Geriatric screening and frailty intervention in older patients with cancer.

Frailty in older patients with cancer increases the risk of treatment related toxicity, mortality, physical decline, and quality of life. This review summarises various screening tools. Screening tools identifying frailty serve multiple purposes, providing awareness of health issues impacting oncologic treatment and prognosis and facilitating the delivery of a Comprehensive Geriatric Assessment (CGA). CGA is an overall health assessment and treatment targeting frailty. Providing CGA to older patients with cancer reduces the risk of toxicity and functional decline, increases treatment completion, and prevents loss of quality of life.

The prevalence of sarcopenia and cachexia in older patients with localized colorectal cancer.

INTRODUCTION: The incidence of colorectal cancer (CRC) increases with age. In combination with an ageing population, the number of older patients undergoing surgical treatment for CRC is therefore expected to increase. Sarcopenia and cachexia are potentially modifiable risk factors of a negative surgical outcome. Sarcopenia can be categorized into primary (age-related) and secondary where diseases, such as malignancy, are influential factors. We aimed to investigate the prevalence of preoperative sarcopenia and cachexia in older (≥65 years) vulnerable patients with localized CRC. MATERIALS AND METHODS: Patients included in the randomized study "Geriatric assessment and intervention in older vulnerable patients undergoing resection for colorectal cancer," were screened for sarcopenia and cachexia prior to surgery. All patients in the present cohort were considered vulnerable with Geriatric 8 ≤ 14 points. Sarcopenia was defined according to European Guidelines (EWGSOP2), based on low muscle strength-low handgrip-strength and/or slow 5xChair-Stand-Test-and low appendicular lean mass assessed by dual-energy X-ray absorptiometry. Cachexia was defined as self-reported unintended weight loss >5% within three months or 2-5% with body mass index <20 kg/m2. RESULTS: Sixty-four patients (mean age 79.6 years ±6.4 years, 36 women) were assessed. Of these, 28% (n = 18, 11 women) had low muscle strength and 13% (n = 8, 4 women) fulfilled the criteria for sarcopenia, however, 33% (n = 21, 13 women) had low muscle mass. There was no correlation between low muscle strength and low muscle mass (r = 0.16, P = 0.22). The prevalence of cachexia was 36% (n = 23, 16 women). Low muscle mass was associated with cachexia (φ = 0.38, P = 0.005), but there was no association between sarcopenia and cachexia (φ = 0.01, P = 1.0). DISCUSSION: Despite the included patients who fulfilled the criteria for vulnerability according to G8, relatively few (28%) had low muscle strength. Moreover, there was poor overlap between the prevalence of sarcopenia according to the EWGSOP2 guidelines (13%) and prevalence of low muscle mass (33%) in older patients with CRC. Of note also, there was no association between sarcopenia and cachexia, but an association between cachexia and low muscle mass, which highlights the importance of assessing muscle mass in patients with cancer. TRIAL REGISTRATION: The GEPOC trial has been prospectively registered at http://clinicaltrials.gov (NCT03719573).

Physical exercise program to older frail patients receiving chemotherapy for colorectal cancer - feasibility and experiences from the GERICO study.

INTRODUCTION: Older and frail patients with cancer are at high risk of physical and functional decline during chemotherapy. Exercise interventions can often counteract chemotherapy related toxicity and may help patients to improve or retain physical function and quality of life. Studies evaluating feasibility and the effect of exercise in older patients are lacking. The aim of this study was to investigate the feasibility and effect of an exercise intervention in older frail patients during chemotherapy for colorectal cancer (CRC). MATERIALS AND METHODS: This is a secondary analysis from the GERICO study investigating the effect of geriatric interventions in frail patients ≥70 years receiving chemotherapy for CRC. All patients in the present analysis were patients randomized to geriatric interventions and who were found physically frail (low handgrip strength or slow 10 m gait speed) and therefore offered referral to the exercise program for twelve weeks. We evaluated reasons for dropping out and feasibility of an individually tailored exercise program twice a week for twelve weeks. Each 60 min session comprised warm-up followed by progressive resistance training and cool-down followed by an oral protein supplement. Baseline characteristics and the effect of exercise for patients with high and low adherence (attendance of <50% of exercise sessions) were compared. RESULTS: Of 71 patients in the intervention group, 47 (66%) were found physically frail and were offered referral to the exercise program. Seven patients were referred to municipal physiotherapy before study start. In the remaining population (N = 40) 19 had exercise adherence >50% and 21 had no or low exercise adherence. Baseline characteristics were similar between patients with high and low/no adherence, except for sex (68% and 33% were men in high and low/ no adherence group, respectively). Patients with >50% attendance had significant improvements in physical tests after twelve weeks of exercise. DISCUSSION: Low adherence to the exercise program was seen due to lack of energy and/or treatment related adverse events. Patients with high adherence benefitted from exercise during chemotherapy but did not differ from patients with low adherence at baseline. Consequently, exercise should be offered to all older frail patients receiving chemotherapy for CRC.

Muscle mass and physical function in patients with bladder cancer-Data from a prematurely terminated prospective cohort study.

Background: Patients with bladder cancer (BC) have a high prevalence of comorbidity and low adherence to systemic anticancer treatment but it is unknown whether this is associated with sarcopenia. Objective: We aimed to investigate if the sarcopenia-defining parameters (muscle strength, muscle mass and physical performance) were associated with reduced adherence to systemic anticancer treatment in patients with BC, and if these muscle domains changed during treatment. Methods: Patients >18 years of age with BC referred for chemotherapy or immunotherapy at Department of Oncology, Rigshospitalet, Denmark were eligible for study inclusion. Measurements were performed before treatment initiation and within one week after treatment termination, and consisted of assessments of muscle strength, muscle mass, and physical performance. Data was compared with thresholds outlined by the European Working Group on Sarcopenia in Older Patient's (EWGSOP2) guidelines and a healthy, age-matched Danish cohort. Results: Over a period of 29 months, we included 14 patients of whom two completed follow-up measurements. The recruitment rate was <50% of planned due to logistics and Covid-19 related limitations. Consequently, a decision to prematurely terminate the study was made. No patients fulfilled EWGSOP2 criteria for sarcopenia, but the majority had reduction in one or more muscle domains compared to healthy, age-matched individuals. The majority of patients had poor treatment tolerance, leading to dose reductions and postponed treatments. Conclusions: In this prematurely terminated study, no patients fulfilled EWGSOP2 criteria for sarcopenia, yet, most patients were affected in one or more muscle domains and the majority had compromised treatment adherence.

Effectiveness of different types, delivery modes and extensiveness of exercise in patients with breast cancer receiving systemic treatment - A systematic review and meta-analysis.

BACKGROUND: Effects of exercise in patients with breast cancer have been thoroughly investigated. The aim was to explore differences in effects regarding type, delivery mode and extensiveness (e.g. intensity; volume) of the interventions. METHODS: We searched for randomised controlled trials including patients with breast cancer receiving systemic treatment, exercise-based interventions, and measures on patient reported- and objectively measured outcomes. RESULTS: Exercise showed significant and moderate effects on the primary outcomes quality of life and physical function, Standardised Mean Difference: 0.52 (95 % CI 0.38-0.65) and 0.52 (95 % CI 0.38-0.66), respectively. Type of exercise had little influence on the effects, however combined aerobic- and resistance exercise seemed superior for increasing physical function, compared to aerobic or resistance exercise. Supervised interventions were superior to partly and unsupervised. Extensiveness of the intervention only influenced physical function. CONCLUSIONS: Supervised interventions, more than type or extensiveness of interventions, seem to increase effects.

Age-related Differences in Recall of Information and Handling of Chemotherapy-related Side Effects in Cancer Patients: The ReCap Study.

BACKGROUND: To prevent severe toxicity and hospital admissions, adequate management and recall of information about side effects are crucial and health literacy plays an important role. If age-related factors impact recall of given information and handling of side effects, revised ways to give information are required. PATIENTS AND METHODS: We undertook a questionnaire-based survey among 188 newly diagnosed patients with pancreatic cancer or colorectal cancer and chemo-naive patients with prostate cancer treated with adjuvant or first-line palliative chemotherapy comprising satisfaction with given information, recall of potential side effects, and handling of hypothetical side effect scenarios. We evaluated the association between baseline characteristics, ie, age, frailty (G8 score), comorbidity (Charlson Comorbidity Index), cognitive function (Mini-Cog), satisfaction, recall of information, and handling of side effects. RESULTS: Reduced ability to recall information about several side effects (eg, chest pain) was associated with older age (odds ratio adjusted for cancer [aOR] 0.94 [95% CI, 0.88-0.98]) and poor cognitive screening (aOR 0.56 [95% CI, 0.33-0.91]). Insufficient or dangerous handling of side effects was associated with older age (aOR 0.96 (95% CI, 0.92-0.99)) and cognitive impairment (aOR 0.70 [95% CI, 0.50-0.95]). CONCLUSION: Older age and poor cognitive screening may impact patients' ability to understand and adequately handle chemotherapy-related side effects. Cognitive screening and focus on individual ways to give information including assessment of recall and handling are needed.

Predictive value of geriatric oncology screening and geriatric assessment of older patients with cancer: A randomized clinical trial protocol (PROGNOSIS-RCT).

INTRODUCTION: Comprehensive geriatric assessment (CGA) has been shown to reduce frailty in older patients in general. In older patients with cancer, frailty affects quality of life (QoL), physical function, and survival. However, few studies have examined the effect of CGA as an additional intervention to antineoplastic treatment. This protocol presents a randomized controlled trial, which aims to evaluate the effects of CGA-based interventions in older patients with cancer and Geriatric 8 (G8) identified frailty. MATERIALS AND METHODS: This randomized controlled trial will include patients, age 70+ years, with solid malignancies and G8 frailty (G8 ≤ 14). Patients will be separated into two groups, with different primary endpoints, depending on palliative or curative antineoplastic treatment initiation, and subsequently randomized 1:1 to either CGA with corresponding interventions or standard of care, along with standardized antineoplastic treatment. A geriatrician led CGA with corresponding interventions and clinical follow-up will be conducted within one month of antineoplastic treatment initiation. The interdisciplinary CGA will cover multiple geriatric domains and employ a standard set of validated assessment tools. Primary endpoints will be physical decline measured with the 30-s Chair-Stand-Test at three months (palliative setting) and unplanned hospital admissions at six months (curative setting). Additional outcomes include QoL, treatment toxicity and adherence, occurrence of polypharmacy, potential drug interactions, potential inappropriate medications, and survival. The primary outcomes will be analyzed using a mixed model regression analysis (30-s chair stand test) and linear regression models (unplanned hospitalizations), with an intention to treat approach. Power calculations reveal the need to enroll 134 (palliative) and 188 (curative) patients. DISCUSSION: The present study will examine whether CGA, as an additional intervention to antineoplastic treatment, can improve endpoints valued by older patients with cancer. Inclusion began November 2020 and is ongoing, with 37 and 29 patients recruited April 15th, 2021. Registration:NCT04686851.

"Doing What Only I Can Do": Experiences From Participating in a Multimodal Exercise-Based Intervention in Older Patients With Advanced Cancer-A Qualitative Explorative Study.

BACKGROUND: Sparse evidence exists regarding the feasibility and patients' experiences of exercise programs among older cancer populations. OBJECTIVE: The aim of this study was to explore the experiences of older patients with advanced cancer who participated in a 12-week supervised and multimodal exercise program in a hospital setting. METHODS: Individual interviews were conducted with 18 participants (≥65 years) with advanced cancer who completed the intervention program regardless of compliance rate. In addition, written evaluation questionnaires were collected. Data were analyzed using thematic analysis. RESULTS: Three main themes were identified: (1) Motivated to strengthen body and mind, with the subthemes "Doing what only I can do" and "Reaching goals with support from healthcare professionals and peers"; (2) Exercise as an integrated part of the treatment course; and (3) Overcoming undeniable physical limitations. CONCLUSIONS: The participants experienced several benefits from participation, including physical improvements, increased energy, reduction of symptoms, and improved social engagement. Goal setting, being positively pushed and cheered on, and integration of fun games increased motivation. In contrast, being pushed beyond physical limitations and experiencing severe symptoms were experienced as barriers toward exercising. Adherence to the exercise program was facilitated by coordinating a tailored program with medical appointments and receiving comprehensive support and guidance. IMPLICATIONS FOR PRACTICE: Multimodal exercise programs seem to be beneficial for older patients with advanced cancer and should be coordinated with oncological treatment in combination with targeted support and advice on symptom management.

Predictive Value of Geriatric Oncology Screening and Geriatric Assessment in Older Patients with Solid Cancers: Protocol for a Danish prospective cohort study (PROGNOSIS-G8).

INTRODUCTION: Older patients with cancer constitute a heterogeneous group with varying degrees of frailty; therefore, geriatric assessment with initial geriatric oncology screening is recommended. The Geriatric 8 (G8) and the modified Geriatric 8 (mG8) are promising screening tools with high accuracy and an association with survival. However, evidence is sparse regarding patient-centered outcomes. This protocol describes a study, which aims to address the predictive and prognostic value of the G8 and mG8, with quality of life (QoL) as the primary outcome. MATERIALS AND METHODS: In this single-center prospective cohort study, patients, age ≥70 years with solid malignancies, will be screened with the G8 and mG8 prior to receiving 1st line antineoplastic treatment. Patients will contribute medical record data including; cancer type, Charlson comorbidity index score, performance status, and treatment intent, type, and dosage, at baseline. Patients will complete QoL questionnaires (EORTC QLQ-C30 and ELD-14) at baseline, 3, 6, 9, and 12-months follow-up. Two functional measurements (the 30-s chair stand test and the handgrip strength test) will be conducted at baseline to assess the added predictive and prognostic value. At 12 months follow-up, initially administered treatment and treatment adherence will be recorded and assessed with generalized linear models, while overall survival and cancer-specific survival will be assessed using survival analysis models with time-varying covariates. The relationship between frailty (G8 ≤ 14, mG8 ≥ 6) and QoL within 12 months will be examined using mixed regression models. DISCUSSION: Geriatric oncology screening may identify a subgroup of older patients with frailty, at risk of experiencing diminishing QoL and poor treatment adherence. With the proposed screening program, patients who require treatment modification and additional support to maintain their QoL may be identified. It is our hope, that these insights may facilitate the formation of national guidelines for the treatment of older patients with cancer. Registration:NCT04644874.

The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO).

BACKGROUND: Older patients with colorectal cancer (CRC) experience chemotherapy dose reductions or discontinuation. Comprehensive geriatric assessment (CGA) predicts survival and chemotherapy completion in patients with cancer, but the benefit of geriatric interventions remains unexplored. METHODS: The GERICO study is a randomised Phase 3 trial including patients ≥70 years receiving adjuvant or first-line palliative chemotherapy for CRC. Vulnerable patients (G8 questionnaire ≤14 points) were randomised 1:1 to CGA-based interventions or standard care, along with guideline-based chemotherapy. The primary outcome was chemotherapy completion without dose reductions or delays. Secondary outcomes were toxicity, survival and quality of life (QoL). RESULTS: Of 142 patients, 58% received adjuvant and 42% received first-line palliative chemotherapy. Interventions included medication changes (62%), nutritional therapy (51%) and physiotherapy (39%). More interventional patients completed scheduled chemotherapy compared with controls (45% vs. 28%, P = 0.0366). Severe toxicity occurred in 39% of controls and 28% of interventional patients (P = 0.156). QoL improved in interventional patients compared with controls with the decreased burden of illness (P = 0.048) and improved mobility (P = 0.008). CONCLUSION: Geriatric interventions compared with standard care increased the number of older, vulnerable patients with CRC completing adjuvant chemotherapy, and may improve the burden of illness and mobility. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02748811.

Clinical presentation and mortality in hospitalized patients aged 80+ years with COVID-19-A retrospective cohort study.

BACKGROUND: COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has great health implications in older patients, including high mortality. In general, older patients often have atypical symptom presentations during acute illness due to a high level of comorbidity. The purpose of this study was to investigate the presentation of symptoms at hospital admissions in older patients with COVID-19 and evaluate its impact on disease outcome. METHODS: This retrospective study included patients ≥80 years of age with a positive test for SARS-CoV-2, who were admitted to one of three medical departments in Denmark from March 1st to June 1st, 2020. RESULTS: A total of 102 patients (47% male) with a mean age of 85 years were included. The most common symptoms at admission were fever (74%), cough (62%), and shortness of breath (54%). Furthermore, atypical symptoms like confusion (29%), difficulty walking (13%), and falls (8%) were also present. In-hospital and 30-day mortality were 31% (n = 32) and 41% (n = 42), respectively. Mortality was highest in patients with confusion (50% vs 38%) or falls (63% vs 39%), and nursing home residency prior to hospital admission was associated with higher mortality (OR 2.7, 95% CI 1.1-6.7). CONCLUSIONS: Older patients with SARS-Cov-2 displayed classical symptoms of COVID-19 but also geriatric frailty symptoms such as confusion and walking impairments. Additionally, both in-hospital and 30-day mortality was very high. Our study highlights the need for preventive efforts to keep older people from getting COVID-19 and increased awareness of frailty among those with COVID-19.

Pre- and Perioperative Inflammatory Biomarkers in Older Patients Resected for Localized Colorectal Cancer: Associations with Complications and Prognosis.

The association between pre- and perioperative inflammatory biomarkers, major complications, and survival rates after resection of colorectal cancer (CRC) in older patients is largely unknown. The aim was to investigate age-dependent differences in these associations. Serum CRP, IL-6, and YKL-40 were measured preoperatively and on the first and second day after resection of CRC (stages I-III) in 210 older (≥70 years) and 191 younger patients (<70 years). The results from the complications was presented as an odds ratio (OR, with a 95% confidence interval (CI)) with logistic regression. Results from the mortality rates were presented as a hazard ratio (HR, with a 95% CI) using Cox proportional hazards regression. The preoperative inflammatory biomarkers were higher in the older vs. the younger patients. The risk of complications was increased in older patients with a high preoperative CRP (OR = 1.25, 95% CI 1.03-1.53), IL-6 (OR = 1.57, 95% CI 1.18-2.08), and YKL-40 (OR = 1.66, 95% CI 1.20-2.28), but not in younger patients. Mortality was higher in younger patients with high preoperative YKL-40 (HR = 1.66, 95% CI 1.06-2.60). This was not found in older patients. Elevated preoperative inflammatory biomarkers among older patients were associated with an increased risk of complications, but not mortality. Preoperative inflammatory biomarkers may be useful in assessing the risk of a complicated surgical course in older patients with CRC.

Wnt5a expression and prognosis in stage II-III colon cancer.

Cancer metastases accounts for most cancer deaths. The secreting glycoprotein Wnt5a impairs tumor cell migration and reduces invasiveness and metastasis. High Wnt5a expression in tumor cells is correlated to better outcomes in patients with breast, prostate and epithelial ovarian cancer. We aimed to investigate the association between the Wnt5a expression and outcomes in patients with colon cancer (CC) stage II/III. We performed a retrospective single-center study evaluating 345 patients with radical resection for primary CC, stage II/III, who started 6 months of adjuvant chemotherapy with 5-FU or capecitabine ±â€¯oxaliplatin between 2001 and 2015. Archived formalin-fixed paraffin embedded tumor tissue from resection specimens were stained with Wnt5a antibody using immunohistochemistry. Cytoplasmatic Wnt5a staining was assessed according to intensity and percentage of stained cells. Patients were divided in groups depending on high (n = 230) or low (n = 115) Wnt5a expression. Disease free survival (DFS) and overall survival (OS) were analyzed for the two groups using Kaplan-Meier plots and Long rank test. Patients with Wnt5a-negative tumors had significantly poorer performance status (PS) than patients with high Wnt5a expression (p = 0.046). No significant difference was seen between patients with low and high Wnt5a expression in terms of 5-year DFS (p = 0.517) or 5-year OS (p = 0.415). Poor PS was associated with lower DFS (p = 0.002) and OS (p < 0.001). In conclusion, we found no significant difference in prognosis for patients with stage II/III CC depending on their Wnt5a expression. Patients with Wnt5a-negative tumors had significant poorer PS than patients with higher levels. Poor PS was associated with lower DFS and OS.

Exercise in older women with breast cancer during systemic therapy: study protocol of a randomised controlled trial (BREACE).

INTRODUCTION: Exercise interventions have been widely investigated in patients with cancer and demonstrate beneficial effects. However, intervention studies that include older women with breast cancer exercising during medical treatment are scarce. Hence, the aim of this study is to investigate the effect of a 12-week exercise-based intervention in older women (≥65 years) with breast cancer receiving (neo)adjuvant or first-line or second-line systemic therapy. METHODS AND ANALYSIS: This is a single-centre, two-armed randomised controlled trial. We anticipate including 100 patients, who will be randomised 1:1 to exercise-based intervention or control stratified by treatment setting ((neo)adjuvant or metastatic) and treatment (chemotherapy or endocrine therapy + cyclin-dependent kinase (CDK) 4/6 inhibitors). The intervention group will receive standard oncological treatment and a 12-week supervised exercise-based intervention comprising a progressive resistance exercise programme two times per week, a protein supplement after exercise and a home-based walking programme based on daily step counts. The control group will receive standard oncological treatment. Assessments will be performed at baseline and 6, 12 and 24 weeks after start of the intervention. Primary outcome is physical function, measured by the 30-second Chair Stand Test. Secondary outcomes are feasibility (compliance and adherence to intervention), objective and patient-reported functional measures (6-meter and 10-meter gait speed; 6-min Walk Test; Handgrip Strength; Stair Climb Test; Physical Activity Questionnaire), symptom burden and well-being (MD Anderson Symptom Inventory; Hospital Anxiety and Depression Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and B23), body composition (dual-energy X-ray absorptiometry scan), side effects, inflammatory biomarkers, hospitalisation and survival. ETHICS AND DISSEMINATION: The protocol was reviewed and accepted by the Scientific Ethics Review Committee of the Capital Region of Denmark, 17 June 2018 (VEK ref.: H-18021013). Trial results will be submitted for publication in a peer-reviewed journal and presented on conferences, in oncology wards, exercise centres in municipalities and patient organisations, ensuring dissemination to relevant stakeholders. TRIAL REGISTRATION NUMBER: https://clinicaltrials.gov/ on 3 September 2018. Identifier: NCT03656731.

The effect of exercise-based interventions on health-related quality of life and physical function in older patients with cancer receiving medical antineoplastic treatments: a systematic review.

Older patients with cancer are underrepresented in trials investigating the effect of exercise therapy. The aim of this systematic review was to investigate the effect of exercise therapy during medical antineoplastic treatment in older patients (≥ 65 years) with cancer. A systematic review following the Cochrane guidelines was performed. Randomized controlled trials were identified through a systematic literature search in MEDLINE, EMBASE, CENTRAL, and CINAHL up to December 2019. Study selection was performed independently by two reviewers. Four randomized controlled trials published between 2014 and 2019 were included comprising a total of 412 participants. Most participants were diagnosed with breast, prostate or colorectal cancer. The studies were characterized by large differences in design, interventions and outcomes, which prevented meta-analyses. The interventions ranged from 4 weeks to 12 months and involved both supervised and unsupervised exercise programs. Some evidence of beneficial effects from the interventions were documented on physical function, muscle strength, physical activity and cognitive function. No evidence of effects was found for health-related quality of life, aerobic capacity, body composition, cancer-related symptoms and side effects, or for any clinical outcomes. No adverse events were reported. Exercise therapy seems to be safe and feasible in older patients with cancer. However, due to a limited number of studies, small sample sizes and heterogeneity across study design, the effects of exercise in older patients with cancer receiving medical antineoplastic treatment are inconclusive.

Incidence and risk markers of 5-fluorouracil and capecitabine cardiotoxicity in patients with colorectal cancer.

Background: Fluoropyrimidines are mainstay chemotherapeutics in the treatment of gastrointestinal cancers and are also used to treat breast cancer and head and neck cancers. However, 5-flourouracil (5-FU) and capecitabine may induce cardiotoxicity that mostly presents as acute coronary syndromes. We compared the incidence of cardiotoxicity induced by 5-FU and capecitabine in patients with colorectal cancer and sought to identify risk markers for cardiotoxicity.Methods: We reviewed all consecutive patients with colorectal cancer who received 5-FU or capecitabine at one institution in the neoadjuvant (2007-2016), adjuvant (2000-2016) or metastatic setting (2007-2016).Results: Totally, 995 patients received 5-FU and 1241 received capecitabine. The incidence of cardiotoxicity induced by 5-FU was 5.2% [95% confidence interval (CI): 3.8-6.6%] and 4.1% (95% CI: 3.0-5.2%) induced by capecitabine (p = .21). The most common events were angina without ischemia (5-FU: 1.6%, capecitabine: 1.3%, p = .53), angina with ischemia on ECG (5-FU: 0.9%, capecitabine: 0.8%, p = .53), unspecified chest pain (5-FU: 0.9%, capecitabine: 0.6%, p = .34), ST-elevation myocardial infarction (5-FU: 0.5%; capecitabine: 0.4%, p = .76) and non-ST-elevation myocardial infarction (5-FU: 0.7%, capecitabine: 0.5%, p = .50). Cardiac arrest or sudden death occurred in 0.5 and 0.4%, respectively (p = 1). No risk markers for cardiotoxicity induced by 5-FU were identified. In the capecitabine group, ischemic heart disease was a risk marker (odds ratio: 2.9, 95% CI: 1.2-7.0, p = .016).Conclusions: Five percent of patients treated with 5-FU developed cardiotoxicity and 4% treated with capecitabine. Ischemic heart disease was a risk marker for cardiotoxicity induced by capecitabine.

Attitudes towards physical activity and exercise in older patients with advanced cancer during oncological treatment - A qualitative interview study.

PURPOSE: Older patients with cancer are underrepresented in exercise-based trials. To engage older patients in physical activity (PA), it is necessary to consider age-related decline in health, comorbidities and practicalities. The study aim was to explore attitudes towards PA and exercise among older patients with cancer to inform future exercise-based interventions. METHOD: Individual interviews (N = 23) were conducted in patients ≥ 65 years with advanced lung, biliary tract and pancreatic cancer receiving palliative oncological treatment. Patients were recruited with a purposive sampling strategy. A semi-structured interview guide focusing on attitudes towards PA and exercise, including barriers, facilitators and motivators, was used. Data on the informants' medical history, demographics and PA level was collected. RESULTS: Identified themes were: 1) a general positive perception of physical activity is expressed 2) comorbidities and external circumstances prevent physical activity, 3) fatigue overshadows life, 4) social support is key to short and long-term motivation, 5) fixed conditions keep one focused, 6) familiarity raises confidence and motivation. CONCLUSIONS: Even though perceptions of PA were positive among older patients with cancer, most struggled to stay physically active during oncological treatment. Several factors related to cancer and aging were identified as barriers; most profoundly was the overwhelming feeling of fatigue. Improving physical and mental well-being, fixed conditions (e.g. group-based exercise and supervision) and social support were identified as motivators and facilitators. Preferences for PA varied, but activities that were familiar increased motivation. Exercise programs for older patients with cancer must be adjustable to each patient's limitations, needs and personal resources.

Engaging the older cancer patient; Patient Activation through Counseling, Exercise and Mobilization - Pancreatic, Biliary tract and Lung cancer (PACE-Mobil-PBL) - study protocol of a randomized controlled trial.

BACKGROUND: Several intervention studies have demonstrated that exercise training has beneficial effects among cancer patients. However, older cancer patients are underrepresented in clinical trials, and only few exercise-based studies have focused specifically on older patients with cancer. In particular, research investigating the effects of exercise training among older patients with advanced cancer is lacking. The purpose of the current study is to investigate the effect of a 12-week multimodal and exercise-based intervention among older patients (≥65 years) with advanced pancreatic, biliary tract or lung cancer, who are treated with first-line palliative chemotherapy, immunotherapy or targeted therapy. METHODS: PACE-Mobil-PBL is a two-armed randomized controlled trial. Participants will be randomized 1:1 to an intervention group (N = 50) or a control group (N = 50). Participants in the intervention group will receive standard oncological treatment and a 12-week multimodal intervention, comprised of: (I) supervised exercise training, twice weekly in the hospital setting, (II) home-based walking with step counts and goal-setting, (III) supportive and motivational nurse-led counseling, and (IV) protein supplement after each supervised training session. Participants in the control group will receive standard oncological treatment. The primary outcome is physical function measured by the 30-s chair stand test. Secondary outcomes include measures of feasibility, activity level, physical capacity and strength, symptom burden, quality of life, toxicity to treatment, dose reductions, inflammatory biomarkers, body weight and composition, hospitalizations and survival. Assessments will be conducted at baseline, and after 6, 12 and 16 weeks. DISCUSSION: The current study is one of the first to investigate the effect of an exercise-based intervention specifically targeting older patients with advanced cancer. PACE-Mobil-PBL supports the development of health promoting guidelines for older patients with cancer, and the study results will provide new and valuable knowledge in this understudied field. TRIAL REGISTRATION: The study was prospectively registered at ClinicalTrials.gov on January 26, 2018 (ID: NCT03411200 ).

[High hospital standardized mortality ratio does not always indicate low quality].

Hospital standardized mortality ratio (HSMR) is increasingly used to assess quality of care. At Frederiksberg Hospital HSMR increased significantly during the first and second quarter in 2012. We therefore reviewed records of all deceased, including patients deceased during the comparative period in 2011 (n = 413). Information about cancer and infection with Clostridium difficile was specifically noted. We found that the increasing HSMR reflected an increase in the number of terminal cancer patients. Thus, insufficient adjustment for a change in case-mix explained the higher HSMR.