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Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?

ABSTRACT: Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues to be standardly recommended for most women with DCIS. Three molecular biomarkers have been studied to better estimate LR risk after BCS-Oncotype DX DCIS score, DCISionRT Decision Score and its associated Residual Risk subtypes, and Oncotype 21-gene Recurrence Score. All these molecular biomarkers represent important efforts towards improving predicted risk of LR after BCS. To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one-the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial-incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research.

SUBMITTER: Hahn E

PROVIDER: S-EPMC10297044 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?

Hahn Ezra E Rodin Danielle D Sutradhar Rinku R Nofech-Mozes Sharon S Trebinjac Sabina S Paszat Lawrence Frank LF Rakovitch Eileen E

Current oncology (Toronto, Ont.) 20230613 6

Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues ...[more]

PMID: 37366916

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Project description:IntroductionAntimicrobial treatment of asymptomatic bacteriuria (ASB) is one of the most common unnecessary uses of antimicrobials. Earlier studies have shown that the prevalence of this inappropriate treatment ranges from 45% to 83%. Multifaceted interventions based on international guidelines and antimicrobial stewardship can decrease overtreatment of ASB. We have designed a study protocol with the main objective of reducing overtreatment of ASB by 50% through use of a deimplementation strategy.Methods and analysisWe will use a stepped-wedge cluster randomised design, comparing outcomes before and after introduction of our intervention in the emergency department (ED) of five hospitals (clusters) in the Netherlands. All patients (≥18 years old) who have a urine test performed in the ED will be screened for eligibility. The deimplementation strategy consists of a combination of interventions, including education, audit and feedback. The primary endpoint is overtreatment of ASB in patients without risk factors (eg, pregnancy, planned invasive urological procedures and neutropenia). Secondary endpoints are the duration of antimicrobial treatment for ASB, the number of urine cultures and urinalysis per 1000 patients, and overtreatment of positive urinalysis in asymptomatic patients.Ethics and disseminationEthical approval was obtained from the medical ethics research committee of the Academic Medical Centre (Amsterdam, the Netherlands) with a waiver for informed consent. Local feasibility was obtained by the local institutional review boards of all participating hospitals. Our study aims to reduce inappropriate screening and treatment of ASB in EDs, improve healthcare quality, lower the increase in antimicrobial resistance and save costs. If proven (cost)-effective, this study provides a well-suited strategy for a nationwide approach to reduce overtreatment of ASB. Relevant results of our study will be disseminated through publications in peer-reviewed journals and presentations at relevant (scientific) conferences.Trial registration numberNL8242; Pre-results.

Project description:BackgroundIntensive glycemic control is of unclear benefit and carries increased risk for older adults with diabetes. The American Geriatrics Society's (AGS) Choosing Wisely (CW) guideline promotes less aggressive glycemic targets and reduction in pharmacologic therapy for older adults with type II diabetes. Meanwhile, behavioral economic (BE) approaches offer promise in influencing hard-to-change behavior, and previous studies have shown the benefits of using electronic health record (EHR) technology to encourage guideline adherence.ObjectiveThis study aimed to develop and pilot test an intervention that leverages BE with EHR technology to promote appropriate diabetes management in older adults.DesignA pilot study within the New York University Langone Health (NYULH) EHR and Epic system to deliver BE-inspired nudges at five NYULH clinics at varying time points from July 12, 2018, through October 31, 2019.ParticipantsClinicians across five practices in the NYULH system whose patients were older adults (age 76 and older) with type II diabetes.InterventionsA BE-EHR module comprising six nudges was developed through a series of design workshops, interviews, user-testing sessions, and clinic visits. BE principles utilized in the nudges include framing, social norming, accountable justification, defaults, affirmation, and gamification.Main measuresPatient-level CW compliance.Key resultsCW compliance increased 5.1% from a 16-week interval at baseline to a 16-week interval post intervention. From February 14 to June 5, 2018 (prior to the first nudge launch in Vanguard clinics), CW compliance for 1278 patients was mean (95% CI)-16.1% (14.1%, 18.1%). From July 3 to October 22, 2019 (after BE-EHR module launch at all five clinics), CW compliance for 680 patients was 21.2% (18.1%, 24.3%).ConclusionsThe BE-EHR module shows promise for promoting the AGS CW guideline and improving diabetes management in older adults. A randomized controlled trial will commence to test the effectiveness of the intervention across 66 NYULH clinics.Nih trial registry numberNCT03409523.

Project description:ImportanceAlthough growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.ObjectiveTo evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.Design, setting, and participantsInternational, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.Main outcomes and measuresFrequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.ResultsConsensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.Conclusions and relevanceThyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.

Project description:BackgroundAsymptomatic bacteriuria (ASB) is the presence of bacteria in the urine of patients without symptoms of a urinary tract infection. Generally, treating ASB is not beneficial.ObjectiveWe aimed to reduce overtreatment of ASB in the emergency department (ED) through a multifaceted de-implementation strategy.DesignA stepped-wedge cluster randomised trial.MethodsWe performed our study in five EDs in the Netherlands from December 2020 to December 2021. Adult patients with urine cultures obtained during ED presentation were screened for inclusion and we excluded patients with indications for antibiotic therapy. The de-implementation strategy included education, reminders and competitive feedback on baseline results. The primary endpoint was patients with ASB treated with antibiotics. Secondary endpoints included the treatment duration and the number of urine tests ordered (urinalyses and urine cultures) in the ED per 1000 adult patients.ResultsIn total, 6837 urine cultures were screened. ASB was present in 224/3289 (7%) and 201/3548 (6%) patients, from whom 65/224 (29%) and 46/201 (23%) were inappropriately treated with antibiotics in the baseline and intervention period, respectively (adjusted odds ratio 1.20, 95% CI 0.56-2.62, p = 0.65). The number of urinalyses ordered decreased from 182 to 153 per 1000 patients (incidence rate difference -29.10, 95% CI -46.36 to -11.78, p < 0.001). Further, the treatment duration was shortened for patients with ASB in the intervention period (baseline period: 7.98 days (standard deviation (SD) 4.31) vs 5.79 days (SD 3.33), p = 0.006).ConclusionDiagnostic stewardship by our de-implementation strategy reduced the number of urinalyses ordered and treatment duration in the ED, but we found no significant reduction in overtreatment of ASB.Trial registrationThe trial was registered at https://onderzoekmetmensen.nl/en/trial/25918, on 17-12-2019, registration number NL8242. The first participants were enrolled on 01-12-2020.

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Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?

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Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?

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