Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy for Primary Breast Cancer Comparing Interim Ultrasound, Shear Wave Elastography and MRI

Abstract Background Prediction of pathological complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NACT) may influence planned surgical approaches in the breast and axilla. The aim of this project is to assess the value of interim shear wave elastography (SWE), ultrasound (US) and magnetic resonance imaging (MRI) after 3 cycles in predicting pCR. Methods 64 patients receiving NACT had baseline and interim US, SWE and MRI examinations. The mean lesion stiffness at SWE, US and MRI diameter was measured at both time points. We compared four parameters with pCR status: a) Interim mean stiffness ≤ or &gt; 50 kPa; b) Percentage stiffness reduction; c) Percentage US diameter reduction and d) Interim MRI response using RECIST criteria. The Chi square test was used to assess significance. Results Interim stiffness of ≤ or &gt; 50 kPa gave the best prediction of pCR with pCR seen in 10 of 14 (71 %) cancers with an interim stiffness of ≤ 50 kPa, compared to 7 of 50 (14 %) of cancers with an interim stiffness of &gt; 50 kPa, (p &lt; 0.0001) (sensitivity 59 %, specificity 91 %, PPV 71 %, NPV 86 % and diagnostic accuracy 83 %). Percentage reduction in stiffness was the next best parameter (sensitivity 59 %, specificity 85 %, p &lt; 0.0004) followed by reduction in MRI diameter of &gt; 30 % (sensitivity 50 % and specificity 79 %, p = 0.03) and % reduction in US diameter (sensitivity 47 %, specificity 81 %, p = 0.03). Similar results were obtained from ROC analysis. Conclusion SWE stiffness of breast cancers after 3 cycles of NACT and changes in stiffness from baseline are strongly associated with pCR after 6 cycles.</jats:p

Effectiveness of mental health and wellbeing interventions for children and young people in foster, kinship, and residential care: systematic review and meta-analysis

The mental health and wellbeing of children and young people who have been in care, primarily foster care, kinship care or residential care, remains a public health priority. The Care-experienced cHildren and young people’s Interventions to improve Mental health and wEll-being outcomes Systematic review (CHIMES) synthesized evidence for the effectiveness of interventions targeting: subjective wellbeing; mental, behavioral and neurodevelopmental disorders; and suicide-related outcomes. Searches were conducted in 16 bibliographic databases and 22 websites between 1990 and 2022. This was supplemented by citation tracking, screening of relevant systematic reviews, and expert recommendation. We identified 35 interventions, with 44 evaluations via randomized controlled trials. Through meta-analyses, we found that interventions have a small beneficial impact on a variety of mental health outcomes in the short term (0–6 months). Interventions improved total social, emotional, and behavioral problems (d = −0.15, 95% CI [−0.28, −0.02]), social-emotional functioning difficulties (d = −0.18, 95% CI [−0.31, −0.05]), externalizing problem behaviors (d = −0.30, 95% CI [−0.53, −0.08]), internalizing problem behaviors (d = −0.35, 95% CI [−0.61, −0.08]); and depression and anxiety (d = −0.26, 95% CI [−0.40, −0.13]). Interventions did not demonstrate any effectiveness for outcomes assessed in the longer term (>6 months). Certainty of effectiveness was limited by risk of bias and imprecision. There was limited available evidence for interventions targeting subjective wellbeing and suicide-related outcomes. Future intervention design and delivery must ensure that programs are sufficient to activate causal mechanisms and facilitate change. Evaluation research should use a robust methodology

Interventions targeting the mental health and wellbeing of care-experienced children and young people in higher-income countries: Evidence map and systematic review

Background: The mental health and wellbeing of care-experienced children and young people (i.e. foster care, kinship care, residential care) is poorer than non-care-experienced populations. The Care-experienced cHildren and young people’s Interventions to improve Mental health and wEll-being outcomes Systematic review (CHIMES) aimed to synthesise the international evidence base for interventions targeting subjective wellbeing, mental health and suicide amongst care-experienced young people aged ≤ 25 years. Methods: For the first phase of the review, we constructed an evidence map identifying key clusters and gaps in interventions and evaluations. Studies were identified through 16 electronic databases and 22 health and social care websites, in addition to expert recommendations, citation tracking and screening of relevant systematic reviews. We charted interventions and evaluations with a summary narrative, tables and infographics. Results: In total, 64 interventions with 124 associated study reports were eligible. The majority of study reports were from the USA (n = 77). Interventions primarily targeted children and young people’s skills and competencies (n = 9 interventions), the parental functioning and practices of carers (n = 26), or a combination of the two (n = 15). While theoretically under-specified, interventions were largely informed by theories of Attachment, Positive Youth Development, and Social Learning Theory. Current evaluations prioritised outcomes (n = 86) and processes (n = 50), with a paucity of study reports including theoretical descriptions (n = 24) or economic evaluations (n = 1). Interventions most frequently targeted outcomes related to mental, behavioural or neurodevelopmental disorders, notably total social, emotional and behavioural problems (n = 48 interventions) and externalising problem behaviours (n = 26). There were a limited number of interventions targeting subjective wellbeing or suicide-related outcomes. Conclusions: Future intervention development might focus on structural-level intervention theories and components, and target outcomes related to subjective wellbeing and suicide. In accordance with current methodological guidance for intervention development and evaluation, research needs to integrate theoretical, outcome, process and economic evaluation in order to strengthen the evidence base. Systematic review registration: PROSPERO CRD42020177478

Mental health and wellbeing interventions for care-experienced children and young people: Systematic review and synthesis of process evaluations

Background The mental health and well-being of care-experienced children and young people remains a concern. Despite a range of interventions, the existing evidence base is limited in scope, with a reliance on standalone outcome evaluations which limits understanding of how contextual factors influence implementation and acceptability. The Care-experienced cHildren and young people’s Interventions to improve Mental health and wEll-being outcomes Systematic review (CHIMES) aimed to synthesise evidence of intervention theory, outcome, process and economic effectiveness. This paper reports the process evaluation synthesis, exploring how system factors facilitate and inhibit implementation and acceptability of mental health and wellbeing interventions for care-experienced children and young people. Methods Sixteen databases and 22 websites were searched between 2020 and 2022 for studies published from 1990 and May 2022. This was supplemented with contacting experts in the field, citation tracking, screening of relevant systematic reviews and stakeholder consultations. We drew on framework synthesis of qualitative data and incorporated a systems lens, taking account of contextual influences across socio-ecological domains. Quality appraisal assessed reliability and usefulness. Confidence in synthesised findings was assessed with the GRADE-CERQual tool. We report the review in accordance with relevant elements of both the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and the Enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) checklist. Results Searches retrieved 15,068 unique study reports, and 23 of these were eligible for process evaluation synthesis, reporting on sixteen interventions. Studies were published between 2003 and 2021. Nine interventions were from the UK and Ireland, six interventions were from the USA, and one was from Australia. They were largely classified as interpersonal, where the aim was to modify carer-child relationships. Five key context factors were identified that supported and prohibited intervention delivery: (1) lack of system resources; (2) intervention burden, which encompasses the time, cognitive, and emotional burden associated with implementation and participation; (3) interprofessional relationships between health and social care professionals; (4) care-experienced young people’s identity; and (5) carer identity. Conclusion We identified several supportive and restrictive factors across social and health care systems that may impact intervention implementation and acceptability. Key implications include: the importance of involving diverse stakeholders in intervention development and delivery; the need to better resource and support those involved in interventions, particularly training and support for carers; and ensuring future evaluations integrate process evaluations in order to optimise interventions

Development and Evaluation of Machine Learning in Whole-Body Magnetic Resonance Imaging for Detecting Metastases in Patients With Lung or Colon Cancer: A Diagnostic Test Accuracy Study

OBJECTIVES: Whole-body magnetic resonance imaging (WB-MRI) has been demonstrated to be efficient and cost-effective for cancer staging. The study aim was to develop a machine learning (ML) algorithm to improve radiologists' sensitivity and specificity for metastasis detection and reduce reading times. MATERIALS AND METHODS: A retrospective analysis of 438 prospectively collected WB-MRI scans from multicenter Streamline studies (February 2013-September 2016) was undertaken. Disease sites were manually labeled using Streamline reference standard. Whole-body MRI scans were randomly allocated to training and testing sets. A model for malignant lesion detection was developed based on convolutional neural networks and a 2-stage training strategy. The final algorithm generated lesion probability heat maps. Using a concurrent reader paradigm, 25 radiologists (18 experienced, 7 inexperienced in WB-/MRI) were randomly allocated WB-MRI scans with or without ML support to detect malignant lesions over 2 or 3 reading rounds. Reads were undertaken in the setting of a diagnostic radiology reading room between November 2019 and March 2020. Reading times were recorded by a scribe. Prespecified analysis included sensitivity, specificity, interobserver agreement, and reading time of radiology readers to detect metastases with or without ML support. Reader performance for detection of the primary tumor was also evaluated. RESULTS: Four hundred thirty-three evaluable WB-MRI scans were allocated to algorithm training (245) or radiology testing (50 patients with metastases, from primary 117 colon [n = 117] or lung [n = 71] cancer). Among a total 562 reads by experienced radiologists over 2 reading rounds, per-patient specificity was 86.2% (ML) and 87.7% (non-ML) (-1.5% difference; 95% confidence interval [CI], -6.4%, 3.5%; P = 0.39). Sensitivity was 66.0% (ML) and 70.0% (non-ML) (-4.0% difference; 95% CI, -13.5%, 5.5%; P = 0.344). Among 161 reads by inexperienced readers, per-patient specificity in both groups was 76.3% (0% difference; 95% CI, -15.0%, 15.0%; P = 0.613), with sensitivity of 73.3% (ML) and 60.0% (non-ML) (13.3% difference; 95% CI, -7.9%, 34.5%; P = 0.313). Per-site specificity was high (>90%) for all metastatic sites and experience levels. There was high sensitivity for the detection of primary tumors (lung cancer detection rate of 98.6% with and without ML [0.0% difference; 95% CI, -2.0%, 2.0%; P = 1.00], colon cancer detection rate of 89.0% with and 90.6% without ML [-1.7% difference; 95% CI, -5.6%, 2.2%; P = 0.65]). When combining all reads from rounds 1 and 2, reading times fell by 6.2% (95% CI, -22.8%, 10.0%) when using ML. Round 2 read-times fell by 32% (95% CI, 20.8%, 42.8%) compared with round 1. Within round 2, there was a significant decrease in read-time when using ML support, estimated as 286 seconds (or 11%) quicker (P = 0.0281), using regression analysis to account for reader experience, read round, and tumor type. Interobserver variance suggests moderate agreement, Cohen κ = 0.64; 95% CI, 0.47, 0.81 (with ML), and Cohen κ = 0.66; 95% CI, 0.47, 0.81 (without ML). CONCLUSIONS: There was no evidence of a significant difference in per-patient sensitivity and specificity for detecting metastases or the primary tumor using concurrent ML compared with standard WB-MRI. Radiology read-times with or without ML support fell for round 2 reads compared with round 1, suggesting that readers familiarized themselves with the study reading method. During the second reading round, there was a significant reduction in reading time when using ML support

Pre-operative stromal stiffness measured by shear wave elastography is independently associated with breast cancer-specific survival.

INTRODUCTION: With the increased use of neoadjuvant therapy for breast cancer, there is a need for pre-operative prediction of prognosis. We aimed to assess the prognostic value of tumour stiffness measured by ultrasound shear wave elastography (SWE). METHODS: A consecutive cohort of patients with invasive breast cancer underwent breast ultrasound (US) including SWE. The following were recorded prospectively: US diameter, stiffness at SWE, presentation source, core biopsy grade, oestrogen receptor (ER) status and pre-operative nodal status. Breast cancer-specific survival (BCSS) was analysed with regard to US size and stiffness, tumour grade on core biopsy, ER status, presentation mode and pre-operative nodal status. Analysis used Cox proportional hazards regression. RESULTS: Of the 520 patients, 42 breast cancer and 53 non-breast cancer deaths were recorded at mean follow-up of 5.4 years. Hazard ratios (HR) for tertiles of stiffness were 1, 4.8 and 8.1 (P = 0.0001). HR for 2 groups based on US size < or ≥ 20 mm were 1 and 5.1 (P < 0.0001). HR for each unit increase in tumour grade on core biopsy was 3.9 (P < 0.0001). The HR for ER positivity compared to ER negativity was 0.21 (P < 0.001). BCSS was also associated with presentation mode and pre-operative nodal status. In a multivariable model, stiffness, US size and ER status were independently associated with BCSS. CONCLUSION: Multiple pre-operative factors including stromal stiffness at SWE have independent prognostic significance. A larger dataset with longer follow-up could be used in the future to construct a pre-operative prognostic model to guide treatment decisions

Evaluating the effectiveness of abbreviated breast MRI (abMRI) interpretation training for mammogram readers : a multi-centre study assessing diagnostic performance, using an enriched dataset

Background Abbreviated breast MRI (abMRI) is being introduced in breast screening trials and clinical practice, particularly for women with dense breasts. Upscaling abMRI provision requires the workforce of mammogram readers to learn to effectively interpret abMRI. The purpose of this study was to examine the diagnostic accuracy of mammogram readers to interpret abMRI after a single day of standardised small-group training and to compare diagnostic performance of mammogram readers experienced in full-protocol breast MRI (fpMRI) interpretation (Group 1) with that of those without fpMRI interpretation experience (Group 2). Methods Mammogram readers were recruited from six NHS Breast Screening Programme sites. Small-group hands-on workstation training was provided, with subsequent prospective, independent, blinded interpretation of an enriched dataset with known outcome. A simplified form of abMRI (first post-contrast subtracted images (FAST MRI), displayed as maximum-intensity projection (MIP) and subtracted slice stack) was used. Per-breast and per-lesion diagnostic accuracy analysis was undertaken, with comparison across groups, and double-reading simulation of a consecutive screening subset. Results 37 readers (Group 1: 17, Group 2: 20) completed the reading task of 125 scans (250 breasts) (total = 9250 reads). Overall sensitivity was 86% (95% confidence interval (CI) 84–87%; 1776/2072) and specificity 86% (95%CI 85–86%; 6140/7178). Group 1 showed significantly higher sensitivity (843/952; 89%; 95%CI 86–91%) and higher specificity (2957/3298; 90%; 95%CI 89–91%) than Group 2 (sensitivity = 83%; 95%CI 81–85% (933/1120) p < 0.0001; specificity = 82%; 95%CI 81–83% (3183/3880) p < 0.0001). Inter-reader agreement was higher for Group 1 (kappa = 0.73; 95%CI 0.68–0.79) than for Group 2 (kappa = 0.51; 95%CI 0.45–0.56). Specificity improved for Group 2, from the first 55 cases (81%) to the remaining 70 (83%) (p = 0.02) but not for Group 1 (90–89% p = 0.44), whereas sensitivity remained consistent for both Group 1 (88–89%) and Group 2 (83–84%). Conclusions Single-day abMRI interpretation training for mammogram readers achieved an overall diagnostic performance within benchmarks published for fpMRI but was insufficient for diagnostic accuracy of mammogram readers new to breast MRI to match that of experienced fpMRI readers. Novice MRI reader performance improved during the reading task, suggesting that additional training could further narrow this performance gap