Machine learning prediction of pathological complete response and overall survival of breast cancer patients in an underserved inner-city population.

BACKGROUND: Generalizability of predictive models for pathological complete response (pCR) and overall survival (OS) in breast cancer patients requires diverse datasets. This study employed four machine learning models to predict pCR and OS up to 7.5 years using data from a diverse and underserved inner-city population. METHODS: Demographics, staging, tumor subtypes, income, insurance status, and data from radiology reports were obtained from 475 breast cancer patients on neoadjuvant chemotherapy in an inner-city health system (01/01/2012 to 12/31/2021). Logistic regression, Neural Network, Random Forest, and Gradient Boosted Regression models were used to predict outcomes (pCR and OS) with fivefold cross validation. RESULTS: pCR was not associated with age, race, ethnicity, tumor staging, Nottingham grade, income, and insurance status (p > 0.05). ER-/HER2+ showed the highest pCR rate, followed by triple negative, ER+/HER2+, and ER+/HER2- (all p < 0.05), tumor size (p < 0.003) and background parenchymal enhancement (BPE) (p < 0.01). Machine learning models ranked ER+/HER2-, ER-/HER2+, tumor size, and BPE as top predictors of pCR (AUC = 0.74-0.76). OS was associated with race, pCR status, tumor subtype, and insurance status (p < 0.05), but not ethnicity and incomes (p > 0.05). Machine learning models ranked tumor stage, pCR, nodal stage, and triple-negative subtype as top predictors of OS (AUC = 0.83-0.85). When grouping race and ethnicity by tumor subtypes, neither OS nor pCR were different due to race and ethnicity for each tumor subtype (p > 0.05). CONCLUSION: Tumor subtypes and imaging characteristics were top predictors of pCR in our inner-city population. Insurance status, race, tumor subtypes and pCR were associated with OS. Machine learning models accurately predicted pCR and OS.

Deep learning applications to breast cancer detection by magnetic resonance imaging: a literature review.

Deep learning analysis of radiological images has the potential to improve diagnostic accuracy of breast cancer, ultimately leading to better patient outcomes. This paper systematically reviewed the current literature on deep learning detection of breast cancer based on magnetic resonance imaging (MRI). The literature search was performed from 2015 to Dec 31, 2022, using Pubmed. Other database included Semantic Scholar, ACM Digital Library, Google search, Google Scholar, and pre-print depositories (such as Research Square). Articles that were not deep learning (such as texture analysis) were excluded. PRISMA guidelines for reporting were used. We analyzed different deep learning algorithms, methods of analysis, experimental design, MRI image types, types of ground truths, sample sizes, numbers of benign and malignant lesions, and performance in the literature. We discussed lessons learned, challenges to broad deployment in clinical practice and suggested future research directions.

Socio-demographic predictors of unintended pregnancy and late antenatal booking in Honiara, Solomon Islands.

BACKGROUND: The Solomon Islands is a Pacific nation with a maternal mortality of 114 per 100 000 births. Around 57% of pregnancies are unintended and only 15% of women attend their first antenatal visit in the first 12 weeks as recommended by the World Health Organization. AIMS: We sought to examine the socio-demographic predictors of unintended pregnancy and late antenatal booking (>18 weeks) among women attending antenatal care in Honiara. MATERIALS AND METHODS: From January 2014 to May 2015 we undertook a cross-sectional survey using a structured questionnaire on women presenting to the National Referral Hospital and community clinics in Honiara for antenatal care. RESULTS: Of 1441 women, 41.0% of pregnancies were intended, 55.7% were ambivalent and 3.3% were fully unintended. Unintended pregnancy was significantly associated with being unemployed (adjusted odds ratio (aOR) 1.45, P = 0.024), being a teenager at first intercourse (aOR 1.53; P = 0.004), shared family planning decision making (aOR 0.54; P = 0.006) living with a husband (aOR 0.31 P < 0.001) and a short interpregnancy interval (OR 4.48, P ≤ 0.001). Late booking occurred in 1168 (84.7%) women and independent predictors of this included ambivalent or unintended pregnancy (aOR 1.74, P = 0.005) and multiparity (aOR 2.05, P = 0.001). CONCLUSIONS: Unintended pregnancy and late antenatal booking remain a challenge to improving maternal health in the Solomon Islands. Investments in family planning could target reproductive health education and post-partum family planning. Improving the quality of antenatal care as well as addressing social determinants of health, including gender equity, education and employment of women, is required if maternal mortality is to be reduced.

Whistle-blowing in Medical School: A National Survey on Peer Accountability and Professional Misconduct in Medical Students.

OBJECTIVE: This study examines medical students' attitudes towards peer accountability. METHODS: A nationally representative sample of 564 third year medical students was surveyed. Students reported their agreement or disagreement with two statements: "I feel professionally obligated to report peers whose personal behaviors compromise their professional responsibilities" and "I feel professionally obligated to report peers who I believe are seriously unfit to practice medicine." RESULTS: The majority of students (81.6 %) either agreed strongly or agreed somewhat that they feel obligated to report peers whose personal behaviors compromise their professional responsibilities. The majority (84.1 %) also agreed that they feel professionally obligated to report peers who they believe are seriously unfit to practice medicine. CONCLUSION: In contrast with previous studies, this national study found that a significant majority of students reported that they feel obligated to report unfit peers.

Fibroepithelial Lesion Spectrum: A Case Report Documenting a Possible Transformation to a Malignant Phyllodes Tumor.

We discuss the radiological-pathological aspects of a rare case of transformation of a presumed fibroadenoma (FA) to a malignant phyllodes tumor (PT) and review the literature. Phyllodes tumors often show heterogeneous histologic features with some areas indistinguishable on core needle biopsy. A core biopsy is often a small representation of a larger lesion. As such, a complete excisional biopsy is often needed for a definitive pathologic diagnosis. Careful clinical and imaging correlation and follow-up are necessary, even in a benign fibroepithelial lesion (FEL).

Mammographic Findings of Diffuse Axillary Tail Trabecular Thickening After the Second Booster of COVID-19 Vaccination.

Axillary adenopathy post-coronavirus disease 2019 (COVID-19) vaccination has been well-documented and is seen with other types of vaccinations. Isolated trabecular thickening on mammography, however, is singular to COVID-19 vaccination, which implies that this finding may result from a distinct pathophysiologic mechanism. Herein, we describe the first case of axillary tail trabecular thickening resulting from the second booster of the COVID-19 vaccination series. Both breast cancer and mastitis may present similar findings. Ipsilateral injection of COVID-19 vaccine/booster and spontaneous resolution on follow-up provide clues to the etiology. It has been hypothesized that proinflammatory conditions may predispose to axillary tail trabecular thickening on mammography post-COVID-19 vaccination. Proinflammatory conditions such as hypertension, obesity, and diabetes may also predispose to breast cancer, making this scenario even more of a diagnostic dilemma. This scenario would more likely be seen in lower socioeconomic communities, African Americans, and Hispanics, who demonstrate a higher prevalence of these diseases, and who are also more vulnerable due to health care disparities negatively affecting these groups. We discuss our case and the importance of this public health issue. Sequela of COVID vaccination and boosters will be encountered in the foreseeable future and could pose a diagnostic dilemma, thus potentially straining the healthcare system with unnecessary biopsies and patient anxiety if not recognized and appropriately managed.

Mammographic findings of diffuse axillary tail trabecular thickening following immunization with mRNA COVID-19 vaccines: Case series study.

Axillary lymphadenopathy has been reported after ipsilateral COVID-19 vaccination and can cause confusion for possible malignancy [1]. Intrinsic findings isolated to the breast has not been previously reported. This is the first case series of ipsilateral reversible changes of diffuse axillary tail trabecular thickening on screening mammography in totally asymptomatic patients in connection with COVID vaccination, 3 of which were isolated findings, confirmed by complete resolution of all imaging findings on follow up. In all instances, imaging was performed within 1 week of the first or third dose of an mRNA COVID-19 vaccine. These findings can be confused with breast cancer. Spontaneous resolution distinguishes vaccine-related findings from breast cancer.

Internal mammary lymph nodal response to neoadjuvant chemotherapy on imaging and breast cancer prognosis.

Background: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is an important prognostic indicator in breast cancer. Internal mammary lymph node involvement is not currently included in pCR determination, as sampling at the time of surgery is not routinely performed. Methods: Pre and post neoadjuvant chemotherapy MRI or PET/CT imaging response of the internal mammary lymph node chain was utilized as a surrogate to pCR and imaging data was correlated with patient outcomes. Results: Internal mammary lymph node response to NAC was associated with disease free survival over the course of this study, regardless of whether axillary nodal pCR was achieved. Conclusion: Internal mammary lymph nodal response to NAC is an important prognostic indicator. Potential use of internal mammary lymph node resolution as an imaging data input for AI models that predict pCR post-NAC may improve accuracy and other metrics in pCR prediction.

Invasive Lobular Cancer Arising in a Surgical Scar From Lumpectomy for a Previous Invasive Ductal Cancer of the Breast.

We describe a case of pathology-proven invasive lobular breast cancer (ILC) arising in a scar over 15 years after lumpectomy for previous invasive ductal carcinoma (IDC). The tumor was detected on screening mammography as a new focal asymmetry at the scar site and confirmed at diagnostic mammography. Ultrasound demonstrated an irregular, shadowing, hypoechoic mass at the scar site. Ultrasound-guided biopsy revealed poorly differentiated invasive lobular carcinoma. MRI and CT showed an irregular mass with pectoralis muscle invasion. Multimodality imaging findings are described. This is the first case to our knowledge reporting multimodality imaging findings of a breast cancer developing at the site of a surgical scar that is histologically different from the originally resected cancer.

Assessment of MRI to estimate metastatic dissemination risk and prometastatic effects of chemotherapy.

Metastatic dissemination in breast cancer is regulated by specialized intravasation sites called "tumor microenvironment of metastasis" (TMEM) doorways, composed of a tumor cell expressing the actin-regulatory protein Mena, a perivascular macrophage, and an endothelial cell, all in stable physical contact. High TMEM doorway number is associated with an increased risk of distant metastasis in human breast cancer and mouse models of breast carcinoma. Here, we developed a novel magnetic resonance imaging (MRI) methodology, called TMEM Activity-MRI, to detect TMEM-associated vascular openings that serve as the portal of entry for cancer cell intravasation and metastatic dissemination. We demonstrate that TMEM Activity-MRI correlates with primary tumor TMEM doorway counts in both breast cancer patients and mouse models, including MMTV-PyMT and patient-derived xenograft models. In addition, TMEM Activity-MRI is reduced in mouse models upon treatment with rebastinib, a specific and potent TMEM doorway inhibitor. TMEM Activity-MRI is an assay that specifically measures TMEM-associated vascular opening (TAVO) events in the tumor microenvironment, and as such, can be utilized in mechanistic studies investigating molecular pathways of cancer cell dissemination and metastasis. Finally, we demonstrate that TMEM Activity-MRI increases upon treatment with paclitaxel in mouse models, consistent with prior observations that chemotherapy enhances TMEM doorway assembly and activity in human breast cancer. Our findings suggest that TMEM Activity-MRI is a promising precision medicine tool for localized breast cancer that could be used as a non-invasive test to determine metastatic risk and serve as an intermediate pharmacodynamic biomarker to monitor therapeutic response to agents that block TMEM doorway-mediated dissemination.

Clinical assessment incorporating a personal genome.

BACKGROUND: The cost of genomic information has fallen steeply, but the clinical translation of genetic risk estimates remains unclear. We aimed to undertake an integrated analysis of a complete human genome in a clinical context. METHODS: We assessed a patient with a family history of vascular disease and early sudden death. Clinical assessment included analysis of this patient's full genome sequence, risk prediction for coronary artery disease, screening for causes of sudden cardiac death, and genetic counselling. Genetic analysis included the development of novel methods for the integration of whole genome and clinical risk. Disease and risk analysis focused on prediction of genetic risk of variants associated with mendelian disease, recognised drug responses, and pathogenicity for novel variants. We queried disease-specific mutation databases and pharmacogenomics databases to identify genes and mutations with known associations with disease and drug response. We estimated post-test probabilities of disease by applying likelihood ratios derived from integration of multiple common variants to age-appropriate and sex-appropriate pre-test probabilities. We also accounted for gene-environment interactions and conditionally dependent risks. FINDINGS: Analysis of 2.6 million single nucleotide polymorphisms and 752 copy number variations showed increased genetic risk for myocardial infarction, type 2 diabetes, and some cancers. We discovered rare variants in three genes that are clinically associated with sudden cardiac death-TMEM43, DSP, and MYBPC3. A variant in LPA was consistent with a family history of coronary artery disease. The patient had a heterozygous null mutation in CYP2C19 suggesting probable clopidogrel resistance, several variants associated with a positive response to lipid-lowering therapy, and variants in CYP4F2 and VKORC1 that suggest he might have a low initial dosing requirement for warfarin. Many variants of uncertain importance were reported. INTERPRETATION: Although challenges remain, our results suggest that whole-genome sequencing can yield useful and clinically relevant information for individual patients. FUNDING: National Institute of General Medical Sciences; National Heart, Lung And Blood Institute; National Human Genome Research Institute; Howard Hughes Medical Institute; National Library of Medicine, Lucile Packard Foundation for Children's Health; Hewlett Packard Foundation; Breetwor Family Foundation.

The problems reported by cancer patients with major depression.

OBJECTIVE: To describe the problems reported by people with cancer and major depressive disorder as elicited before starting problem-solving therapy (PST). METHODS: Ninety-eight outpatients, with a variety of cancers who met criteria for major depression, received PST as part of a system of treatment called 'Depression Care for People with Cancer' within a randomized trial. During the first session of PST, each patient was asked to provide an exhaustive list of problems defined as 'anything that was bothering them'. A coding system, based on thematic content, was developed to categorize the problems listed. Each problem was then coded by two raters independently (κ=0.81). The resulting categories were organized into larger conceptual domains using a card-sorting task. RESULTS: Thirty-six problem categories were generated which were in turn organized into 11 larger conceptual domains. Patients reported problems in a mean of 9.2 different categories (range 3-21) and 5.7 domains (range 2-9). The most common problem categories were 'concerns about other people's well-being' (65%), 'problems in interpersonal relations' (61%), 'loss of interest' (56%), 'low mood' (55%), and 'cancer recurrence or relapse' (54%). CONCLUSIONS: People with cancer and major depression report a wide variety of problems that include, but go beyond concerns about, both cancer and depression. The large number of problems related to concerns about other people's well-being and difficulties in interpersonal relationships, stresses the importance of these topics to patients and should be given more weight in the assessment and management of depressed cancer patients.

What is a psychological intervention? A metareview and practical proposal.

OBJECTIVE: What do we mean by a 'psychological intervention' in the context of cancer care? It is critical to know what treatments are included under this term, if data from diverse treatment trials are to be summarized in order to inform clinical practice. We, therefore, aimed to determine how the term 'psychological intervention' has been defined and used to group and compare interventions in reviews of cancer care. METHODS: We conducted a review of existing reviews (a metareview). These included systematic and narrative reviews and meta-analyses of interventions that were described as 'psychological', with the aim of determining: (a) the definitions for 'psychological interventions' that were used and (b) the treatments that were included within this category. RESULTS: We identified 66 relevant reviews. Surprisingly, we were unable to find any explicit definition of the term 'psychological intervention' in these reviews. The reviews included 79 different treatments with little consistency between reviews in which treatments were included. CONCLUSIONS: There is confusion about what 'psychological intervention' means in the cancer review literature. A clearer definition is essential to summarize research findings. We propose that rather than simply grouping interventions as 'psychological', it would be more useful if reviews focussed on specified domains of the interventions, namely content, proposed mechanism, target outcome, and methods of delivery. This would enable greater specificity in the review question, more meaningful comparisons, and would hopefully provide clearer answers for the readers of the reviews. A checklist for the summarizing of reports of interventions for review is provided.

Monitoring symptoms at home: what methods would cancer patients be comfortable using?

PURPOSE: This study aimed to determine which methods of remote symptom assessment cancer outpatients would be comfortable using, including those involving information technology, and whether this varied with age and gender. METHODS: A questionnaire survey of 477 outpatients attending the Edinburgh Cancer Centre in Edinburgh, UK. RESULTS: Most patients reported that they would not feel comfortable using methods involving technology such as a secure website, email, mobile phone text message, or a computer voice on the telephone but that they would be more comfortable using more traditional methods such as a paper questionnaire, speaking to a nurse on the telephone, or giving information in person. CONCLUSIONS: The uptake of new, potentially cost-effective technology-based methods of monitoring patients' symptoms at home might be limited by patients' initial discomfort with the idea of using them. It will be important to develop methods of addressing this potential barrier (such as detailed explanation and supervised practice) if these methods are to be successfully implemented.

Fear of recurrence and psychological distress in head and neck cancer patients and their carers.

BACKGROUND: Fear of recurrence (FOR) has been increasingly recognised as an issue of significant burden for most cancer patients, and has been associated with psychological morbidity and reduced quality of life. More recently, the impact of recurrence fears has been indicated in the families of cancer patients. However, there has been a lack of prospective research. AIM: To systematically examine distress and illness concerns among patient-carer dyads. METHODS: A multi-centre prospective study of head and neck cancer patients and their carers (patients, n=101; carers, n=101), surveyed at two time-points following diagnosis. RESULTS: Carers recorded higher recurrence concerns on average than the patient group (p<0.001). A predictive path model of patient and carer self-reports of distress and FORs was explored, with an excellent overall fit of the final model (chi(2)=15.4, df=12, p=0.22, Comparative Fit Index (CFI)=0.994, Root Mean Square Estimate of Approximation (RMSEA)=0.053). CONCLUSIONS: The preliminary results establish that early fears and distress within individuals govern later reports on these same attributes, but that there is some weak evidence of influence from one attribute to another within and across individuals in the dyad. Future prospective dyadic research is warranted to ascertain the level of these fears over an extended time and their relationship to patient and carer adaptation. Intervention may be needed to reduce this disease concern to a manageable level at an early stage of the illness trajectory.

Association and linkage analysis of candidate genes GRP, GRPR, CRHR1, and TACR1 in panic disorder.

Panic disorder (PD) is a debilitating anxiety disorder, characterized by recurrent episodes of intense fear that are accompanied by autonomic and psychological symptoms leading to behavioral impairment. Basic research implicates neuropeptide-signaling genes in the modulation of anxiety and stress. The genes encoding corticotropin releasing hormone receptor 1 (CRHR1), tachykinin receptor 1 (TACR1), gastrin releasing peptide (GRP), and gastrin releasing peptide receptor (GRPR) were selected as candidates for PD based on their biology. Linkage and association analysis in 120 multiplex U.S. PD pedigrees was performed using 21 single nucleotide polymorphisms (SNPs). Parametric and non-parametric linkage tests in pedigrees, for single point and multipoint analysis, revealed limited support for genetic linkage to TACR1 (parametric and non-parametric lod scores approximately 1). The family-based association test (FBAT) generated nominal support for allelic association in TACR1 (P = 0.02), and GRP (P = 0.02), findings which must be considered in the light of multiple comparisons. Further exploration of the GRP and TACR1 findings in large case-control PD samples may provide more definitive evidence implicating these loci in the genetic etiology of PD.

Substrate-dependent effects of human ABCB1 coding polymorphisms.

One of the many obstacles to effective drug treatment is the efflux transporter P-glycoprotein (P-gp), which can restrict the plasma and intracellular concentrations of numerous xenobiotics. Variable drug response to P-gp substrates suggests that genetic differences in ABCB1 may affect P-gp transport. The current study examined how ABCB1 variants alter the P-gp-mediated transport of probe substrates in vitro. Nonsynonymous ABCB1 variants and haplotypes with an allele frequency >/=2% were transiently expressed in HEK293T cells, and the transport of calcein acetoxymethyl ester and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY-FL)-paclitaxel was measured in the absence or presence of the P-gp inhibitor cyclosporin A. The A893S, A893T, and V1251I variants and the N21D/1236C>T/A893S/3435C>T haplotype altered intracellular accumulation compared with reference P-gp in a substrate-dependent manner. It is interesting that certain variants showed altered sensitivity to cyclosporin A inhibition that was also substrate-specific. These functional data demonstrate that nonsynonymous polymorphisms in ABCB1 may selectively alter P-gp transport and drug-drug interactions in a substrate- and inhibitor-dependent manner.

The effectiveness of internet-delivered cognitive behavioural therapy for those with bulimic symptoms: a systematic review : A review of iCBT treatment for bulimic symptoms.

OBJECTIVE: This review looked at internet-delivered cognitive behavioural therapy (iCBT) as a possible treatment for patients with bulimic symptoms. CBT has been established as an effective treatment; however, waiting lists lead to delayed initiation of treatment. iCBT is a possible delivery method to combat this. Medline, EMBASE and PsycInfo were searched for controlled trials using iCBT as a treatment for patients with bulimia nervosa (BN), subthreshold BN or 'eating disorders not otherwise specified' with bulimic characteristics (EDNOS-BN). The literature search returned 482 papers. 5 met the review criteria and were compared in characteristics, methodological quality and outcomes. Outcomes were analysed by calculation of effect sizes; iCBT was evaluated on reduction in binge eating and purging post treatment and at follow-up. RESULTS: Participants were mostly female with an average age range of 23.7-31 years. 4 studies demonstrated good methodological quality. 1 did not report all of the outcome data, increasing the likelihood of bias. Only 1 study showed widespread benefit over waiting list controls. iCBT was shown to reduce behaviours but was not found to be superior to bibliotherapy or waiting list. Further large-scale studies are required to make conclusive recommendations.

A pragmatic group sequential, placebo-controlled, randomised trial to determine the effectiveness of glyceryl trinitrate for retained placenta (GOT-IT): a study protocol.

INTRODUCTION: A retained placenta is diagnosed when the placenta is not delivered following delivery of the baby. It is a major cause of postpartum haemorrhage and treated by the operative procedure of manual removal of placenta (MROP). METHODS AND ANALYSIS: The aim of this pragmatic, randomised, placebo-controlled, double-blind UK-wide trial, with an internal pilot and nested qualitative research to adjust strategies to refine delivery of the main trial, is to determine whether sublingual glyceryl trinitrate (GTN) is (or is not) clinically and cost-effective for (medical) management of retained placenta. The primary clinical outcome is need for MROP, defined as the placenta remaining undelivered 15 min poststudy treatment and/or being required within 15 min of treatment due to safety concerns. The primary safety outcome is measured blood loss between administration of treatment and transfer to the postnatal ward or other clinical area. The primary patient-sided outcome is satisfaction with treatment and a side effect profile. The primary economic outcome is net incremental costs (or cost savings) to the National Health Service of using GTN versus standard practice. Secondary outcomes are being measured over a range of clinical and economic domains. The primary outcomes will be analysed using linear models appropriate to the distribution of each outcome. Health service costs will be compared with multiple trial outcomes in a cost-consequence analysis of GTN versus standard practice. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North-East Newcastle & North Tyneside 2 Research Ethics Committee (13/NE/0339). Dissemination plans for the trial include the Health Technology Assessment Monograph, presentation at international scientific meetings and publication in high-impact, peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISCRTN88609453; Pre-results.