Bio

Bio


Marcy Winget, PhD is the Director, Evaluation Sciences Unit and Clinical Associate Professor in the Division of Primary Care and Population Health, Stanford School of Medicine. She is an epidemiologist/ health services researcher with a passion for research aimed at improving the quality of the healthcare system. Dr. Winget has led several large studies that developed and implemented population-based methods to evaluate the quality of cancer care in breast, lung and colorectal cancer patients in Alberta, Canada. Her research involves linking multiple sources of large clinical and administrative data in order to understand gaps in the healthcare system to inform positive change. Currently she is leading evaluation efforts for the Stanford Cancer Center and Stanford Primary Care 2.0. Dr. Winget also mentors others in developing, implementing and evaluating quality improvement projects related to healthcare.

Academic Appointments


Administrative Appointments


  • Director, Evaluation Sciences Unit, Division of General Medical Disciplines (2014 - Present)

Professional Education


  • PhD, Johns Hopkins Bloomberg School of Public Health, Epidemiology (1996)
  • MHS, Johns Hopkins Bloomberg School of Public Health, Biostatistics (1992)
  • BS, University of California, Davis, Genetics (1985)

Research & Scholarship

Current Research and Scholarly Interests


My primary research interest is in studies and their evaluation intended to improve the quality of patient care particularly those related to cancer care, primary care, and the points of intersection between primary and specialty care. Currently I am the Director and quantitative lead for the evaluation of the Cancer Transformation Initiative, a 5-year project to transform the quality of care for cancer patients seen and treated at the Stanford Cancer Institute. I am also a PI for the evaluation of Primary Care 2.0. Additionally, I am a co-investigator and lead for the province of Alberta, in a large 5-year inter-provincial Canadian team grant focused on assessing models of care to improve the points of care for cancer patients that intersect primary and specialty care across the entire care trajectory. In my research I work with a broad group of stakeholders including administrators, physicians, program planners, and patients. I am always interested in learning about collaborative opportunities with others interested in improving the quality of healthcare for patients.

Projects


  • Evaluation of the Cancer Care Transformation Intitative, Stanford School of Medicine

    Location

    Stanford CA

Publications

All Publications


  • Primary Care 2.0: Design of a Transformational Team-Based Practice Model to Meet the Quadruple Aim. American journal of medical quality : the official journal of the American College of Medical Quality Brown-Johnson, C. G., Chan, G. K., Winget, M., Shaw, J. G., Patton, K., Hussain, R., Olayiwola, J. N., Chang, S., Mahoney, M. 2018: 1062860618802365

    Abstract

    A new transformational model of primary care is needed to address patient care complexity and provider burnout. An 18-month design effort (2015-2016) included the following: (1) Needs Finding, (2) Integrated Facility Design, (3) Design Process Assessment, and (4) Development of Evaluation. Initial outcome metrics were assessed. The design team successfully applied Integrated Facility Design to primary care transformation design; qualitative survey results suggest that design consensus was facilitated by team-building activities. Initial implementation of Quadruple Aim-related outcome metrics showed positive trends. Redesign processes may benefit from emphasis on team building to facilitate consensus and increased patient involvement to incorporate patient voices successfully.

    View details for DOI 10.1177/1062860618802365

    View details for PubMedID 30409021

  • Re-excision and survival following breast conserving surgery in early stage breast cancer patients: a population-based study BMC HEALTH SERVICES RESEARCH Fisher, S., Yasui, Y., Dabbs, K., Winget, M. 2018; 18: 94

    Abstract

    Increasing population-based evidence suggests that patients who receive breast conserving surgery (BCS) plus radiotherapy have superior survival than those who receive mastectomy. It is unclear, however, how BCS followed by re-excision is associated with all-cause and breast cancer-specific mortality, and whether the BCS survival advantage is maintained if re-excision is needed. The aim of this study was to investigate the clinical, patient, provider and geographic variation associated with receipt of re-excision surgery, and to examine the relationship between re-excision and all-cause and breast cancer-specific mortality.All women diagnosed with stage I-III breast cancer in Alberta, Canada from 2002 to 2009 were identified from the Alberta Cancer Registry, of which 11,626 were eligible for study inclusion. Type of first breast cancer surgery after diagnosis, subsequent re-excisions within 1 year, surgeon (anonymized), and hospital were obtained from provincial physician claims data. Multilevel logistic regression with surgeons and hospitals as crossed random effects was used to estimate the adjusted odds ratios of re-excision by the factors of interest. Poisson regression models were fitted to compare all-cause and breast cancer-specific mortality by surgical pattern.Re-excision surgery was received by 19% (N = 5659) of patients who initially received BCS. The adjusted odds of re-excision varied significantly by geography of surgery, and by individual surgeon among stage I and II patients beyond the variation explained by the factors investigated (Stage I OR standard deviation (SD) = 0.43; stage II OR SD = 0.39). Patients who were treated with BCS plus re-excision surgery with either mastectomy or further BCS had similar all-cause and breast cancer-specific mortality as those treated with BCS without re-excision.These results suggest that breast cancer patients who are treated with BCS plus re-excision surgery by either mastectomy or further BCS have similar survival as those treated with BCS without re-excision. The significant variation in the likelihood of re-excision by geography and by individual surgeon is concerning, especially given the costs to the patient associated with additional surgery and the financial costs to the health system.

    View details for DOI 10.1186/s12913-018-2882-7

    View details for Web of Science ID 000424670000003

    View details for PubMedID 29422097

    View details for PubMedCentralID PMC5806481

  • Development of a Tailored Survey to Evaluate a Patient-Centered Initiative AMERICAN JOURNAL OF MANAGED CARE Winget, M., Haji-Sheikhi, F., Asch, S. M. 2018; 24 (2): E37–E44

    Abstract

    Patient-centered care initiatives have proliferated, but assessing their effectiveness requires measures tailored to their likely effects. In this article, we describe the development and pilot testing of patient surveys used to assess change in patients' cancer care experiences over time in response to a patient-centered care initiative.Prospective case series.Domains of patient-centered care were informed by the goals of the initiative and a review of existing tools. Items were selected and modified from 6 domains of validated or semivalidated instruments. Items were piloted with patients with cancer in waiting room settings to further assess the relevance and clarity of items, whether important concepts were missing, and acceptability regarding place and timing of the surveys and to estimate baseline top box scores (percentage of patients scoring an item the highest quality level) to minimize likely ceiling effects. The instrument was then administered to a consecutive sample of Stanford Cancer Center patients. Baseline item responses, Cronbach's alpha, and response bias were estimated.Items were modified based on patient feedback, top box scores, and reassessment of the domains. Over 6 months, 11,273 patients were surveyed, with a 49.7% response rate. Baseline top box scores ranged from 41.7% to 75.0% for any given item. Reliability and internal consistency were high for all domains (Cronbach's alpha ≥0.80) except for the access domain.We developed reliable instruments to evaluate the essential elements of a patient-centered care initiative at an academic medical center, which minimized patient burden and maximized the response rate.

    View details for Web of Science ID 000425326700002

    View details for PubMedID 29461850

  • Lean-Based Redesign of Multidisciplinary Rounds on General Medicine Service. Journal of hospital medicine Kane, M., Rohatgi, N., Heidenreich, P., Thakur, A., Winget, M., Shum, K., Hereford, J., Shieh, L., Lew, T., Horn, J., Chi, J., Weinacker, A., Seay-Morrison, T., Ahuja, N. 2018

    Abstract

    Multidisciplinary rounds (MDR) facilitate timely communication amongst the care team and with patients. We used Lean techniques to redesign MDR on the teaching general medicine service.To examine if our Lean-based new model of MDR was associated with change in the primary outcome of length of stay (LOS) and secondary outcomes of discharges before noon, documentation of estimated discharge date (EDD), and patient satisfaction.This is a pre-post study. The preperiod (in which the old model of MDR was followed) comprised 4000 patients discharged between September 1, 2013, and October 22, 2014. The postperiod (in which the new model of MDR was followed) comprised 2085 patients between October 23, 2014, and April 30, 2015.Lean-based redesign of MDR.LOS, discharges before noon, EDD, and patient satisfaction.There was no change in the mean LOS. Discharges before noon increased from 6.9% to 10.7% (P < .001). Recording of EDD increased from 31.4% to 41.3% (P < .001). There was no change in patient satisfaction.Lean-based redesign of MDR was associated with an increase in discharges before noon and in recording of EDD.

    View details for DOI 10.12788/jhm.2908

    View details for PubMedID 29394300

  • Patient Perception of Speech Outcomes: The Relationship Between Clinical Measures and Self-Perception of Speech Function Following Surgical Treatment for Oral Cancer. American journal of speech-language pathology Constantinescu, G., Rieger, J., Winget, M., Paulsen, C., Seikaly, H. 2017; 26 (2): 241-247

    Abstract

    Treatment for oral cancer can result in speech impairments that can have varying impacts on patient quality of life. This study explored the relationship between clinical measures of speech impairment and the perception that patients had of this change in the early stage of recovery.This was a quasi-experimental 1-group pre-post study design carried out on 10 patients with surgical intervention for oral cancer. Two clinical measures (word intelligibility and consonant phoneme error) and 2 patient-perception measures (Speech Handicap Index total score and Speech Handicap Index patient criteria score) were collected at preoperative and 1-month postoperative appointments.Qualitative analysis revealed discordance between clinical and patient-perceived measures in 4 of 10 patients. Change in consonant phoneme error and change in word intelligibility were significantly correlated (r = .827). Furthermore, on average, statistically significant relationships were not found between clinical and patient-perceived measures or between the 2 patient-perception measures.Discordance between clinical and patient-perceived measures was observed in almost half of the sample, indicating that clinical tests did not fully explain the extent of impairment perceived by patients. Speech outcomes should focus on both types of measures, and patient perception outcomes should be carefully considered when recommending speech therapy.

    View details for DOI 10.1044/2016_AJSLP-15-0170

    View details for PubMedID 28359083

  • Use of physician services during the survivorship phase: a multi-province study of women diagnosed with breast cancer. Current oncology KENDELL, C., Decker, K. M., Groome, P. A., McBride, M. L., Jiang, L., Krzyzanowska, M. K., Porter, G., Turner, D., Urquhart, R., Winget, M., Grunfeld, E. 2017; 24 (2): 81-89

    Abstract

    Oncologists have traditionally been responsible for providing routine follow-up care for cancer survivors; in recent years, however, primary care providers (pcps) are taking a greater role in care during the follow-up period. In the present study, we used a longitudinal multi-province retrospective cohort study to examine how primary care and specialist care intersect in the delivery of breast cancer follow-up care.Various databases (registry, clinical, and administrative) were linked in each of four provinces: British Columbia, Manitoba, Ontario, and Nova Scotia. Population-based cohorts of breast cancer survivors were identified in each province. Physician visits were identified using billings or claims data and were classified as visits to primary care (total, breast cancer-specific, and other), oncology (medical oncology, radiation oncology, and surgery), and other specialties. The mean numbers of visits by physician type and specialty, or by combinations thereof, were examined. The mean numbers of visits for each follow-up year were also examined by physician type.The results showed that many women (>64%) in each province received care from both primary care and oncology providers during the follow-up period. The mean number of breast cancer-specific visits to primary care and visits to oncology declined with each follow-up year. Interprovincial variations were observed, with greater surgeon follow-up in Nova Scotia and greater primary care follow-up in British Columbia. Provincial differences could reflect variations in policies and recommendations, relevant initiatives, and resources or infrastructure to support pcp-led follow-up care.Optimizing the role of pcps in breast cancer follow-up care might require strategies to change attitudes about pcp-led follow-up and to better support pcps in providing survivorship care.

    View details for DOI 10.3747/co.24.3454

    View details for PubMedID 28490921

  • Factors associated with mode of colorectal cancer detection and time to diagnosis: a population level study BMC HEALTH SERVICES RESEARCH Sikdar, K. C., Dickinson, J., Winget, M. 2017; 17

    Abstract

    Although it is well-known that early detection of colorectal cancer (CRC) is important for optimal patient survival, the relationship of patient and health system factors with delayed diagnosis are unclear. The purpose of this study was to identify the demographic, clinical and healthcare factors related to mode of CRC detection and length of the diagnostic interval.All residents of Alberta, Canada diagnosed with first-ever incident CRC in years 2004-2010 were identified from the Alberta Cancer Registry. Population-based administrative health datasets, including hospital discharge abstract, ambulatory care classification system and physician billing data, were used to identify healthcare services related to CRC diagnosis. The time to diagnosis was defined as the time from the first CRC-related healthcare visit to the date of CRC diagnosis. Mode of CRC detection was classified into three groups: urgent, screen-detected and symptomatic. Quantile regression was performed to assess factors associated with time to diagnosis.9626 patients were included in the study; 25% of patients presented as urgent, 32% were screen-detected and 43% were symptomatic. The median time to diagnosis for urgent, screen-detected and symptomatic patients were 6 days (interquartile range (IQR) 2-14 days), 74 days (IQR 36-183 days), 84 days (IQR 39-223 days), respectively. Time to diagnosis was greater than 6 months for 27% of non-urgent patients. Healthcare factors had the largest impact on time to diagnosis: 3 or more visits to a GP increased the median by 140 days whereas 2 or more visits to a GI-specialist increased it by 108 days compared to 0-1 visits to a GP or GI-specialist, respectively.A large proportion of CRC patients required urgent work-up or had to wait more than 6 months for diagnosis. Actions are needed to reduce the frequency of urgent presentation as well as improve the timeliness of diagnosis. Findings suggest a need to improve coordination of care across multiple providers.

    View details for DOI 10.1186/s12913-016-1944-y

    View details for Web of Science ID 000391888300001

    View details for PubMedID 28056946

  • The impact of false positive breast cancer screening mammograms on screening retention: A retrospective population cohort study in Alberta, Canada CANADIAN JOURNAL OF PUBLIC HEALTH-REVUE CANADIENNE DE SANTE PUBLIQUE Shen, Y., Winget, M., Yuan, Y. 2017; 108 (5-6): E539–E545
  • Waiting Time Intervals for Non-small Cell Lung Cancer Diagnosis and Treatment in Alberta: Quantification of Intervals and Identification of Risk Factors Associated with Delays. Clinical oncology Kim, J. O., Davis, F., Butts, C., Winget, M. 2016; 28 (12): 750-759

    Abstract

    Very little is known regarding the time required to diagnose and treat patients with non-small cell lung cancer (NSCLC) in Canada. We sought to quantify diagnostic and treatment intervals for NSCLC care in Alberta and identify risk factors for delays.The Alberta Cancer Registry identified all cases of stage I-III NSCLC diagnosed and treated in Alberta, Canada from 2004 to 2011. Diagnostic data were obtained from physician billing, inpatient/outpatient hospital data and electronic medical records to quantify the duration of diagnostic and treatment intervals and their sum (system interval). Multivariable logistic regression was carried out to identify factors associated with delays.Of the 3009 eligible patients included, the median and 90th percentile system interval was 78 (95% confidence interval 76-80) and 185 days (95% confidence interval 178-195), respectively. The treatment interval was longer than the diagnostic interval, with medians of 51 (95% confidence interval 49-53) and 38 (95% confidence interval 36-40) days, respectively. After adjustment, age > 60 years and treatment by modalities other than supportive care (especially surgery) were associated with delays. Factors associated with prompt care included high acuity presentations and stage III disease.The majority of Albertans with potentially curable NSCLC exceeded guidelines for the timeliness of their care.

    View details for DOI 10.1016/j.clon.2016.06.010

    View details for PubMedID 27357099

  • Primary care physician use across the breast cancer care continuum: CanIMPACT study using Canadian administrative data. Canadian family physician Medecin de famille canadien Jiang, L., Lofters, A., Moineddin, R., Decker, K., Groome, P., Kendell, C., Krzyzanowska, M., Li, D., McBride, M. L., Mittmann, N., Porter, G., Turner, D., Urquhart, R., Winget, M., Zhang, Y., Grunfeld, E. 2016; 62 (10): e589-e598

    Abstract

    To describe primary care physician (PCP) use and continuity of PCP care across the breast cancer care continuum.Population-based, retrospective cohort study using provincial cancer registries linked to health administrative databases.British Columbia, Manitoba, and Ontario.All women with incident invasive breast cancer from 2007 to 2012 in Manitoba and Ontario and from 2007 to 2011 in British Columbia.The number and proportions of visits to PCPs were determined. Continuity of care was measured using the Usual Provider of Care index calculated as the proportion of visits to the most-often-visited PCP in the 6 to 30 months before a breast cancer diagnosis (baseline) and from 1 to 3 years following a breast cancer diagnosis (survivorship).More than three-quarters of patients visited their PCPs 2 or more times during the breast cancer diagnostic period, and more than 80% of patients had at least 1 PCP visit during breast cancer adjuvant treatment. Contact with the PCP decreased over time during breast cancer survivorship. Of the 3 phases, women appeared to be most likely to not have PCP contact during adjuvant treatment, with 10.7% (Ontario) to 18.7% (British Columbia) of women having no PCP visits during this phase. However, a sizable minority of women had at least monthly visits during the treatment phase, particularly in Manitoba and Ontario, where approximately a quarter of women saw a PCP at least monthly. We observed higher continuity of care with PCPs in survivorship (compared with baseline) in all provinces.Primary care physicians were generally involved throughout the breast cancer care continuum, but the level of involvement varied across care phases and by province. Future interventions will aim to further integrate primary and oncology care.

    View details for PubMedID 27737994

    View details for PubMedCentralID PMC5063785

  • Electronic Release of Pathology and Radiology Results to Patients: Opinions and Experiences of Oncologists. Journal of oncology practice / American Society of Clinical Oncology Winget, M., Haji-Sheikhi, F., Brown-Johnson, C., Rosenthal, E. L., Sharp, C., Buyyounouski, M. K., Asch, S. M. 2016; 12 (8): e792-9

    Abstract

    There is an emerging standard to provide patients rapid electronic access to elements of their medical records. Although surveys of patients generally support it, this practice is controversial among oncologists, because few empiric data are available for scenarios of potentially life-threatening conditions like cancer. We report the views of oncologists about patient electronic access to radiology and pathology results that could potentially indicate disease progression.Four months before oncologists were surveyed, final results of radiology/pathology reports were routinely made available to patients online through a secure portal after a 7-day, hold to provide clinicians time to review and communicate results with the patients. Mixed methods were used to assess physician attitudes and experiences toward this change.One hundred twenty-nine oncologists were surveyed, and 82 (64%) responded. A small majority (54%) responded that the release of reports was somewhat or very beneficial for patients who received normal radiology/pathology results before discussion with a physician, but 87% said it was somewhat or very harmful for patients to receive abnormal results before discussion. Forty-nine percent reported that release of reports had a somewhat or very negative impact on communication with their patients.Almost half of oncologists reported that sharing digital radiology and pathology records had a negative impact on their communication with patients. Patient surveys in similar cancer populations would complement the physician perspective. Efforts are needed to improve consensus among oncologists and patients on how to best communicate such results in a timely fashion.

    View details for DOI 10.1200/JOP.2016.011098

    View details for PubMedID 27382001

  • Using Multilevel Models to Explain Variation in Clinical Practice: Surgeon Volume and the Surgical Treatment of Breast Cancer ANNALS OF SURGICAL ONCOLOGY Fisher, S., Yasui, Y., Dabbs, K., Winget, M. 2016; 23 (6): 1845-1851

    Abstract

    To investigate the relationship between surgeon caseload and surgery type, and variation in the surgical treatment of early stage breast cancer patients in Alberta, Canada.All women diagnosed with stage I to III breast cancer in Alberta from 2002 to 2010 were identified from the Alberta Cancer Registry. Type of surgery, surgeon (anonymized), and hospital were obtained from provincial physician claims data. Multilevel logistic regression with surgeons and hospitals as crossed random effects was used to estimate adjusted odds ratios (OR) of receiving mastectomy by surgeon volume. Empirical Bayes estimation was used to estimate adjusted OR for individual surgeons and hospitals.Mastectomy was found to be inversely related to surgeon volume among stage I and II patients. Patients whose surgery was conducted by a low-volume surgeon had twice the odds of receiving mastectomy as those that had surgery performed by a very high-volume surgeon (stage I OR 2.36, 95 % confidence interval 1.40, 3.97; stage II OR 1.96, 95 % confidence interval 1.13, 3.42). OR of mastectomy varied widely by individual surgeon beyond the variation explained by the factors investigated.Surgeon characteristics, including surgeon volume, are associated with surgery type received by breast cancer patients in Alberta. Significant variation in the likelihood of breast-conserving surgery (BCS) by surgeon is concerning given the potential benefits of BCS for those who are eligible.

    View details for DOI 10.1245/s10434-016-5118-2

    View details for Web of Science ID 000375613500011

    View details for PubMedID 26842490

  • Factors related to breast cancer detection mode and time to diagnosis in Alberta, Canada: a population-based retrospective cohort study BMC HEALTH SERVICES RESEARCH Yuan, Y., Li, M., Yang, J., Elliot, T., Dabbs, K., Dickinson, J. A., Fisher, S., Winget, M. 2016; 16

    Abstract

    Understanding the factors affecting the mode and timeliness of breast cancer diagnosis is important to optimizing patient experiences and outcomes. The purposes of the study were to identify factors related to the length of the diagnostic interval and assess how they vary by mode of diagnosis: screen or symptom detection.All female residents of Alberta diagnosed with first primary breast cancer in years 2004-2010 were identified from the Alberta Cancer Registry. Data were linked to Physician Claims and screening program databases. Screen-detected patients were identified as having a screening mammogram within 6-months prior to diagnosis; remaining patients were considered symptom-detected. Separate quantile regression was conducted for each detection mode to assess the relationship between demographic/clinical and healthcare factors.Overall, 38 % of the 12,373 breast cancer cases were screen-detected compared to 47 % of the screen-eligible population. Health region of residence was strongly associated with cancer detection mode. The median diagnostic interval for screen and symptom-detected cancers was 19 and 21 days, respectively. The variation by health region, however, was large ranging from an estimated median of 4 to 37 days for screen-detected patients and from 17 to 33 days for symptom-detected patients. Cancer stage was inversely associated with the diagnostic interval for symptom-detected cancers, but not for screen-detected cancers.Significant variation by health region in both the percentage of women with screen-detected cancer and the length of the diagnostic interval for screen and symptom-detected breast cancers suggests there could be important differences in local breast cancer diagnostic care coordination.

    View details for DOI 10.1186/s12913-016-1303-z

    View details for Web of Science ID 000370405000001

    View details for PubMedID 26892589

  • Survival in stage I-III breast cancer patients by surgical treatment in a publicly funded health care system ANNALS OF ONCOLOGY Fisher, S., Gao, H., Yasui, Y., Dabbs, K., Winget, M. 2015; 26 (6): 1161-1169

    Abstract

    Recent investigations of breast cancer survival in the United States suggest that patients who receive mastectomy have poorer survival than those who receive breast-conserving surgery (BCS) plus radiotherapy, despite clinically established equivalence. This study investigates breast cancer survival in the publicly funded health care system present in Alberta, Canada.Surgically treated stage I-III breast cancer cases diagnosed in Alberta from 2002 to 2010 were included. Demographic, treatment and mortality information were collected from the Alberta Cancer Registry. Unadjusted overall and breast cancer-specific mortality was assessed using Kaplan-Meier and cumulative incidence curves, respectively. Cox proportional hazards models were used to calculate stage-specific mortality hazard estimates associated with surgical treatment received.A total of 14 939 cases of breast cancer (14 633 patients) were included in this study. The unadjusted 5-year all-cause survival probabilities for patients treated with BCS plus radiotherapy, mastectomy, and BCS alone were 94% (95% CI 93% to 95%), 83% (95% CI 82% to 84%) and 74% (95% CI 70% to 78%), respectively. Stage II and III patients who received mastectomy had a higher all-cause (stage II HR = 1.36, 95% CI 1.13-1.48; stage III HR = 1.74, 95% CI 1.24-2.45) and breast cancer-specific (stage II HR = 1.39, 95% CI 1.09-1.76; stage III HR = 1.79, 95% CI 1.21-2.65) mortality hazard compared with those who received BCS plus radiotherapy, adjusting for patient and clinical characteristics. BCS alone was consistently associated with poor survival.Stage II and III breast cancer patients diagnosed in Alberta, Canada, who received mastectomy had a significantly higher all-cause and breast cancer-specific mortality hazard compared with those who received BCS plus radiotherapy. We suggest greater efforts toward educating and encouraging patients to receive BCS plus radiotherapy rather than mastectomy when it is medically feasible and appropriate.

    View details for DOI 10.1093/annonc/mdv107

    View details for Web of Science ID 000357997500018

    View details for PubMedID 25712459

  • Using administrative data to estimate time to breast cancer diagnosis and percent of screen-detected breast cancers - a validation study in Alberta, Canada EUROPEAN JOURNAL OF CANCER CARE Yuan, Y., Li, M., Yang, J., Winget, M. 2015; 24 (3): 367-375

    Abstract

    Appropriate use of administrative data enables the assessment of care quality at the population level. Our objective was to develop/validate methods for assessing quality of breast cancer diagnostic care using administrative data, specifically by identifying relevant medical tests to estimate the percentage screen/symptom-detected cancers and time to diagnosis. Two databases were created for all women diagnosed with a first-ever breast cancer in years 2007-2010 in Alberta, Canada, with dates of medical tests received in years 2006-2010. One purchased database had test results and was used to determine the 'true' first relevant test of a cancer diagnosis. The other free administrative database had test types but no test results. Receiver operating characteristic curves and concordance rates were used to assess estimates of percent screen/symptom-detected breast cancers; Log-rank test was used to assess time to diagnosis obtained from the two databases. Using a look-back period of 4-6 months from cancer diagnosis to identify relevant tests resulted in over 94% concordance, sensitivity and specificity for classifying patients into screen/symptom-detected group; good agreement between the distributions of time to diagnosis was also achieved. Our findings support the use of administrative data to accurately identify relevant tests for assessing the quality of breast cancer diagnostic care.

    View details for DOI 10.1111/ecc.12277

    View details for Web of Science ID 000353660500009

    View details for PubMedID 25521706

  • Treatment variation in patients diagnosed with early stage breast cancer in Alberta from 2002 to 2010: a population-based study BMC HEALTH SERVICES RESEARCH Fisher, S., Gao, H., Yasui, Y., Dabbs, K., Winget, M. 2015; 15
  • The relationship between lingual and hypoglossal nerve function and quality of life in head and neck cancer JOURNAL OF ORAL REHABILITATION Elfring, T., Boliek, C. A., Winget, M., Paulsen, C., Seikaly, H., Rieger, J. M. 2014; 41 (2): 133-140

    Abstract

    Sensorimotor impairment of the tongue has the potential to affect speech and swallowing. The purpose of this study was to critically examine the effects of nerve preservation and reinnervation after reconstruction of the base of tongue on patient-perceived outcomes of quality of life (QoL) related to speech and swallowing through completion of the EORTC QLQ-H&N35 standardised questionnaire. Thirty participants with a diagnosis of base of tongue cancer underwent primary resection and reconstruction with a radial forearm free flap, which may or may not have included nerve repair to the lingual nerve, hypoglossal nerve or both. Eight QoL domains sensitive to changes in motor and sensory nerve function were included in the analysis. Transected lingual and hypoglossal nerves were associated with difficulty in swallowing, social eating, dry mouth and social contact. There were fewer problems reported when these nerves were either repaired or left intact. There were no significant differences between patient nerve status and QoL outcomes for speech, sticky saliva and use of feeding tubes. This study was the first to examine the impact of sensory or motor nerve transection and reconstruction on health-related QoL outcomes.

    View details for DOI 10.1111/joor.12116

    View details for Web of Science ID 000329945800008

    View details for PubMedID 24289234

  • Aggressiveness of End-of-Life Care for Patients With Colorectal Cancer in Alberta, Canada: 2006-2009 JOURNAL OF PAIN AND SYMPTOM MANAGEMENT Hu, W., Yasui, Y., White, J., Winget, M. 2014; 47 (2): 231-244

    Abstract

    North American studies have documented practice variations and deficiencies in end-of-life (EOL) cancer care, such as trends toward treating dying patients aggressively and disparities in access to palliative care or hospice services.To assess the frequency of aggressive health care usage at the EOL and identify factors associated with receiving aggressive care among patients who died of colorectal cancer.Data from the Alberta Cancer Registry, in/outpatient hospital records, and cancer electronic medical records were linked. Death in an acute care hospital, chemotherapy use in the last 14 days of life, more than one emergency room (ER) visit, more than one hospital admission, and any intensive care unit (ICU) admission in the last 30 days of life were used as indicators of aggressive care. Logistic regression was used to identify risk factors associated with each indicator.A total of 2074 patients were included: 50.1% died in an acute care hospital; 3.7% received chemotherapy in the last 14 days of life; and 12.5% had multiple ER visits, 9.5% had multiple hospitalizations, and 2.2% had an ICU admission during the last 30 days of life. Age had the strongest association with chemotherapy use. Geographical region of residence had the strongest association with multiple ER visits and hospitalizations and dying in an acute care hospital. Tumor stage and duration of disease were associated with the ICU admission.The percentage of patients who died in an acute care hospital is higher than the 17% U.S. benchmark. Other indicators of receiving aggressive EOL care are consistent with existing care quality benchmarks. The considerable regional variation, however, indicates potential for system improvements.

    View details for DOI 10.1016/j.jpainsymman.2013.03.021

    View details for Web of Science ID 000331150000008

    View details for PubMedID 23870414

  • Timeliness of cancer care from diagnosis to treatment: a comparison between patients with breast, colon, rectal or lung cancer INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE Li, X., Scarfe, A., King, K., Fenton, D., Butts, C., Winget, M. 2013; 25 (2): 197-204

    Abstract

    The purpose of this study was to assess the value in measuring specific time intervals across cancer sites to identify potentially important variation in the timeliness of cancer care that may inform needed changes and/or improvements in coordination of care.Retrospective population-level study. Demographic and treatment information were obtained from the Alberta Cancer Registry. Date of oncologist-consult was obtained from cancer medical records.Alberta, Canada.All patients diagnosed in 2005 with breast, colon, rectal or lung cancer who were residents of Alberta, Canada.(i) Number of days from diagnosis to first treatment by treatment modality and cancer site, (ii) number of days from surgery to post-surgery consultation and subsequent treatment and (iii) relationship between clinical and demographic factors and the cancer-specific provincial median time for outcome measures (i) and (ii).Time from diagnosis to surgery, if first treatment, was ∼4 months for lung cancer compared with 1-2 months for breast and colorectal cancers. Factors associated with this time interval for breast and colorectal cancers was stage at diagnosis but was region of residence for lung cancer.Important variation within and across cancer sites identified in the care intervals evaluated in this study provides relevant information to inform local areas for improvement. Comparisons of these intervals across healthcare systems may also provide insights into strengths of different models for coordinating care.

    View details for DOI 10.1093/intqhc/mzt003

    View details for Web of Science ID 000316966800013

    View details for PubMedID 23349426

  • Validation of administrative data sources for endoscopy utilization in colorectal cancer diagnosis BMC HEALTH SERVICES RESEARCH Li, X., Hilsden, R., Hossain, S., Fleming, J., Winget, M. 2012; 12

    Abstract

    Validation of administrative data is important to assess potential sources of bias in outcome evaluation and to prevent dissemination of misleading or inaccurate information. The purpose of the study was to determine the completeness and accuracy of endoscopy data in several administrative data sources in the year prior to colorectal cancer diagnosis as part of a larger project focused on evaluating the quality of pre-diagnostic care.Primary and secondary data sources for endoscopy were collected from the Alberta Cancer Registry, cancer medical charts and three different administrative data sources. 1672 randomly sampled patients diagnosed with invasive colorectal cancer in years 2000-2005 in Alberta, Canada were included. A retrospective validation study of administrative data for endoscopy in the year prior to colorectal cancer diagnosis was conducted. A gold standard dataset was created by combining all the datasets. Number and percent identified, agreement and percent unique to a given data source were calculated and compared across each dataset and to the gold standard with respect to identifying all patients who underwent endoscopy and all endoscopies received by those patients.The combined administrative data and physician billing data identified as high or higher percentage of patients who had one or more endoscopy (84% and 78%, respectively) and total endoscopy procedures (89% and 81%, respectively) than the chart review (78% for both).Endoscopy data has a high level of completeness and accuracy in physician billing data alone. Combined with hospital in/outpatient data it is more complete than chart review alone.

    View details for DOI 10.1186/1472-6963-12-358

    View details for Web of Science ID 000311722800001

    View details for PubMedID 23062117

  • Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery BRITISH JOURNAL OF CANCER Lieffers, J. R., Bathe, O. F., Fassbender, K., Winget, M., Baracos, V. E. 2012; 107 (6): 931-936

    Abstract

    Skeletal muscle depletion (sarcopenia) predicts morbidity and mortality in the elderly and cancer patients.We tested whether sarcopenia predicts primary colorectal cancer resection outcomes in stage II-IV patients (n=234). Sarcopenia was assessed using preoperative computed tomography images. Administrative hospitalisation data encompassing the index surgical admission, direct transfers for inpatient rehabilitation care and hospital re-admissions within 30 days was searched for International Classification of Disease (ICD)-10 codes for postoperative infections and inpatient rehabilitation care and used to calculate length of stay (LOS).Overall, 38.9% were sarcopenic; 16.7% had an infection and 9.0% had inpatient rehabilitation care. Length of stay was longer for sarcopenic patients overall (15.9 ± 14.2 days vs 12.3 ± 9.8 days, P=0.038) and especially in those ≥ 65 years (20.2 ± 16.9 days vs 13.1 ± 8.3 days, P=0.008). Infection risk was greater for sarcopenic patients overall (23.7% vs 12.5%; P=0.025), and especially those ≥ 65 years (29.6% vs 8.8%, P=0.005). Most (90%) inpatient rehabilitation care was in patients ≥ 65 years. Inpatient rehabilitation was more common in sarcopenic patients overall (14.3% vs 5.6%; P=0.024) and those ≥ 65 years (24.1% vs 10.7%, P=0.06). In a multivariate model in patients ≥ 65 years, sarcopenia was an independent predictor of both infection (odds ratio (OR) 4.6, (95% confidence interval (CI) 1.5, 13.9) P<0.01) and rehabilitation care (OR 3.1 (95% CI 1.04, 9.4) P<0.04).Sarcopenia predicts postoperative infections, inpatient rehabilitation care and consequently a longer LOS.

    View details for DOI 10.1038/bjc.2012.350

    View details for Web of Science ID 000308703400006

    View details for PubMedID 22871883

  • Validation of colorectal cancer surgery data from administrative data sources BMC MEDICAL RESEARCH METHODOLOGY Li, X., King, C., Degara, C., White, J., Winget, M. 2012; 12

    Abstract

    Surgery is the primary treatment for colorectal cancer for both curative and palliative intent. Availability of high quality surgery data is essential for assessing many aspects of the quality of colorectal cancer care. The objective of this study was to determine the quality of different administrative data sources in identifying surgery for colorectal cancer with respect to completeness and accuracy.All residents in Alberta, Canada who were diagnosed with invasive colorectal cancer in years 2000-2005 were identified from the Alberta Cancer Registry and included in the study. Surgery data for these patients were obtained from the Cancer Registry (which collects the date of surgery for which the primary tumor was removed) and compared to surgery data obtained from two different administrative data sources: Physician Billing and Hospital Inpatient data. Sensitivity, specificity, positive predictive value, negative predictive value and observed agreement were calculated compared to the Cancer Registry data.The Physician Billing data alone or combined with Hospital Inpatient data demonstrated equally high sensitivity (97% for both) and observed agreement with the Cancer Registry data (93% for both) for identifying surgeries. The Hospital Inpatient data, however, had the highest specificity (80%). The positive predictive value varied by disease stage and across data sources for stage IV (99% for stages I-III and 83-89% for stage IV), the specificity is better for colon cancer surgeries (72-85%) than for rectal cancer surgeries (60-73%); validation measures did not vary over time.Physician Billing data identify the colorectal cancer surgery more completely than Hospital Inpatient data although both sources have a high level of completeness.

    View details for DOI 10.1186/1471-2288-12-97

    View details for Web of Science ID 000306907200001

    View details for PubMedID 22784239

  • Referral Rate to Oncologists and its Variation by Hospital for Colorectal Cancer Patients ANNALS OF SURGICAL ONCOLOGY Kreiter, E., Yasui, Y., de Gara, C., WHITE, J., Winget, M. 2012; 19 (3): 714-721

    Abstract

    Recent population-based studies in Alberta, Canada, found that approximately 50% of patients with stage III colon or stages II/III rectal adenocarcinoma did not receive guideline-recommended treatment (surgery plus chemotherapy or chemoradiation); a primary reason was not having an oncologist consult. We assessed the relationship between the hospital where the surgery was performed and the probability of a patient not having an oncologist consult.All patients diagnosed with stage III colon or stage II/III rectal adenocarcinoma between 2002 and 2005 in Alberta who had surgery were identified from the Alberta Cancer Registry and included in the study. Multivariable logistic regression modeling with hospitals as random effects was used to estimate cancer-type-specific odds ratios of not having an oncologist consult for each hospital, adjusted for age, sex, and comorbidities, relative to the overall nonconsultation rate.Overall, 21% of stage III colon, 25% of stage II rectal, and 13% of stage III rectal adenocarcinoma patients did not have an oncologist consult. Rates varied appreciably across hospitals and between cancer types within hospitals, even after the case-mix adjustment (adjusted odds ratios of nonconsultation ranged from 0.4 to 8.1). Small hospitals that performed 12 or fewer surgeries had nearly 100% consultation rates.The variation in oncologist-consult rates, particularly for stage II rectal cancer patients, is concerning. We are presenting the findings to the surgical community and discussing interventions to improve oncologist-consult rates.

    View details for DOI 10.1245/s10434-011-2063-y

    View details for Web of Science ID 000300313800004

    View details for PubMedID 21922337

  • Adherence to Treatment Guidelines in Stage II/III Rectal Cancer in Alberta, Canada CLINICAL ONCOLOGY Eldin, N. S., Yasui, Y., Scarfe, A., Winget, M. 2012; 24 (1): E9-E17
  • Variation in risk of second primary cancer CANADIAN MEDICAL ASSOCIATION JOURNAL Winget, M., Yasui, Y. 2012; 184 (1): 19-20

    View details for DOI 10.1503/cmaj.111424

    View details for Web of Science ID 000299654100004

    View details for PubMedID 22125335

  • Association Between Receipt and Timing of Adjuvant Chemotherapy and Survival for Patients With Stage III Colon Cancer in Alberta, Canada CANCER Lima, I. S., Yasui, Y., Scarfe, A., Winget, M. 2011; 117 (16): 3833-3840

    Abstract

    Surgery followed by adjuvant chemotherapy has been standard treatment for stage III colon cancer since 1990. However, to date, clinical trials have not been conducted to determine the definitive outer time limit by which adjuvant chemotherapy should be received for optimal survival benefit. The objective of the current study was to assess the association between the receipt/timing of adjuvant chemotherapy and patient survival in clinical practice.Residents of Alberta who were diagnosed with stage III colon adenocarcinoma in years 2000 to 2005 who underwent surgery were included in the study. Patients were identified from the Alberta Cancer Registry and were linked to hospital data and neighborhood-level socioeconomic data from the 2001 Canadian Census. Cox proportional hazards models were used to estimate hazard ratios of death according to the timing of chemotherapy.There were 1053 patients in the study; 648 (61%) initiated adjuvant chemotherapy within 16 weeks of surgery. There was no difference in overall survival or colon cancer-specific survival between those who received adjuvant chemotherapy from 8 to 12 weeks postsurgery compared with those who received it within 8 weeks. However, those who received chemotherapy 12 to 16 weeks after surgery and those who either received it >16 weeks after surgery or received no treatment had a 43% and 107% greater risk of dying, respectively, than those who received chemotherapy within 8 weeks of surgery (hazard ratio, 1.43 [95% confidence interval, 0.96-2.13] and hazard ratio, 2.07 [95% confidence interval, 1.56-2.76], respectively). Analyses were controlled for age, year, and region of residence at diagnosis; sex; neighborhood-level socioeconomic factors; and number of comorbidities.The results from this study were consistent with current guideline recommendations in Alberta that patients with stage III adenocarcinoma should receive chemotherapy within 12 weeks of surgery.

    View details for DOI 10.1002/cncr.25954

    View details for Web of Science ID 000293672700025

    View details for PubMedID 21319156

  • Utilization of oncology services and receipt of treatment: a comparison between patients with breast, colon, rectal, or lung cancer ANNALS OF ONCOLOGY Li, X., Butts, C., Fenton, D., King, K., Scarfe, A., Winget, M. 2011; 22 (8): 1902-1909

    Abstract

    Higher awareness could translate into better care for patients with breast cancer than for those with other cancers. This study examines utilization of two key oncology services across cancer sites: consultation with an oncologist and receipt of treatment.All residents of Alberta, Canada, who were diagnosed in 2005 with breast, colon, rectal, or lung cancer and had a disease stage that should be treated with chemotherapy, radiation therapy, or hormonal therapy were included. Data were obtained from the Alberta Cancer Registry and electronic cancer medical records. Percentages of patients who had a consultation and who received treatment were compared. Multivariable log-binomial regression models were used to identify patient characteristics associated with not having the outcomes.A much higher percentage of patients with breast cancer had consultations and received treatment (92% and 83%, respectively) than those with colon (83% and 59%), rectal (86% and 73%), or lung (77% and 66%) cancer. Age, disease stage, region of residence, and surgery status are related to having a consultation and/or receiving treatment but the relationship varies by cancer site.Efforts are needed to eliminate disparities in utilization of key cancer services across cancer sites.

    View details for DOI 10.1093/annonc/mdq692

    View details for Web of Science ID 000293300700030

    View details for PubMedID 21278218

  • A Comparison of Charlson and Elixhauser Comorbidity Measures to Predict Colorectal Cancer Survival Using Administrative Health Data CANCER Lieffers, J. R., Baracos, V. E., Winget, M., Fassbender, K. 2011; 117 (9): 1957-1965

    Abstract

    Cancer survival is related to features of the primary malignancy and concurrent presence of nonmalignant diseases (comorbidities), including weight-related conditions (obesity, weight loss). The Charlson and Elixhauser methods are 2 well-known methods that take comorbidities into account when explaining survival. They differ in both the number and categorization of comorbidities.Cancer, comorbidity, and survival data were acquired from inpatient administrative hospital records in 574 colorectal cancer patients. Robust Poisson regression was used to analyze 2- and 3-year survival according to cancer features and comorbidities classified by the Charlson and Elixhauser methods. Data for weight-related conditions (body mass index, weight loss) and performance status were acquired upon a new patient visit to the regional cancer center. Discrimination was assessed with the concordance (c) statistic.A base model (age, sex, stage) had excellent discrimination (c-statistic, 0.824 [2-year survival] and 0.827 [3-year survival]). The addition of Charlson comorbidities did not outperform the base model (c-statistic, 0.831 [2-year survival] and 0.833 [3-year survival]). Elixhauser comorbidities added higher discrimination compared with the base model, both in stage and overall (c-statistic, 0.852 [2-year survival] and 0.854 [3-year survival]; P < .01). The greatest increase in the c-statistic contributed by the addition of the Elixhauser comorbidities occurred in stage II patients (increased from 0.683 to 0.838). Overall, the Elixhauser comorbidities outperformed the Charlson comorbidities (P < .05). The use of self-reported weight and performance status data significantly increased discrimination by the Elixhauser method in 2-year but not 3-year survival.The Elixhauser method is a superior comorbidity risk-adjustment model for colorectal cancer survival prediction.

    View details for DOI 10.1002/cncr.25653

    View details for Web of Science ID 000289833100022

    View details for PubMedID 21509773

  • Uptake and tolerance of adjuvant chemotherapy in early stage NSCLC patients in Alberta, Canada LUNG CANCER Winget, M., Fleming, J., Li, X., Gao, Z., Butts, C. 2011; 72 (1): 52-58

    Abstract

    Adjuvant chemotherapy for early stage non-small cell lung cancer was approved for provincial insurance coverage in Alberta, Canada in 2004. The purpose of this study was to measure factors related to uptake of chemotherapy in eligible patients and compare toxicity and survival outcomes in the Alberta population with those found in clinical trials. All Alberta residents diagnosed with stage IB-IIB NSCLC from 2004 to 2006 who had surgery and a consultation with an oncologist to discuss initial treatment were included in the study. Diagnostic, demographic, and vital statistics data were obtained from the Alberta Cancer Registry; chart reviews were conducted to identify details related to treatments discussed, refused, co-morbidities, and toxicity. Analyses were conducted to identify factors associated with discussion and receipt of chemotherapy and toxicity. Toxicity and survival were calculated and compared to clinical trial results. 226 patients were included in the study. Adjuvant chemotherapy was not recommended to 57 patients (25%) and 30 patients (13%) refused chemotherapy. Primary reasons for not recommending chemotherapy were co-morbidities and/or frailty (24 patients). Of the 139 patients who began chemotherapy, 47 (34%) stopped treatment early. Stage II patients who received adjuvant chemotherapy had over a 2-fold decrease in risk of death compared to those who did not receive chemotherapy after adjusting for age and co-morbidities. Efforts to improve uptake of adjuvant chemotherapy in patients with stage II NSCLC should be made as the survival advantage appears to be comparable to that found in clinical trials.

    View details for DOI 10.1016/j.lungcan.2010.07.005

    View details for Web of Science ID 000289130700009

    View details for PubMedID 20708293

  • Characteristics of Patients With Stage III Colon Adenocarcinoma Who Fail to Receive Guideline-Recommended Treatment CANCER Winget, M., Hossain, S., Yasui, Y., Scarfe, A. 2010; 116 (20): 4849-4856

    Abstract

    Many patients with stage III colon adenocarcinoma do not receive adjuvant chemotherapy despite the proven survival advantage it offers. To enhance the provision of optimal cancer care, patient characteristics associated with not receiving guideline-adherent treatment must be identified among patients with operable, stage III colon adenocarcinoma.This was a population-based, retrospective study of all patients who underwent surgery for stage III colon adenocarcinoma diagnosed from 2002 through 2005 in Alberta, Canada. Demographic and treatment information captured in the Alberta Cancer Registry were linked to: 1) hospital discharge data to determine comorbidities, 2) electronic medical records to identify consults with oncologists, and 3) the 2001 Canadian census for neighborhood-level socioeconomic data. Multivariate log-binomial regression models were used to identify patient characteristics that were associated with not having a consultation with a medical oncologist and not receiving adjuvant chemotherapy.Of the 772 patients who underwent surgery for stage III colon adenocarcinoma and met the eligibility criteria, 618 patients (80%) had a consultation with an oncologist. Of those, 388 patients (63%) initiated adjuvant chemotherapy within 84 days of their surgery. Patient characteristics that were associated with not having a consultation with an oncologist were neighborhood income, geography, age, and comorbidities. Of those patients who had a consultation, after adjusting for comorbidities, only older age was related to not receiving adjuvant chemotherapy.The current results indicated that the proportion of patients with stage III colon adenocarcinoma who did not receive treatment according to evidence-based guidelines was appreciable. The authors concluded that the association of this failure with patient age, geography, and income is concerning and that evaluation of referral patterns and interventions are needed.

    View details for DOI 10.1002/cncr.25250

    View details for Web of Science ID 000282910800001

    View details for PubMedID 20578180

  • Comparison of Treatment Received Versus Long-Standing Guidelines for Stage III Colon and Stage II/III Rectal Cancer Patients Diagnosed in Alberta, Saskatchewan, and Manitoba in 2004 CancerCare 2008 Meeting Cree, M., Tonita, J., Turner, D., Nugent, Z., Alvi, R., Barss, R., King, C., Winget, M. CIG MEDIA GROUP, LP. 2009: 141–45

    Abstract

    Guideline-recommended treatment for stage II/III colorectal cancer includes postsurgical chemotherapy and/or radiation as standard of care. This study measures adherence to guidelines across 3 Canadian provinces and evaluates the relationship of patient characteristics with receiving standard care.All surgically treated patients diagnosed in 2004 with stage III colon or stage II/III rectal cancer and residing in Alberta, Saskatchewan, or Manitoba were identified from provincial cancer registries. Sex, age at diagnosis, and area of residence were also obtained from the cancer registry. The primary outcome of interest was receipt of standard care: surgery followed by chemotherapy or radiation therapy (adjuvant therapy). chi2 tests and binary regression with log link assessed the relationship of patient demographic characteristics (age, sex, residence, cancer disease stage) with receipt of standard care.About half of the patients received adjuvant therapy. Patients with stage III rectal cancer were more likely to receive adjuvant treatment than stage II patients in Alberta and Saskatchewan. There was a large decrease in the percentage of patients who received adjuvant treatment with increasing age in all the provinces (P < .001), ranging from about 80% of those aged < 65 years to about 20% of those aged >or= 75 years for colon cancer patients and from about 70% to 30%, respectively, for rectal cancer patients. The decrease of adjuvant treatment with increasing age was most marked in Alberta.The percentage of patients receiving guideline-recommended treatment is low. Reasons for lack of adherence to guidelines need to be addressed.

    View details for DOI 10.3816/CCC.2009.n.023

    View details for Web of Science ID 000268129500003

    View details for PubMedID 19632928

  • Predictors of Surgery and Consult with an Oncologist for Adjuvant Chemotherapy in Early Stage NSCLC Patients in Alberta, Canada JOURNAL OF THORACIC ONCOLOGY Winget, M., Stanger, J., Gao, Z., Butts, C. 2009; 4 (5): 629-634

    Abstract

    In the fall of 2004, adjuvant chemotherapy for early stage non-small cell lung cancer (NSCLC) patients was approved for coverage by the Alberta Cancer Board, the provincial agency responsible for systemic therapy in the province of Alberta. The purpose of this study was to measure the proportion of early stage NSCLC patients diagnosed between 2004 and 2006 that received surgery and subsequently had a consult with an oncologist at a cancer facility, and to identify factors related to receiving surgery and having a consult that could be addressed.A retrospective observational study was conducted. All patients diagnosed with stage IB, IIA, or IIB NSCLC in Alberta from 2004 to 2006 were identified from the Alberta cancer registry. Date of definitive surgery, gender, age at diagnosis, and area of residence were also obtained from the cancer registry and evaluated as predictors for surgery and oncology consult. Date of consult with an oncologist was obtained from the electronic medical record of the Alberta Cancer Board.There were 561 patients diagnosed with stage IB-IIB NSCLC from 2004 to 2006, 352 of whom had surgery and 255 of whom subsequently had a consult with an oncologist. Age and residence at diagnosis were both strongly associated with the likelihood of receiving surgery and the likelihood of attending a consult with an oncologist.Several areas of further research have been identified by this study including age and rural residence on treatment/referral patterns.

    View details for Web of Science ID 000265557700012

    View details for PubMedID 19276835

  • Palliative radiotherapy for women with breast cancer CLINICAL ONCOLOGY Danielson, B., Winget, M., Gao, Z., MURRAY, B., Pearcey, R. 2008; 20 (7): 506-512

    Abstract

    Palliative radiotherapy (PRT) plays an important role in women with metastatic breast cancer. However, not all cancer patients with an indication for PRT receive it. The aim of this study was to measure the use of PRT for women who have died of breast cancer in the Canadian province of Alberta, and to identify factors that might affect this use.All women who died of breast cancer in Alberta between 2000 and 2004 were identified from the Alberta Cancer Registry. PRT, defined as any radiotherapy given with palliative intent, was abstracted from the radiotherapy databases of the treatment facilities of the Alberta Cancer Board (ACB). The variables evaluated were: age at death, regional health authority (RHA), driving distance to nearest radiotherapy facility, receipt of initial treatment at an ACB facility, receipt of radiotherapy as part if initial treatment, residence in a city with an ACB facility, residence in a city with radiotherapy facilities or visiting radiation oncologists, median household income, and municipality population. Backwards stepwise logistic regression was used to determine the final set of predictor variables for the use of PRT.In total, 1906 women were identified as having died of breast cancer between 2000 and 2004, inclusive. Of these, 50.4% received at least one course of PRT. Factors associated with not receiving PRT in the final multiple logistic regression model for women who lived outside of the cities with radiotherapy facilities were: age>75 years, community size>10,000, median income<$47,000, and residence in RHA 4. For women living in cities with radiotherapy facilities, only age was significant.There are many factors that influence the receipt of PRT in Alberta that are unrelated to patient need. The education of physicians and patients, as well as the establishment of more radiotherapy facilities, will help to improve the use of PRT.

    View details for DOI 10.1016/j.clon.2008.04.013

    View details for Web of Science ID 000259748700003

    View details for PubMedID 18524556

  • Across-province standardization and comparative analysis of time-to-care intervals for cancer BMC CANCER Winget, M., Turner, D., Tonita, J., King, C., Nugent, Z., Alvi, R., Barss, R. 2007; 7

    Abstract

    A set of consistent, standardized definitions of intervals and populations on which to report across provinces is needed to inform the Provincial/Territorial Deputy Ministries of Health on progress of the Ten-Year Plan to Strengthen Health Care. The objectives of this project were to: 1) identify a set of criteria and variables needed to create comparable measures of important time-to-cancer-care intervals that could be applied across provinces and 2) use the measures to compare time-to-care across participating provinces for lung and colorectal cancer patients diagnosed in 2004.A broad-based group of stakeholders from each of the three participating cancer agencies was assembled to identify criteria for time-to-care intervals to standardize, evaluate possible intervals and their corresponding start and end time points, and finalize the selection of intervals to pursue. Inclusion/exclusion criteria were identified for the patient population and the selected time points to reduce potential selection bias. The provincial 2004 colorectal and lung cancer data were used to illustrate across-province comparisons for the selected time-to-care intervals.Criteria identified as critical for time-to-care intervals and corresponding start and end points were: 1) relevant to patients, 2) relevant to clinical care, 3) unequivocally defined, and 4) currently captured consistently across cancer agencies. Time from diagnosis to first radiation or chemotherapy treatment and the smaller components, time from diagnosis to first consult with an oncologist and time from first consult to first radiation or chemotherapy treatment, were the only intervals that met all four criteria. Timeliness of care for the intervals evaluated was similar between the provinces for lung cancer patients but significant differences were found for colorectal cancer patients.We identified criteria important for selecting time-to-care intervals and appropriate inclusion criteria that were robust across the agencies that did not result in an overly selective sample of patients to be compared. Comparisons of data across three provinces of the selected time-to-care intervals identified several important differences related to treatment and access that require further attention. Expanding this collaboration across Canada would facilitate improvement of and equitable access to quality cancer care at a national level.

    View details for DOI 10.1186/1471-2407-7-186

    View details for Web of Science ID 000251424400001

    View details for PubMedID 17916257

  • Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility CLINICAL CHEMISTRY Semmes, O. J., Feng, Z., Adam, B. L., Banez, L. L., Bigbee, W. L., Campos, D., Cazares, L. H., Chan, D. W., Grizzle, W. E., IZBICKA, E., Kagan, J., Malik, G., McLerran, D., Moul, J. W., Partin, A., Prasanna, P., Rosenzweig, J., Sokoll, L. J., Srivastava, S., Srivastava, S., Thompson, I., Welsh, M. J., White, N., Winget, M., Yasui, Y., Zhang, Z., Zhu, L. 2005; 51 (1): 102-112

    Abstract

    Protein expression profiling for differences indicative of early cancer has promise for improving diagnostics. This report describes the first stage of a National Cancer Institute/Early Detection Research Network-sponsored multiinstitutional evaluation and validation of this approach for detection of prostate cancer.Two sequential experimental phases were conducted to establish interlaboratory calibration and standardization of the surface-enhanced laser desorption (SELDI) instrumental and assay platform output. We first established whether the output from multiple calibrated Protein Biosystem II SELDI-ionization time-of-flight mass spectrometry (TOF-MS) instruments demonstrated acceptable interlaboratory reproducibility. This was determined by measuring mass accuracy, resolution, signal-to-noise ratio, and normalized intensity of three m/z "peaks" present in a standard pooled serum sample. We next evaluated the ability of the calibrated and standardized instrumentation to accurately differentiate between selected cases of prostate cancer and control by use of an algorithm developed from data derived from a single site 2 years earlier.When the described standard operating procedures were established at all laboratory sites, the across-laboratory measurements revealed a CV for mass accuracy of 0.1%, signal-to-noise ratio of approximately 40%, and normalized intensity of 15-36% for the three pooled serum peaks. This was comparable to the intralaboratory measurements of the same peaks. The instrument systems were then challenged with sera from a selected group of 14 cases and 14 controls. The classification agreement between each site and the established decision algorithm were examined by use of both raw peak intensity boosting and ranked peak intensity boosting. All six sites achieved perfect blinded classification for all samples when boosted alignment of raw intensities was used. Four of six sites achieved perfect blinded classification with ranked intensities, with one site passing the criteria of 26 of 28 correct and one site failing with 19 of 28 correct.These results demonstrate that "between-laboratory" reproducibility of SELDI-TOF-MS serum profiling approaches that of "within-laboratory" reproducibility as determined by measuring discrete m/z peaks over time and across laboratories.

    View details for DOI 10.1373/clinchem.2004.038950

    View details for Web of Science ID 000225991100019

    View details for PubMedID 15613711

  • A web-based system for managing and co-ordinating multiple multisite studies CLINICAL TRIALS Winget, M., Kincaid, H., Lin, P., Li, L., Kelly, S., Thornquist, M. 2005; 2 (1): 42-49

    Abstract

    Efficient and secure collection and management of information is essential in any modern biomedical study. Data management and coordination of multisite studies is a complex process. It involves development of systems for data collection, data cleaning with quality assurance checks, and specimen tracking, as well as development of procedures for conducting the study, training clinical sites, and communicating with sites to answer study questions and resolve and track data inquiries and resolutions. We developed a secure web-based system that is designed to automate evaluation of eligibility criteria and data collection, track specimens, serve as a resource for study-specific information, facilitate communication across sites in multisite studies, track data queries and resolutions, and allow administrative management of studies. The system combines a common framework across studies that defines the internal structure for all the web pages, with a study-specific one that defines the content of each page via a relational database. This combination creates a flexible and efficient environment enabling several multisite studies to be simultaneously or consecutively implemented and managed in a timely manner. We describe the development process, the system and its evaluation, current status, lessons learned, and future development plans.

    View details for Web of Science ID 000232622500007

    View details for PubMedID 16279578

  • An automated peak identification/calibration procedure for high-dimensional protein measures from mass spectrometers JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY Yasui, Y., McLerran, D., Adam, B. L., Winget, M., Thornquist, M., Feng, Z. D. 2003: 242-248
  • A data-analytic strategy for protein biomarker discovery: profiling of high-dimensional proteomic data for cancer detection BIOSTATISTICS Yasui, Y., Pepe, M., Thompson, M. L., Adam, B. L., Wright, G. L., Qu, Y. S., Potter, J. D., Winget, M., Thornquist, M., Feng, Z. D. 2003; 4 (3): 449-463

    Abstract

    With recent advances in mass spectrometry techniques, it is now possible to investigate proteins over a wide range of molecular weights in small biological specimens. This advance has generated data-analytic challenges in proteomics, similar to those created by microarray technologies in genetics, namely, discovery of 'signature' protein profiles specific to each pathologic state (e.g. normal vs. cancer) or differential profiles between experimental conditions (e.g. treated by a drug of interest vs. untreated) from high-dimensional data. We propose a data-analytic strategy for discovering protein biomarkers based on such high-dimensional mass spectrometry data. A real biomarker-discovery project on prostate cancer is taken as a concrete example throughout the paper: the project aims to identify proteins in serum that distinguish cancer, benign hyperplasia, and normal states of prostate using the Surface Enhanced Laser Desorption/Ionization (SELDI) technology, a recently developed mass spectrometry technique. Our data-analytic strategy takes properties of the SELDI mass spectrometer into account: the SELDI output of a specimen contains about 48,000 (x, y) points where x is the protein mass divided by the number of charges introduced by ionization and y is the protein intensity of the corresponding mass per charge value, x, in that specimen. Given high coefficients of variation and other characteristics of protein intensity measures (y values), we reduce the measures of protein intensities to a set of binary variables that indicate peaks in the y-axis direction in the nearest neighborhoods of each mass per charge point in the x-axis direction. We then account for a shifting (measurement error) problem of the x-axis in SELDI output. After this pre-analysis processing of data, we combine the binary predictors to generate classification rules for cancer, benign hyperplasia, and normal states of prostate. Our approach is to apply the boosting algorithm to select binary predictors and construct a summary classifier. We empirically evaluate sensitivity and specificity of the resulting summary classifiers with a test dataset that is independent from the training dataset used to construct the summary classifiers. The proposed method performed nearly perfectly in distinguishing cancer and benign hyperplasia from normal. In the classification of cancer vs. benign hyperplasia, however, an appreciable proportion of the benign specimens were classified incorrectly as cancer. We discuss practical issues associated with our proposed approach to the analysis of SELDI output and its application in cancer biomarker discovery.

    View details for Web of Science ID 000184100800011

    View details for PubMedID 12925511

  • Development of common data elements: the experience of and recommendations from the early detection research network INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS Winget, M. D., Baron, J. A., Spitz, M. R., Brenner, D. E., Warzel, D., Kincaid, H., Thornquist, M., Feng, Z. D. 2003; 70 (1): 41-48

    Abstract

    There have been an increasing number of large research consortia in recent years funded by the National Cancer Institute (NCI) to facilitate multi-disciplinary, multi-institutional cancer research. Some of these consortia have central data collection plans similar to a multi-center clinical trial whereas others plan to store data locally and pool or share the data at a later date. Regardless of the goal of the consortium, there is a need to standardize the way certain data are collected and stored, transferred, or reported across the institutions involved. This communication is a report of the process and current status of the development of common data elements (CDEs) by the Early Detection Research Network (EDRN). The development of the CDEs involved several stages with each stage requiring input from multi-disciplinary experts in oncology, epidemiology, biostatistics, pathology, informatics, and study coordination. An effort was made to be consistent with other consortia developing similar CDEs and to follow data standards when available. Initial focus was on identifying the minimum data that would be necessary to collect on all EDRN study participants and EDRN specimens. There are currently CDEs in the development or pilot phase for eight different organ sites and 13 different types of specimen procurements and plans to develop CDEs for 12 or more additional types of specimens.

    View details for DOI 10.1016/S1386-5056(03)00005-4

    View details for Web of Science ID 000182905900005

    View details for PubMedID 12706181

  • A national virtual specimen database for early cancer detection 16th IEEE Symposium on Computer-Based Medical Systems Kincaid, H., Kelly, S., Crichton, D., Johnsey, D., Winget, M., Srivastava, S. IEEE COMPUTER SOC. 2003: 117–123
  • Phases of biomarker development for early detection of cancer JOURNAL OF THE NATIONAL CANCER INSTITUTE Pepe, M. S., Etzioni, R., Feng, Z. D., Potter, J. D., Thompson, M. L., Thornquist, M., Winget, M., Yasui, Y. 2001; 93 (14): 1054-1061

    View details for Web of Science ID 000169829000009

    View details for PubMedID 11459866

  • Breast cancer risk and "delayed" primary Epstein-Barr virus infection CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Yasui, Y., Potter, J. D., Stanford, J. L., Rossing, M. A., Winget, M. D., Bronner, M., Daling, J. 2001; 10 (1): 9-16

    Abstract

    Parallel to its established causal association with both infectious mononucleosis (IM) and young adulthood Hodgkin disease (YAHD), we propose a hypothesis that "delayed" primary EBV infection (i.e., primary infection occurring during adolescence or adulthood) is associated with elevated breast cancer risk. We evaluated this hypothesis with two investigations, one descriptive and the other analytic. The descriptive study used international/United States cancer registry data to assess the association between incidence rates of breast cancer and those of YAHD. The incidence rates of the seemingly unrelated neoplasms were strongly correlated (correlation coefficients of 0.74 and 0.88 for international and United States data, respectively; these were higher than the correlation coefficients of YAHD with two other cancers that we considered). Populations with higher incidence rates corresponded to those with higher likelihood of delayed primary EBV infection. The analytical study was based on a population-based case-control study of breast cancer in middle-aged women. Age-adjusted odds ratios of breast cancer in women who reported a history of IM, relative to women who did not, increased monotonically from 0.55 [95% confidence interval (CI), 0.05-6.17] for women with 0-9 years of age at IM onset to 2.67 (CI, 1.04-6.89) for women with > or =25 years of age at IM onset (P = 0.016). An older age at tonsillectomy, another surrogate of delayed EBV exposure, was also associated with increased risk of breast cancer: odds ratios, 0.92 (CI, 0.57-1.48) and 1.76 (CI, 1.15-2.69) for women with tonsillectomy at 0-4 years of age and > or =15 years of age, respectively (P = 0.018). Adjusting for additional potential confounders did not modify the associations appreciably. The implications of the findings and a potential biological mechanism are presented.

    View details for Web of Science ID 000166651600003

    View details for PubMedID 11205495

  • An empirical evaluation of various priors in the empirical Bayes estimation of small area disease risks STATISTICS IN MEDICINE Yasui, Y., Liu, H., Benach, J., Winget, M. 2000; 19 (17-18): 2409-2420

    Abstract

    Empirical and fully Bayes estimation of small area disease risks places a prior distribution on area-specific risks. Several forms of priors have been used for this purpose including gamma, log-normal and non-parametric priors. Spatial correlation among area-specific risks can be incorporated in log-normal priors using Gaussian Markov random fields or other models of spatial dependence. However, the criterion for choosing one prior over others has been mostly logical reasoning. In this paper, we evaluate empirically the various priors used in the empirical Bayes estimation of small area disease risks. We utilize a Spanish mortality data set of a 12-year period to give the underlying true risks, and estimate the true risks using only a 3-year portion of the data set. Empirical Bayes estimates are shown to have substantially smaller mean squared errors than Poisson likelihood-based estimates. However, relative performances of various priors differ across a variety of mortality outcomes considered. In general, the non-parametric prior provides good estimates for lower-risk areas, while spatial priors provide good estimates for higher-risk areas. Ad hoc composite estimates averaging the estimates from the non-parametric prior and those from a spatial log-normal prior appear to perform well overall. This suggests that an empirical Bayes prior that strikes a balance between these two priors, if one can construct such a prior, may prove to be useful for the estimation of small area disease risks.

    View details for Web of Science ID 000089275000016

    View details for PubMedID 10960862

  • Antibody to human immunodeficiency virus type 1 (HIV-1) gp160 in mucosal specimens of asymptomatic HIV-1-infected volunteers parenterally immunized with an experimental recombinant HIV-1 IIIB gp160 vaccine CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY Lambert, J. S., Viscidi, R., Walker, M. C., Clayman, B., Winget, M., Wolff, M., Schwartz, D. H. 1997; 4 (3): 302-308

    Abstract

    Twenty-two human immunodeficiency virus type 1 (HIV-1)-infected, asymptomatic volunteers with CD4 cell counts of >600 cells/mm3 who were enrolled in a phase I immunotherapy trial comparing two schedules of immunization of an HIV-1 IIIB-based recombinant gp160 (rgp160) experimental vaccine were evaluated for rgp160-specific antibodies in parotid saliva, genital secretions, and serum. When the study was unblinded, it was determined that five volunteers had received rgp160 on a month 0, 1, 2, 3, 4, and 5 immunization schedule, seven volunteers had received rgp160 on a month 0, 1, 2, and 5 schedule, five had received alum/deoxycholate placebo, and seven had received a licensed hepatitis B virus vaccine. Five volunteers consented to the donation of parotid saliva but not genital secretions. Prior to immunization, parotid saliva specimens were available for 11 of 22 volunteers, seminal plasma (SP) specimens were available for 7 of 22 volunteers, cervicovaginal lavage (CVL) specimens were available for 5 of 22 volunteers, and serum was available for 22 of 22 volunteers. These baseline specimens and specimens collected at 1 and 7 months after the final immunizations were assessed by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) and IgA antibodies specific for HIV-1 LAI rgp160 or HIV-1 MN rgp160. No augmentation in HIV rgp160-specific IgG or IgA antibody production in either parotid saliva or serum specimens of vaccinees compared to that in controls was observed after immunization. There were insufficient numbers of SP or CVL specimens available for statistical comparisons between vaccinees and controls. Overall, anti-LAI rgp160 IgG antibodies were detected in the parotid saliva specimens of 20 of 22 volunteers, the seminal plasma specimens of 11 of 11 volunteers, and the CVL specimens of 6 of 6 volunteers and in 21 of 22 serum specimens. Fewer volunteers expressed anti-LAI rgp160 IgA antibodies in mucosal or serum specimens: 11 of 22 parotid saliva specimens, 3 of 11 SP specimens, 3 of 5 CVL samples, and 12 of 22 sera.

    View details for Web of Science ID A1997WX24900013

    View details for PubMedID 9144368

  • Wood-burning stoves and lower respiratory illnesses in Navajo children PEDIATRIC INFECTIOUS DISEASE JOURNAL Robin, L. F., Lees, P. S., Winget, M., Steinhoff, M., Moulton, L. H., Santosham, M., Correa, A. 1996; 15 (10): 859-865

    Abstract

    Acute lower respiratory illnesses (ALRI) have been associated with exposure to domestic smoke. To examine further this association, a case-control study was conducted among Navajo children seen at the Public Health Service Indian Hospital at Fort Defiance, AZ.Cases, children hospitalized with an ALRI (n = 45), were ascertained from the inpatient logs during October, 1992, through March, 1993. Controls, children who had a health record at the same hospital and had never been hospitalized for ALRI, were matched 1:1 to cases on date of birth and gender. Home interviews of parents of subjects during March and April, 1993, elicited information on heating and cooking fuels and other household characteristics. Indoor air samples were collected for determination of time-weighted average concentrations of respirable particles (i.e. < 10 microns in diameter).Age of cases at the time of admission ranged from 1 to 24 months (median, 7 months); 60% of the cases were male. Matched pair analysis revealed an increased risk of ALRI for children living in households that cooked with any wood (odds ratio (OR), 5.0; 95% confidence interval (CI), 0.6 to 42.8), had indoor air concentrations of respirable particles > or = 65 micrograms/m3 (i.e. 90th percentile) (OR 7.0, 95% CI 0.9 to 56.9), and where the primary caretaker was other than the mother (OR 9, 95% CI 1.1 to 71.4). Individual adjustment for potential confounders resulted in minor change (i.e. < 20%) in these results. Indoor air concentration of respirable particles was positively correlated with cooking and heating with wood (P < 0.02) but not with other sources of combustion emissions.Cooking with wood-burning stoves was associated with higher indoor air concentrations of respirable particles and with an increased risk of ALRI in Navajo children.

    View details for Web of Science ID A1996VL70800004

    View details for PubMedID 8895916

  • Immunoglobulin G subclass responses of children during infection with Onchocerca volvulus CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY Gbakima, A. A., Nutman, T. B., Bradley, J. E., McReynolds, L. A., Winget, M. D., Hong, Y., Scott, A. L. 1996; 3 (1): 98-104

    Abstract

    To characterize the patterns of immunoglobulin G (IgG) subclass and IgE reactivity during the early stages of onchocerciasis, sera were collected from 224 children (age groups, 2 to 5, 6 to 10, and 11 to 15 years) residing in a region of Sierra Leone where Onchocerca volvulus is endemic, and these samples were tested by enzyme-linked immunosorbent assay for their reactivity to adult antigens (OvAg) and against four recombinant proteins (OV11, OV27, OV29, and OV16). Over 88% of the samples contained detectable levels of anti-OvAg IgG. In samples from microfilaria (MF)-positive children, IgG4 responses were significantly elevated and constituted on average 39, 35 and 28% of the total IgG responses for the age groups of 2 to 5, 6 to 10, and 11 to 15 years, respectively. For MF-negative individuals, the mean contributions of IgG4 to the total IgG response were 11% (2 to 5 years), 27% (6 to 10 years), and 56% (11 to 15 years). OvAg-specific IgE was detectable in the sera from both MF-negative and MF-positive individuals. To increase the specificity of the response, recombinant antigens OV11, OV27, and OV29 were tested individually or as a cocktail. Nearly 50% of the MF-negative children and 85% of the MF-positive children had detectable levels of IgG against at least one of the recombinant antigens. Only a small portion of the IgG against the recombinant peptides was IgG4. The prevalence of IgG against OV16 in samples from MF-negative children was 51%, and that for MF-positive children was 75%. The general profile of the humoral immune responses mounted by both MF-positive and a large percentage of the MF-negative children during the initial phases of infection with O. volvulus is similar to the profile reported for adults harboring chronic O. volvulus infections. These results suggest that very quickly after infection, the interactions between parasite and host result in an immunological environment that may contribute to the maintenance of a long-term, chronic infection.

    View details for Web of Science ID A1996TP77700018

    View details for PubMedID 8770512

  • IMPACT OF VITAMIN-A SUPPLEMENTATION ON HEMATOLOGICAL INDICATORS OF IRON-METABOLISM AND PROTEIN STATUS IN CHILDREN NUTRITION RESEARCH Semba, R. D., MUHILAL, M. P., West, K. P., Winget, M., Natadisastra, G., Scott, A., Sommer, A. 1992; 12 (4-5): 469-478
  • THE EXTRACELLULAR DOMAIN OF HER2/NEU IS A POTENTIAL IMMUNOGEN FOR ACTIVE SPECIFIC IMMUNOTHERAPY OF BREAST-CANCER JOURNAL OF BIOLOGICAL RESPONSE MODIFIERS Fendly, B. M., Kotts, C., Vetterlein, D., LEWIS, G. D., Winget, M., CARVER, M. E., Watson, S. R., SARUP, J., SAKS, S., Ullrich, A., SHEPARD, H. M. 1990; 9 (5): 449-455

    Abstract

    The proto-oncogene HER2/neu encodes a protein tyrosine kinase (p185HER2) that is homologous to the human epidermal growth factor receptor. Amplification and/or overexpression of HER2/neu occurs in multiple human malignancies and appears to be integrally involved in progression of some breast and ovarian cancers. Because of this fact, HER2/neu is an intriguing target for specific cancer therapeutic strategies. One such strategy is active specific immunotherapy, in which the immune system is targeted at specific antigens expressed by tumor cells. We have employed a transfected cell line that secretes the extracellular domain of p185HER2 as a source of HER2-derived immunogen in a guinea pig model. The immunized animals developed a cellular immune response, as monitored by delayed-type hypersensitivity, and antisera derived from immunized animals specifically inhibited the in vitro growth of human breast tumor cells overexpressing p185HER2. These data provide support for an immunotherapeutic approach to cancers characterized by overexpression of the HER2/neu proto-oncogene.

    View details for Web of Science ID A1990EB95400001

    View details for PubMedID 1979347

  • CHARACTERIZATION OF MURINE MONOCLONAL-ANTIBODIES REACTIVE TO EITHER THE HUMAN EPIDERMAL GROWTH-FACTOR RECEPTOR OR HER2 NEU GENE-PRODUCT CANCER RESEARCH Fendly, B. M., Winget, M., Hudziak, R. M., Lipari, M. T., NAPIER, M. A., Ullrich, A. 1990; 50 (5): 1550-1558

    Abstract

    High levels of expression of either the epidermal growth factor receptor or the receptor-like HER2/neu gene product p185HER2 have been observed in a variety of human malignancies. Because of the association of this high level expression with certain human tumors, we have generated a panel of monoclonal antibodies specific for either the epidermal growth factor receptor or p185HER2 to study their structure, function, and antigenic domains in the normal and neoplastic states. We used the epidermoid carcinoma line A431 to generate five monoclonal antibodies which immunoprecipitate the epidermal growth factor receptor. These monoclonal antibodies bind to the extracellular domain of the epidermal growth factor receptor and demonstrate variable effects on epidermal growth factor binding. We used a stably transfected NIH 3T3 cell line expressing the HER2/neu gene to produce and characterize 10 monoclonal antibodies which immunoprecipitate p185HER2. These monoclonal antibodies bind to the extracellular domain of p185HER2 and do not cross-react with the epidermal growth factor receptor. The characteristics and potential applications of these monoclonal antibodies will be discussed.

    View details for Web of Science ID A1990CQ37700032

    View details for PubMedID 1689212

  • EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH FACTOR-ALPHA BIND DIFFERENTLY TO THE EPIDERMAL GROWTH-FACTOR RECEPTOR BIOCHEMISTRY Winkler, M. E., OCONNOR, L., Winget, M., FENDLY, B. 1989; 28 (15): 6373-6378

    Abstract

    Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) compete with each other for binding to the EGF receptor. These two growth factors have similar actions, but there are distinguishable differences in their biological activities. It has never been clear how this one receptor can mediate different responses. A monoclonal antibody to the EGF receptor (13A9) has been identified which has only small effects on the binding of EGF to the EGF receptor, but which has very large effects on the binding of TGF alpha to the EGF receptor; 5 micrograms/mL antibody has been shown to totally block 0.87 microM TGF alpha from binding to purified EGF receptor and to lower both the high- and low-affinity binding constants of TGF alpha binding to EGF receptor on A431 cells by about 10-fold. The 13A9 antibody causes a 2.5-fold stimulation of the tyrosine kinase activity of partially purified EGF receptor, compared to a 4.0-fold stimulation of the tyrosine kinase activity by EGF under the same conditions. The data suggest either that the antibody stabilizes a conformation of the EGF receptor which is not favorable for TGF alpha binding or that it blocks a part of the surface of the receptor which is necessary for TGF alpha binding but not EGF binding.

    View details for Web of Science ID A1989AH82900032

    View details for PubMedID 2790004

  • P185HER2 MONOCLONAL-ANTIBODY HAS ANTIPROLIFERATIVE EFFECTS INVITRO AND SENSITIZES HUMAN-BREAST TUMOR-CELLS TO TUMOR NECROSIS FACTOR MOLECULAR AND CELLULAR BIOLOGY Hudziak, R. M., LEWIS, G. D., Winget, M., Fendly, B. M., SHEPARD, H. M., Ullrich, A. 1989; 9 (3): 1165-1172

    Abstract

    The HER2/c-erbB-2 gene encodes the epidermal growth factor receptorlike human homolog of the rat neu oncogene. Amplification of this gene in primary breast carcinomas has been show to correlate with poor clinical prognosis for certain cancer patients. We show here that a monoclonal antibody directed against the extracellular domain of p185HER2 specifically inhibits the growth of breast tumor-derived cell lines overexpressing the HER2/c-erbB-2 gene product and prevents HER2/c-erbB-2-transformed NIH 3T3 cells from forming colonies in soft agar. Furthermore, resistance to the cytotoxic effect of tumor necrosis factor alpha, which has been shown to be a consequence of HER2/c-erbB-2 overexpression, is significantly reduced in the presence of this antibody.

    View details for Web of Science ID A1989T444300032

    View details for PubMedID 2566907