Cachexia and Sarcopenia in Older Adults with Cancer: A Comprehensive Review.
ABSTRACT: Cancer cachexia is a syndrome characterized by weight loss with accompanying loss of muscle and/or fat mass and leads to impaired patient function and physical performance and is associated with a poor prognosis. It is prevalent in older adults with cancer; age-associated physiologic muscle wasting and weakness, also known as sarcopenia, can compound deficits associated with cancer cachexia in older adults and makes studying this condition more complex in this population. Multiple measurement options are available to assess the older patient with cancer and cachexia and/or sarcopenia including anthropometric measures, imaging modalities such as Dual X-ray absorptiometry (DEXA) and Computed Tomography (CT), muscular strength and physical performance testing, and patient-reported outcomes (PROs). A geriatric assessment (GA) is a useful tool when studying the older patient with cachexia given its comprehensive ability to capture aging-sensitive PROs. Interventions focused on nutrition and increasing physical activity may improve outcomes in older adults with cachexia. Efforts to develop targeted pharmacologic therapies with cachexia have not been successful thus far. Formal treatment guidelines, an updated consensus definition for cancer cachexia and the development of a widely adapted assessment tool, much like the GA utilized in geriatric oncology, could help advance the field of cancer cachexia over the next decade.
Project description:BACKGROUND:to distinguish direct and indirect pathways to frailty phenotype, and quantify associations between two frailty components (i.e., sarcopenia and cachexia) regarding mortality and morbidity in older adults with cancer. METHODS:all consecutive older outpatients with cancer were included in a prospective two-centre cohort study between 2013 and 2017 and had geriatric assessment. We used the frailty phenotype. Sarcopenia and cachexia were built as latent variables by including observed variables related to physical performances and related to nutrition and inflammation respectively. Structural equation modelling was used to distinguish between direct and indirect effects of the frailty parameters on the risk of death (Model 1) and the risk of morbidity (defined by unplanned hospitalization and/or disability and/or a fall; Model 2). The root mean square error of approximation (RMSEA) and the comparative fit index (CFI) were used to assess the model fit. RESULTS:603 older outpatients were included (mean age: 81.2 ± 6.1; women: 54%; frailty phenotype: 58%). The 6-month mortality and morbidity rates were 18% and 64%, respectively. The fit was good for both models (RMSEA and CFI = 0.029 [0.017-0.039] and 0.99 for Model 1, and 0.028 [0.017-0.039] and 0.99 for Model 2, respectively). Sarcopenia and cachexia were both directly and significantly associated with 6-month mortality (?sarcopenia = 0.18, p = 0.01; ?cachexia = 0.52, p < 0.0001) and morbidity (?sarcopenia = 0.37, p < 0.0001; ?cachexia = 0.19, p < 0.02). CONCLUSIONS:sarcopenia and cachexia had a direct pathway with 6-month mortality and morbidity in older cancer patients.
Project description:BACKGROUND:Sarcopenia is defined as low skeletal muscle mass with poor physical performance, representing a strong prognostic factor for mortality in older people. Although highly prevalent in hospitalized geriatric patients, it is unknown whether sarcopenia can also predict mortality in these patients. OBJECTIVE:To determine the association between sarcopenia according the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP), International Working Group on Sarcopenia (IWGS), Special Interest Group of Sarcopenia, Cachexia and Wasting Disorders (SIG) and Foundation for the National Institutes of Health (FNIH) and 2-year mortality in acutely hospitalized geriatric patients. DESIGN:81 patients (84±5 y) admitted to the acute geriatric ward participated in this study. Body composition assessment (bio-impedance, Maltron Bioscan 920-II) and physical performance tests were performed, and mortality information was retrieved through patient files. RESULTS:Prevalence rates of sarcopenia were 51% (EWGSOP), 75% (IWGS), 69% (SIG), and 27% (FNIH). Based on Cox proportional hazard ratio (HR) analysis, 2-year mortality was significantly higher in sarcopenic patients versus non-sarcopenic patients when using the EWGSOP (2-y: HR 4.310; CI-95%:2.092-8.850; P<0.001) and FNIH criteria (2-y: HR 3.571; CI-95%:1.901-6.711; P<0.001). Skeletal muscle mass index, fat mass index, body mass index, phase angle and gait speed were significantly lower in the geriatric patients who deceased after 2 years versus those who were still alive. Cox proportional HR analyses showed that higher phase angle (HR 0.678; CI-95%:0.531- 0.864; P=0.002) and higher fat mass index (HR 0.839; CI-95%:0.758-0.928; P=0.001) significantly reduced 2-y mortality probability. Combining sarcopenia criteria and separate patient characteristics finally resulted in a model in which HRs for sarcopenia (EWGSOP and FNIH) as well as phase angle significantly predicted mortality probability. CONCLUSION:Sarcopenia is prevalent in acutely hospitalized geriatric patients and is associated with significantly higher 2-year mortality according the EWGSOP and FNIH criteria.
Project description:BACKGROUND:Hospitalized older adults have significant geriatric deficits that may lead to poor outcomes. We conducted a randomized trial to investigate the effectiveness of providing clinicians with a real-time geriatric assessment (GA) report in nonelectively hospitalized older patients with cancer. SUBJECTS, MATERIALS, AND METHODS:We developed a web-based software platform for administering a modified GA (Cancer 2005;104:1998-2005) to older (>70?years) nonelectively hospitalized patients with pathologically confirmed malignancy. Patients were randomized to have their GA report provided to their treating clinicians (Intervention arm) or not provided (Control arm). RESULTS:Our study included 135 patients, median age 76 years, 52% female, 75% white, 21% black, 79% greater than high school education, 59% married, and 17% living alone. All patients had at least one GA-identified deficit, including physical function deficits (90%), cognitive impairment (22%), >5 comorbidities (28%), polypharmacy (>9 medications; 38%), weight loss ?10% in the past 6 months (40%), anxiety (32%), or depression (30%). There was no difference between the Intervention (6%) and Control arms (9%) in the proportion of patients who were referred by their clinical team for an intervention to address a deficit (p = .53). CONCLUSION:Many older nonelectively hospitalized patients with cancer have geriatric deficits that are amenable to evidence-based interventions. Real-time GA reports provided to the care team prior to discharge did not influence provider referral for such interventions. There is a need for systems-level interventions to address deficits in this vulnerable patient population. IMPLICATIONS FOR PRACTICE:Geriatric deficits are common in hospitalized older adults with cancer and lead to poor outcomes. Addressing modifiable deficits represents an appealing way to improve outcomes. Widespread geriatrician consultation is impractical owing to resource and personnel constraints. This work tested whether prompt delivery of a mostly self-administered, web-based geriatric assessment report to clinicians improved referral rates for evidence-informed interventions. It confirmed frequent geriatric deficits and high readmission rates in this population but found that real-time geriatric assessment reporting did not influence provider referral for evidence-informed interventions on geriatric assessment identified deficits. These findings highlight the need for systems-level intervention to improve outcomes in this vulnerable patient population.
Project description:Malnutrition predicts poorer clinical outcomes for people with cancer. Older adults with cancer are a complex, growing population at high risk of weight-losing conditions. A number of malnutrition screening tools exist, however the best screening tool for this group is unknown. The aim was to systematically review the published evidence regarding markers and measures of nutritional status in older adults with cancer (age???70). A systematic search was performed in Ovid Medline, EMBASE, Web of Science, CINAHL, British Nursing Database and Cochrane CENTRAL; search terms related to malnutrition, cancer, older adults. Titles, abstracts and papers were screened and quality-appraised. Data evaluating ability of markers of nutritional status to predict patient outcomes were subjected to meta-analysis or narrative synthesis. Forty-two studies, describing 15 markers were included. Meta-analysis found decreased food intake was associated with mortality (OR 2.15 [2.03-4.20] p?=?<?0.00001) in univariate analysis. Prognostic Nutritional Index (PNI) was associated with overall survival (HR 1.89 [1.03-3.48] p?=?0.04). PNI markers (albumin, total lymphocyte count) could be seen as markers of inflammation rather than nutrition. There a suggested relationship between very low body mass index (BMI) (<18?kg/m2) and clinical outcomes. No tool was identified as appropriate to screen for malnutrition, as distinct from inflammatory causes of weight-loss. Risk of cancer-cachexia and sarcopenia in older adults with cancer limits the tools analysed. Measures of food intake predicted mortality and should be included in clinical enquiry. A screening tool that distinguishes between malnutrition, cachexia and sarcopenia in older adults with cancer is needed.
Project description:The incidence of acute myeloid leukemia (AML) increases with age, but the outcomes for older adults with AML are poor due to underlying tumor biology, poor tolerance to aggressive treatment, and the physiologic changes of aging. Because of the underlying heterogeneity in health status, treatment decisions are difficult in this population. A geriatric assessment (GA) refers to the use of various validated tools to assess domains that are important in older adults including physical function, cognition, comorbidities, polypharmacy, social support, and nutritional status. In older patients with cancer, a GA can guide treatment decision-making, predict treatment toxicity, and guide supportive care interventions. Compared to solids tumors, there is a relative lack of studies evaluating the use of a GA in older patients with AML. In this review, we will discuss the principles, common domains, feasibility, and benefits of GA, with a focus on older patients with AML that includes practical applications for clinical management.
Project description:Geriatric assessment (GA) is used in oncology to identify deficits in older patients with cancer that may affect treatment choice. We examine GA in 550 patients with early breast cancer, including both younger (<65 years) and older women (aged 65 years or older), to assess the potential value of this tool in younger, presumed "healthier" patients. Although older women have more GA-identified deficits overall, younger patients are more anxious. Suboptimal physical function was problematic across the age spectrum. GA domains can identify major deficits in younger patients beyond those likely to be uncovered in routine investigation.
Project description:BACKGROUND:Older adults receiving cancer therapy have heightened risk for treatment-related toxicity. Geriatric assessment (GA) can identify impairments, which may contribute to vulnerability and adverse outcomes. GA management interventions can address these impairments and have the potential to improve outcomes when implemented. METHODS:We conducted a randomized pilot study comparing GA with management interventions versus usual care in patients with stage III/IV solid tumor malignancies (N = 71). In all patients, a trained coordinator conducted and scored a baseline GA with pre-determined cutoffs for impairment. For patients randomized to the intervention arm, an algorithm was used to identify GA management recommendations based upon identified impairments. Recommendations were relayed to the primary oncologist for implementation. GA was repeated at 3 months. The primary outcome was grade 3-5 chemotherapy toxicity. Secondary outcomes included feasibility, hospitalizations, dose reductions, dose delays, and early treatment discontinuation. RESULTS:The mean participant age was 76 (70-89). The total number of GA management recommendations relayed was 409, of which 35.4% were implemented by the primary oncologist. Incidence of grade 3-5 chemotherapy toxicity did not differ between the two groups. Prevalence of hospitalization, dose reductions, dose delays, and early treatment discontinuation also did not differ between the two groups. CONCLUSIONS:An algorithm can be used to guide GA management recommendations in older adults with cancer. However, reliance upon the primary oncologist for execution resulted in a low prevalence of implementation. Future work should aim to understand barriers to implementation and explore alternate models of implementing geriatric-focused care for older adults with cancer.
Project description:BACKGROUND:Systemic inflammation and cachexia are associated with adverse clinical outcomes in diffuse large B-cell lymphoma (DLBCL). The Geriatric Nutritional Risk Index (GNRI) is one of the main parameters used to assess these conditions, but its efficacy in DLBCL is inconclusive. METHODS:We retrospectively reviewed 228 DLBCL patients who were treated with R-CHOP immunochemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The patients were stratified according to GNRI score (>?98, 92 to 98, 82 to <?92, and?<?82) as defined in previous studies. Additionally, the extent of sarcopenia was categorized as sarcopenia-both, sarcopenia-L3/PM alone, and non-sarcopenia-both according to skeletal muscle index. RESULTS:Survival curves plotted against a combination of GNRI and sarcopenia scores revealed two clear groups as follows: high cachexia risk (HCR) group (GNRI <?82, sarcopenia-both, or GNRI 82-92 with sarcopenia-L3/PM alone) and low cachexia risk (LCR) group (others). The HCR group had a lower complete response rate (46.5% vs. 86.6%) and higher frequency of treatment-related mortality (19.7% vs. 3.8%) and early treatment discontinuation (43.7% vs. 8.3%) compared with the LCR group. The median progression-free survival (PFS) (not reached vs. 10.3?months, p?<? 0.001) and overall survival (OS) (not reached vs. 12.9?months, p?<? 0.001) were much shorter in the HCR group than in the LCR group. On multivariable analyses, the HCR group was shown to be an independent negative prognostic factor for PFS and OS after adjusting the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI). CONCLUSIONS:A combined model of GNRI and sarcopenia may provide prognostic information independently of the NCCN-IPI in DLBCL.
Project description:INTRODUCTION:The geriatric syndromes of frailty, sarcopenia, weight loss, and dementia are highly prevalent in elderly individuals across all care continuums. Despite their deleterious impact on quality of life, disability, and mortality in older adults, they are frequently under-recognized. At Saint Louis University, the Rapid Geriatric Assessment (RGA) was developed as a brief screening tool to identify these four geriatric syndromes. MATERIALS AND METHODS:From 2015-2019, the RGA, comprised of the FRAIL, SARC-F, Simplified Nutritional Appetite Questionnaire (SNAQ), and Rapid Cognitive Screen (RCS) tools and a question on Advance Directives, was administered to 11,344 individuals ? 65 years of age across Missouri in community, office-based, hospital, Programs of All-Inclusive Care for the Elderly (PACE), and nursing home care settings. Standard statistical methods were used to calculate the prevalence of frailty, sarcopenia, weight loss, and dementia across the sample. RESULTS:Among the 11,344 individuals screened by the RGA, 41.0% and 30.4% met the screening criteria for pre-frailty and frailty respectively, 42.9% met the screening criteria for sarcopenia, 29.3% were anorectic and at risk for weight loss, and 28.1% screened positive for dementia. The prevalence of frailty, risk for weight loss, sarcopenia, and dementia increased with age and decreased when hospitalized patients and those in the PACE program or nursing home were excluded. CONCLUSIONS:Using the RGA as a valid screening tool, the prevalence of one or more of the geriatric syndromes of frailty, sarcopenia, weight loss, and dementia in older adults across all care continuums is quite high. Management approaches exist for each of these syndromes that can improve outcomes. It is suggested that the brief RGA screening tool be administered to persons 65 and older yearly as part of the Medicare Annual Wellness Visit.
Project description:<h4>Aim</h4>In Japan, the number of older patients with cancer has been increasing. Assessment of performance status, cognitive function and social background is necessary for the treatment of older patients. The aims of the present study were: (i) to establish an evaluation system using electronic medical records; and (ii) to distinguish older patients as fit versus vulnerable or frail according to a geriatric assessment (GA) system score.<h4>Methods</h4>We incorporated GA tools in our electronic medical records system and carried out comprehensive assessments for patients with newly diagnosed lung cancer aged ?65?years. The decision about primary treatment followed consultation with the clinical team and was not guided by GA scores. Subsequent treatment and outcomes were recorded.<h4>Results</h4>A total of 100 patients had completed GA. The average age was 75?years (range 65-94?years). Regarding GA results, 63% were positive on the Comprehensive Geriatric Assessment 7, 39% on the Vulnerable Elderly Survey-13 and 84% on the Geriatric?8. The percentage of vulnerable patients (positive on all three GA) was significantly higher in the non-standard therapy group (n =?19) than in the standard therapy group (n =?81; 78.9% vs 21.0%, P <?0.001). Among vulnerable patients who received standard therapy, 47% discontinued chemotherapy as a result of toxicity. Even if a patient was considered vulnerable based on GA scores, chemotherapy is possibly safe for those with EGFR mutations.<h4>Conclusions</h4>We confirmed the feasibility of this system. During decision-making for older patients with cancer, a combination of GA helps prevent undertreatment or overtreatment. Geriatr Gerontol Int 2019; 19: 1108-1111.