Supriya G. Mohile

Predicting Chemotherapy Toxicity in Older Adults With Cancer: A Prospective Multicenter Study

PURPOSE Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. PATIENTS AND METHODS Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P < .001). CONCLUSION A risk stratification schema can establish the risk of chemotherapy toxicity in older adults. Geriatric assessment variables independently predicted the risk of toxicity.

International Society of Geriatric Oncology Consensus on Geriatric Assessment in Older Patients With Cancer

PURPOSE To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer. METHODS SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment–related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care. RESULTS GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensity. The panel recommended that the following domains be evaluated in a GA: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and presence of geriatric syndromes. Although several combinations of tools and various models are available for implementation of GA in oncology practice, the expert panel could not endorse one over another. CONCLUSION There is mounting data regarding the utility of GA in oncology practice; however, additional research is needed to continue to strengthen the evidence base.

A pilot study of the vulnerable elders survey‐13 compared with the comprehensive geriatric assessment for identifying disability in older patients with prostate cancer who receive androgen ablation

Impairments in geriatric domains adversely affect health outcomes of the elderly. The Comprehensive Geriatric Assessment (CGA) is a key component of the treatment approach for older cancer patients, but it is time consuming. In this pilot study, the authors evaluated the validity of a brief, functionally based screening tool, the Vulnerable Elders Survey‐13 (VES‐13), for identifying older patients with prostate cancer (PCa) with impairment in the oncology clinic setting.

A Practical Approach to Geriatric Assessment in Oncology

More than half of new cancers are diagnosed in elderly patients, but data from randomized clinical trials do not represent the elderly population. Comprehensive geriatric assessment (CGA) can contribute valuable information to oncologists for risk stratification of elderly cancer patients. Functional impairments, frailty markers, cognitive impairments, and physical disabilities increase the risk for adverse outcomes during cancer treatment. Evidence is accumulating that selected elderly cancer patients benefit from CGA and geriatric interventions. However, perceived barriers to CGA include time, familiarity, cost, and lack of a well-defined procedure to interpret and apply the information. We present a model for rapid selection of elderly who would benefit from CGA using screening tools such as the Vulnerable Elders-13 Survey. We also define important geriatric functional risk factors, including mobility limitation, frailty, and dementia, and demonstrate how brief screening tests can make use of data realistically available to clinical oncologists to determine a stage of aging. Summary tables and a decision tree demonstrate how these data can be compiled to determine the risk for toxicities and to anticipate ancillary support needs.

Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†

BACKGROUND Screening tools are proposed to identify those older cancer patients in need of geriatric assessment (GA) and multidisciplinary approach. We aimed to update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on the use of screening tools. MATERIALS AND METHODS SIOG composed a task group to review, interpret and discuss evidence on the use of screening tools in older cancer patients. A systematic review was carried out and discussed by an expert panel, leading to a consensus statement on their use. RESULTS Forty-four studies reporting on the use of 17 different screening tools in older cancer patients were identified. The tools most studied in older cancer patients are G8, Flemish version of the Triage Risk Screening Tool (fTRST) and Vulnerable Elders Survey-13 (VES-13). Across all studies, the highest sensitivity was observed for: G8, fTRST, Oncogeriatric screen, Study of Osteoporotic Fractures, Eastern Cooperative Oncology Group-Performance Status, Senior Adult Oncology Program (SAOP) 2 screening and Gerhematolim. In 11 direct comparisons for detecting problems on a full GA, the G8 was more or equally sensitive than other instruments in all six comparisons, whereas results were mixed for the VES-13 in seven comparisons. In addition, different tools have demonstrated associations with outcome measures, including G8 and VES-13. CONCLUSIONS Screening tools do not replace GA but are recommended in a busy practice in order to identify those patients in need of full GA. If abnormal, screening should be followed by GA and guided multidisciplinary interventions. Several tools are available with different performance for various parameters (including sensitivity for addressing the need for further GA). Further research should focus on the ability of screening tools to build clinical pathways and to predict different outcome parameters.

AN UPDATE ON CANCER- AND CHEMOTHERAPY-RELATED COGNITIVE DYSFUNCTION: CURRENT STATUS

The purpose of this review is to summarize the current literature on the effects of cancer treatment-related cognitive difficulties, with a focus on the effects of chemotherapy. Numerous patients have cognitive difficulties during and after cancer treatments and, for some, these effects last years after treatment. We do not yet fully understand which factors increase susceptibility to cognitive difficulties during treatment and which cause persistent problems. We review possible contributors, including genetic and biological factors. Mostly we focus is on cognitive effects of adjuvant chemotherapy for breast cancer; however, cognitive effects of chemotherapy on the elderly and brain tumor patients are also discussed.

Association of a cancer diagnosis with vulnerability and frailty in older Medicare beneficiaries.

BACKGROUND Few studies have evaluated the independent effect of a cancer diagnosis on vulnerability and frailty, which have been associated with adverse health outcomes in older adults. METHODS We used data in the 2003 Medicare Current Beneficiary Survey from a nationally representative sample of 12,480 community-dwelling elders. Multivariable logistic regression models were used to evaluate whether cancer was independently associated with vulnerability and frailty. Measures of vulnerability and frailty included disability, geriatric syndromes, self-rated health, and scores on two assessment tools for elderly cancer patients-the Vulnerable Elders Survey-13 (VES-13) and the Balducci frailty criteria. All statistical tests were two-sided. RESULTS Diagnosis of a non-skin cancer was reported by 18.8% of the respondents. Compared with respondents without a cancer history, respondents with a personal history of cancer had a statistically significantly higher prevalence of limitations in activities of daily living (31.9% vs 26.9%), limitations in instrumental activities of daily living (49.5% vs 42.3%), geriatric syndromes (60.8% vs 53.9%), low self-rated health (27.4% vs 20.9%), score of 3 or higher on the VES-13 (45.8% vs 39.5%), and satisfying criteria for frailty as defined by Balducci (79.6% vs 73.4%) (P < .001 for all characteristics). After adjustment for confounders, a cancer diagnosis was found to be associated with low self-rated health (adjusted odds ratio [OR] = 1.46, 95% confidence interval [CI] = 1.30 to 1.64; relative risk [RR] = 1.33), limitations in activities of daily living (adjusted OR = 1.19, 95% CI = 1.06 to 1.33; RR = 1.13), limitations in instrumental activities of daily living (adjusted OR = 1.25, 95% CI = 1.13 to 1.38; RR = 1.13), a geriatric syndrome (adjusted OR = 1.27, 95% CI = 1.15 to 1.41; RR = 1.11), VES-13 score of 3 or higher (adjusted OR = 1.26, 95% CI = 1.13 to 1.41; RR = 1.14), and frailty (adjusted OR = 1.46, 95% CI = 1.29 to 1.65; RR = 1.09) as defined by Balducci criteria. CONCLUSION Diagnosis of a non-skin cancer was associated with increased levels of having disability, having geriatric syndromes, and meeting criteria for vulnerability and frailty.

Falls and Physical Performance Deficits in Older Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy

OBJECTIVES Men experience a decrease in lean muscle mass and strength during the first year of androgen deprivation therapy (ADT). The prevalence of falls and physical and functional impairment in this population have not been well described. METHODS A total of 50 men aged 70 years and older (median 78) receiving ADT for systemic prostate cancer (80% biochemical recurrence) underwent functional and physical assessments. The functional assessments included Katzs Activities of Daily Living (ADLs) and Lawtons Instrumental Activities of Daily Living (IADLs). Patients completed the Vulnerable Elders Survey-13, a short screening tool of self-perceived functional and physical performance ability. Physical performance was assessed using the Short Physical Performance Battery. The history of falls was recorded. Of the 50 patients, 40 underwent follow-up assessment with the same instruments 3 months after the initial assessment. RESULTS Of the 50 men, 24% had impairment in the ADLs, 42% had impairment in the IADLs, 56% had abnormal Short Physical Performance Battery findings, and 22% reported falls within the previous 3 months. Within the Short Physical Performance Battery, deficits occurred within all subcomponents (balance, walking, and chair stands). On univariate analysis, age, deficits in ADLs and IADLs, and abnormal cognitive and functional screen findings were associated with an increased risk of abnormal physical performance. ADL deficits, the use of an assistive device, and abnormal functional screen findings were associated with an increased risk of falling. CONCLUSIONS The results of our study have shown that older men with prostate cancer receiving long-term ADT exhibit significant functional and physical impairment and are at risk of falls that is greater than that for similar-aged cohorts. Careful assessment of the functional and physical deficits in older patients receiving ADT is warranted.

End Points and Trial Design in Geriatric Oncology Research: A Joint European Organisation for Research and Treatment of Cancer–Alliance for Clinical Trials in Oncology–International Society of Geriatric Oncology Position Article

Selecting the most appropriate end points for clinical trials is important to assess the value of new treatment strategies. Well-established end points for clinical research exist in oncology but may not be as relevant to the older cancer population because of competing risks of death and potentially increased impact of therapy on global functioning and quality of life. This article discusses specific clinical end points and their advantages and disadvantages for older individuals. Randomized or single-arm phase II trials can provide insight into the range of efficacy and toxicity in older populations but ideally need to be confirmed in phase III trials, which are unfortunately often hindered by the severe heterogeneity of the older cancer population, difficulties with selection bias depending on inclusion criteria, physician perception, and barriers in willingness to participate. All clinical trials in oncology should be without an upper age limit to allow entry of eligible older adults. In settings where so-called standard therapy is not feasible, specific trials for older patients with cancer might be required, integrating meaningful measures of outcome. Not all questions can be answered in randomized clinical trials, and large observational cohort studies or registries within the community setting should be established (preferably in parallel to randomized trials) so that treatment patterns across different settings can be compared with impact on outcome. Obligatory integration of a comparable form of geriatric assessment is recommended in future studies, and regulatory organizations such as the European Medicines Agency and US Food and Drug Administration should require adequate collection of data on efficacy and toxicity of new drugs in fit and frail elderly subpopulations.

Prostate cancer in the elderly: frequency of advanced disease at presentation and disease-specific mortality.

The objectives of this study were to determine the frequency of metastatic (M1) prostate cancer (PC) at presentation in different age groups, to examine the association of age with PC‐specific mortality, and to calculate the relative contribution of different age groups to the pool of M1 cases and PC deaths.