Decision-making in cancer care for people living with dementia

Objective: Increasing numbers of people are expected to live with comorbid cancer and dementia. Cancer treatment decision-making for these individuals is complex, particularly for those lacking capacity, requiring support across the cancer care pathway. There is little research to inform practice in this area. This ethnographic study reports on the cancer decision-making experiences of people with cancer and dementia, their families, and healthcare staff. Methods: Participant observations, informal conversations, semi-structured interviews, and medical note review, in two NHS trusts. Seventeen people with dementia and cancer, 22 relatives and 19 staff members participated. Results: Decision-making raised complex ethical dilemmas and challenges and raised concerns for families and staff around whether correct decisions had been made. Whose decision it was and to what extent a person with dementia and cancer was able to make decisions was complex, requiring careful and ongoing consultation and close involvement of relatives. The potential impact dementia might have on treatment understanding and toleration required additional consideration by clinicians when evaluating treatment options. Conclusions: Cancer treatment decision-making for people with dementia is challenging, should be an ongoing process and has emotional impacts for the individual, relatives, and staff. Longer, flexible, and additional appointments may be required to support decision-making by people with cancer and dementia. Evidence-based decision-making guidance on how dementia impacts cancer prognosis, treatment adherence and efficacy is required

Epithelial TGFβ engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features

The pro-tumourigenic role of epithelial TGFβ signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort of born to be bad early-stage (T1) colorectal tumours, with aggressive features and a propensity to disseminate early, that are characterised by high epithelial cell-intrinsic TGFβ signalling. In the presence of concurrent Apc and Kras mutations, activation of epithelial TGFβ signalling rampantly accelerates tumourigenesis and share transcriptional signatures with those of the born to be bad T1 human tumours and predicts recurrence in stage II CRC. Mechanistically, epithelial TGFβ signalling induces a growth-promoting EGFR-signalling module that synergises with mutant APC and KRAS to drive MAPK signalling that re-sensitise tumour cells to MEK and/or EGFR inhibitors. Together, we identify epithelial TGFβ signalling both as a determinant of early dissemination and a potential therapeutic vulnerability of CRC’s with born to be bad traits

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Evaluation of Dyspnea through Education and Implementation of the Bedside Lung Ultrasound in Emergency (BLUE) Protocol by Prehospital Paramedics

BACKGROUND: It has been demonstrated that emergency medical service (EMS) providers have very poor sensitivity for identifying patients who present with dyspnea due to congestive heart failure versus other causes such as asthma or chronic obstructive pulmonary disease (COPD)1. Prior research has shown that focused lung ultrasound has high accuracy for differentiating respiratory distress in various clinical settings2. Paramedics have the requisite background to obtain adequate prehospital lung ultrasound images3. OBJECTIVES: The goal of this study was to demonstrate that paramedic-performed and paramedic-interpreted lung ultrasound is an accurate diagnostic tool for prehospital advanced life support providers in order to differentiate the etiology of respiratory distress. METHODS: This study was a randomized trial utilizing 911 paramedics to perform both ultrasound and standard, non-ultrasound clinical diagnostics on patients experiencing respiratory distress. Paramedics were trained in ultrasonography and randomized on a per-shift basis to perform ultrasound diagnostics or traditional diagnostics while assessing respiratory patients in the prehospital setting. The primary outcome was the accuracy of the paramedics’ two diagnostic methods compared to the clinical diagnoses determined by in-hospital providers after discharge from either the emergency department or in-patient care. RESULTS: Paramedics from four different EMS agencies (urban, suburban, and rural ground EMS, helicopter EMS) were trained in lung ultrasonography by study personnel. There were 53 patients who underwent focused lung ultrasound by paramedics and 109 patients who had non-ultrasound clinical diagnoses obtained. Paramedics’ diagnoses in both cases were compared to hospital diagnoses. Paramedic ultrasound for dyspnea had an overall accuracy of 79.2% compared to the non-ultrasound diagnostics accuracy of 63.3%. Ultrasound improved the diagnostic accuracy of the paramedics by 15.9% (95% CI [1.8%, 30.1%, p=0.028) compared to traditional protocols and skills. CONCLUSIONS/FUTURE WORK: Ultrasound has been shown to provide statistically significant increase in paramedic diagnostic accuracy for undifferentiated respiratory distress. Further research into improvement in patient outcomes from the application of prehospital ultrasound would likely show benefit from more accurate and precise prehospital interventions.In preparation versio

Characteristics and general practice resource use of people with comorbid cancer and dementia in England: a retrospective cross-sectional study

Background Cancer and dementia are common in older people and management of the conditions as comorbidities can be challenging, yet little is known about the size or characteristics of this group. We aimed to estimate the prevalence, characteristics and general practice resource usage of people living with both conditions in England. Methods Anonymised electronic healthcare records from 391 National Health Service general practices across England using the TPP SystmOne general practice system were obtained from ResearchOne. Data included demographic and clinical characteristics, and general practice healthcare useage (appointments, prescriptions, referrals and secondary care contacts) for people aged 50 and over with a cancer and/or dementia diagnosis consistent with the Quality and Outcomes Framework between 2005 and 2016. Multi-level negative binomial regression was used to analyse the number of general practice appointments. Results Data from 162,371 people with cancer and/or dementia were analysed; 3,616 (2.2%) people were identified as having comorbid cancer and dementia. Of people with cancer, 3.1% also had dementia, rising to 7.5% (1 in 13 people) in those aged 75 and over. Fewer people with both conditions were female (50.7%) compared to those with dementia alone (65.6%) and those with comorbid cancer and dementia were older than those with cancer alone [mean ages 83 (sd=7), 69 (sd=12) respectively]. Those with both conditions were less likely to have lung cancer than those with cancer alone (7.5% vs. 10.3%) but more likely to have prostate cancer (20.9% vs. 15.8%). Additional comorbidities were more prevalent for those with both conditions than those with cancer or dementia alone (68.4% 54 vs. 50.2% vs. 54.0%). In the year following the first record of either condition, people with cancer and dementia had 9% more general practice appointments (IRR:1.09, 95% 56 CI:1.01-1.17) than those with cancer alone and 37% more appointments than those with dementia alone (IRR: 1.37, 95% CI: 1.28-1.47). Conclusions A significant number of people are living with comorbid cancer and dementia in England. This group have additional comorbidity and higher general practice usage than those with cancer/dementia alone. The needs of this group should be considered in future general practice care planning and research

Characteristics and general practice resource use of people with comorbid cancer and dementia in England: a retrospective cross-sectional study

Background Cancer and dementia are common in older people and management of the conditions as comorbidities can be challenging, yet little is known about the size or characteristics of this group. We aimed to estimate the prevalence, characteristics and general practice resource usage of people living with both conditions in England. Methods Anonymised electronic healthcare records from 391 National Health Service general practices across England using the TPP SystmOne general practice system were obtained from ResearchOne. Data included demographic and clinical characteristics, and general practice healthcare useage (appointments, prescriptions, referrals and secondary care contacts) for people aged 50 and over with a cancer and/or dementia diagnosis consistent with the Quality and Outcomes Framework between 2005 and 2016. Multi-level negative binomial regression was used to analyse the number of general practice appointments. Results Data from 162,371 people with cancer and/or dementia were analysed; 3,616 (2.2%) people were identified as having comorbid cancer and dementia. Of people with cancer, 3.1% also had dementia, rising to 7.5% (1 in 13 people) in those aged 75 and over. Fewer people with both conditions were female (50.7%) compared to those with dementia alone (65.6%) and those with comorbid cancer and dementia were older than those with cancer alone [mean ages 83 (sd=7), 69 (sd=12) respectively]. Those with both conditions were less likely to have lung cancer than those with cancer alone (7.5% vs. 10.3%) but more likely to have prostate cancer (20.9% vs. 15.8%). Additional comorbidities were more prevalent for those with both conditions than those with cancer or dementia alone (68.4% 54 vs. 50.2% vs. 54.0%). In the year following the first record of either condition, people with cancer and dementia had 9% more general practice appointments (IRR:1.09, 95% 56 CI:1.01-1.17) than those with cancer alone and 37% more appointments than those with dementia alone (IRR: 1.37, 95% CI: 1.28-1.47). Conclusions A significant number of people are living with comorbid cancer and dementia in England. This group have additional comorbidity and higher general practice usage than those with cancer/dementia alone. The needs of this group should be considered in future general practice care planning and research

Navigating cancer treatment and care when living with comorbid dementia: an ethnographic study

Abstract Objectives The risks of developing cancer and dementia increase as we age; however, this comorbidity remains relatively under-researched. This study reports on the challenges that people affected by comorbid cancer and dementia face when navigating engagement with cancer treatment within secondary care. Materials and methods An ethnographic study recruiting 17 people with cancer and dementia, 22 relatives and 19 oncology staff in two UK National Health Service Trusts. Observations (46 h) and informal conversations were conducted during oncology appointments involving people with dementia. Semi-structured interviews (n = 37) with people living with cancer and dementia, their relatives and staff working in various roles across oncology services were also carried out. Data were analysed using ethnographically informed thematic analysis. Results People with cancer and dementia experienced challenges across three areas of navigating cancer treatment and care: navigating through multiple services, appointments and layers of often complex information; repeatedly navigating transport to and from hospital; and navigating non-dementia-friendly hospital outpatient environments alongside the cognitive problems associated with dementia. Conclusions Dementia impacts patients’ abilities to navigate the many practical aspects of attending hospital for cancer treatment and care. This study indicates the importance of addressing ways to improve the experience of travelling to and from the hospital, alongside extending the ongoing efforts to develop ‘dementia-friendly’ hospital in-patient areas and practices, to outpatient departments. Such steps will serve to improve hospital-based cancer treatment and care and more broadly outpatient appointment experiences for people with dementia and their families. </jats:sec