Age-related differences in patient-reported outcomes in patients with advanced lung cancer receiving anti-PD-1/PD-L1 therapy.

BACKGROUND: Older adults with lung cancer often have comorbidities that may increase risk of symptomatic adverse events (AEs) and physical function decline. The objective of this study was to examine age-related differences in patient-reported symptoms and functional domains in patients with advanced lung cancer receiving immunotherapy drugs. METHODS: Three randomized controlled trials of anti-programmed death receptor-1/programmed death-ligand 1 therapy in patients with advanced non-small cell lung cancer that included patient-reported outcomes (PROs) were identified. Baseline PRO data were pooled for treatment arms from 2 trials that included the same PRO tools. Age-related differences in baseline mean scores for each of the health-related quality of life functional and symptom scales were assessed for patients ≥70 years and <70 years. Mean change from Baseline at 3 months was also calculated and plotted for each age group. The adequacy of PRO assessments was assessed by comparing clinician-reported AE data in the 3 trials to the item content of the PRO tools included. RESULTS: Across the 3 trials, 75 of patients were under 70 and 26% patients were 70 and older. Comparing baseline scores in the 2 trials with the same PRO tool, older adults reported small differences including lower physical functioning, less pain, insomnia and financial difficulties, and higher social functioning than younger patients at baseline. No large differences in the distributions of mean change from baseline in function or symptom were identified. Several common clinician-reported symptomatic AEs were not assessed by the PRO strategy employed in the 3 trials. Three clinician-reported symptomatic AEs (rash, fever, and pruritus) that were commonly reported in the safety data (9%-19%) were not assessed using the PRO tools employed. CONCLUSION: While several small differences were seen, there did not appear to be large differences at baseline or in the distributions of change from baseline in PRO functional domains between younger and older patients with lung cancer undergoing anti-programmed death receptor -1/programmed death-ligand 1 therapy. Relevant symptomatic side effects were not assessed by PRO measures in these trials, and this is a limitation of current PRO assessment strategies.

Measuring frailty using self-report and test-based health measures.

BACKGROUND: previously, frailty indices were constructed using mostly subjective health measures. The reporting error in this type of measure can have implications on the robustness of frailty findings. OBJECTIVE: to examine whether frailty assessment differs when we construct frailty indices using solely self-reported or test-based health measures. DESIGN: secondary analysis of data from The Irish LongituDinal study on Ageing (TILDA). SUBJECTS AND METHODS: 4,961 Irish residents (mean age: 61.9 ± 8.4; 54.2% women) over the age of 50 years who underwent a health assessment were included in this analysis. We constructed three frailty indices using 33 self-reported health measures (SRFI), 33 test-based health measures (TBFI) and all 66 measures combined (CFI). The 2-year follow-up outcomes examined were all-cause mortality, disability, hospitalisation and falls. RESULTS: all three indices had a right-skewed distribution, an upper limit to frailty, a non-linear increase with age, and had a dose-response relationship with adverse outcomes. Levels of frailty were lower when self-reported items were used (SRFI: 0.12 ± 0.09; TBFI: 0.17 ± 0.15; CFI: 0.14 ± 0.13). Men had slightly higher frailty index scores than women when test-based measures were used (men: 0.17 ± 0.09; women: 0.16 ± 0.10). CFI had the strongest prediction for risk of adverse outcomes (ROC: 0.64-0.81), and age was not a significant predictor when it was included in the regression model. CONCLUSIONS: except for sex differences, characteristics of frailty are similar regardless of whether self-reported or test-based measures are used exclusively to construct a frailty index. Where available, self-reported and test-based measures should be combined when trying to identify levels of frailty.

CASP-19 special section: how does chronic disease status affect CASP quality of life at older ages? Examining the WHO ICF disability domains as mediators of this relationship.

OBJECTIVES: The effect of chronic disease status on quality of life (QoL) has been well established. However, less is known about how chronic diseases affect QoL. This article examines impairment in three domains of the WHO International Classification of Functioning, Health and Disability (ICF) - body function, activity and participation, as well as affective well-being, - as potential mediators of the relationship between chronic disease and QoL. METHOD: A cross-sectional sample (n = 4961) of the general Irish community-dwelling population aged 50+ years was obtained from the Irish Longitudinal Study of Ageing (TILDA). The CASP measure of QoL was examined as two dimensions - control/autonomy and self-realisation/pleasure. Structural equation modelling was used to test the direct and indirect effects of chronic disease on QoL, via variables capturing body function, activity, participation and positive affect. RESULTS: A factor analysis showed that indicators of body function and activity loaded onto a single overall physical impairment factor. This physical impairment factor fully mediated the effect of chronic disease on positive affect and QoL. The total effect of chronic disease on control/autonomy (-0.160) was primarily composed of an indirect effect via physical impairment (-0.86), and via physical impairment and positive affect (-0.45). The decomposition of effects on self-realisation/pleasure was similar, although the direct effect of physical impairment was weaker. The model fitted the data well (RMSEA = 0.02, TLI = 0.96, CFI = 0.96). CONCLUSION: Chronic disease affects QoL through increased deficits in physical body function and activity. This overall physical impairment affects QoL both directly and indirectly via reduced positive affect.

Structural equation modeling of health-related quality-of-life data illustrates the measurement and conceptual perspectives on response shift.

OBJECTIVE: To illustrate different perspectives on response shift with cancer patients' health-related quality-of-life (HRQL) data. In measurement perspective, the focus is on bias in the measurement of HRQL. In conceptual perspective, the focus is on bias in the explanation of HRQL. STUDY DESIGN AND SETTING: Data came from a consecutive series of 202 newly diagnosed cancer patients, heterogeneous to cancer site, all undergoing surgery. A HRQL questionnaire was administered before and after surgery. Using structural equation modeling, biases and response shifts in measurement and explanation of HRQL were investigated with respect to patient's cancer site, health status, sex, age, optimism, and social comparison. RESULTS: Six measurement biases were found, five of which were considered response shift. The "general health" (GH) scale appeared most susceptible to response shift. For example, GH scores were not fully determined by HRQL but also by optimism before surgery and female sex and downward social comparison after surgery. Additionally, two explanation biases were found, neither of which were considered response shift-before and after surgery the mental component of HRQL was not only affected by cancer site and health status but also by optimism and downward social comparison. CONCLUSION: Our approach enables the distinction and testing of biases and response shifts in the measurement and explanation of HRQL.