Selecting the right treatment: Health outcome priorities in older patients with bladder cancer.

INTRODUCTION: Selecting the appropriate treatment for older patients with non-muscle invasive (NMIBC) or muscle-invasive bladder cancer (MIBC) is challenging due to smoking-related comorbidities, treatment toxicity, and an increased risk of adverse health outcomes. Considering patient preferences prior to treatment is therefore crucial. Here, we aimed to identify the health outcome priorities of older patients with high-risk NMIBC (HR-NMIBC) or MIBC. MATERIALS AND METHODS: Patients aged 70 years or older or at risk for frailty, diagnosed with HR-NMIBC or MIBC without distant metastases, were referred for a comprehensive geriatric assessment (CGA). The CGA consisted of an interview, physical examination, and several tests to examine physical, cognitive, functional, and social status. Quality of life was assessed using EQ5D and EORTC QLQ-C30 questionnaires. Health outcome priorities were discussed using the Outcome Prioritization Tool (OPT) and associations between health outcome priorities and CGA-determinants and quality of life were studied. RESULTS: Of 146 patients (14 HR-NMIBC, 132 MIBC), OPT data was available for 139. Life extension was most often prioritized (44%), closely followed by preserving independence (40%). Reducing pain (7%) and other symptoms (9%) were less often prioritized. Patients prioritizing life extension had fewer musculoskeletal problems than patients prioritizing reducing pain or other symptoms (p = 0.02). Patients at risk of or suffering from malnutrition more frequently selected reducing pain or other symptoms as their health outcome priority (p = 0.004). For all other CGA-determinants and quality of life, there were no significant differences between groups based on health outcome priorities. DISCUSSION: In older patients with HR-NMIBC and MIBC, life extension and preserving independence are the most common health outcomes priorities. CGA-determinants and quality of life are generally not associated with the prioritization of health outcomes. As health outcome priorities cannot be predicted by CGA-determinants or quality of life, it is crucial to discuss health outcome priorities with patients to promote shared decision-making.

Creatinine, cystatin C, muscle mass, and mortality: Findings from a primary and replication population-based cohort.

BACKGROUND: Serum creatinine is used as initial test to derive eGFR and confirmatory testing with serum cystatin C is recommended when creatinine-based eGFR is considered less accurate due to deviant muscle mass. Low muscle mass is associated with increased risk of premature mortality. However, the associations of serum creatinine and cystatin C with muscle mass and mortality remain unclear and require further investigation to better inform clinical decision-making. METHODS: We included 8437 community-dwelling adults enrolled in the Dutch PREVEND study and 5033 in the US NHANES replication cohort. Associations of serum creatinine and/or cystatin C with muscle mass surrogates and mortality were quantified with linear and Cox proportional hazards regression, respectively. Missing observations in covariates were multiply imputed using Substantive Model Compatible Fully Conditional Specification. RESULTS: Mean (SD) age of PREVEND and NHANES participants (50% and 48% male) were 49.8 (12.6) and 48.7 (18.7) years, respectively. Median (Q1-Q3) serum creatinine and cystatin C were 71 (61-80) and 80 (62-88) µmol/L and 0.87 (0.78-0.98) and 0.91 (0.80-1.10) mg/L, respectively. Higher serum creatinine was associated with greater muscle mass, while serum cystatin C was not associated with muscle mass. Adjusting both markers for each other strengthened the positive relationship between serum creatinine and muscle mass and revealed an inverse association between serum cystatin C and muscle mass. In the PREVEND cohort, 1636 (19%) deaths were registered over a median follow-up of 12.9 (5.8-16.3) years with a 10-year mortality rate (95% CI) of 7.6% (7.1-8.2%). In the NHANES, 1273 (25%) deaths were registered over a median follow-up of 17.9 (17.3-18.5) years with a 10-year mortality rate of 13.8% (12.8-14.7%). Both markers were associated with increased mortality. Notably, when adjusted for each other, higher serum creatinine was associated with decreased mortality, while the association between serum cystatin C and increased mortality strengthened. The shapes of the associations in the PREVEND study and NHANES were almost identical. CONCLUSIONS: The strong association between serum creatinine and muscle mass challenges its reliability as GFR marker, necessitating a more cautious approach in its clinical use. The minimal association between serum cystatin C and muscle mass supports its increased use as a more reliable alternative in routine clinical practice.

Frailty in Non-geriatric Patients With Head and Neck cancer.

OBJECTIVE: Patients with head and neck cancer (HNC) are characterized by a poor lifestyle and comorbidity. The Geriatric 8 (G8) is an established screening tool to identify frail older patients with cancer. However, studies evaluating frailty in younger HNC patients are lacking. The aim of this study is to evaluate if the G8 can identify frailty and if it is related to mortality in younger HNC patients. STUDY DESIGN: Case-control study design. SETTING: Tertiary cancer center. METHODS: We studied patients <70 years with HNC. Patients with G8 ≤ 14 were considered frail. Patients were matched to nonfrail (G8 > 14) control patients. Patients were matched according to sex, age, smoking, tumor location, and period of first consultation. Baseline health characteristics were compared between frail patients and nonfrail controls. Second, the treatment plan and adverse outcomes were compared. RESULTS: Forty-five patients with G8 ≤ 14 were included and matched to 90 nonfrail controls. The median follow-up time was 357 days. Frail patients had a significantly lower body mass index and level of education, a worse World Health Organization performance status, and reported lower experienced overall health. 28.9% of the frail patients died after 1 year versus 10% of the nonfrail control patients (hazard ratio: 3.87 [95% confidence interval: 1.32-11.36], p = 0.014). CONCLUSION: The G8 is a valid screening tool to identify frail patients in younger HNC patients.

A prospective, multicentre study to assess frailty in elderly patients with leg ulcers (GERAS study).

BACKGROUND: Although leg ulcers are a burdensome disease most common in those aged 65 years and older, frailty in this population has not yet been well established. OBJECTIVES: The aim of this study was to prospectively explore and compare the presence of frailty in elderly patients with chronic leg or foot ulcers by applying different validated frailty screening methods in three healthcare settings and to assess the feasibility of frailty screening. METHODS: We compared frailty of leg ulcer patients referred to an academic hospital with a non-academic hospital, leg ulcer patients receiving (primary) homecare, and a dermato-oncology patient population (control group). Frailty and quality of life were assessed using four validated questionnaires: the Groninger Frailty Indicator, Geriatric-8, Mini-Cog and Wound Quality of Life. To analyse data multiple (non)-parametric tests were performed. RESULTS: Fifty of 60 included leg ulcer patients (83%) scored "frail" on at least one frailty questionnaire (GFI, G8 or Mini-Cog). The number of patients scoring "frail" on two or three out of three applied frailty questionnaires were significantly higher in the academic and homecare ulcer population compared with the non-academic ulcer population and control group (p = 0.002). In the academic ulcer population mean Wound Quality of Life scores were 30.2 (SD 17.6), compared with 17.7 (SD 13.1) in the non-academic and 15.0 (SD 10.4) in the homecare ulcer population (p = 0.002). CONCLUSION: The majority of patients suffering from leg ulcers in this study was frail. The highest frailty prevalence was observed in the academic and homecare ulcer populations. The largest impaired quality of life was reported in the academic ulcer population. In dermatology practice, implementing frailty screening and initiating appropriate (paramedical) supportive care should be considered to improve patient outcomes.

Muscle mass and estimates of renal function: a longitudinal cohort study.

BACKGROUND: Creatinine is the most widely used test to estimate the glomerular filtration rate (GFR), but muscle mass as key determinant of creatinine next to renal function may confound such estimates. We explored effects of 24-h height-indexed creatinine excretion rate (CER index) on GFR estimated with creatinine (eGFRCr ), muscle mass-independent cystatin C (eGFRCys ), and the combination of creatinine and cystatin C (eGFRCr-Cys ) and predicted probabilities of discordant classification given age, sex, and CER index. METHODS: We included 8076 adults enrolled in the PREVEND study. Discordant classification was defined as not having eGFRCr  <60 mL/min per 1.73 m2 when eGFRCys was <60 mL/min/1.73 m2 . Baseline effects of age and sex on CER index were quantified with linear models using generalized least squares. Baseline effects of CER index on eGFR were quantified with quantile regression and logistic regression. Effects of annual changes in CER index on trajectories of eGFR were quantified with linear mixed-effects models. Missing observations in covariates were multiply imputed. RESULTS: Mean (SD) CER index was 8.0 (1.7) and 6.1 (1.3) mmol/24 h per meter in male and female participants, respectively (Pdifference  < 0.001). In male participants, baseline CER index increased until 45 years of age followed by a gradual decrease, whereas a gradual decrease across the entire range of age was observed in female participants. For a 70-year-old male participant with low muscle mass (CER index of 2 mmol/24 h per meter), predicted baseline eGFRCr and eGFRCys disagreed by 24.7 mL/min/1.73 m2 (and 30.1 mL/min/1.73 m2 when creatinine was not corrected for race). Percentages (95% CI) of discordant classification in male and female participants aged 60 years and older with low muscle mass were 18.5% (14.8-22.1%) and 15.2% (11.4-18.5%), respectively. For a 70-year-old male participant who lost muscle during follow-up, eGFRCr and eGFRCys disagreed by 1.5, 5.0, 8.5, and 12.0 mL/min/1.73 m2 (and 6.7, 10.7, 13.5, and 15.9 mL/min/1.73 m2 when creatinine was not corrected for race) at baseline, 5 years, 10 years, and 15 years of follow-up, respectively. CONCLUSIONS: Low muscle mass may cause considerable overestimation of single measurements of eGFRCr . Muscle wasting may cause spurious overestimation of repeatedly measured eGFRCr . Implementing muscle mass-independent markers for estimating renal function, like cystatin C as superior alternative to creatinine, is crucial to accurately assess renal function in settings of low muscle mass or muscle wasting. This would also eliminate the negative consequences of current race-based approaches.

Health outcome priorities in older patients with head and neck cancer.

OBJECTIVES: Older patients with head and neck cancer often have comorbidity, have reduced life-expectancy and await intensive treatment. For the decision-making process, knowledge of a patient's health outcome prioritization is of paramount importance. We aim to study the health outcome priorities of older patients with head and neck cancer, and to evaluate whether general health, markers of physical, cognitive, and social functioning, and quality of life are associated with health outcome prioritization. MATERIALS AND METHODS: Patients aged ≥70 years with head and neck cancer received a Comprehensive Geriatric Assessment and their priorities were assessed using the Outcome Prioritization Tool (OPT). Distribution of first priority, and associations with general health, markers of physical, cognitive, and social functioning, and quality of life were evaluated using ANOVA or chi-square. RESULTS: Of the 201 included patients, the OPT was available in 170 patients. The majority prioritized maintaining independence (n = 91, 53.3%), followed by extending life (n = 58, 34.1%), reducing pain (n = 14, 8.2%), and reducing other symptoms (n = 7, 4.1%). Housing situation, Body Mass Index, presence of musculoskeletal diseases, and quality of life were significantly related to prioritization of health outcomes. Reducing pain or other symptoms was more often prioritized by patients who lived alone, had a history of musculoskeletal problems, or had poor perceived quality of life. Age, sex, comorbidity, and markers of physical and cognitive functioning were not associated with health prioritization. CONCLUSION: Maintaining independence is most often prioritized by older patients with head and neck cancer. In addition, we found that health outcome priorities of older patients are only limited based on general and specific health characteristics. We suggest to systematically discuss patients' priorities in order to facilitate complex treatment decisions in older patients with cancer.

The Multidimensional Prognostic Index as a Measure of Frailty in Elderly Patients with Head and Neck Cancer.

PURPOSE: The multidimensional prognostic index (MPI) is a prognostic model derived from the comprehensive geriatric assessment (CGA) which can predict 1-year mortality risk in elderly individuals. We hypothesized that the MPI also reflects the degree of frailty and thus will correlate with established measures of frailty. Therefore, the aim of this study is to explore whether the MPI-score is a measure of frailty in older head and neck cancer patients and is associated with several physical functioning measurements. PATIENTS AND METHODS: From November 2019 to July 2020, a prospective cohort study enrolled patients with head and neck cancer aged ≥70 years, and patients <70 years with an abnormal G8 score. The MPI-score ranged from 0 to 1 and was categorized in MPI-stage 1 (≤0.33, non-frail); MPI-stage 2 (0.34-0.66, mildly frail), and MPI-stage 3 (≥0.67, severe frail). Pearson's correlation coefficient and multivariable linear regression were used to study the association between MPI-score and the physical functioning measurements handgrip strength, gait speed, and the timed up and go test (TUGT). RESULTS: A total of 163 patients were included. One hundred four (63.8%) patients were categorized as non-frail according MPI-stage 1, and 59 (36.2%) patients as mildly or severe frail (n=55 MPI-stage 2; n=4 MPI-stage 3, respectively). A higher MPI-score was significantly associated with lower hand grip strength (B -0.49 [95% CI -0.71; -0.28] p<0.001), lower gait speed (B -0.41 [95% CI -0.55; -0.25] p<0.001), and a slower TUGT (B 0.53 [95% CI 0.66; 0.85] p<0.001). CONCLUSION: Almost one-third of the included patients with head and neck cancer was mild or severe frail. A higher MPI-score, indicating higher degree of frailty, was associated with worse physical performance by lower handgrip strength, gait speed, and a slower TUGT. Thus, the MPI reflects the degree of frailty.