Quality-of-life methodology in hormone receptor–positive advanced breast cancer: Current tools and perspectives for the future

Health-related quality of life (HRQOL) is increasingly recognized as important when evaluating cancer treatments. The use, reporting, and analysis of patient-reported outcome measures (PROMs), however, are not standardized in clinical trials and are often poorly implemented in clinical practice. We report the results of a systematic literature review (PubMed search: January 1, 2000 to August 15, 2020) of PROM use, reporting, and analysis in phase 3 clinical trials of hormone receptor–positive (HR+) advanced breast cancer (ABC). Further inspection of cyclin-dependent kinase 4/6 (CDK4/6) inhibitor publications was performed to examine PROMs in the HR+/human epidermal growth factor receptor 2–negative setting. A total of 88 results were identified in the initial search; 32 were included in the final analysis. Among included studies, most (66%) had been published in the last 5 years (2015 to 2020). CDK4/6 inhibitors (38%) were the most common agents reported. No clear standard for PROM use, reporting, or analysis was found. The most common PROMs were European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30; 59%) and the Functional Assessment of Cancer Therapy–Breast (FACT-B; 34%). Important differences, among studies that reported them, ranged from 5 to 10 points for the EORTC QLQ-C30 and 8 points for the FACT-B total score. This review showed that a lack of clear consistency remains for PROM use, reporting, and analysis in phase 3 clinical trials of HR+ ABC. However, HRQOL is of high interest in the literature, including for CDK4/6 inhibitors

A real-time electronic symptom monitoring system for patients after discharge following surgery: a pilot study in cancer-related surgery

Background: Advances in peri-operative care of surgical oncology patients result in shorter hospital stays. Earlier discharge may bring benefits, but complications can occur while patients are recovering at home. Electronic patient-reported outcome (ePRO) systems may enhance remote, real-time symptom monitoring and detection of complications after hospital discharge, thereby improving patient safety and outcomes. Evidence of the effectiveness of ePRO systems in surgical oncology is lacking. This pilot study evaluated the feasibility of a real-time electronic symptom monitoring system for patients after discharge following cancer-related upper gastrointestinal surgery. Methods: A pilot study in two UK hospitals included patients who had undergone cancer-related upper gastrointestinal surgery. Participants completed the ePRO symptom-report at discharge, twice in the first week and weekly post-discharge. Symptom-report completeness, system actions, barriers to using the ePRO system and technical performance were examined. The ePRO surgery system is an online symptom-report that allows clinicians to view patient symptom-reports within hospital electronic health records and was developed as part of the eRAPID project. Clinically derived algorithms provide patients with tailored self-management advice, prompts to contact a clinician or automated clinician alerts depending on symptom severity. Interviews with participants and clinicians determined the acceptability of the ePRO system to support patients and their clinical management during recovery. Results: Ninety-one patients were approached, of which 40 consented to participate (27 male, mean age 64 years). Symptom-report response rates were high (range 63–100%). Of 197 ePRO completions analysed, 76 (39%) triggered self-management advice, 72 (36%) trigged advice to contact a clinician, 9 (5%) triggered a clinician alert and 40 (20%) did not require advice. Participants found the ePRO system reassuring, providing timely information and advice relevant to supporting their recovery. Clinicians regarded the system as a useful adjunct to usual care, by signposting patients to seek appropriate help and enhancing their understanding of patients’ experiences during recovery. Conclusion: Use of the ePRO system for the real-time, remote monitoring of symptoms in patients recovering from cancer-related upper gastrointestinal surgery is feasible and acceptable. A definitive randomised controlled trial is needed to evaluate the impact of the system on patients’ wellbeing after hospital discharge

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Feasibility test of a UK-scalable electronic system for regular collection of patient-reported outcome measures and linkage with clinical cancer registry data: The electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system

<p>Abstract</p> <p>Background</p> <p>Cancer survivors can face significant physical and psychosocial challenges; there is a need to identify and predict which survivors experience what sorts of difficulties. As highlighted in the UK National Cancer Survivorship Initiative, routine post-diagnostic collection of patient reported outcome measures (PROMs) is required; to be most informative, PROMs must be linked and analysed with patients' diagnostic and treatment information. We have designed and built a potentially cost-efficient UK-scalable electronic system for collecting PROMs via the internet, at regular post-diagnostic time-points, for linking these data with patients' clinical data in cancer registries, and for electronically managing the associated patient monitoring and communications; the electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system. This study aims to test the feasibility of the ePOCS system, by running it for 2 years in two Yorkshire NHS Trusts, and using the Northern and Yorkshire Cancer Registry and Information Service.</p> <p>Methods/Design</p> <p>Non-metastatic breast, colorectal and prostate cancer patients (largest survivor groups), within 6 months post-diagnosis, will be recruited from hospitals in the Yorkshire Cancer Network. Participants will be asked to complete PROMS, assessing a range of health-related quality-of-life outcomes, at three time-points up to 15 months post-diagnosis, and subsequently to provide opinion on the ePOCS system via a feedback questionnaire. Feasibility will be examined primarily in terms of patient recruitment and retention rates, the representativeness of participating patients, the quantity and quality of collected PROMs data, patients' feedback, the success and reliability of the underpinning informatics, and the system running costs. If sufficient data are generated during system testing, these will be analysed to assess the health-related quality-of-life outcomes reported by patients, and to explore if and how they relate to disease, treatment and/or individual differences characteristics.</p> <p>Discussion</p> <p>There is currently no system in the UK for collecting PROMs online and linking these with patients' clinical data in cancer registries. If feasible, ePOCS has potential to provide an affordable UK-scalable technical platform to facilitate and support longitudinal cohort research, and improve understanding of cancer survivors' experiences. Comprehensive understanding of survivorship difficulties is vital to inform the development and provision of supportive services and interventions.</p

Transcriptome analysis of extended-spectrum ß-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus exposed to cefotaxime

Previous studies on bacterial response to antibiotics mainly focused on susceptible strains. Here we characterized the transcriptional responses of distinct cephalosporin-resistant bacteria of public health relevance to cefotaxime (CTX), a cephalosporin widely used in clinical practice. Adaptation to therapeutic concentrations of CTX (30 µg/ml) was investigated by RNA sequencing in mid-exponential phase cultures of a methicillin-resistant Staphylococcus aureus (MRSA) and two genetically diverse E. coli producing CTX-M-15 or CMY-2 β-lactamase following genome sequencing and annotation for each strain. MRSA showed the most notable adaptive changes in the transcriptome after exposure to CTX, mainly associated with cell envelope functions. This reprogramming coincided with a transient reduction in cell growth, which also occurred in the CMY-2-producing E. coli but not in the CTX-M-15-producing strain. Re-establishment of growth in the CMY-2 producer proceeded without any notable adaptive transcriptional response, while limited reprogramming of gene transcription was observed in the CTX-M-15 producer. Our data show that the transcriptional response of CTX-resistant bacteria to CTX depends on the bacterial species, level of resistance and resistance determinant involved. Gene products induced in the presence of CTX may play an essential role for bacterial survival during therapy and merit further investigation as possible targets for potentiating CTX

Analytical methods applied to diverse types of Brazilian propolis

Propolis is a bee product, composed mainly of plant resins and beeswax, therefore its chemical composition varies due to the geographic and plant origins of these resins, as well as the species of bee. Brazil is an important supplier of propolis on the world market and, although green colored propolis from the southeast is the most known and studied, several other types of propolis from Apis mellifera and native stingless bees (also called cerumen) can be found. Propolis is usually consumed as an extract, so the type of solvent and extractive procedures employed further affect its composition. Methods used for the extraction; analysis the percentage of resins, wax and insoluble material in crude propolis; determination of phenolic, flavonoid, amino acid and heavy metal contents are reviewed herein. Different chromatographic methods applied to the separation, identification and quantification of Brazilian propolis components and their relative strengths are discussed; as well as direct insertion mass spectrometry fingerprinting

Integrating cancer survivors' experiences into UK cancer registries: design and development of the ePOCS system (electronic Patient-reported Outcomes from Cancer Survivors)

BACKGROUND: Understanding the psychosocial challenges of cancer survivorship, and identifying which patients experience ongoing difficulties, is a key priority. The ePOCS (electronic patient-reported outcomes from cancer survivors) project aims to develop and evaluate a cost-efficient, UK-scalable electronic system for collecting patient-reported outcome measures (PROMs), at regular post-diagnostic timepoints, and linking these with clinical data in cancer registries. METHODS: A multidisciplinary team developed the system using agile methods. Design entailed process mapping the system's constituent parts, data flows and involved human activities, and undertaking usability testing. Informatics specialists built new technical components, including a web-based questionnaire tool and tracking database, and established component-connecting data flows. Development challenges were overcome, including patient usability and data linkage and security. RESULTS: We have developed a system in which PROMs are completed online, using a secure questionnaire administration tool, accessed via a public-facing website, and the responses are linked and stored with clinical registry data. Patient monitoring and communications are semiautomated via a tracker database, and patient correspondence is primarily Email-based. The system is currently honed for clinician-led hospital-based patient recruitment. CONCLUSIONS: A feasibility test study is underway. Although there are possible challenges to sustaining and scaling up ePOCS, the system has potential to support UK epidemiological PROMs collection and clinical data linkage

Inhibition of NOS- like activity in maize alters the expression of genes involved in H2O2 scavenging and glycine betaine biosynthesis

Nitric oxide synthase-like activity contributes to the production of nitric oxide in plants, which controls plant responses to stress. This study investigates if changes in ascorbate peroxidase enzymatic activity and glycine betaine content in response to inhibition of nitric oxide synthase-like activity are associated with transcriptional regulation by analyzing transcript levels of genes (betaine aldehyde dehydrogenase) involved in glycine betaine biosynthesis and those encoding antioxidant enzymes (ascorbate peroxidase and catalase) in leaves of maize seedlings treated with an inhibitor of nitric oxide synthase-like activity. In seedlings treated with a nitric oxide synthase inhibitor, transcript levels of betaine aldehyde dehydrogenase were decreased. In plants treated with the nitric oxide synthase inhibitor, the transcript levels of ascorbate peroxidase-encoding genes were down-regulated. We thus conclude that inhibition of nitric oxide synthase-like activity suppresses the expression of ascorbate peroxidase and betaine aldehyde dehydrogenase genes in maize leaves. Furthermore, catalase activity was suppressed in leaves of plants treated with nitric oxide synthase inhibitor; and this corresponded with the suppression of the expression of catalase genes. We further conclude that inhibition of nitric oxide synthase-like activity, which suppresses ascorbate peroxidase and catalase enzymatic activities, results in increased H2O2 content