Geriatric impairments are associated with reduced quality of life and physical function in older patients with cancer receiving radiotherapy - A prospective observational study.

INTRODUCTION: Quality of life (QoL) and function are important outcomes for older adults with cancer. We aimed to assess differences in trends in patient-reported outcomes (PROs) during radiotherapy (RT) between (1) groups with curative or palliative treatment intent and (2) groups defined according to the number of geriatric impairments. MATERIALS AND METHODS: A prospective observational study including patients aged ≥65 years receiving curative or palliative RT was conducted. Geriatric assessment (GA) was performed before RT, and cut-offs for impairments within each domain were defined. Patients were grouped according to the number of geriatric impairments: 0, 1, 2, 3, and ≥ 4. Our primary outcomes, global QoL and physical function (PF), were assessed by The European Organisation for Research and Treatment of Cancer Quality-of-Life Core Questionnaire (EORTC) (QLQ-C30) at baseline, RT completion, and two, eight, and sixteen weeks later. Differences in trends in outcomes between the groups were assessed by linear mixed models. RESULTS: 301 patients were enrolled, mean age was 73.6 years, 53.8% received curative RT. Patients receiving palliative RT reported significantly worse global QoL and PF compared to the curative group. The prevalence of 0, 1, 2, 3 and ≥ 4 geriatric impairments was 16.6%, 22.7%, 16.9%, 16.3% and 27.5%, respectively. Global QoL and PF gradually decreased with an increasing number of impairments. These group differences remained stable from baseline throughout follow-up without any clinically significant changes for any of the outcomes. DISCUSSION: Increasing number of geriatric impairments had a profound negative impact on global QoL and PF, but no further decline was observed for any group or outcome, indicating that RT was mainly well tolerated. Thus, geriatric impairments per se should not be reasons for withholding RT. GA is key to identifying vulnerable patients in need of supportive measures, which may have the potential to improve treatment tolerance. Registered at clinicaltrials.gov (NCT03071640).

Cognitive Trajectories in Older Patients with Cancer Undergoing Radiotherapy-A Prospective Observational Study.

Cognitive function can be affected by cancer and/or its treatment, and older patients are at a particular risk. In a prospective observational study including patients ≥65 years referred for radiotherapy (RT), we aimed to investigate the association between patient- and cancer-related factors and cognitive function, as evaluated by the Montreal Cognitive Assessment (MoCA), and sought to identify groups with distinct MoCA trajectories. The MoCA was performed at baseline (T0), RT completion (T1), and 8 (T2) and 16 (T3) weeks later, with scores ranging between 0 and 30 and higher scores indicating better function. Linear regression and growth mixture models were estimated to assess associations and to identify groups with distinct MoCA trajectories, respectively. Among 298 patients with a mean age of 73.6 years (SD 6.3), the baseline mean MoCA score was 24.0 (SD 3.7). Compared to Norwegian norm data, 37.9% had cognitive impairment. Compromised cognition was independently associated with older age, lower education, and physical impairments. Four groups with distinct trajectories were identified: the very poor (6.4%), poor (8.1%), fair (37.9%), and good (47.7%) groups. The MoCA trajectories were mainly stable. We conclude that cognitive impairment was frequent but, for most patients, was not affected by RT. For older patients with cancer, and in particular for those with physical impairments, we recommend an assessment of cognitive function.

Geriatric impairments are prevalent and predictive of survival in older patients with cancer receiving radiotherapy: a prospective observational study.

BACKGROUND: A systematic assessment of problems that are frequent in older age (geriatric assessment [GA]) provides prognostic information for patients undergoing cancer surgery and systemic cancer treatment. We aimed to investigate the prevalence of geriatric impairments and their impact on survival in older patients with cancer receiving radiotherapy (RT). MATERIAL AND METHODS: A single-centre prospective observational study was conducted including patients ≥65 years referred for curative or palliative RT. Prior to RT, we performed a modified GA (mGA) assessing comorbidities, medications, nutritional status basic- and instrumental activities of daily living (IADL) mobility, falls, cognition and depressive symptoms. Impairments in each mGA domain were defined. Overall survival (OS) was presented by Kaplan Meier plots for groups defined according to the number of impairments, and compared by log-rank test. The association between mGA domains and OS was assessed by Cox proportional hazard regression analysis. RESULTS: Between February 2017 and July 2018, 301 patients were included, 142 (47.2%) were women. Mean age was 73.6 (SD 6.3) years, 162 (53.8%) received curative RT. During the median observation time of 24.2 months (min 0.3, max 25.9), 123 (40.9%) patients died. In the overall cohort, 49 (16.3%) patients had no geriatric impairment, 81 (26.9%) had four or more. OS significantly decreased with an increasing number of impairments (p < .01). Nutritional status (HR 0.90, 95% CI [0.81; 0.99], p = .038) and IADL function (HR 0.98, 95% CI [0.95; 1.00], p = .027) were independent predictors of OS. CONCLUSION: Geriatric impairments were frequent among older patients with cancer receiving RT and nutritional status and IADL function predicted OS. Targeted interventions to remediate modifiable impairments may have the potential to improve OS. TRIAL REGISTRATION: Cinicaltrials.gov ID:NCT03071640.

Effect of lifestyle and/or statin treatment on soluble markers of atherosclerosis in hypertensives.

OBJECTIVES: To investigate the independent and combined effects of lifestyle changes and statin treatment on soluble markers of atherosclerotic activity. DESIGN: The study was a randomised, 2 x 2 factorial 1 year intervention trial. Participants (n=177) were sedentary, drug-treated, hypertensive men (aged 40-74 years). They were randomised to placebo, lifestyle intervention (diet and physical activity), fluvastatin 40 mg, or the combination of lifestyle and fluvastatin. RESULTS: Lifestyle intervention significantly reduced intercellular adhesion molecule-1 (sICAM-1) compared to usual care (p=0.003). Thrombomodulin level remained higher among individuals receiving lifestyle intervention (p=0.025). sICAM-1 was less reduced among fluvastatin treated participants compared to the placebo treated (p=0.029). Changes of blood pressure, weight or waist circumference were not significantly different between treatment groups. Individuals who achieved improvement of classical risk factors also had a significant reduction of endothelial markers (E-selectin, von Willebrands factor, tissue plasminogen activator antigen). CONCLUSIONS: One year of lifestyle intervention reduced the level of sICAM-1 in sedentary, drug-treated hypertensives, in spite of no impact on traditional risk factors. Low dose fluvastatin had no beneficial effect on the measured markers.

Markers of inflammation are inversely related to physical activity and fitness in sedentary men with treated hypertension.

BACKGROUND: Physical inactivity is an important risk factor for atherosclerotic disease. We studied the relationship between physical activity and physical fitness and soluble markers of atherosclerotic activity in men with drug-treated hypertension. METHODS: The participants (n = 177, 40 to 74 years of age), who were randomly recruited from the Hypertension High Risk Management Trial (HYRIM), were overweight and had sedentary lifestyles. The inflammatory markers high-sensitivity C-reactive protein (hs-CRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (SICAM-1) and soluble E-selectin (sE-selectin) and the hemostatic markers soluble thrombomodulin (sTM), von Willebrand factor (vWf), and tissue plasminogen activator antigen (tPAag) were measured. Physical activity was measured by use of a questionnaire. Time to exhaustion in a bicycle test was used as an expression of physical fitness. RESULTS: The hs-CRP showed a significant inverse relationship with physical fitness independent of major cardiovascular risk factors (P = .017) but was not related to physical activity. The sE-selectin was significantly related to physical activity, although only when other factors were taken into account (P = .033), and it had no significant association with physical fitness. In addition there were strong associations between hs-CRP and sICAM-1 and the Framingham Coronary Heart Disease risk score (P < .001). CONCLUSIONS: The observed inverse relations between physical fitness and hs-CRP and between level of physical activity and sE-selectin in drug-treated, hypertensive sedentary men indicates a beneficial effect of good fitness status as well as activity of low intensity on vessel wall inflammation.

Fluvastatin and lifestyle modification for reduction of carotid intima-media thickness and left ventricular mass progression in drug-treated hypertensives.

OBJECTIVES: The Hypertension High Risk Management trial (HYRIM) investigated the effect of fluvastatin treatment and lifestyle intervention on development of carotid intima-media thickness (IMT) in drug-treated hypertensive patients. METHODS AND RESULTS: HYRIM was a placebo-controlled, 2 x 2 factorial trial in which 568 drug-treated hypertensive men aged 40-74 years with total cholesterol 4.5-8.0 mmol/L, triglycerides <4.5 mmol/L, body mass index 25-35 kg/m2, and a sedentary lifestyle were randomized to receive either fluvastatin, 40 mg daily, or placebo, and either intensive lifestyle intervention (physical activity and diet) or usual care (treatment of hypertension and other disorders by own private physician). Carotid IMT was assessed by B-mode ultrasound vasculography and left ventricular (LV) mass was calculated from ultrasound recordings of the heart. Fluvastatin alone reduced the primary study endpoint of 4-year development of IMT in the common carotid artery (CCA) compared with placebo (p=0.0297). Carotid bulb IMT progression over 4 years was also significantly (p=0.0214) reduced by fluvastatin compared with placebo. Fluvastatin significantly lowered LDL-C levels (mean net difference through 4 years, 0.6 mmol/L; p<0.0001), and reduced the 2-year development of LV mass (p=0.0144) compared with placebo. Lifestyle intervention had no significant effect on LDL-C, carotid IMT or LV mass, and did not increase the effects of fluvastatin. CONCLUSIONS: In drug-treated hypertensive patients in a usual care setting, fluvastatin treatment reduces progression of carotid IMT and LV mass.