Mammographic microcalcifications and breast cancer tumorigenesis: a radiologic-pathologic analysis.

BACKGROUND: Microcalcifications (MCs) are tiny deposits of calcium in breast soft tissue. Approximately 30% of early invasive breast cancers have fine, granular MCs detectable on mammography; however, their significance in breast tumorigenesis is controversial. This study had two objectives: (1) to find associations between mammographic MCs and tumor pathology, and (2) to compare the diagnostic value of mammograms and breast biopsies in identifying malignant MCs. METHODS: A retrospective chart review was performed for 937 women treated for breast cancer during 2000-2012 at St. Michael's Hospital. Demographic information (age and menopausal status), tumor pathology (size, histology, grade, nodal status and lymphovascular invasion), hormonal status (ER and PR), HER-2 over-expression and presence of MCs were collected. Chi-square tests were performed for categorical variables and t-tests were performed for continuous variables. All p-values less than 0.05 were considered statistically significant. RESULTS: A total of 937 patient charts were included. About 38.3% of the patients presented with mammographic MCs on routine mammographic screening. Patients were more likely to have MCs if they were HER-2 positive (52.9%; p < 0.001). There was a significant association between MCs and peri-menopausal status with a mean age of 50 (64%; p = 0.012). Patients with invasive ductal carcinomas (40.9%; p = 0.001) were more likely to present with MCs than were patients with other tumor histologies. Patients with a heterogeneous breast density (p = 0.031) and multifocal breast disease (p = 0.044) were more likely to have MCs on mammograms. There was a positive correlation between MCs and tumor grade (p = 0.057), with grade III tumors presenting with the most MCs (41.3%). A total of 52.2% of MCs were missed on mammograms which were visible on pathology (p < 0.001). CONCLUSION: This is the largest study suggesting the appearance of MCs on mammograms is strongly associated with HER-2 over-expression, invasive ductal carcinomas, peri-menopausal status, heterogeneous breast density and multifocal disease.

Is knowledge translation adequate? A quality assurance study of staging investigations in early stage breast cancer patients.

After primary surgery, patients diagnosed with early stage breast cancer undergo radiological investigations based on pathologic stage of disease to rule out distant metastases. Published guidelines can aid clinicians in determining which tests are appropriate based on stage of disease. We wished to assess the consistency of radiological staging in an academic community oncology setting with standard guidelines and to determine the overall impact of non-adherence to these guidelines. A retrospective cohort study was conducted for new breast cancer patients seen at a single institution between January 2009 and April 2010. Patients were included if initial diagnosis and primary surgery was at this institution. Pathologic stage and radiological tests completed were recorded. A literature review was performed and the results were compared with those from this study to determine overall adherence rates. Subsequently, a cost analysis was performed to determine the financial impact at this centre. 231 patients met eligibility criteria for inclusion in this study. A large proportion of patients were over-staged with 129 patients (55%) undergoing unnecessary investigations according to guidelines. Specifically, 59% of stage I patients and 58% of stage II patients were over-investigated. Distant metastases at the time of diagnosis were found in three patients, all of whom had stage III disease (1.3%). The literature reviewed revealed similar non-adherence rates in other centres. The estimated cost of such non-adherence is in the range of $78 (CDN) per new early stage breast cancer patient seen at this centre. This oncology centre has a low adherence to practice guidelines for staging investigations in breast cancer patients, with 55% of patients undergoing unnecessary tests. Very few patients had metastases at diagnosis, and all had pathological stage III disease. Efforts may need to focus on improving knowledge translation across clinical oncology settings to increase guideline adherence.

Impact of new chemotherapeutic and targeted agents on survival in stage IV non-small cell lung cancer.

PURPOSE: Significant advances in the systemic management of metastatic non-small cell lung cancer (NSCLC) have occurred over the past decade, with options now including multiple lines of chemotherapy, epidermal growth factor receptor inhibitors, and antiangiogenic agents. Improvements in overall survival have been demonstrated in randomized controlled trials comparing these newer agents with best supportive care or standard therapy. This study examined uptake of these therapies in general practice and their impact on survival. METHODS: This retrospective cohort study compared demographic, treatment, and survival data among 987 patients diagnosed with stage IV NSCLC at two institutions in 1998, 2003, and 2008. Cohorts were selected based on intervals when doublet chemotherapy, second-line chemotherapy, and targeted agents were incorporated into the standard treatment regimen. RESULTS: The proportion of patients receiving systemic therapy increased over time (20% in 1998, 42% in 2008). Overall survival improved significantly across cohorts (p < .001), with 2-year survival rates of 0.3% in 1998, 4% in 2003, and 15% in 2008. In a multivariate survival analysis, the 2003 and 2008 cohorts were independently associated with longer survival, as was the use of one or more lines of systemic therapy. Elderly patients (aged ≥70 years) were also more likely to receive systemic therapy over time, with longer overall survival (p < .001). CONCLUSION: Over the past decade, there has been an increasing use of systemic therapy in stage IV NSCLC patients, including the elderly. This has been associated with significantly longer overall survival.

Perceived barriers to guideline adherence: a survey among general practitioners.

BACKGROUND: Despite considerable efforts to promote and support guideline use, adherence is often suboptimal. Barriers to adherence vary not only across guidelines but also across recommendations within guidelines. The aim of this study was to assess the perceived barriers to guideline adherence among GPs by focusing on key recommendations within guidelines. METHODS: We conducted a cross-sectional electronic survey among 703 GPs in the Netherlands. Sixteen key recommendations were derived from four national guidelines. Six statements were included to address the attitudes towards guidelines in general. In addition, GPs were asked to rate their perceived adherence (one statement) and the perceived barriers (fourteen statements) for each of the key recommendations, based on an existing framework. RESULTS: 264 GPs (38%) completed the questionnaire. Although 35% of the GPs reported difficulties in changing routines and habits to follow guidelines, 89% believed that following guidelines leads to improved patient care. Perceived adherence varied between 52 and 95% across recommendations (mean: 77%). The most perceived barriers were related to external factors, in particular patient ability and behaviour (mean: 30%) and patient preferences (mean: 23%). Lack of applicability of recommendations in general (mean: 22%) and more specifically to individual patients (mean: 25%) were also frequently perceived as barriers. The scores on perceived barriers differed largely between recommendations [minimum range 14%; maximum range 67%]. CONCLUSIONS: Dutch GPs have a positive attitude towards the NHG guidelines, report high adherence rates and low levels of perceived barriers. However, the perceived adherence and perceived barriers varied largely across recommendations. The most perceived barriers across recommendations are patient related, suggesting that current guidelines do not always adequately incorporate patient preferences, needs and abilities. It may be useful to provide tools such as decision aids, supporting the flexible use of guidelines to individual patients in practice.

Cost Effectiveness of Treatments for Chronic Constipation: A Systematic Review.

BACKGROUND: Chronic constipation (CC) has a significant impact on patients' quality of life and imposes an economic burden on individuals and the healthcare system. Treatment options include dietary changes, lifestyle modifications, fibre supplements, stool softeners, and laxatives. OBJECTIVE: We undertook this systematic review to comprehensively evaluate the cost effectiveness of treatments for CC. METHODS: We searched ten common databases to identify economic evaluations published to 13 June 2017. Abstract and full-text review were completed in duplicate. The quality of the included studies was assessed using the Consensus on Health Economic Criteria. Data extracted included costs and outcomes of treatments for CC and cost-effectiveness methods. A narrative synthesis was completed. RESULTS: From the 4338 unique citations identified, 79 proceeded to full-text review, with 10 studies forming the final dataset. Eight different definitions of CC were used to define the study populations. Study designs used were decision-tree models (4), Markov model (1), and retrospective (1) and prospective (4) studies. Quality-adjusted life-years (QALY) were reported in five studies; other outcomes included, discontinuation of laxative treatment and frequency of bowel movements. The majority of studies stated that their results were from a payer perspective; however, some of these studies only considered treatment costs, a subset of costs included in the payer perspective. Lifestyle advice, dietary treatments and abdominal massage were each compared with current care with laxatives, while polyethylene glycol (PEG) and senna-fibre combination were each compared with lactulose. Two studies compared newer treatments in patients who had not responded to laxatives: prucalopride was compared with continuing laxatives, and linaclotide was compared with lubiprostone. All of the interventions were reported by the study authors to be cost effective, with the exception of abdominal massage. CONCLUSIONS: A consistent definition of CC is needed and the QALY should be used to capture the diverse symptoms of CC. Further analysis is needed comparing all available treatments for patients who have not responded to laxatives. Overall, results from economic evaluations appear to align with stepwise practice guidelines.

Do the American Society of Clinical Oncology Value Framework and the European Society of Medical Oncology Magnitude of Clinical Benefit Scale Measure the Same Construct of Clinical Benefit?

Purpose Whether the ASCO Value Framework and the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) measure similar constructs of clinical benefit is unclear. It is also unclear how they relate to quality-adjusted life-years (QALYs) and funding recommendations in the United Kingdom and Canada. Methods Randomized clinical trials of oncology drug approvals by the US Food and Drug Administration, European Medicines Agency, and Health Canada between 2006 and August 2015 were identified and scored using the ASCO version 1 (v1) framework, ASCO version 2 (v2) framework, and ESMO-MCBS by at least two independent reviewers. Spearman correlation coefficients were calculated to assess construct (between frameworks) and criterion validity (against QALYs from the National Institute for Health and Care Excellence [NICE] and the pan-Canadian Oncology Drug Review [pCODR]). Associations between scores and NICE/pCODR recommendations were examined. Inter-rater reliability was assessed using intraclass correlation coefficients. Results From 109 included randomized clinical trials, 108 ASCOv1, 111 ASCOv2, and 83 ESMO scores were determined. Correlation coefficients for ASCOv1 versus ESMO, ASCOv2 versus ESMO, and ASCOv1 versus ASCOv2 were 0.36 (95% CI, 0.15 to 0.54), 0.17 (95% CI, -0.06 to 0.37), and 0.50 (95% CI, 0.35 to 0.63), respectively. Compared with NICE QALYs, correlation coefficients were 0.45 (ASCOv1), 0.53 (ASCOv2), and 0.46 (ESMO); with pCODR QALYs, coefficients were 0.19 (ASCOv1), 0.20 (ASCOv2), and 0.36 (ESMO). None of the frameworks were significantly associated with NICE/pCODR recommendations. Inter-rater reliability was good for all frameworks. Conclusion The weak-to-moderate correlations of the ASCO frameworks with the ESMO-MCBS, as well as their correlations with QALYs and with NICE/pCODR funding recommendations, suggest different constructs of clinical benefit measured. Construct convergent validity with the ESMO-MCBS did not increase with the updated ASCO framework.

General practitioners' preferences for interventions to improve guideline adherence.

RATIONALE, AIMS AND OBJECTIVES: Interventions aimed at improving guideline adherence should take into account the specific features of the target users; however, it is unclear how general practitioners (GPs) evaluate the different types of interventions. The aim of this paper was to identify GPs' preferences for interventions to improve guideline adherence in practice and whether these differ across key guideline recommendations. METHOD: An electronic survey was conducted among 703 GPs working in the south-western part of the Netherlands. Each survey focused on two of four guidelines: cerebrovascular accident, eye inflammation, thyroid disorders and urinary tract infection. GPs were asked to rate potential interventions in terms of their usefulness in improving guideline adherence in general and for specific key guideline recommendations. RESULTS: 264 GPs (38%) completed the questionnaire. In general, GPs preferred interactive small group meetings (84% rated this as much or very much encouraging), audit and feedback (53%), organizational interventions (50%) and the use of local opinion leaders (50%) as methods for improving guideline adherence. Financial interventions (24%), distribution of educational materials (22%) and big group educational meetings (21%) were of least interest. Some interventions were preferred by GPs irrespective of the specific key recommendations (e.g. audit and feedback), while ratings for other interventions differed across key recommendations (reminders/computer support). CONCLUSIONS: To implement guidelines, interventions need to be identified that are acceptable and appealing to the target group. GPs seem to have general and recommendation-specific preferences regarding interventions, these should be taken into account when developing plans for guideline implementation to encourage the uptake of guidelines in practice.

Early economic evaluation of emerging health technologies: protocol of a systematic review.

BACKGROUND: The concept of early health technology assessment, discussed well over a decade, has now been collaboratively implemented by industry, government, and academia to select and expedite the development of emerging technologies that may address the needs of patients and health systems. Early economic evaluation is essential to assess the value of emerging technologies, but empirical data to inform the current practice of early evaluation is limited. We propose a systematic review of early economic evaluation studies in order to better understand the current practice. METHODS/DESIGN: This protocol describes a systematic review of economic evaluation studies of regulated health technologies in which the evaluation is conducted prior to regulatory approval and when the technology effectiveness is not well established. Included studies must report an economic evaluation, defined as the comparative analysis of alternatives with respect to their associated costs and health consequences, and must evaluate some regulated health technology such as pharmaceuticals, biologics, high-risk medical devices, or biomarkers. We will conduct the literature search on multiple databases, including MEDLINE, EMBASE, the Centre for Reviews and Dissemination Databases, and EconLit. Additional citations will be identified via scanning reference lists and author searching. We suspect that many early economic evaluation studies are unpublished, especially those conducted for internal use only. Additionally, we use a chain-referral sampling approach to identify authors of unpublished studies who work in technology discovery and development, starting out with our contact lists and authors who published relevant studies. Citation screening and full-text review will be conducted by pairs of reviewers. Abstracted data will include those related to the decision context and decision problem of the early evaluation, evaluation methods (e.g., data sources, methods, and assumptions used to identify, measure, and value the likely effectiveness and the costs and consequences of the new technology, handling of uncertainty), and whether the study results adequately address the main study question or objective. Data will be summarized overall and stratified by publication status. DISCUSSION: This study is timely to inform early economic evaluation practice, given the international trend in early health technology assessment initiatives.

Overcoming obstacles in accessing unfunded oral chemotherapy: physician experience and challenges.

PURPOSE: Previous studies have shown hematologists and medical oncologists may not accept the financial limits set by governing agencies on patient access to oral chemotherapy. The purpose of this study was to capture the methods physicians used to overcome barriers to accessing chemotherapeutic regimens for their patients. METHODS: A total of 640 medical oncologists and hematologists across Canada were surveyed using a 13-item Web-based survey tool. The survey was delivered by e-mail with three follow-up reminders. After a response period of 3 months, results were collated and analyzed with descriptive statistics. RESULTS: Of the 640 invitations, 568 were successfully delivered, and 183 responses were received (response rate, 32.0%). Among respondents, 101 treated solid malignancies (55.2%), 49 treated nonsolid malignancies (26.8%), and 33 treated both (18.0%). To overcome funding barriers, participating oncologists enrolled patients onto clinical trials (90.5%), used compassionate access programs (96.1%), and made special requests to government (91.8%). Other methods included writing false claims on forms to fit funding criteria for drugs (31.1%) and using leftover drug supplies (31.0%). Physicians felt their inability to obtain unfunded medications had a negative impact on their patients' clinical outcomes (56.0%) and psychosocial quality of life (73.0%). Only 28.5% of physicians contacted their governing body with concerns about oral chemotherapy funding. CONCLUSION: Canadian physicians use numerous methods to obtain unfunded oral chemotherapies, including falsifying claims on access forms and submitting special requests to government agencies. Further study is warranted to explore the disconnection between policymakers and physicians with regard to funding of oral chemotherapies.