Fear-avoidant beliefs and behaviours after upper limb fracture in older people: a systematic review and meta-ethnography.

PURPOSE: This systematic review aimed to understand older people's perspectives of associated fear-avoidant beliefs following upper limb fracture. METHODS: Published and unpublished literature databases were systematically searched from inception to 1st April 2023. Qualitative studies reporting the perspectives of fear-avoidant beliefs or behaviours in people who had sustained an upper limb fracture were eligible. Data extracted included characteristics of people interviewed, experiences and perceptions of fear, fear of falling, and fear-avoidant beliefs and behaviours. Data were synthesised using a meta-ethnography approach and the GRADE-CERQUAL tool. RESULTS: Eight studies were eligible (n = 150 participants; 109 distal radial/41 humeral fracture). Three overarching themes were identified: (1) type of fear-avoidant experiences, (2) drivers of fear-avoidant beliefs and behaviours, and (3) consequences of fear-avoidant beliefs and behaviours. The themes generated were based on moderate confidence evidence. In summary, whilst some patients initially consider upper limb fractures to be relatively minor injuries, over time, the realisation occurs that they have wide-ranging consequences with longer-term perspectives on recovery. This often occurs following an initial period of reduced fear. Providing education and support immediately post-fracture to prevent or challenge initial health beliefs around fear of falls and fear of movement is imperative to recovery. CONCLUSIONS: Fear-avoidant beliefs can impact heavily on certain older people's recovery, as well as their longer-term health and wellbeing. Consideration of fear avoidance and taking steps to mitigate against this in the acute upper limb trauma setting will better serve these patients in their ongoing recovery from injury.

Diagnosis, treatment, and outcome of patients with oesophagogastric cancer during the COVID-19 pandemic: national study.

BACKGROUND: The national response to COVID-19 has had a significant impact on cancer services. This study investigated the effect of national lockdown on diagnosis, management, and outcomes of patients with oesophagogastric cancers in Scotland. METHODS: This retrospective cohort study included consecutive new patients presenting to regional oesophagogastric cancer multidisciplinary teams in National Health Service Scotland between October 2019 and September 2020. The study interval was divided into before and after lockdown, based on the first UK national lockdown. Electronic health records were reviewed and results compared. RESULTS: Some 958 patients with biopsy-proven oesophagogastric cancer in 3 cancer networks were included: 506 (52.8 per cent) before and 452 (47.2 per cent) after lockdown. Median age was 72 (range 25-95) years and 630 patients (65.7 per cent) were men. There were 693 oesophageal (72.3 per cent) and 265 gastric (27.7 per cent) cancers. Median time to gastroscopy was 15 (range 0-337) days before versus 19 (0-261) days after lockdown (P < 0.001). Patients were more likely to present as an emergency after lockdown (8.5 per cent before versus 12.4 per cent after lockdown; P = 0.005), had poorer Eastern Cooperative Oncology group performance status, were more symptomatic, and presented with a higher stage of disease (stage IV: 49.8 per cent before versus 58.8 per cent after lockdown; P = 0.04). There was a shift to treatment with non-curative intent (64.6 per cent before versus 77.4 per cent after lockdown; P < 0.001). Median overall survival was 9.9 (95 per cent c.i. 8.7 to 11.4) months before and 6.9 (5.9 to 8.3) months after lockdown (HR 1.26, 95 per cent c.i. 1.09 to 1.46; P = 0.002). CONCLUSION: This national study has highlighted the adverse impact of COVID-19 on oesophagogastric cancer outcomes in Scotland. Patients presented with more advanced disease and a shift towards treatment with non-curative intent was observed, with a subsequent negative impact on overall survival.

Resistance to immune checkpoint inhibitors in advanced gastro-oesophageal cancers.

Immune checkpoint inhibitors (ICIs) have altered the treatment paradigm across a range of tumour types, including gastro-oesophageal cancers. For patients with any cancer type who respond, ICIs can confer long-term disease control and significantly improve survival and quality of life, but for patients with gastro-oesophageal cancer, ICIs can be transformative, as durable responses in advanced disease have hitherto been rare, especially in those patients who are resistant to first-line cytotoxic therapies. Results from trials in patients with advanced-stage gastro-oesophageal cancer have raised hopes that ICIs will be successful as adjuvant and neoadjuvant treatments in early-stage disease, when the majority of patients relapse after potential curative treatments, and several trials are ongoing. Unfortunately, however, ICI-responding patients appear to constitute a minority subgroup within gastro-oesophageal cancer, and resistance to ICI therapy (whether primary or acquired) is common. Understanding the biological mechanisms of ICI resistance is a current major research challenge and involves investigation of both tumour and patient-specific factors. In this review, we discuss the mechanisms underlying ICI resistance and their potential specific applications of this knowledge towards precision medicine strategies in the management of gastro-oesophageal cancers in clinical practice.

The impact of COVID-19 on systemic anticancer treatment delivery in Scotland.

Understanding the impact of the COVID-19 pandemic on systemic anticancer therapy delivery (SACT) is crucial to appreciate the short- and long-term consequences for cancer patients and plan future care. Here, we report real-time national SACT delivery data from NHS Scotland. We demonstrate an initial rapid reduction in patient attendance of 28.7% with subsequent rapid recovery following service redesign. The smallest decrease was seen in breast cancer (19.7%), which also had the most rapid recovery and the largest decrease seen in colorectal cancer (43.4%). Regional variation in the magnitude of impact on SACT delivery was observed, but nadirs occurred at the same time and the rate of recovery was similar across all regions. This recovery reflected a coordinated national approach and associated patient and clinician support structures, which facilitated the creation of COVID-19-protected areas for SACT delivery in Scottish cancer centres enabling rapid sharing of successful and innovative strategies. The data show that these actions have limited the disadvantage to cancer patients.

Combining precision medicine and prophylaxis in oesophageal squamous cell carcinoma.

A trial update confirms improved survival for prophylactic elective nodal irradiation and addition of erlotinib to definitive chemoradiotherapy in oesophageal squamous cell carcinoma (ESCC). High tumour EGFR protein expression shows promise to identify those who will benefit from erlotinib. This represents therapeutic progress, and has wider relevance for precision medicine strategies in ESCC.

Lenvatinib and its use in the treatment of unresectable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver accounting for approximately 90% of cases. Patients often present at an advanced stage when treatment options are limited. Sorafenib, a multitargeted tyrosine kinase inhibitor, has been the first-line treatment in this setting for almost a decade. Several subsequent targeted therapies have failed to demonstrate significant improvement in survival. The results of the REFLECT study suggest that lenvatinib, a multikinase inhibitor, may have promised as a first-line treatment in patients with advanced HCC. This article will review the development of lenvatinib and the evidence behind its potential use in patients with advanced HCC.

Airways resistance in bronchial challenge testing.

INTRODUCTION: Measurement of airways resistance is an alternative to spirometry to assess airflow obstruction. This can be measured by the interrupter technique (RInt) using a handheld device. We wished to know how RInt compared to forced expiratory volume in 1 s (FEV1) during a histamine challenge test. METHODS: Twenty-nine (13 male) patients, aged 48.9 (SD 15.3) years, referred for a histamine challenge test, were enrolled. Patients had measurement of RInt then FEV1 after administration of saline and following doubling concentrations of histamine from 0.06 to 8 mg/ml. Extrapolation of the log dose-response curve was undertaken to calculate the concentration (provocation concentration, PC) causing an increase airways resistance of 20, 40, 60, 80, 100, 120, 140 and 160% (RInt PC1.2 to RInt PC2.6) and a reduction in FEV1 by 20% (FEV1 PC20). The number of patients with a negative challenge (i.e. PC>8 mg/ml histamine) was calculated for FEV1 and each change in airway resistance. Patients assessed their procedure-provoked symptoms of breathlessness, dizziness and tiredness on a visual analogue scale. RESULTS: Geometric (SD) PC20 for FEV1 was 1.87 (0.5) mg/ml with 11 patients having a negative challenge. A RInt PC20 had the best agreement with FEV1 PC20 [Kappa 0.39 (p=0.024)]. There is a significant negative correlation between RInt and FEV1 (r=-0.94). The respective mean (SD) breathlessness, dizziness and tiredness scores for RInt were 26 (4) mm, 18 (3) mm, 22 (4) mm and for spirometry were 40 (4) mm, 27 (5) mm, 31 (5) mm. There was a significant (p<0.05) difference for breathlessness. CONCLUSION: RInt was tolerated better than spirometry. A doubling of airways resistance had the best agreement with PC20 FEV1.

Emergency presentation of colorectal cancer in older adults: A retrospective cohort analysis.

INTRODUCTION: Adults aged 70 years and over account for almost 60% of colorectal cancer (CRC) diagnoses in the United Kingdom. Whilst emergency presentation of CRC is known to be associated with poorer outcomes across all ages, older adults are less likely to be treated with curative intent and have poorer overall survival (OS). We aimed to investigate whether presentation, management, or outcome differed in older (≥70 years) versus younger (<70 years) adults in our population. MATERIALS AND METHODS: The electronic records of patients diagnosed with CRC within the period 2016 to 2019 in National Health Service (NHS) Tayside, Scotland were retrospectively analysed. Patients were grouped by age (<70 years and ≥70 years). Demographics were compared by Chi-squared or t-test, and Kaplan-Meier and Cox proportional hazard regression were used for survival analyses. RESULTS: In total, 1245 patients were diagnosed with CRC (median age 71 years, range 20-98). Of these, 215 patients (17.3%) presented emergently and were included in the analysis. Older adults accounted for 65.1% (n = 140) of emergency presentations. Older adults were less likely to present with classical symptoms of CRC (80.0% vs 90.7%, p = 0.04) and more likely to present via the medical assessment unit (46.4% vs 30.7%, p = 0.03). Additionally, older adults were less likely to receive a histological diagnosis of CRC (71.4% vs 97.3%, p < 0.001) or have complete staging investigations performed (78.6% vs 96.0%, p < 0.001). Fewer older adults underwent surgical management (55.0% vs 86.7%, p < 0.001) and fewer were treated with chemotherapy (14.3% vs 69.3%, p < 0.001). Whilst older adults had poorer median OS than those aged <70 years (12.0 vs 34.4 months, p < 0.001), multivariate Cox proportional hazards regression demonstrated that higher stage (stage III hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.7, stage IV HR 16.7, 95% CI 9.7-28.8, incomplete HR 8.2, 95% CI 4.6-14.7) and not receiving chemotherapy (HR 2.6, 95% CI 1.7-4.0) were associated with poorer survival, whereas age and sex were not. DISCUSSION: Emergency presentation of colorectal cancer was more common in older adults. Older adults were more likely to present atypically, less likely to have completed staging, and had lower rates of intervention, which were associated with poorer survival outcome.

Female Sex but Not Oestrogen Receptor Expression Predicts Survival in Advanced Gastroesophageal Adenocarcinoma-A Post-hoc Analysis of the GO2 Trial.

Gastroesophageal adenocarcinoma is a disease of older adults that is associated with a very poor prognosis. It is less common and has better outcomes in females. The reason for this is unknown but may relate to signalling via the main oestrogen receptors (ER) α and ß. In this study, we sought to investigate this using the GO2 clinical trial patient cohort. GO2 recruited older and/or frail patients with advanced gastroesophageal cancer. Immunohistochemistry was performed on tumour samples from 194 patients. The median age of the population was 76 years (range 52-90), and 25.3% were female. Only one (0.5%) tumour sample was positive for ERα, compared to 70.6% for ERß expression. There was no survival impact according to ERß expression level. Female sex and younger age were associated with lower ERß expression. Female sex was also associated with improved overall survival. To our knowledge, this is the largest study worldwide of ER expression in a cohort of patients with advanced gastroesophageal adenocarcinoma. It is also unique, given the age of the population. We have demonstrated that female sex is associated with better survival outcomes with palliative chemotherapy but that this does not appear to be related to ER IHC expression. The differing ER expression according to age supports the concept of a different disease biology with age.

Geriatric Oncology as an Unmet Workforce Training Need in the United Kingdom-A Narrative Review by the British Oncology Network for Undergraduate Societies (BONUS) and the International Society of Geriatric Oncology (SIOG) UK Country Group.

Cancer is a disease associated with ageing. Managing cancer in older adults may prove challenging owing to pre-existing frailty, comorbidity, and wider holistic needs, as well as the unclear benefits and harms of standard treatment options. With the ongoing advances in oncology and the increasing complexity of treating older adults with cancer, the geriatric oncology field must be a priority for healthcare systems in education, research, and clinical practice. However, geriatric oncology is currently not formally taught in undergraduate education or postgraduate training programmes in the United Kingdom (UK). In this commentary, we outline the landscape of geriatric oncology undergraduate education and postgraduate training for UK doctors. We highlight current challenges and opportunities and provide practical recommendations for better preparing the medical workforce to meet the needs of the growing population of older adults with cancer. This includes key outcomes to be considered for inclusion within undergraduate and postgraduate curricula.

Gastroesophageal adenocarcinoma in older adults: A comprehensive narrative review of management by the Young International Society of Geriatric Oncology.

Gastroesophageal adenocarcinoma is a disease of older adults with very poor survival rates. Its incidence has risen dramatically across the world in recent decades. Current treatment approaches for older adults are based largely on extrapolated evidence from clinical trials conducted in younger and fitter participants than those more commonly encountered in clinical practice. Understanding how to apply available evidence to our patients in the clinic setting is essential given the high morbidity of both curative and palliative treatment. This review aims to use available data to inform the management of an older adult with gastroesophageal adenocarcinoma.

Best supportive care and prognosis: advanced gastroesophageal adenocarcinoma.

OBJECTIVES: Real-world data are lacking on survival in patients with advanced gastroesophageal adenocarcinoma (GOA) treated with best supportive care (BSC) alone. This knowledge is vital to personalise cancer treatment and obtain informed consent. This study aimed to define and compare survival in patients with advanced GOA treated with and without palliative chemotherapy (CTx), and to explore the factors that impact prognosis. METHODS: Patients in NHS Tayside, Scotland, diagnosed with advanced GOA (defined as non-resectable) over a 2-year period were identified retrospectively. Clinical data were obtained from electronic records. Kaplan-Meier and Cox regression analysis were performed to determine median overall survival (mOS) and investigate contributing factors. RESULTS: 127 eligible patients were identified. There was a significant difference in mOS between patients in the BSC and CTx groups (3.1 months vs 8.9 months, p=0.00089). This was maintained when those deemed not fit for CTx were removed. One-year survival was 16% versus 33%. Cox regression analysis in the BSC group identified stage (p<0.001) and Eastern Cooperative Oncology Group performance status (ECOG PS) (p=0.013) as having independent predictive value for survival. Age was not related to outcome. Palliative stents were inserted in 48 patients (37.8%). CONCLUSIONS: To our knowledge, this is the largest reported study in Europe of outcomes in patients with advanced GOA treated with BSC only. The mOS with BSC is approximately 3 months. Cancer stage and ECOG PS have a role in prognostication at diagnosis. Our findings support the benefit of palliative chemotherapy in this population, and real-world survival corresponds to published trial data.

Cardiotoxicity and Chemotherapy-The Role of Precision Medicine.

Cancer and cardiovascular disease are the leading causes of death in the United Kingdom. Many systemic anticancer treatments are associated with short- and long-term cardiotoxicity. With improving cancer survival and an ageing population, identifying those patients at the greatest risk of cardiotoxicity from their cancer treatment is becoming a research priority and has led to a new subspecialty: cardio-oncology. In this concise review article, we discuss cardiotoxicity and systemic anticancer therapy, with a focus on chemotherapy. We also discuss the challenge of identifying those at risk and the role of precision medicine as we strive for a personalised approach to this clinical scenario.

Real­world challenge for clinicians treating advanced gastroesophageal adenocarcinoma (Review).

Gastroesophageal adenocarcinoma (GOA) is a disease of older people. Incidence is rising in the developed world and the majority of patients present with advanced disease. Based on clinical trial data, systemic chemotherapy in the advanced setting is associated with improvements in quality of life and survival. However, there is a recognised mismatch between trial populations and the patients encountered in clinical practice in terms of age, comorbidity and fitness. Appropriate patient selection is essential to safely deliver effective treatment. In this narrative review, we discuss the challenges faced by clinicians when assessing real­world patients with advanced GOA for systemic therapy. We also highlight the importance of frailty screening and the current available evidence we can use to guide our management.

Cancer Treatment Helpline: a retrospective study of the NHS Tayside experience.

BACKGROUND: Treatment-related toxicity and delays in the management of this toxicity can impact the outcomes of patient with cancer. In Scotland, a national cancer helpline was established to provide triage assessment for patients receiving systemic anticancer therapy (SACT) in an attempt to minimise delays in toxicity management. In this article, we describe the use and impact of the helpline in our region over the last 5 years. METHODS: Patients who contacted the NHS Tayside cancer helpline between 1 January 2016 and 31 December 2020 were retrospectively identified. Patient demographics as well as the reason and outcome of each call was recorded. A descriptive analysis was performed. RESULTS: 6562 individual patients received SACT and 8385 calls were recorded during the time period. Median age of callers was 63 years (range 17-98) and 59.2% were women. Use of the helpline increased by 83.6% between 2016 and 2020, driven by an increase in in-hours calls. 41% of calls required review by a healthcare professional only, 24% required review and admission and the remaining 35% telephone advice only. The majority of cases (85%) were either assessed or advised solely by oncology. The proportional use of general practitioner services has decreased. CONCLUSIONS: The helpline provides a way for patients to report symptoms directly to their clinical team and receive appropriate specialist advice at an early stage. We demonstrate that most of these calls can be managed solely by our oncology team. This system can reduce pressure on other parts of the local health system.

Observational study investigating Tolerance Of Anticancer Systemic Therapy In the Elderly (TOASTIE): a protocol.

INTRODUCTION: The number of older adults diagnosed with cancer is increasing. Older adults are more likely to have pre-existing frailty, which is associated with greater chemotherapy-related toxicity. Early identification of those at risk of toxicity is important to reduce patient morbidity and mortality. Current chemotherapy toxicity prediction tools including the Cancer and Ageing Research Group (CARG) tool exist but are not in routine clinical use and have not been prospectively validated in a UK population. This study is the first prospective study to investigate the CARG tool in a UK population with cancer. METHODS AND ANALYSIS: Tolerance Of Anticancer Systemic Therapy In the Elderly is a prospective observational study of patients, aged ≥65 years, commencing first-line (any indication) chemotherapy for a solid-organ malignancy. Patients receiving other systemic anticancer agents or radiotherapy will be excluded. The primary objective will be to validate the ability of the CARG score to predict grade 3+ toxicity in this population. Secondary objectives include describing the feasibility of screening for frailty, as well as the prevalance of frailty in this population and assessing patient and clinician perception of chemotherapy toxicity risk. 500 patients will be recruited over a two year period. Baseline assessments will be recorded. At the end of the 6-month follow-up period, toxicity data will be retrospectively collected. A descriptive analysis of the recruited population will be performed. The validity of the CARG model will be analysed using receiver-operating characteristic curves and calculation of the area under the curve (c-statistic). ETHICS AND DISSEMINATION: The study has received ethical approval from the East of Scotland Research Ethics Service 20/ES/0114. Results will be reported in peer-reviewed scientific journals and disseminated to patient organisations and media.

Testicular cancer: improving outcomes with national quality performance indicators.

Testicular cancer is the most common malignancy in young adult men. The prognosis is excellent in limited disease and cure is possible even in advanced disease. Quality performance indicators (QPI) are used in many developed countries as a measure of healthcare performance. We report and discuss the development of a national set of QPIs in Scotland for testicular cancer as a method of gathering demographic data and driving improvement in nationwide testicular cancer outcomes.