Heidi D. Klepin

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.

Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia

We investigated the predictive value of geriatric assessment (GA) on overall survival (OS) for older adults with acute myelogenous leukemia (AML). Consecutive patients ≥ 60 years with newly diagnosed AML and planned intensive chemotherapy were enrolled at a single institution. Pretreatment GA included evaluation of cognition, depression, distress, physical function (PF) (self-reported and objectively measured), and comorbidity. Objective PF was assessed using the Short Physical Performance Battery (SPPB, timed 4-m walk, chair stands, standing balance) and grip strength. Cox proportional hazards models were fit for each GA measure as a predictor of OS. Among 74 patients, the mean age was 70 years, and 78.4% had an Eastern Cooperative Oncology Group (ECOG) score ≤ 1. OS was significantly shorter for participants who screened positive for impairment in cognition and objectively measured PF. Adjusting for age, gender, ECOG score, cytogenetic risk group, myelodysplastic syndrome, and hemoglobin, impaired cognition (Modified Mini-Mental State Exam < 77) and impaired objective PF (SPPB < 9) were associated with worse OS. GA methods, with a focus on cognitive and PF, improve risk stratification and may inform interventions to improve outcomes for older AML patients.

Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer

PURPOSE Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = 500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250). PATIENTS AND METHODS Patients age ≥ 65 years with a solid tumor, fluent in English, and who were scheduled to receive a new chemotherapy regimen were recruited from eight institutions. Risk of chemotherapy toxicity was calculated (low, medium, or high risk) on the basis of the prediction model before the start of chemotherapy. Chemotherapy-related toxicity was captured (grade 3 [hospitalization indicated], grade 4 [life threatening], and grade 5 [treatment-related death]). Validation of the prediction model was performed by calculating the area under the receiver-operating characteristic curve. RESULTS The study sample (N = 250) had a mean age of 73 years (range, 65 to 94 [standard deviation, 5.8]). More than one half of patients (58%) experienced grade ≥ 3 toxicity. Risk of toxicity increased with increasing risk score (36.7% low, 62.4% medium, 70.2% high risk; P < .001). The area under the curve of the receiver-operating characteristic curve was 0.65 (95% CI, 0.58 to 0.71), which was not statistically different from the development cohort (0.72; 95% CI, 0.68 to 0.77; P = .09). There was no association between Karnofsky Performance Status and chemotherapy toxicity (P = .25). CONCLUSION This study externally validated a chemotherapy toxicity predictive model for older adults with cancer. This predictive model should be considered when discussing the risks and benefits of chemotherapy with older adults.

The Feasibility of Inpatient Geriatric Assessment for Older Adults Receiving Induction Chemotherapy for Acute Myelogenous Leukemia

To test the feasibility and utility of a bedside geriatric assessment (GA) to detect impairment in multiple geriatric domains in older adults initiating chemotherapy for acute myelogenous leukemia (AML).

Physical Performance and Subsequent Disability and Survival in Older Adults with Malignancy: Results from the Health, Aging and Body Composition Study

OBJECTIVES: To evaluate objective physical performance measures as predictors of survival and subsequent disability in older patients with cancer.

ACUTE MYELOGENOUS LEUKEMIA IN OLDER ADULTS

The incidence of acute myelogenous leukemia (AML) increases with age. Older AML patients, generally defined by age > or = 60 years, have worse treatment outcomes than younger patients. While selected older patients can benefit from standard therapies, as a group they experience greater treatment-related toxicity, lower remission rates, shorter disease-free survival times, and shorter overall survival times. Outcome disparity is in part explained by age-related biologic features. Older patients are more likely to present with unfavorable cytogenetic abnormalities, multidrug resistance phenotypes, and secondary AML. However, even older adults with favorable tumor biology have a worse prognosis than younger patients. Patient-specific factors, including impaired physical function and comorbidity, independently predict greater treatment toxicity and shorter survival. Improving patient assessment strategies is critical to identify those patients who are most likely to benefit from induction and postremission therapies. In addition, continued efforts to identify more effective and tolerable induction and postremission strategies are needed for this population. Investigations of hypomethylating agents and signal transduction inhibitors hold promise for the treatment of AML patients. Steady advances in the field of hematopoietic transplantation, including use of reduced intensity transplants, may result in additional curative options available to selected older adults. Finally, improved supportive care strategies are needed to maximize treatment outcomes.

Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Adults

Treatment of older adults with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is challenging because of disease morbidity and associated treatments. Both diseases represent a genetically heterogeneous group of disorders primarily affecting older adults, with treatment strategies ranging from supportive care to hematopoietic stem-cell transplantation. Although selected older adults can benefit from intensive therapies, as a group they experience increased treatment-related morbidity, are more likely to relapse, and have decreased survival. Age-related outcome disparities are attributed to both tumor and patient characteristics, requiring an individualized approach to treatment decision making beyond consideration of chronologic age alone. Selection of therapy for any individual requires consideration of both disease-specific risk factors and estimates of treatment tolerance and life expectancy derived from evaluation of functional status and comorbidity. Although treatment options for older adults are expanding, clinical trials accounting for the heterogeneity of tumor biology and aging are needed to define standard-of-care treatments for both disease groups. In addition, trials should include outcomes addressing quality of life, maintenance of independence, and use of health care services to assist in patient-centered decision making. This review will highlight available evidence in treatment of older adults with AML or MDS and unanswered clinical questions for older adults with these diseases.

Polypharmacy and Potentially Inappropriate Medication Use in Older Adults with Cancer Undergoing Chemotherapy: Effect on Chemotherapy‐Related Toxicity and Hospitalization During Treatment

To evaluate the prevalence of polypharmacy and potentially inappropriate medication (PIM) use and the association between these and chemotherapy‐related adverse events in older adults with cancer undergoing chemotherapy.

Physical Function in Older Candidates for Renal Transplantation: An Impaired Population

BACKGROUND AND OBJECTIVES Although physical function is a major determinant of health outcomes and quality of life in older adults, standard tools for its assessment have not been routinely applied to the fastest growing segment of the kidney transplant candidate population, which is at high risk of comorbidity and disability--people over age 60. The objective of this study was to describe the baseline physical function in older adults with renal failure referred for transplantation and compare them with older adults with other significant comorbidity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS An observational sample comparing physical performance in renal transplant candidates over age 60 (Renal Failure) to older people with diastolic heart failure (Heart Failure), chronic obstructive pulmonary disease (COPD), or at high risk for cardiovascular disease (High CV Risk) was studied. RESULTS Older people with Renal Failure were significantly impaired by objective measures of physical function, including lower Short Physical Performance Battery, slower gait speed, and lower grip strength. CONCLUSIONS Older people referred for renal transplantation had poorer physical performance than older adults with other common chronic diseases and may be at high risk for disability while awaiting transplantation.

A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy

Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes.