Influence of tides on the dissemination and related health risks of intestinal helminths along the Kribi beaches (Atlantic Coast, Southern Cameroon).

Kribi is a seaside town that welcomes thousands of tourists each year. However, the poor sanitation condition of its beaches along the Atlantic coast is not without risk for visitors. In this study, we used the formol-ether concentration technique to identify and quantify larvae or eggs of intestinal helminths in waters of three regularly visited Kribi beaches (Mpalla, Ngoyè, and Mboamanga). Results revealed that all identified larvae and eggs were cestodes (Hymenolepis nana) and nematodes (Strongyloides sp., Ascaris sp., Ancylostoma duodenale and Trichuris trichiura). All the helminth eggs and larvae showed high abundance at low tide during rainy seasons. Ancylostoma duodenale eggs, totally absent at Mpalla, were densely present at low tide at Ngoyè (301 ± 15 eggs/L). Trichuris trichiura eggs showed the lowest abundance (0 to 62 eggs/L) at all sites. Abiotic variables indicated that waters at the various beaches were basic (pH: 8.75-9.77), generally warmer (32.44°C at Mpalla in the Short Rainy Season), more oxygenated at low tide, and moderately mineralized at high tide. Positive and significant correlations were observed at Ngoyè at low tide between Strongyloides sp. larvae and dissolved oxygen (P ˂ 0.05); and between Ancylostoma duodenale eggs and temperature (P ˂ 0.05). The overall results indicated that the beaches studied are subjected to fecal pollution. This pollution is more accentuated during low tides than during high tides. Depending on tidal movements, swimmers risk exposure to helminth eggs and larvae known to be responsible for gastroenteritis.

Comparison of Mammography AI Algorithms with a Clinical Risk Model for 5-year Breast Cancer Risk Prediction: An Observational Study.

Background Although several clinical breast cancer risk models are used to guide screening and prevention, they have only moderate discrimination. Purpose To compare selected existing mammography artificial intelligence (AI) algorithms and the Breast Cancer Surveillance Consortium (BCSC) risk model for prediction of 5-year risk. Materials and Methods This retrospective case-cohort study included data in women with a negative screening mammographic examination (no visible evidence of cancer) in 2016, who were followed until 2021 at Kaiser Permanente Northern California. Women with prior breast cancer or a highly penetrant gene mutation were excluded. Of the 324 009 eligible women, a random subcohort was selected, regardless of cancer status, to which all additional patients with breast cancer were added. The index screening mammographic examination was used as input for five AI algorithms to generate continuous scores that were compared with the BCSC clinical risk score. Risk estimates for incident breast cancer 0 to 5 years after the initial mammographic examination were calculated using a time-dependent area under the receiver operating characteristic curve (AUC). Results The subcohort included 13 628 patients, of whom 193 had incident cancer. Incident cancers in eligible patients (additional 4391 of 324 009) were also included. For incident cancers at 0 to 5 years, the time-dependent AUC for BCSC was 0.61 (95% CI: 0.60, 0.62). AI algorithms had higher time-dependent AUCs than did BCSC, ranging from 0.63 to 0.67 (Bonferroni-adjusted P < .0016). Time-dependent AUCs for combined BCSC and AI models were slightly higher than AI alone (AI with BCSC time-dependent AUC range, 0.66-0.68; Bonferroni-adjusted P < .0016). Conclusion When using a negative screening examination, AI algorithms performed better than the BCSC risk model for predicting breast cancer risk at 0 to 5 years. Combined AI and BCSC models further improved prediction. © RSNA, 2023 Supplemental material is available for this article.

Key Informant Perspectives on Barriers to Advance Personal Planning: Results from a Qualitative Interview Study.

Advance Care Planning (ACP) relates to the process of thinking about, discussing, and potentially documenting future wishes and preferences relating to personal and health matters. Existing literature has explored ACP from the perspective of health care professionals and older people. However, data exploring the broader process of Advance Personal Planning (APP), which also accounts for plans relating to legal and financial matters, are limited. This article reports on an interview study that explored barriers to APP engagement, factors influencing the quality and future use of instruments, and opportunities for improving APP processes for older adults from the perspectives of key informants working in the fields of law, health, and aged care. Data were coded in NVivo and analysed thematically. Opportunities for improvement include education, normalising conversations, integration into usual practice, and reform. Recommendations are made at professional, community, and structural levels, with the aim of improving APP outcomes for all involved.

Views of healthcare consumer representatives on defensive practice: 'We are your biggest advocate and supporter not the enemy'.

BACKGROUND: The patient-clinician interaction is a site at which defensive practice could occur, when clinicians provide tests, procedures and treatments mainly to reduce perceived legal risks, rather than to advance patient care. Defensive practice is a driver of low-value care and exposes patients to the risks of unnecessary interventions. To date, patient perspectives on defensive practice and its impacts on them are largely missing from the literature. This exploratory study conducted in Australia aimed to examine the views and experiences of healthcare consumer representatives in this under-examined area. METHODS: Semi-structured interviews were conducted with healthcare consumer representatives involved in healthcare consumer advocacy organisations in Australia. Data were transcribed and analysed thematically. RESULTS: Nine healthcare consumer representatives participated. Most had over 20 years of involvement and advocacy in healthcare, including personal experiences as a patient or carer and/or formal service roles on committees or complaint bodies for healthcare organisations. Participants uniformly viewed defensive practice as having a negative impact on the clinician-patient relationship. Themes identified the importance of fostering patient-clinician partnership, effective communication and informed decision-making. The themes support a shift from the concept of defensive practice to preventive practice in partnership, which focuses on the shared interests of patients and clinicians in achieving safe and high-value care. CONCLUSION: This Australian study offers healthcare consumers' perspectives on the impacts of defensive practice on patients. The findings highlight the features of clinician-patient partnership that will help to improve communication and decision-making, and prevent the defensive provision of low-value care. PATIENT OR PUBLIC CONTRIBUTION: Healthcare consumer representatives were involved as participants in this study.

A qualitative interview study of Australian physicians on defensive practice and low value care: "it's easier to talk about our fear of lawyers than to talk about our fear of looking bad in front of each other".

BACKGROUND: Defensive practice occurs when physicians provide services, such as tests, treatments and referrals, mainly to reduce their perceived legal or reputational risks, rather than to advance patient care. This behaviour is counter to physicians' ethical responsibilities, yet is widely reported in surveys of doctors in various countries. There is a lack of qualitative research on the drivers of defensive practice, which is needed to inform strategies to prevent this ethically problematic behaviour. METHODS: A qualitative interview study investigated the views and experiences of physicians in Australia on defensive practice and its contribution to low value care. Interviewees were recruited based on interest in medico-legal issues or experience in a health service involved in 'Choosing Wisely' initiatives. Semi-structured interviews averaged 60 min in length. Data were coded using the Theoretical Domains Framework, which encapsulates theories of behaviour and behaviour change. RESULTS: All participants (n = 17) perceived defensive practice as a problem and a contributor to low value care. Behavioural drivers of defensive practice spanned seven domains in the TDF: knowledge, focused on inadequate knowledge of the law and the risks of low value care; skills, emphasising patient communication and clinical decision-making skills; professional role and identity, particularly clinicians' perception of patient expectations and concern for their professional reputation; beliefs about consequences, especially perceptions of the beneficial and harmful consequences of defensive practice; environmental context and resources, including processes for handling patient complaints; social influences, focused on group norms that encourage or discourage defensive behaviour; and emotions, especially fear of missing a diagnosis. Overall, defensive practice is motivated by physicians' desire to avoid criticism or scrutiny from a range of sources, and censure from their professional peers can be a more potent driver than perceived legal consequences. CONCLUSIONS: The findings call for strengthening knowledge and skills, for example, to improve clinicians' understanding of the law and their awareness of the risks of low value care and using effective communication strategies with patients. Importantly, supportive cultures of practice and organisational environments are needed to create conditions in which clinicians feel confident in avoiding defensive practice and other forms of low value care.

Enduring Powers of Attorney and Financial Exploitation of Older People: A Conceptual Analysis and Strategies for Prevention.

Enduring powers of attorney (POAs) are commonly used legal instruments that enable older people to plan for asset management in the event of future incapacity. The policy objective of POAs - empowering control over money and property - are frustrated when POAs are misused to financially exploit older people. This commentary integrates theory and evidence to propose a conceptual framework for POA-facilitated financial exploitation (POA-FE). Identified risk factors include inadequate knowledge about the POA role; family conflicts; attitudes of entitlement; and lack of planning and preparation for financial decision-making. POA-FE occurs on a continuum of behavior and strategies for preventing POA-FE are suggested using strengths-based approaches for older people and their attorneys.

Mean Apparent Diffusion Coefficient Is a Sufficient Conventional Diffusion-weighted MRI Metric to Improve Breast MRI Diagnostic Performance: Results from the ECOG-ACRIN Cancer Research Group A6702 Diffusion Imaging Trial.

Background The Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Cancer Research Group A6702 multicenter trial helped confirm the potential of diffusion-weighted MRI for improving differential diagnosis of suspicious breast abnormalities and reducing unnecessary biopsies. A prespecified secondary objective was to explore the relative value of different approaches for quantitative assessment of lesions at diffusion-weighted MRI. Purpose To determine whether alternate calculations of apparent diffusion coefficient (ADC) can help further improve diagnostic performance versus mean ADC values alone for analysis of suspicious breast lesions at MRI. Materials and Methods This prospective trial (ClinicalTrials.gov identifier: NCT02022579) enrolled consecutive women (from March 2014 to April 2015) with a Breast Imaging Reporting and Data System category of 3, 4, or 5 at breast MRI. All study participants underwent standardized diffusion-weighted MRI (b = 0, 100, 600, and 800 sec/mm2). Centralized ADC measures were performed, including manually drawn whole-lesion and hotspot regions of interest, histogram metrics, normalized ADC, and variable b-value combinations. Diagnostic performance was estimated by using the area under the receiver operating characteristic curve (AUC). Reduction in biopsy rate (maintaining 100% sensitivity) was estimated according to thresholds for each ADC metric. Results Among 107 enrolled women, 81 lesions with outcomes (28 malignant and 53 benign) in 67 women (median age, 49 years; interquartile range, 41-60 years) were analyzed. Among ADC metrics tested, none improved diagnostic performance versus standard mean ADC (AUC, 0.59-0.79 vs AUC, 0.75; P = .02-.84), and maximum ADC had worse performance (AUC, 0.52; P < .001). The 25th-percentile ADC metric provided the best performance (AUC, 0.79; 95% CI: 0.70, 0.88), and a threshold using median ADC provided the greatest reduction in biopsy rate of 23.9% (95% CI: 14.8, 32.9; 16 of 67 BI-RADS category 4 and 5 lesions). Nonzero minimum b value (100, 600, and 800 sec/mm2) did not improve the AUC (0.74; P = .28), and several combinations of two b values (0 and 600, 100 and 600, 0 and 800, and 100 and 800 sec/mm2; AUC, 0.73-0.76) provided results similar to those seen with calculations of four b values (AUC, 0.75; P = .17-.87). Conclusion Mean apparent diffusion coefficient calculated with a two-b-value acquisition is a simple and sufficient diffusion-weighted MRI metric to augment diagnostic performance of breast MRI compared with more complex approaches to apparent diffusion coefficient measurement. © RSNA, 2020 Online supplemental material is available for this article.

Denoising and Multiple Tissue Compartment Visualization of Multi-b-Valued Breast Diffusion MRI.

BACKGROUND: Multi-b-valued/multi-shell diffusion provides potentially valuable metrics in breast MRI but suffers from low signal-to-noise ratio and has potentially long scan times. PURPOSE: To investigate the effects of model-based denoising with no loss of spatial resolution on multi-shell breast diffusion MRI; to determine the effects of downsampling on multi-shell diffusion; and to quantify these effects in multi-b-valued (three directions per b-value) acquisitions. STUDY TYPE: Prospective ("fully-sampled" multi-shell) and retrospective longitudinal (multi-b). SUBJECTS: One normal subject (multi-shell) and 10 breast cancer subjects imaging at four timepoints (multi-b). FIELD STRENGTH/SEQUENCE: 3T multi-shell acquisition and 1.5T multi-b acquisition. ASSESSMENT: The "fully-sampled" multi-shell acquisition was retrospectively downsampled to determine the bias and error from downsampling. Mean, axial/parallel, radial diffusivity, and fractional anisotropy (FA) were analyzed. Denoising was applied retrospectively to the multi-b-valued breast cancer subject dataset and assessed subjectively for image noise level and tumor conspicuity. STATISTICAL TESTS: Parametric paired t-test (P < 0.05 considered statistically significant) on mean and coefficient of variation of each metric-the apparent diffusion coefficient (ADC) from all b-values, fast ADC, slow ADC, and perfusion fraction. Paired and two-sample t-tests for each metric comparing normal and tumor tissue. RESULTS: In the multi-shell data, denoising effectively suppressed FA (-45% to -78%), with small biases in mean diffusivity (-5% in normal, +23% in tumor, and -4% in vascular compartments). In the multi-b data, denoising resulted in small biases to the ADC metrics in tumor and normal contralateral tissue (by -3% to +11%), but greatly reduced the coefficient of variation for every metric (by -1% to -24%). Denoising improved differentiation of tumor and normal tissue regions in most metrics and timepoints; subjectively, image noise level and tumor conspicuity were improved in the fast ADC maps. DATA CONCLUSION: Model-based denoising effectively suppressed erroneously high FA and improved the accuracy of diffusivity metrics. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY STAGE: 1.

Mask-Guided Convolutional Neural Network for Breast Tumor Prognostic Outcome Prediction on 3D DCE-MR Images.

In this proof-of-concept work, we have developed a 3D-CNN architecture that is guided by the tumor mask for classifying several patient-outcomes in breast cancer from the respective 3D dynamic contrast-enhanced MRI (DCE-MRI) images. The tumor masks on DCE-MRI images were generated using pre- and post-contrast images and validated by experienced radiologists. We show that our proposed mask-guided classification has a higher accuracy than that from either the full image without tumor masks (including background) or the masked voxels only. We have used two patient outcomes for this study: (1) recurrence of cancer after 5 years of imaging and (2) HER2 status, for comparing accuracies of different models. By looking at the activation maps, we conclude that an image-based prediction model using 3D-CNN could be improved by even a conservatively generated mask, rather than overly trusting an unguided, blind 3D-CNN. A blind CNN may classify accurately enough, while its attention may really be focused on a remote region within 3D images. On the other hand, only using a conservatively segmented region may not be as good for classification as using full images but forcing the model's attention toward the known regions of interest.

Conceptualizing interprofessional working - when a lawyer joins the healthcare mix.

Research, policy and practice in the field of interprofessional collaboration have focused on how medical, nursing, allied health and social care practitioners work together to positively impact patient care. This paper extends conceptual thinking about interprofessional practice by focusing on lawyers as part of the interprofessional mix. This attention is prompted by medical-legal partnerships (MLPs), a service model by which lawyers join health care settings to assist patients with unmet, and often health-harming, legal needs. MLPs are present in around 450 hospitals and other health care sites across the United States and the model has spread to other countries, including Australia, the United Kingdom and Canada. However, enthusiasm for the MLP model is not yet matched by good evidence on how, when and for whom the model works. Interprofessional scholars contend that imprecise terminology and poor conceptualization of interprofessional arrangements hinder high-quality research and evaluation. In response to their critiques, this paper formulates a stepwise conceptual framework to guide the design, implementation and study of interprofessional arrangements that connect health, social care and legal practitioners. This framework draws on findings from national surveys of MLP initiatives in several countries and adapts several key conceptual frameworks that have been developed from systematic reviews of interprofessional working in primary health care. These conceptual frameworks are valuable because they promote clarity about different modes of interprofessional working and characterize the factors at macro (policy, funding), meso (organizational) and micro (practitioner, patient) levels that help or hinder professionals from different disciplines in working together. The paper considers factors at these three levels that require particular attention when lawyers join health care settings and proposes questions for future research in this emerging area.

Bioethics and Universal Vulnerability: Exploring the Ethics and Practices of Research Participation.

In this article, we advocate the adoption of universal vulnerability as a core value in bioethics. We argue that understanding vulnerability as the universal human condition-and rejecting the labelling of particular individuals or groups as vulnerable-would benefit bioethics and the research it governs. Bioethics first engaged with vulnerability in the context of participation in research and this continues to define how the value is typically understood. Thus, vulnerability is generally deployed to describe individuals (or populations), where real or perceived deficiencies limit the ability to function and to protect themselves from risks. Revisiting this initial context and the participation in research of people living with dementia, we note that the bioethical position of excluding the 'vulnerable' from research has led to major gaps in evidence and knowledge to inform care and support. Turning to universal vulnerability, we consider the research design and practices that the approach would mandate. We emphasise the importance of inclusive design and mechanisms of institutional support that enable participation. We argue that these positively impact on the scientific value of research and address social justice concerns around social inclusion. Our aim is to provoke a fundamental reassessment of how vulnerability is conceived of in bioethics.

Advance Research Directives: Legal and Ethical Issues and Insights from a National Survey of Dementia Researchers in Australia.

Advance research directives (ARDs) are a means by which people can document their wishes about research participation in the event of future incapacity. ARDs have been endorsed in some ethics guidelines and position statements, however, formal legal recognition is limited. A few empirical studies have investigated the views of researchers and other stakeholders on ARDs and tested strategies to implement such directives. To further knowledge in this area, we undertook a survey of dementia researchers in Australia (n= 63) to examine their views on ARDs. Most of the survey respondents (>80%) thought ARDs would promote autonomy in decision-making and enable opportunities for people with cognitive impairment to be included in research. Respondents indicated concern about directives not being available when needed (71%) and that ethics committees would not accept ARDs (60%). Few respondents had used ARDs, but a majority (from 57-80%) would be willing to offer ARDs for a range of research activities, such as observing behaviour and taking measures, blood samples or scans. Nearly all respondents (92%) agreed that current dissent should override prior wishes stated in an ARD. The survey findings are contextualised with attention to ethics guidelines, laws and practices to support advance research planning.

Pubertal timing and breast density in young women: a prospective cohort study.

BACKGROUND: Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. METHODS: From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. RESULTS: The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)). CONCLUSIONS: Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.

Adaptive Randomization of Neratinib in Early Breast Cancer.

BACKGROUND: The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e., absence of residual cancer in the breast or lymph nodes at the time of surgery). METHODS: We used adaptive randomization to compare standard neoadjuvant chemotherapy plus the tyrosine kinase inhibitor neratinib with control. Eligible women were categorized according to eight biomarker subtypes on the basis of human epidermal growth factor receptor 2 (HER2) status, hormone-receptor status, and risk according to a 70-gene profile. Neratinib was evaluated against control with regard to 10 biomarker signatures (prospectively defined combinations of subtypes). The primary end point was pathological complete response. Volume changes on serial magnetic resonance imaging were used to assess the likelihood of such a response in each patient. Adaptive assignment to experimental groups within each disease subtype was based on Bayesian probabilities of the superiority of the treatment over control. Enrollment in the experimental group was stopped when the 85% Bayesian predictive probability of success in a confirmatory phase 3 trial of neoadjuvant therapy reached a prespecified threshold for any biomarker signature ("graduation"). Enrollment was stopped for futility if the probability fell to below 10% for every biomarker signature. RESULTS: Neratinib reached the prespecified efficacy threshold with regard to the HER2-positive, hormone-receptor-negative signature. Among patients with HER2-positive, hormone-receptor-negative cancer, the mean estimated rate of pathological complete response was 56% (95% Bayesian probability interval [PI], 37 to 73%) among 115 patients in the neratinib group, as compared with 33% among 78 controls (95% PI, 11 to 54%). The final predictive probability of success in phase 3 testing was 79%. CONCLUSIONS: Neratinib added to standard therapy was highly likely to result in higher rates of pathological complete response than standard chemotherapy with trastuzumab among patients with HER2-positive, hormone-receptor-negative breast cancer. (Funded by QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.

BACKGROUND: The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. METHODS: In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. RESULTS: With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control. CONCLUSIONS: The process used in our trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

Additive value of diffusion-weighted MRI in the I-SPY 2 TRIAL.

BACKGROUND: The change in apparent diffusion coefficient (ADC) measured from diffusion-weighted imaging (DWI) has been shown to be predictive of pathologic complete response (pCR) for patients with locally invasive breast cancer undergoing neoadjuvant chemotherapy. PURPOSE: To investigate the additive value of tumor ADC in a multicenter clinical trial setting. STUDY TYPE: Retrospective analysis of multicenter prospective data. POPULATION: In all, 415 patients who enrolled in the I-SPY 2 TRIAL from 2010 to 2014 were included. FIELD STRENGTH/SEQUENCE: 1.5T or 3T MRI system using a fat-suppressed single-shot echo planar imaging sequence with b-values of 0 and 800 s/mm2 for DWI, followed by a T1-weighted sequence for dynamic contrast-enhanced MRI (DCE-MRI) performed at pre-NAC (T0), after 3 weeks of NAC (T1), mid-NAC (T2), and post-NAC (T3). ASSESSMENT: Functional tumor volume and tumor ADC were measured at each MRI exam; pCR measured at surgery was assessed as the binary outcome. Breast cancer subtype was defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. STATISTICAL TESTS: A logistic regression model was used to evaluate associations between MRI predictors with pCR. The cross-validated area under the curve (AUC) was calculated to assess the predictive performance of the model with and without ADC. RESULTS: In all, 354 patients (128 HR+/HER2-, 60 HR+/HER2+, 34 HR-/HER2+, 132 HR-/HER2-) were included in the analysis. In the full cohort, adding ADC predictors increased the AUC from 0.76 to 0.78 at mid-NAC and from 0.76 to 0.81 at post-NAC. In HR/HER2 subtypes, the AUC increased from 0.52 to 0.65 at pre-NAC for HR+/HER2-, from 0.67 to 0.73 at mid-NAC and from 0.72 to 0.76 at post-NAC for HR+/HER2+, from 0.71 to 0.81 at post-NAC for triple negatives. DATA CONCLUSION: The addition of ADC to standard functional tumor volume MRI showed improvement in the prediction of treatment response in HR+ and triple-negative breast cancer. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2019;50:1742-1753.

Test-retest repeatability and reproducibility of ADC measures by breast DWI: Results from the ACRIN 6698 trial.

BACKGROUND: Quantitative diffusion-weighted imaging (DWI) MRI is a promising technique for cancer characterization and treatment monitoring. Knowledge of the reproducibility of DWI metrics in breast tumors is necessary to apply DWI as a clinical biomarker. PURPOSE: To evaluate the repeatability and reproducibility of breast tumor apparent diffusion coefficient (ADC) in a multi-institution clinical trial setting, using standardized DWI protocols and quality assurance (QA) procedures. STUDY TYPE: Prospective. SUBJECTS: In all, 89 women from nine institutions undergoing neoadjuvant chemotherapy for invasive breast cancer. FIELD STRENGTH/SEQUENCE: DWI was acquired before and after patient repositioning using a four b-value, single-shot echo-planar sequence at 1.5T or 3.0T. ASSESSMENT: A QA procedure by trained operators assessed artifacts, fat suppression, and signal-to-noise ratio, and determine study analyzability. Mean tumor ADC was measured via manual segmentation of the multislice tumor region referencing DWI and contrast-enhanced images. Twenty cases were evaluated multiple times to assess intra- and interoperator variability. Segmentation similarity was assessed via the Sørenson-Dice similarity coefficient. STATISTICAL TESTS: Repeatability and reproducibility were evaluated using within-subject coefficient of variation (wCV), intraclass correlation coefficient (ICC), agreement index (AI), and repeatability coefficient (RC). Correlations were measured by Pearson's correlation coefficients. RESULTS: In all, 71 cases (80%) passed QA evaluation: 44 at 1.5T, 27 at 3.0T; 60 pretreatment, 11 after 3 weeks of taxane-based treatment. ADC repeatability was excellent: wCV = 4.8% (95% confidence interval [CI] 4.0, 5.7%), ICC = 0.97 (95% CI 0.95, 0.98), AI = 0.83 (95% CI 0.76, 0.87), and RC = 0.16 * 10-3 mm2 /sec (95% CI 0.13, 0.19). The results were similar across field strengths and timepoint subgroups. Reproducibility was excellent: interreader ICC = 0.92 (95% CI 0.80, 0.97) and intrareader ICC = 0.91 (95% CI 0.78, 0.96). DATA CONCLUSION: Breast tumor ADC can be measured with excellent repeatability and reproducibility in a multi-institution setting using a standardized protocol and QA procedure. Improvements to DWI image quality could reduce loss of data in clinical trials. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1617-1628.

Effect of Background Parenchymal Enhancement on Breast MR Imaging Interpretive Performance in Community-based Practices.

Purpose To evaluate the effect of background parenchymal enhancement (BPE) on breast magnetic resonance (MR) imaging interpretive performance in a large multi-institutional cohort with independent analysis of screening and diagnostic MR studies. Materials and Methods Analysis of 3770 breast MR studies was conducted. Examinations were performed in 2958 women at six participating facilities in the San Francisco Bay Area from January 2010 to October 2012. Findings were recorded prospectively in the San Francisco Mammography Registry. Performance measures were compared between studies with low BPE (mild or minimal) and those with high BPE (moderate or marked) by using binomial tests of proportions. Results Of 1726 MR imaging studies in the screening group, 1301 were classified as having low BPE and 425 were classified as having high BPE (75% vs 25%, respectively; P < .001). Of 2044 MR imaging studies in the diagnostic group, 1443 were classified as having low BPE and 601 were classified as having high BPE (71% vs 29%, respectively; P < .001). For low versus high BPE groups at screening, abnormal interpretation rate was 157 of 1301 versus 111 of 424 (12% vs 26%, P < .001); biopsy recommendation rate was 85 of 1301 versus 54 of 424 (7% vs 13%, P < .001); and specificity was 89% (95% confidence interval [CI]: 87, 91) versus 75% (95% CI: 71, 80) (P = .01). For the low versus high BPE groups at diagnostic MR imaging, biopsy recommendation rate was 325 of 1443 versus 195 of 601 (23% vs 32%, P < .001); and specificity was 86% (95% CI: 84, 88) versus 75% (95% CI: 74, 82) (P < .001). There were no significant differences between studies with low versus high BPE in sensitivity for screening (76% [95% CI: 55, 91] vs 83% [95% CI: 52, 98]; P = .94) or diagnostic (93% [95% CI: 87, 97] vs 96% [95% CI: 87, 99]; P = .69) MR imaging, nor were there significant differences in cancer detection rate per 1000 patients between the low BPE versus high BPE groups for screening (15 per 1000 vs 24 per 1000, P = .30) or diagnostic (78 per 1000 vs 85 per 1000, P = .64) MR imaging. Conclusion Relative to MR studies with minimal or mild BPE, those with moderate or marked BPE were associated with higher abnormal interpretation and biopsy rates and lower specificity, with no difference in cancer detection rate. © RSNA, 2017 Online supplemental material is available for this article.

Diffusion-weighted MRI Findings Predict Pathologic Response in Neoadjuvant Treatment of Breast Cancer: The ACRIN 6698 Multicenter Trial.

Purpose To determine if the change in tumor apparent diffusion coefficient (ADC) at diffusion-weighted (DW) MRI is predictive of pathologic complete response (pCR) to neoadjuvant chemotherapy for breast cancer. Materials and Methods In this prospective multicenter study, 272 consecutive women with breast cancer were enrolled at 10 institutions (from August 2012 to January 2015) and were randomized to treatment with 12 weekly doses of paclitaxel (with or without an experimental agent), followed by 12 weeks of treatment with four cycles of anthracycline. Each woman underwent breast DW MRI before treatment, at early treatment (3 weeks), at midtreatment (12 weeks), and after treatment. Percentage change in tumor ADC from that before treatment (ΔADC) was measured at each time point. Performance for predicting pCR was assessed by using the area under the receiver operating characteristic curve (AUC) for the overall cohort and according to tumor hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) disease subtype. Results The final analysis included 242 patients with evaluable serial imaging data, with a mean age of 48 years ± 10 (standard deviation); 99 patients had HR-positive (hereafter, HR+)/HER2-negative (hereafter, HER2-) disease, 77 patients had HR-/HER2- disease, 42 patients had HR+/HER2+ disease, and 24 patients had HR-/HER2+ disease. Eighty (33%) of 242 patients experienced pCR. Overall, ΔADC was moderately predictive of pCR at midtreatment/12 weeks (AUC = 0.60; 95% confidence interval [CI]: 0.52, 0.68; P = .017) and after treatment (AUC = 0.61; 95% CI: 0.52, 0.69; P = .013). Across the four disease subtypes, midtreatment ΔADC was predictive only for HR+/HER2- tumors (AUC = 0.76; 95% CI: 0.62, 0.89; P < .001). In a test subset, a model combining tumor subtype and midtreatment ΔADC improved predictive performance (AUC = 0.72; 95% CI: 0.61, 0.83) over ΔADC alone (AUC = 0.57; 95% CI: 0.44, 0.70; P = .032.). Conclusion After 12 weeks of therapy, change in breast tumor apparent diffusion coefficient at MRI predicts complete pathologic response to neoadjuvant chemotherapy. © RSNA, 2018 Online supplemental material is available for this article.

Accuracy, repeatability, and interplatform reproducibility of T1 quantification methods used for DCE-MRI: Results from a multicenter phantom study.

PURPOSE: To determine the in vitro accuracy, test-retest repeatability, and interplatform reproducibility of T1 quantification protocols used for dynamic contrast-enhanced MRI at 1.5 and 3 T. METHODS: A T1 phantom with 14 samples was imaged at eight centers with a common inversion-recovery spin-echo (IR-SE) protocol and a variable flip angle (VFA) protocol using seven flip angles, as well as site-specific protocols (VFA with different flip angles, variable repetition time, proton density, and Look-Locker inversion recovery). Factors influencing the accuracy (deviation from reference NMR T1 measurements) and repeatability were assessed using general linear mixed models. Interplatform reproducibility was assessed using coefficients of variation. RESULTS: For the common IR-SE protocol, accuracy (median error across platforms = 1.4-5.5%) was influenced predominantly by T1 sample (P < 10-6 ), whereas test-retest repeatability (median error = 0.2-8.3%) was influenced by the scanner (P < 10-6 ). For the common VFA protocol, accuracy (median error = 5.7-32.2%) was influenced by field strength (P = 0.006), whereas repeatability (median error = 0.7-25.8%) was influenced by the scanner (P < 0.0001). Interplatform reproducibility with the common VFA was lower at 3 T than 1.5 T (P = 0.004), and lower than that of the common IR-SE protocol (coefficient of variation 1.5T: VFA/IR-SE = 11.13%/8.21%, P = 0.028; 3 T: VFA/IR-SE = 22.87%/5.46%, P = 0.001). Among the site-specific protocols, Look-Locker inversion recovery and VFA (2-3 flip angles) protocols showed the best accuracy and repeatability (errors < 15%). CONCLUSIONS: The VFA protocols with 2 to 3 flip angles optimized for different applications achieved acceptable balance of extensive spatial coverage, accuracy, and repeatability in T1 quantification (errors < 15%). Further optimization in terms of flip-angle choice for each tissue application, and the use of B1 correction, are needed to improve the robustness of VFA protocols for T1 mapping. Magn Reson Med 79:2564-2575, 2018. © 2017 International Society for Magnetic Resonance in Medicine.