus irinotecan (Cmab + I) combination therapy or panitumumab (Pmab) monotherapy, only in patients with refractory nonmutated RAS mCRC. All patients diagnosed before December 2012 and treated with an EGFR antibody for mCRC were identified from the Ontario drug database and linked to the Ontario Cancer Registry and other administrative databases to ascertain baseline characteristics, health services utilization, and outcomes. Multivariable Cox and logistic models were constructed to compare the time to treatment discontinuation (TTD), OS, emergency department (ED) or hospital visits between Cmab + I and Pmab. Observable confounders were adjusted for using propensity score methods. One thousand and eighty-one patients were identified (Cmab + I: 278, Pmab: 803). Patients receiving Cmab + I were younger (mean age 61 vs 64 years) and had a longer duration of prior irinotecan treatment. The use of Cmab + I as compared to Pmab alone was associated with a prolonged TTD [median: 3.8 months vs 2.8 months] and an improved OS [median: 8.8 months vs. 5.9 months] with an adjusted HR of 0.62 [95% CI 0.53-0.73, p 0.001]. Both treatment regimens afforded similar 14-day mortality and incidence of ED or hospital visits. The findings for patients over and below the age of 65 were similar.
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- 2016
243. Comparing assessment frameworks for cancer drugs between Canada and Europe: What can we learn from the differences?
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Mona Sabharwal, Kelvin K. W. Chan, Anthony Fields, Alexandra Chambers, Matthew C. Cheung, and William K. Evans
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Value (ethics) ,Flexibility (engineering) ,Cancer Research ,Cost effectiveness ,Management science ,business.industry ,media_common.quotation_subject ,Cancer drugs ,Context (language use) ,Value Framework ,Review ,Clinical benefit ,Cancer Drug Funding ,Presentation ,Quality of life (healthcare) ,Oncology ,Risk analysis (engineering) ,Summative assessment ,Medicine ,Cost-effectiveness ,business ,media_common - Abstract
The increasing burden of costs associated with novel cancer therapies is becoming untenable. In Europe and Canada, assessment frameworks have been developed to attribute value to novel therapies and ultimately facilitate access to cancer drug funding. A review of the two frameworks has not previously been undertaken. This review provides insight into the relative strengths and benefits of each approach, the various perspectives of value (patient, physician and societal) and how the frameworks relate to their unique context and core principles. Both frameworks assess the clinical benefit of a new cancer therapy. The European framework considers effectiveness, quality of life, and toxicity in its determination of benefit and has the advantage of providing a simple summary score to facilitate priority setting. The Canadian framework considers other elements including cost-effectiveness, patient preferences and adoption feasibility; its deliberative framework precludes a simple summative presentation of value but can address complex and nuanced drug funding considerations with flexibility. Both frameworks have evolved to meet the needs unique to their jurisdictions and offer potentially complementary tools in the assessment of new cancer drugs. Lessons learnt in both systems can be applied to future iterations of the frameworks, which remain works in progress.
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- 2016
244. P1.01-16 First-Line Pembrolizumab With or Without Chemotherapy in PD-L1 positive NSCLC: A Network Meta-Analysis of Randomized Trials
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Mark Doherty, S. Delos Santos, A. Putri Rahmadian, and Kelvin K. W. Chan
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,First line ,medicine.medical_treatment ,Pembrolizumab ,PD-L1 Positive ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Meta-analysis ,Medicine ,business - Published
- 2018
245. OC-0076: MR-guided vs CT-guided brachytherapy more effective and less costly in locally advanced cervical cancer
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M. Milosevic, Kelvin K. W. Chan, Julia Skliarenko, Kari Tanderup, Lisa Barbera, Wanrudee Isaranuwatchai, Johnna Perdrizet, Ananth Ravi, Padraig Warde, Eric Gutierrez, David D'Souza, and Michelle Ang
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Cervical cancer ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Brachytherapy ,Locally advanced ,Hematology ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business ,Mri guided - Published
- 2018
246. A phase I study of MR-HIFU hyperthermia (HT) with radiation (RT) and chemotherapy (CT) for recurrent rectal cancer
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Yuexi Huang, Kelvin K. W. Chan, Merrylee McGuffin, William Chu, Samuel Pichardo, Shun Wong, Kullervo Hynynen, Gregory J. Czarnota, Robert Staruch, and Ari Partanen
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Hyperthermia ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,medicine.disease ,Phase i study ,Oncology ,Quality of life ,Cancer control ,medicine ,Radiology ,business ,Recurrent Rectal Cancer - Abstract
78 Background: HT may improve cancer control and quality of life by sensitizing tumors to RT and CT. Inoperable recurrent rectal cancer has marginal outcomes with current retreatment regimens. We report the results from a first-in-human phase I study of MR-HIFU hyperthermia combined with RT and CT for recurrent rectal cancer. Methods: This ethics-approved study enrolled 6 patients fit for re-irradiation and chemotherapy; and with a MRI-visible and HIFU-accessible lesion. Patients received 30.6 Gy (17 fractions) and daily oral capecitabine, plus MR-HIFU HT immediately before RT on days 1, 8, and 15. Primary objectives were safety (acute toxicity) and treatment feasibility. Secondary objectives included late toxicity, pain palliation, quality of life, and radiologic response. HT was delivered with the Sonalleve MR-HIFU system on a 3T MRI. MR-based feedback control parameters were prescribed to achieve a mean temperature of 42.5°C in an 18 mm diameter target region for 30 minutes without exceeding 45°C. Results: One patient withdrew after completing 1/3 HT sessions due to scheduling and sedation difficulties. Five patients completed HT, RT and CT. There were no intraoperative complications, no adverse events or unintended tissue damage attributable to HT, RT, or CT. Table shows the best single continuous HT and mean temperatures (T90, T10), cumulative time in range (TIR), cumulative number of equivalent minutes at 43oC(CEM43) and day 90 imaging response. Sonication and MRI suite times were 36±13 and 226±78min. Conclusions: MR-HIFU HT was safely delivered in patients with recurrent rectal cancer. Treatment planning and patient set-up times decreased while beam-on time increased with experience. MR-HIFU HT combined with RT and CT appears feasible for primary tumours. Clinical trial information: NCT02528175. [Table: see text]
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- 2019
247. Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) hyperthermia for primary rectal cancer: A virtual feasibility analysis
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Robert Staruch, Kelvin K. W. Chan, Ari Partanen, Samuel Pichardo, Kullervo Hynynen, William Chu, Merrylee McGuffin, Yuexi Huang, Kaitlyn Perry, Shun Wong, and Gregory J. Czarnota
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Hyperthermia ,Cancer Research ,medicine.diagnostic_test ,business.industry ,Colorectal cancer ,medicine.medical_treatment ,Magnetic resonance imaging ,medicine.disease ,High-intensity focused ultrasound ,Minimal effect ,Oncology ,Treatment modality ,Medicine ,business ,Nuclear medicine - Abstract
77 Background: MR-HIFU Hyperthermia (HT) is a non-invasive treatment modality with real-time thermometry that ensures accurate and precise heating of a target with minimal effect on adjacent tissue. This energy deposition within a tumour can produce local bioeffects resulting in thermal chemo- and radiosensitization. MR-HIFU has been shown to be safe and feasible in a companion phase I study for recurrent rectal cancer. The purpose of this study is to determine the feasibility of MR-HIFU in treating primary rectal tumours. Methods: With ethics approval, the anatomic characteristics and surrounding structures of rectal tumours diagnosed at Sunnybrook from 2014-2019 were retrospectively analyzed. Three orthogonal views of MR images were used to determine the potential ultrasound (US) beam path and organs at risk (OAR). In part 2 of the study, the gross tumour volume was delineated for 30 rectal tumours (10 low, mid &high). Image datasets were imported into the Sonalleve MR-HIFU workstation for virtual treatment simulation and planning to determine tumour targetability, coverage, optimal patient set-up, and transducer positioning. Results: Of the 105 tumours analyzed, 36, 52, and 17 were low, mid, and high, respectively. The average width of the acoustic window (sciatic notch) for the US beam path was 5.8 ± 1.4cm, average tumour length was 5.24 ± 2.0cm, and average beam path (skin to tumour edge) was 7.3 ± 1.9cm. Eighty one percent of tumours were ≤ 0.3cm from an OAR. Of the 24 virtually simulated tumours to date, 6/8 lower, 6/8 mid, and 1/8 upper rectal tumours were targetable by MR-HIFU. Conclusions: This is the first virtual analysis to evaluate MR-HIFU HT targetability in primary rectal cancer. Results from this study will support MR-HIFU HT as an option to enhance the treatment of primary rectal cancer. Acknowledgments: This study has been funded by the Canadian Cancer Society. Patient & tumour characteristics. [Table: see text]
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- 2019
248. Predictors of adherence among post-menopausal women receiving adjuvant endocrine therapy for breast cancer in Ontario, Canada
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Melody Lam, Britney Allen, T. Vandenberg, D. Desautels, Jacques Raphael, Alexander V. Louie, Lucie Richard, Kelvin K. W. Chan, Kathleen I. Pritchard, Salimah Z. Shariff, Craig C. Earle, and Phillip S. Blanchette
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medicine.medical_specialty ,Aromatase inhibitor ,medicine.drug_class ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Lumpectomy ,Hematology ,Odds ratio ,medicine.disease ,Breast cancer ,Oncology ,Internal medicine ,medicine ,business ,Adjuvant ,Tamoxifen ,Mastectomy ,medicine.drug - Abstract
Background Adjuvant endocrine therapy (AET) is an important treatment for post-menopausal hormone receptor positive breast cancer. We used health administrative data to explore factors associated with AET adherence and survival. Methods We used health administrative databases to investigate adherence of post-menopausal women (aged ≥ 66 years) who started endocrine therapy from 2005-2010. Adherence was measured by medical possession ratio (MPR) and characterized as low ( Results We identified 5,692 eligible patients with a median age of 73 years (IQR: 69-78), 67% received lumpectomy, 33% mastectomy, 26% adjuvant radiation, 13% adjuvant chemotherapy and 70% of patient originally started on an aromatase inhibitor versus tamoxifen. AET adherence was low in 13% (n = 749), intermediate in 13% (n = 733) and high in 74% (n = 4,210) of patients. Lower levels of adherence were observed among older patients [low vs. high adherence: odds ratio (OR)=1.03, 95% CI: 1.02-1.05 (per year); intermediate vs. high adherence: OR = 1.02, 95% CI: 1.01-1.04 (per year)]. High adherence was associated with use of adjuvant chemotherapy (low versus high adherence OR = 0.42 95% CI: 0.30-0.59) and short-term follow-up with a medical oncologist within 4 months of starting AET (low vs. high adherence OR = 0.83, 95% CI: 0.69-0.99). Unadjusted analysis showed an increased risk of death among patients with lower AET adherence [low vs. high adherence: hazard ratio (HR)=1.31, 95% CI: 1.12-1.53 and intermediate vs. high adherence: HR = 1.40, 95% CI: 1.21-1.62]. However, a significant association could no longer be detected after multivariable adjustment. Conclusions Non-adherence to endocrine therapy appears to be more common among older breast cancer patients. Short-term follow-up visit by a patient’s medical oncologist after starting AET may help to improve adherence. Developing strategies to optimize endocrine therapy adherence are warranted. Legal entity responsible for the study The authors. Funding Academic Medical Association of South Western Ontario (AMOSO). Disclosure T. Vandenberg: Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche. K. Pritchard: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: Myriad Genetics. A. Louie: Advisory / Consultancy: AstraZeneca; Honoraria (self): Varian Medical Systems Inc. J. Raphael: Honoraria (self): Hoffmann La Roche. All other authors have declared no conflicts of interest.
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- 2019
249. Comparison of Long-term Survival Benefits in Trials of Immune Checkpoint Inhibitor vs Non–Immune Checkpoint Inhibitor Anticancer Agents Using ASCO Value Framework and ESMO Magnitude of Clinical Benefit Scale
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Louis Everest, Monica Shah, and Kelvin K. W. Chan
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Oncology ,medicine.medical_specialty ,Durvalumab ,Antineoplastic Agents ,Ipilimumab ,Pembrolizumab ,Time ,law.invention ,Randomized controlled trial ,law ,Atezolizumab ,Neoplasms ,Internal medicine ,medicine ,Humans ,Molecular Targeted Therapy ,Drug Approval ,health care economics and organizations ,Survival analysis ,Randomized Controlled Trials as Topic ,Original Investigation ,business.industry ,Research ,Absolute risk reduction ,General Medicine ,Survival Analysis ,Online Only ,Treatment Outcome ,Immunotherapy ,Nivolumab ,business ,medicine.drug - Abstract
Key Points Question How frequently do immune checkpoint inhibitor (ICI) agents vs non-ICI agents qualify for American Society of Clinical Oncology Value Framework version 2 (ASCO-VF v2) tail-of-the-curve bonuses or European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) immunotherapy-triggered long-term plateau adjustments? Findings In this cohort study of 100 randomized clinical trials comparing ICI with non-ICI agents, ASCO-VF v2 tail-of-the-curve bonuses and ESMO-MCBS v1.1 immunotherapy-triggered long-term plateau adjustments were not awarded to ICI agents more often than non-ICI agents. Meaning The ASCO-VF v2 and ESMO-MCBS v1.1 may be flawed in accurately capturing long-term survival., This study of 100 randomized clinical trials determines how frequently immune checkpoint inhibitor (ICI) and non-ICI anticancer agents displayed trends of long-term durable survival as defined by the American Society of Clinical Oncology (ASCO) Value Framework and the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale., Importance Recently, anticancer agents have generated excitement owing to their capacity to preserve long-term durable survival in some patients who are represented by a tail of the survival curve. However, because traditional measures of clinical benefit may not accurately capture durable survival, amendments to various valuation frameworks have been proposed to capture this benefit. Objectives To determine how frequently immune checkpoint inhibitor (ICI) anticancer agents vs non-ICI anticancer agents displayed trends of long-term durable survival, as defined by the American Society of Clinical Oncology Value Framework version 2 (ASCO-VF v2) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1), as well as to further analyze the degree of agreement between ASCO and ESMO frameworks. Design, Setting, and Participants In this cohort study, anticancer agents from phase 2 or 3 randomized clinical trials (RCTs) cited for clinical efficacy evidence in drug approval by the US Food and Drug Administration between January 2011 and March 2018 were identified. Data required for the ASCO-VF v2 tail-of-the-curve bonus and the ESMO-MCBS v1.1 immunotherapy-triggered long-term plateau adjustments were extracted from relevant RCTs. Frequency and difference in proportions were calculated to determine how often survival benefits were awarded to anticancer agents overall and to ICI and non-ICI anticancer agents individually. Main Outcomes and Measures American Society of Clinical Oncology Value Framework v2 tail-of-the-curve bonuses and ESMO-MCBS v1.1 immunotherapy-triggered long-term plateau adjustments. Results In total, 247 RCTs were identified, and 100 RCTs involving 57 164 patients were included, with 14 examining ICI agents (1 ipilimumab, 5 pembrolizumab, 5 nivolumab, 2 atezolizumab, and 1 durvalumab) and 86 examining non-ICI agents (74 targeted therapy, 8 chemotherapy, 3 hormone therapy, and 1 radiopharmaceutical). Randomized clinical trials were awarded ASCO-VF v2 tail-of-the-curve bonuses more often than ESMO-MCBS v1.1 immunotherapy-triggered long-term plateau adjustments (ASCO-VF v2, 45.0% [8 of 14 ICI RCTs and 37 of 86 non-ICI RCTs] vs ESMO-MCBS v1.1, 2.6% [1 of 12 ICI RCTs and 1 of 66 non-ICI RCTs). Randomized clinical trials for ICIs were not more likely to receive an ASCO-VF v2 bonus or ESMO-MCBS v1.1 adjustment than non-ICI RCTs (ASCO-VF: risk difference, 0.14; 95% CI, −0.14 to 0.42; P = .32; ESMO-MCBS: risk difference, 0.07; 95% CI, −0.09 to 0.23; P = .40). Poor agreement was found between the framework algorithms in identifying long-term survival benefits from RCTs (κ = 0.01; 95% CI, −0.23 to 0.22; P = .50). Conclusions and Relevance The ASCO-VF v2 and ESMO-MCBS v1.1 may require additional refinement to accurately capture the benefit of durable long-term survival, or ICI agents may not preserve long-term survival as conventionally thought.
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- 2019
250. Impact of smoking on health system costs among cancer patients in a retrospective cohort study in Ontario, Canada
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William K. Evans, Wanrudee Isaranuwatchai, Alice Peter, Rebecca Truscott, Kelvin K. W. Chan, Nicole Mittmann, and Claire de Oliveira
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Male ,Databases, Factual ,medicine.medical_treatment ,0302 clinical medicine ,Rurality ,Risk Factors ,Neoplasms ,Health care ,Medicine ,030212 general & internal medicine ,Aged, 80 and over ,Ontario ,education.field_of_study ,Health Care Costs ,General Medicine ,Health Services ,Middle Aged ,3. Good health ,030220 oncology & carcinogenesis ,behavior and behavior mechanisms ,economic burden ,Regression Analysis ,Female ,Cohort study ,Adult ,Marginal cost ,Adolescent ,Population ,health system costs ,smoking ,healthcare costs ,Young Adult ,03 medical and health sciences ,Health Economics ,Humans ,cancer ,education ,Aged ,Retrospective Studies ,business.industry ,Research ,Retrospective cohort study ,Smoking cessation ,business ,Demography ,Ontario canada - Abstract
ObjectiveSmoking is the main modifiable cancer risk factor. The objective of this study was to examine the impact of smoking on health system costs among newly diagnosed adult patients with cancer. Specifically, costs of patients with cancer who were current smokers were compared with those of non-smokers from a publicly funded health system perspective.MethodsThis population-based cohort study of patients with cancer used administrative databases to identify smokers and non-smokers (1 April 2014–31 March 2016) and their healthcare costs in the 12–24 months following a cancer diagnosis. The health services included were hospitalisations, emergency room visits, drugs, home care services and physician services (from the time of diagnosis onwards). The difference in cost (ie, incremental cost) between patients with cancer who were smokers and those who were non-smokers was estimated using a generalised linear model (with log link and gamma distribution), and adjusted for age, sex, neighbourhood income, rurality, cancer site, cancer stage, geographical region and comorbidities.ResultsThis study identified 3606 smokers and 14 911 non-smokers. Smokers were significantly younger (61 vs 65 years), more likely to be male (53%), lived in poorer neighbourhoods, had more advanced cancer stage,and were more likely to die within 1 year of diagnosis, compared with non-smokers. The regression model revealed that, on average, smokers had significantly higher monthly healthcare costs ($5091) than non-smokers ($4847), pConclusionsSmoking status has a significant impact on healthcare costs among patients with cancer. On average, smokers incurred higher healthcare costs than non-smokers. These findings provide a further rationale for efforts to introduce evidence-based smoking cessation programmes as a standard of care for patients with cancer as they have the potential not only to improve patients’ outcomes but also to reduce the economic burden of smoking on the healthcare system.
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- 2019
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