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).

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.

The course of depressive symptoms and mortality in older patients with cancer.

OBJECTIVE: The Geriatric Depression Scale (GDS-15), a self-report questionnaire, emphasizes the psychological dimension of depression. We aimed to investigate whether GDS-15 scores were associated with mortality in older patients with cancer and describe the course of individual symptoms on the GDS-15. METHODS: An observational, multicenter, prospective study of 288 patients 70 years or older with cancer followed over 24 months. The patients were assessed with the GDS-15 at inclusion, and after four and 12 months. An extended Cox regression model assessed the association between time-dependent GDS-15 scores and mortality. RESULTS: After adjusting for cancer-related prognostic factors, a one-point increase in GDS-15 sum score increased risk of death by 12%. GDS-15 mean score increased during the first four months of the study, as did odds for the presence of the GDS-15 symptoms 'feel you have more problems with memory than most', 'not feel full of energy', and 'think that most people are better off than you'. The most prevalent and persistent GDS-15 symptom was 'prefer to stay at home, rather than going out and doing new things', and 'not to be in good spirits most of the time' was the least prevalent. CONCLUSIONS: More severe depressive symptoms, as measured by the GDS-15, were associated with higher mortality in older patients with cancer. The importance of emotional distress and how to alleviate it should be investigated further in these patients.

CT Derived Muscle Measures, Inflammation, and Frailty in a Cohort of Older Cancer Patients.

BACKGROUND/AIM: Muscle loss, inflammation, and frailty are prevalent among older cancer patients. We aimed to evaluate whether inflammatory markers could identify muscle loss, and if muscle measures differed between frail and non-frail patients. PATIENTS AND METHODS: A total of 115 patients ≥70 years old with solid tumors were included. Inflammation was measured using the Glasgow Prognostic Score (GPS), which is based on C-reactive protein (CRP) and albumin levels, and CRP alone. Frailty was evaluated using a modified geriatric assessment (mGA) of eight domains affecting older patients' health status. Computed tomography-derived muscle measures were collected at the level of the third lumbar vertebra. RESULTS: Patients with GPS=2 and CRP>27 mg/l exhibited poorer muscle measures compared to patients with lower levels. No associations between mGA-based frailty and muscle mass were found. CONCLUSION: Inflammation has detrimental effects on muscle mass. However, GPS or CRP alone cannot be used to identify muscle loss, and muscle measures were not associated with frailty in this series.

Modifiable factors affecting older patients' quality of life and physical function during cancer treatment.

BACKGROUND: Maintaining physical function and quality of life (QoL) are prioritized outcomes among older adults. We aimed to identify potentially modifiable factors affecting older patients' physical function and QoL during cancer treatment. METHODS: Prospective, multicenter study of 307 patients with cancer ≥70 years, referred for systemic treatment. Pre-treatment, a modified geriatric assessment (mGA) was performed, including registration of comorbidities, medications, nutritional status, cognitive function, depressive symptoms (Geriatric Depression Scale-15 [GDS]), and mobility (Timed Up and Go [TUG]). Patient-reported physical function (PF)-, global QoL-, and symptom scores were assessed at baseline, two, four, and six months by the EORTC Quality of Life Core Questionnaire-C30. The impact of mGA components and symptoms on patients' PF and global QoL scores during six months was investigated by linear mixed models. To identify groups following distinct PF trajectories, a growth mixture model was estimated. RESULTS: 288 patients were eligible, mean age was 76.9 years, 68% received palliative treatment. Higher GDS-scores and poorer TUG were independently associated with an overall level of poorer PF and global QoL throughout follow-up, as were more pain, dyspnea, and appetite loss, and sleep disturbance. Three groups with distinct PF trajectories were identified: a poor group exhibiting a non-linear statistically (p < .001) and clinically significant decline (≥10 points), an intermediate group with a statistically (p = .003), but not clinically significant linear decline, and a good group with a stable trajectory. Higher GDS-scores and poorer TUG, more pre-treatment pain and dyspnea were associated with higher odds of belonging to the poor compared to the good PF group. CONCLUSION: Depressive symptoms, reduced mobility, and more physical symptoms increased the risk of decrements in older patients' PF and global QoL scores during cancer treatment, and represent potential targets for interventions aiming at improving these outcomes.

Screening for frailty among older patients with cancer using blood biomarkers of inflammation.

INTRODUCTION: As frailty is associated with inflammation, biomarkers of inflammation may represent objective measures that could facilitate the identification of frailty. Glasgow prognostic score (GPS), combines C-reactive protein (CRP) and albumin, and is scored from 0 to 2 points. Higher score indicates a higher degree of inflammation. OBJECTIVES: To investigate whether (1) GPS is associated with frailty, (2) GPS could be used to screen for frailty, (3) IL-6 and TNF-α add to the accuracy of GPS as a screening tool, and (4) GPS adds prognostic information in frail older patients with cancer. METHODS: Prospective, observational study of 255 patients ≥70 years with solid malignant tumours referred for medical cancer treatment. At baseline, frail patients were identified by a modified Geriatric Assessment (mGA), and blood samples were collected. RESULTS: Mean age was 76.7 years, 49.8% were frail, and 56.1% had distant metastases. The proportion of frail patients increased with higher GPS (GPS zero: 43.2%, GPS one: 52.7%, GPS two: 94.7%). GPS two was significantly associated with frailty (OR 18.5), independent of cancer type, stage, BMI and the use of anti-inflammatory drugs. The specificity of GPS was high (99%), but the sensitivity was low (14%). Frail patients with GPS two had poorer survival than patients with GPS zero-one. TNF-α and IL-6 did not improve the accuracy of GPS when screening for frailty. CONCLUSION: Frailty and GPS two are strongly associated, and GPS two is a significant prognostic factor in frail, older patients with cancer. The inflammatory biomarkers investigated are not suitable screening tools for frailty.

Geriatric assessment is superior to oncologists' clinical judgement in identifying frailty.

BACKGROUND: Frailty is a syndrome associated with increased vulnerability and an important predictor of outcomes in older cancer patients. Systematic assessments to identify frailty are seldom applied, and oncologists' ability to identify frailty is scarcely investigated. METHODS: We compared oncologists' classification of frailty (onc-frail) based on clinical judgement with a modified geriatric assessment (mGA), and investigated associations between frailty and overall survival. Patients ⩾70 years referred for medical cancer treatment were eligible. mGA-frailty was defined as impairment in at least one of the following: daily activities, comorbidity, polypharmacy, physical function or at least one geriatric syndrome (cognitive impairment, depression, malnutrition, falls). RESULTS: Three hundred and seven patients were enroled, 288 (94%) completed the mGA, 286 (93%) were rated by oncologists. Median age was 77 years, 56% had metastases, 85% performance status (PS) 0-1. Overall, 104/286 (36%) were onc-frail and 140/288 (49%) mGA-frail, the agreement was fair (kappa value 0.30 (95% CI 0.19; 0.41)), and 67 mGA-frail patients who frequently had localised disease, good PS and received curative treatment, were missed by the oncologists. Only mGA-frailty was independently prognostic for survival (HR 1.61, 95% CI 1.14; 2.27; P=0.007). CONCLUSIONS: Systematic assessment of geriatric domains is needed to aid oncologists in identifying frail patients with poor survival.

Comparing comorbidity scales: Attending physician score versus the Cumulative Illness Rating Scale for Geriatrics.

OBJECTIVES: Assessing comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and its comprehensive manual is time consuming. We investigated if similar information could be obtained by a simpler assessment based on the original CIRS. MATERIALS AND METHODS: Data from a randomized chemotherapy trial (RCT) on advanced NSCLC (non-small cell lung cancer) were analyzed. Baseline comorbidity was assessed by 1) trained oncologists using hospital records and the CIRS-G manual (CIRS-G), 2) by patients' oncologists/pulmonologists (local investigators=LI-score) using a brief set of instructions. By both methods, the severity of comorbidity in 14 organ systems was graded 0 (no problem) to 4 (extremely severe). The agreement between methods was assessed using Bland-Altman analysis and weighted kappa statistics. The impact of comorbidity on survival was analyzed by Cox regression. RESULTS: Complete data were available for 375/446 (84%) patients enrolled in the RCT. Median age was 65years (25-85). Overall, more comorbidities and higher severity were registered by the CIRS-G compared to the LI-score. Severe comorbidity was registered for 184 (49%) and 94 (25%) patients according to the CIRS-G and LI-scores, respectively. Mean total score was 7.0 (0-17) (CIRS-G) versus 4.2 (0-16) (LI-score), and mean severity index (total score/number of categories with score >0) was 1.73 (SD 0.46) versus 1.43 (SD 0.78). Neither the CIRS-G scores nor the LI-scores were prognostic for survival. CONCLUSION: The CIRS-G scores and LI-scores had poor agreement, indicating that assessment method affects the registration of comorbidity. Thorough descriptions of comorbidity registrations in trials are paramount due to lack of a standardized assessment.