BRCA-DIRECT digital pathway for diagnostic germline genetic testing within a UK breast oncology setting: a randomised, non-inferiority trial.

BACKGROUND: Genetic testing to identify germline high-risk pathogenic variants in breast cancer susceptibility genes is increasingly part of the breast cancer diagnostic pathway. Novel patient-centred pathways may offer opportunity to expand capacity and reduce turnaround time. METHODS: We recruited 1140 women with unselected breast cancer to undergo germline genetic testing through the BRCA-DIRECT pathway (which includes a digital platform, postal saliva sampling and a genetic counsellor telephone helpline). Ahead of consenting to the test, participants were randomised to receive information about genetic testing digitally (569/1140, 49.9%) or via a pre-test genetic counselling consultation (571/1140, 50.1%). RESULTS: 1001 (87.8%) participants progressed to receive their pre-test information and consented to testing. The primary outcome, uptake of genetic testing, was higher amongst participants randomised to receive digital information compared with those randomised to a pre-test genetic counselling consultation (90.8% (95% CI: 88.5% to 93.1%) vs 84.7% (95% CI: 81.8% to 87.6%), p = 0.002, adjusted for participant age and site). Non-inferiority was observed in relation to patient knowledge, anxiety, and satisfaction. CONCLUSIONS: Findings demonstrate that standardised, digital information offers a non-inferior alternative to conventional genetic counselling, and an end-to-end patient-centred, digital pathway (supported by genetic counselling hotline) could feasibly be implemented into breast oncology settings. CLINICAL TRIAL REGISTRATION: The study is registered with, and protocol available on, ClinicalTrials.gov (NCT04842799).

The development and initial evaluation of the Diarrhoea Management Diary (DMD) in patients with metastatic breast cancer.

PURPOSE: Chemotherapy-induced diarrhoea (CID) is a common, but often underreported problem in patients with breast cancer that has a profound effect on quality of life. It is best measured from a patient's perspective, but tools are limited. The aim of this study was to develop and evaluate the Diarrhoea Management Diary (DMD), a self-report measure to assess CID, use of self-management strategies and treatment adherence. METHODS: The DMD was constructed using an iterative process of instrument development: concept elicitation (literature review), item generation and reduction (cognitive debriefing), and pilot testing in the target population. After translation into eight languages, the DMD was used in an international randomised trial for women receiving lapatinib and capecitabine for metastatic breast cancer with or without prophylactic octreotide. Patterns of missing data and sensitivity to change were examined. RESULTS: The understandability and completeness of the 8-item DMD was confirmed in cognitive interviews and pilot testing. Practicability of the DMD was evaluated in 62 women with metastatic breast cancer (median age 57). Up to 68% reported CID at any given time-point, and 19% had diarrhoea at each time-point. Patients also described efficacy of different strategies for diarrhoea management. Missing data were associated with study discontinuation. DMD missing item response was 0.9%. Sensitivity to change was good at most assessment points. CONCLUSIONS: Although further psychometric testing is recommended, initial evaluation of the DMD showed good content validity and practicability in international research with cancer patients.

A study of the validity and the reliability of the Geriatric Anxiety Inventory in screening for anxiety after stroke in older inpatients.

OBJECTIVES: To investigate the validity and reliability of the Geriatric Anxiety Inventory in screening for anxiety in older inpatients post-stroke. DESIGN: Longitudinal. SUBJECTS: A total of 81 inpatients with stroke aged 65 years or older were recruited at four centres in England. MAIN MEASURES: At phase 1 the Geriatric Anxiety Inventory and the Hospital Anxiety and Depression Scale were administered and then the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders 4th edition (phase 2). The Geriatric Anxiety Inventory was repeated a median of seven days later (phase 3). RESULTS: Internal reliability of the Geriatric Anxiety Inventory was high (α = 0.95) and test-retest reliability acceptable (τB = 0.53). Construct validity was evident relative to the Hospital Anxiety and Depression Scale - Anxiety subscale (τB = 0.61). At a cut off of 6/7, sensitivity of the Geriatric Anxiety Inventory was 0.88, specificity 0.84, with respect to the Structured Clinical Interview anxiety diagnosis. Hospital Anxiety and Depressions Scale - Anxiety subscale sensitivity was 0.88, specificity 0.54 at the optimum cut off of 5/6. A comparison of the areas under the curve of the Receiver Operating Characteristics for the two instruments indicated that the area under the curve of the Geriatric Anxiety Inventory was significantly larger than that of the Hospital Anxiety and Depressions Scale - Anxiety subscale, supporting its superiority. CONCLUSIONS: The Geriatric Anxiety Inventory is an internally consistent, reliable (stable) and valid instrument with acceptable sensitivity and specificity to screen for anxiety in older inpatients with stroke.

Predictors of anxiety after stroke: a systematic review of observational studies.

BACKGROUND: Anxiety disorders or symptoms are relatively common after stroke. A better understanding of the predictors of anxiety in stroke patients may improve the management of these disorders. The current review was conducted to determine the predictors of anxiety after stroke. METHODS: Relevant articles concerning population, hospital, or rehabilitation-based studies were identified by searching 10 electronic databases up to May 2014. Methodological quality appraisal, including the validity of prognostic models and data extraction were conducted by 3 reviewers. RESULTS: A total of 18 studies were identified. Data from 3 population-based studies including 8130 patients, 8 hospital-based studies including 1199 patients, and 7 rehabilitation-based studies including 1103 patients were evaluated. Prestroke depression, stroke severity, early anxiety, and dementia or cognitive impairment after stroke were the main predictors of poststroke anxiety. Older age, physical disability or impairment, and use of antidepressant drugs were not associated with the presence of anxiety. Limitations of studies included wide variation in screening tools and cutoff scores, variability in the time frame of screening for anxiety, use of extensive exclusion criteria, and questionable statistical internal and external validity of the models. CONCLUSIONS: Lack of methodological and statistical rigor affects the validity of proposed models to predict anxiety after stroke. Future research should focus on testing proposed models on both internal and external samples to ultimately inform future clinical practice.

Symptomatic presentation of cancer in primary care: a scoping review of patients' experiences and needs during the cancer diagnostic pathway.

OBJECTIVES: The objective was to map the experiences and needs of patients presenting with symptoms of suspected cancer in the primary care interval (from when they first present to primary care to their first appointment or referral to a secondary or tertiary level healthcare facility). DESIGN: This was a scoping review. INCLUSION CRITERIA: Studies or reports written in English which included primary data on the primary care interval experiences and/or needs of adult patients presenting with new symptoms of suspected cancer were eligible. Studies which only included patients with secondary or recurring cancer, conference abstracts and reviews were excluded. No date limits were applied. METHODS: The Joanna Briggs Institute method for Scoping Reviews guided screening, report selection and data extraction. At least two independent reviewers contributed to each stage. Medline, CINAHL, PsychInfo, Embase and Web of Science were searched and several grey literature resources. Relevant quantitative findings were qualitised and integrated with qualitative findings. A thematic analysis was carried out. RESULTS: Of the 4855 records identified in the database search, 18 were included in the review, along with 13 identified from other sources. The 31 included studies were published between 2002 and 2023 and most (n=17) were conducted in the UK. Twenty subthemes across four themes (patient experience, interpersonal, healthcare professional (HCP) skills, organisational) were identified. No studies included patient-reported outcome measures. Patients wanted (1) to feel heard and understood by HCPs, (2) a plan to establish what was causing their symptoms, and (3) information about the next stages of the diagnostic process. CONCLUSIONS: Scoping review findings can contribute to service planning as the cancer diagnostic pathway for symptomatic presentation of cancer evolves. The effectiveness of this pathway should be evaluated not only in terms of clinical outcomes, but also patient-reported outcomes and experience, along with the perspectives of primary care HCPs.

Adjuvant chemotherapy in elderly women with breast cancer: patients' perspectives on information giving and decision making.

BACKGROUND: Decisions about adjuvant chemotherapy in older women with early stage breast cancer (EBC) are often challenging. Uncertainty about benefits due to limited data about treatment efficacy and outcomes complicates decision making. This qualitative study explored older patients' experiences and preferences towards information giving and ultimate decisions about adjuvant chemotherapy. METHODS: Clinicians from 24 UK breast cancer teams reported on adjuvant chemotherapy decisions for women aged ≥70 years with EBC from April 2010 to December 2011. Women who were offered chemotherapy were invited to participate in structured interviews. Self-reported quality of life (QoL) and functional ability were assessed. Qualitative methods were used to identify themes associated with information giving and decision making. RESULTS: A total of 58/95 eligible women (61%) participated. Median age was 73 years (range 70-83). Mean total scores for QoL and functional ability were average. The majority of women preferred to make their treatment decisions collaboratively with a clinician (59%) or on their own (19%). The main reasons influencing decisions to accept chemotherapy were categorised as prevention of recurrence and clinician recommendation. Side effects, length of treatment, impact on QoL, low survival benefits and clinician recommendation influenced decisions to decline chemotherapy. The majority (80%) were satisfied with information provision, the communication with their clinician and explanation of treatment. CONCLUSIONS: Older women with EBC preferred to be involved in clinical decision making. Clinician recommendation plays a significant role in either accepting or declining chemotherapy. Well-informed decision making and effective communication between clinicians, older women and their family members are therefore important.

Sexual functioning in 4,418 postmenopausal women participating in UKCTOCS: a qualitative free-text analysis.

OBJECTIVE: Sexual well-being can contribute significantly to the overall quality of women's lives. This qualitative study aimed to examine sexual activity, functioning, and satisfaction in a large sample of postmenopausal women from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) METHODS:: Thematic analysis was used to evaluate the free-text data of the Fallowfield Sexual Activity Questionnaire (FSAQ) completed by UKCTOCS participants at baseline before annual screening. RESULTS: A total of 24,305 women completed the baseline FSAQ and 4,525 (19%) provided free-text data, with 4,418 comments eligible for analysis. Median age was 64 years; 65% had a partner and 22.5% were sexually active. Four interrelated themes were derived: partner availability, physical and sexual health, mental well-being, and interpersonal relationships. Primary reason for absence of sexual activity was lack of a partner, mainly due to widowhood (n = 1,000). Women discussed how partner's medical condition (27%) or sexual dysfunction (13.5%), their own physical health (18%) or menopause-related symptoms (12.5%), and prescribed medication (7%) affected sexual activity. Impact of low libido in self (16%) or partner (7%), relationship problems (10.5%) or logistics (6%), and perceptions of ageing (9%) were also mentioned. Few (3%) referred to positive sexual experiences or had sought medical help for sexual problems (6%). CONCLUSIONS: This qualitative analysis explored postmenopausal women's perspective on their sexual functioning. Having an intimate partner and good physical health are key factors for continuation of sexual activity and satisfaction. Further sexual education for healthcare professionals is needed to raise awareness about sexuality and sexual difficulties in later life. : Video Summary: Supplemental Digital Content 1, http://links.lww.com/MENO/A426.

Efficient development and usability testing of decision support interventions for older women with breast cancer.

BACKGROUND: Around one-third of breast cancers diagnosed every year in the UK are in women aged ≥70 years. However, there are currently no decision support interventions (DESIs) for older women who have a choice between primary endocrine therapy and surgery followed by adjuvant endocrine therapy (surgery+endocrine therapy), or who can choose whether or not to have chemotherapy following surgery. There is also little evidence-based guidance specifically on the management of these older patients. A large UK cohort study is currently underway to address this lack of evidence and to develop two DESIs to facilitate shared decision-making with older women about breast cancer treatments. Here, we present the development and initial testing of these two DESIs. METHODS: An initial prototype DESI was developed for the choice of primary endocrine therapy or surgery+endocrine therapy. Semi-structured interviews with healthy volunteers and patients explored DESI acceptability, usability, and utility. A framework approach was used for analysis. A second DESI for the choice of having chemotherapy or not was subsequently developed based on more focused development and testing. RESULTS: Participants (n=22, aged 75-94 years, 64% healthy volunteers, 36% patients) found the primary endocrine therapy /surgery+endocrine therapy DESI acceptable, and contributed to improved wording and illustrations to address misunderstandings. The chemotherapy DESI (tested with 14 participants, aged 70-87 years, 57% healthy volunteers, 43% patients) was mostly understandable, however, suggestions for rewording sections were made. Most participants considered the DESIs helpful, but highlighted the importance of complementary discussions with clinicians. CONCLUSION: It was possible to use a template DESI to efficiently create a second prototype for a different treatment option (chemotherapy). Both DESIs were acceptable and considered helpful to support/augment consultations. Development of acceptable additional DESIs for similar target populations using simplified methods may be an efficient way to develop future DESIs. Further research is needed to test the effectiveness of the DESIs.

Case-referent comparison of cognitive functions in patients receiving haematopoietic stem-cell transplantation for haematological malignancies: two-year follow-up results.

During bone marrow or haematopoietic stem-cell transplantation (HSCT), potentially neurotoxic treatments are used. Previous studies identified cognitive disturbances in patients treated with HSCT, but prospective studies with longitudinal assessment are sparse. We examined cognitive functions up to 20 months after a first baseline assessment in 101 patients undergoing HSCT and in 82 reference patients with a haematological malignancy treated with non-myeloablative cancer therapies. Baseline findings revealed no between-group differences and demonstrated mild cognitive impairments in both groups. Follow-up analyses showed no significant changes over time, though poorer performance in attention and executive function, and psychomotor function was found in HSCT patients. Our results suggest limited HSCT-related cognitive dysfunctions. Additional follow-up is necessary to assess long-term effects.

A user-centred approach to developing bWell, a mobile app for arm and shoulder exercises after breast cancer treatment.

PURPOSE: The study aim was to develop a mobile application (app) supported by user preferences to optimise self-management of arm and shoulder exercises for upper-limb dysfunction (ULD) after breast cancer treatment. METHODS: Focus groups with breast cancer patients were held to identify user needs and requirements. Behaviour change techniques were explored by researchers and discussed during the focus groups. Concepts for content were identified by thematic analysis. A rapid review was conducted to inform the exercise programme. Preliminary testing was carried out to obtain user feedback from breast cancer patients who used the app for 8 weeks post surgery. RESULTS: Breast cancer patients' experiences with ULD and exercise advice and routines varied widely. They identified and prioritised several app features: tailored information, video demonstrations of the exercises, push notifications, and tracking and progress features. An evidence-based programme was developed with a physiotherapist with progressive exercises for passive and active mobilisation, stretching and strengthening. The exercise demonstration videos were filmed with a breast cancer patient. Early user testing demonstrated ease of use, and clear and motivating app content. CONCLUSIONS: bWell, a novel app for arm and shoulder exercises, was developed by breast cancer patients, health care professionals and academics. Further research is warranted to confirm its clinical effectiveness. IMPLICATIONS FOR CANCER SURVIVORS: Mobile health has great potential to provide patients with information specific to their needs. bWell is a promising way to support breast cancer patients with exercise routines after treatment and may improve future self-management of clinical care.

Bridging the age gap in breast cancer: evaluation of decision support interventions for older women with operable breast cancer: protocol for a cluster randomised controlled trial.

INTRODUCTION: While breast cancer outcomes are improving steadily in younger women due to advances in screening and improved therapies, there has been little change in outcomes among the older age group. It is inevitable that comorbidities/frailty rates are higher, which may increase the risks of some breast cancer treatments such as surgery and chemotherapy, many older women are healthy and may benefit from their use. Adjusting treatment regimens appropriately for age/comorbidity/frailty is variable and largely non-evidence based, specifically with regard to rates of surgery for operable oestrogen receptor-positive disease and rates of chemotherapy for high-risk disease. METHODS AND ANALYSIS: This multicentre, parallel group, pragmatic cluster randomised controlled trial (RCT) (2015-18) reported here is nested within a larger ongoing 'Age Gap Cohort Study' (2012-18RP-PG-1209-10071), aims to evaluate the effectiveness of a complex intervention of decision support interventions to assist in the treatment decision making for early breast cancer in older women. The interventions include two patient decision aids (primary endocrine therapy vs surgery/antioestrogen therapy and chemotherapy vs no chemotherapy) and a clinical treatment outcomes algorithm for clinicians. ETHICS AND DISSEMINATION: National and local ethics committee approval was obtained for all UK participating sites. Results from the trial will be submitted for publication in international peer-reviewed scientific journals. IRAS REFERENCE: 115550. TRIAL REGISTRATION NUMBER: European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2015-004220-61;Pre-results. Sponsor's Protocol Code Number Sheffield Teaching Hospitals STH17086. ISRCTN 32447*.

A feasibility study exploring the role of pre-operative assessment when examining the mechanism of 'chemo-brain' in breast cancer patients.

BACKGROUND: Women receiving chemotherapy treatment for breast cancer may experience problems with their memory and attention (cognition), which is distressing and interferes with quality of life. It is unclear what causes or contributes to the problems they report: psychological distress, fatigue, coping style, or specific biological changes for example to pro inflammatory cytokines. Research shows however, that approximately a third of women with breast cancer perform poorly on tests of cognition before commencing chemotherapy. We aimed to examine the acceptability and relevance of pre-surgical assessments (bloods, brain imaging, cognitive tests and self-report questionnaires) when investigating the phenomenon of 'chemo-brain' and investigate whether inflammatory markers mediate chemotherapy-induced neuropsychological impairments in women treated for breast cancer. METHODS: Women with early stage breast cancer completed neuropsychological and quality of life assessments at T1 (pre-surgery), T2 (post-surgery before chemotherapy) and T3 (6 months later). Blood cytokine levels were measured at the same time points and brain imaging was performed at T1 and T3. RESULTS: In total, 14/58 women participated (8 chemotherapy, 6 non-chemotherapy). Prior to the start of chemotherapy a decline in cognitive performance compared to baseline was observed in one participant. At T3 women who received chemotherapy reported poorer quality of life and greater fatigue. Increases in soluble tumour necrosis factor receptor II (sTNFRII), interleukin-6, interleukin-10 and vascular endothelial growth factor occurred post chemotherapy only. Levels of sTNFRII were inversely correlated with grey matter volume (GMV) of the right posterior insula in both groups. At T3, the chemotherapy group displayed a greater reduction in GMV in the subgenual and dorsal anterior cingulate, and the inferior temporal gyrus. CONCLUSIONS: Pre-operative recruitment to the study was challenging; however, the lack of significant changes in blood cytokine levels and neuropsychological tests at T2 implies that post surgery may be a valid baseline assessment, but this needs further investigation in a larger study. The preliminary results support the hypothesis that chemotherapy induced fatigue is mediated by a change in peripheral cytokine levels which could explain some symptoms of 'chemo brain' experienced by patients.

Assessment of pre-treatment cognitive performance in adult bone marrow or haematopoietic stem cell transplantation patients: a comparative study.

The aim of this study was to examine cognitive performance in patients prior to bone marrow or haematopoietic stem cell transplantation (SCT) and in haematological patients who received non-myeloablative cancer therapies. A consecutive sample of 101 SCT patients and 82 haematological patients completed a neuropsychological test battery and five questionnaires assessing subjective cognitive complaints, psychological functioning, health-related quality of life and fatigue. Results were compared with normative data. Percentages of cognitively impaired patients were equally divided between groups. Most deficits were observed in visual memory, visuospatial and constructional ability and psychomotor functions. The SCT group showed a higher rate of anxiety cases and reported lower cognitive, emotional and social functioning. Results of neuropsychological testing were not associated with outcome of the questionnaires. This study showed impaired cognitive performance prior to SCT. Haematological patients treated with non-myeloablative cancer therapies proved to be a reliable reference group for longitudinal studies.

Intravenous versus Subcutaneous Drug Administration. Which Do Patients Prefer? A Systematic Review.

BACKGROUND: Intravenous (IV) drug delivery is commonly used for its rapid administration and immediate drug effect. Most studies compare IV to subcutaneous (SC) delivery in terms of safety and efficacy, but little is known about what patients prefer. METHODS: A systematic review was conducted by searching seven electronic databases for articles published up to February 2014. Included studies were randomized controlled trials (RCTs) and/or crossover designs investigating patient preference for SC versus IV administration. The risk of bias in the RCTs was determined using the Cochrane Collaboration tool. Reviewers independently extracted data and assessed the risk of bias. Any discrepancies were resolved by consensus. RESULTS: The search identified 115 publications, but few (6/115) met the inclusion criteria. Patient populations and drugs investigated were diverse. Four of six studies demonstrated a clear patient preference for SC administration. Main factors associated with SC preference were time saving and the ability to have treatment at home. Only three studies used study-specific instruments to measure preference. CONCLUSIONS: Results suggest that patients prefer SC over IV delivery. Patient preference has clearly been neglected in clinical research, but it is important in medical decision making when choosing treatment methods as it has implications for adherence and quality of life. If the safety and efficacy of both administration routes are equivalent, then the most important factor should be patient preference as this will ensure optimal treatment adherence and ultimately improve patient experience or satisfaction. Future drug efficacy and safety studies should include contemporaneous, actual patient preference where possible, utilizing appropriate measures.

Neurocognitive functions and quality of life in haematological patients receiving haematopoietic stem cell grafts: a one-year follow-up pilot study.

Longitudinal data of neurocognitive functions and quality of life (QOL) were obtained for a cohort of 25 patients followed before transplant and through the first year after haematopoietic stem cell transplantation (SCT). A battery of neuropsychological tests and two self-report questionnaires were used to assess neurocognitive functions, QOL and psychological functioning. In comparison to normative data, up to one-fourth of the patients experienced impaired functioning on several cognitive domains before SCT. Random regression modelling revealed a slight improvement in the mean group scores of memory tasks over time, especially for younger patients. Impairment in neurocognitive functions was positively related to depression and anger at baseline, and to the emotional functioning scale at follow-up. These preliminary results emphasize the significance of a pre-treatment assessment and the need of a large baseline sample in future longitudinal studies to overcome the expected dropout rate of more than 50%.

Cognitive functioning and quality of life in long-term adult survivors of bone marrow transplantation.

BACKGROUND: The late neurotoxic effects of bone marrow transplantation (BMT) on cognitive functioning and quality of life (QOL) were investigated in a consecutively treated cohort of long-term adult survivors. METHODS: Progression-free patients treated with BMT or peripheral stem cell grafts for a hematologic malignancy at least 2 years before study participation were examined with a comprehensive battery of neuropsychological tests and questionnaires for QOL and mood states. The results of the neuropsychological tests were compared with healthy population norms. RESULTS: Forty patients were included, 87.5% of whom had undergone an allogeneic transplantation. All received total body irradiation up to 12 Gy (in two fractions). Assessment took place 22-82 months after BMT. Mild to moderate cognitive impairment was found in 24 patients (60%). Compared with healthy population norms, selective attention and executive function, information processing speed, verbal learning, and verbal and visual memory were most likely to be affected. The mean score for the total patient group revealed that these patients scored significantly lower on the information processing speed task compared with expected scores obtained from the normal population. The main predictors for poor neuropsychological performance were fatigue, global health, and educational level. Other correlations with moderate to severe cognitive impairment were subjective cognitive complaints, physical functioning, social functioning, overall mood states, and employment status. CONCLUSIONS: These data indicate that BMT may lead to cognitive complaints and late cognitive deficits in long-term adult survivors. Cognitive functioning should therefore be used as an outcome parameter in BMT studies.