Motivating Older Adults with Cancer to Keep Moving: the Implications of Lifestyle Interventions on Physical Activity.

PURPOSE OF REVIEW: The purposes of this review are to describe the unique needs and preferences of older adults with cancer regarding physical activity and to outline the essential characteristics associated with increased physical activity resulting from lifestyle interventions in older adults. RECENT FINDINGS: Functional decline is accelerated in inactive and sedentary older adults. Even a modest increase in physical activity can improve physical function for older cancer survivors. Participation in physical activity is influenced by diverse individual-level factors, behavioral characteristics and skills and social and environmental factors. Thus, programs that are tailored to older adults' preferences provide social support and remove obstacles to participation may be more effective, particularly for older adults with low physical activity and sedentary lifestyle.

Longitudinal changes in cognitive and physical function and health-related quality of life in older adults with acute myeloid leukemia.

INTRODUCTION: Many older adults with acute myeloid leukemia (AML) do not receive chemotherapy because of physicians' and patients' concern for toxicities and functional decline. This highlights the critical and urgent need to generate knowledge of functional changes following new treatments. MATERIALS AND METHODS: As a part of a pragmatic single-center trial, 59 older adults ≥60 years with AML completed geriatric assessment and health-related quality of life measures before treatment and at one month and three months after chemotherapy initiation. Changes in scores of various geriatric assessment measures were computed by subtracting the baseline score from the one-month and three-month scores for each patient. Established cut-offs were used to determine a clinically meaningful change (improvement or worsening). This study provides results of descriptive exploratory analyses. RESULTS: Patients experienced significant comorbidity burden and a high prevalence of functional impairments before treatment, with 56% of patients having ≥2 comorbid conditions, 69% having abnormal cognitive function (using Montreal Cognitive Assessment), 69% having impaired objective physical function (using Short Physical Performance Battery), and 64% having a positive depression screen (Patient Health Questionnaire-9). Patients (n = 53) received treatment with predominantly low-intensity chemotherapy; six patients received intensive chemotherapy. Among those who completed some or all of the three-month evaluation (N = 43), from baseline before treatment to three months later, cognitive function improved (38.7%) or remained stable (38.7%), objective physical function improved (51.6%) or remained stable (22.6%), and depression scores improved (9.4%) or remained stable (53.1%). Global health status score and role functioning moderately improved by a score of >16. DISCUSSION: An exploratory analysis of our phase 2 trial demonstrated improvement or stabilization of cognitive and physical function and depression score at three months in a high proportion of older survivors of AML, despite a high prevalence of frailty and significant comorbidity burden at baseline. These results demonstrate success of treatment in improving cognitive and physical function and depression score, and, if confirmed in larger studies, should encourage oncologists to offer chemotherapy to older adults with AML. CLINICAL TRIAL REGISTRATION: The study is registered in the ClinicalTrials.gov ID: NCT03226418.

Integrating geriatric assessment and genetic profiling to personalize therapy selection in older adults with acute myeloid leukemia.

INTRODUCTION: Survival benefit associated with intensive over low-intensity chemotherapy in older adults with acute myeloid leukemia (AML) is controversial. Geriatric assessment and genetic risk categories correlate with survival following intensive chemotherapy in older adults with AML and can guide treatment selection. MATERIALS AND METHODS: In a single-center trial, we integrated both geriatric assessment, and genetic risk categories to personalize selection of intensive versus low-intensity chemotherapy in older adults ≥60 years with AML (NCT03226418). In the present report, we demonstrate feasibility of this approach. RESULTS: Broad eligibility criteria and co-management of patients with community oncologists allowed enrollment of 45% of all patients with AML treated at our center during the study period. The median time from enrollment to therapy initiation was two days (range 0-9). Over half of the trial patients had a score of ≥3 on hematopoietic cell transplantation comorbidity index, impairment in physical function (Short Physical Performance Battery), and Montreal Cognitive Assessment. Three fit patients received intensive chemotherapy, whereas other patients received low-intensity chemotherapy. Mortality at 30 days from diagnosis was 3.7% (95% confidence interval [CI] 0.7-18.3%) and at 90 days was 29.6% (95% CI 15.9-48.5%). One-year overall survival was 66% (95% CI 60-87%). DISCUSSION: Our data demonstrate the feasibility of integrating geriatric assessment in precision oncology trials to define fitness for intensive chemotherapy. Broad eligibility criteria and academic-community collaboration can expand access to clinical trials.

Health-related and sociodemographic factors associated with physical frailty among older cancer survivors.

OBJECTIVE: The purpose of this study was to examine factors associated with frailty in older cancer survivors. MATERIALS AND METHODS: This is a cross-sectional study using data from the National Social Health and Aging Project (NSHAP) Wave 2, and includes an in-home, nationally representative sample of community-dwelling adults ≥50 years and older from the United States. Frailty score was computed for each individual using a modified 4-point scale based on the phenotypic frailty. Ordinal logistic regression was used to characterize the association between health-related, sociodemographic factors and frailty. RESULTS: Among the 3377 participants, 461 were cancer survivors (answered "yes" to "ever have cancer other than skin cancer"). A final sample of 394 cancer survivors were included: 59 participants (16.1%) were frail, 219 participants were pre-frail (59.8%), and 88 participants were non-frail (24.0%). The univariate analyses showed increasing age (OR 1.48; CI 1.29-1.72; p-value <.001), comorbidities (OR 1.43; CI 1.25-1.64; p-value <.001), depression (OR 1.27; CI 1.19-1.35; p-value <.001) and low mobility (OR 1.55; CI 1.37-1.78; p-value <.001) were associated with frailty. Participants with high self-rated (good/very good/ excellent) physical health (OR 0.18; CI 0.11-0.30; p < .001) and mental health (OR 0.27; CI 0.15-0.50; p < .001) were less likely to be frail. In a multivariate model, frailty was associated with age, self-rated physical health, depression, ability to perform activities of daily living, and mobility (p < .05). CONCLUSION: The findings highlight the importance of incorporating geriatric assessment into cancer survivorship to prevent and delay the progression of frailty.

Screening for cognitive impairment in older adults with hematological malignancies using the Montreal Cognitive Assessment and neuropsychological testing.

OBJECTIVES: The primary objective of the current study is to describe the prevalence and profile of cognitive domains affected in older adults with hematological malignancies evaluated for hematopoietic cell transplantation (HCT) using the Montreal Cognitive Assessment (MoCA) and neuropsychological tests. The secondary objective is to determine if a specific MoCA cut-off score would correlate with the identification of cognitive impairment detected by neuropsychological tests. This would facilitate interpretation of cognitive screening and referral of patients who would likely need further neuropsychological testing. MATERIALS AND METHODS: Fifty-one patients 60 years and older who were evaluated for HCT were assessed using a battery of standardized neuropsychological tests and MoCA. We analyzed Receiver Operating Characteristics (ROC) comparing MoCA scores and four different neuropsychological test criteria for cognitive impairment. RESULTS: The prevalence of cognitive impairment detected by neuropsychological tests was 53 to 70.6% using the criteria for patients with cancer by the International Cancer Cognition Task Force (ICCTF). The following cognitive domains were most affected: language, learning and memory, visuospatial skills, and executive function. MoCA is an appropriate screening test for cognitive impairment. Using the ICCTF criteria, 86 to 100% of patients are correctly classified as having significant cognitive impairment on neuropsychological tests using a cut-off score of 20 or less. CONCLUSION: There is a high prevalence of cognitive impairment identified by neuropsychological tests in older patients with hematological malignancies evaluated for HCT. Identification of an appropriate MoCA cut-off score in this population is important to identify patients who would benefit from further assessment.

Returning to life activities after hematopoietic cell transplantation in older adults.

OBJECTIVES: The prevalence of hematopoietic cell transplant (HCT) among older adults with hematological malignancies has more than doubled over the last decade and continues to grow. HCT is an intense process that can impact functional status and health-related quality of life. The objective of this paper is to describe the experience of returning to life activities after HCT in patients 60 years of age and older and the resources required to adapt and cope to limitations in physical, psychological, and cognitive function. MATERIALS AND METHODS: Twenty English speaking adults 60 years and older with hematological malignancy 3 to 12 months post-HCT completed semi-structured interviews. Open-ended questions and probes were guided by the Transactional Model of Stress and Coping to explore adaptive functioning, coping resources, and coping strategies. An integrated grounded theory approach was used to code the textual data to identify themes. The study took place at a tertiary comprehensive cancer center in the Midwest United States. RESULTS: Eight allogeneic and twelve autologous HCT recipients participated in the interviews. Nineteen participants were within 6-12 months and 1 participant was at 3 months post-HCT. Our findings identify the significant role of engaging in life activities and social support in the recovery of physical, psychological and cognitive function. CONCLUSION: Older HCT recipients are an understudied population. They are at high risk for functional decline. Our findings may provide community oncologists and primary care physicians with a context for providing care to older HCT survivors during their recovery.

HSP90 inhibitor, DMAG, synergizes with radiation of lung cancer cells by interfering with base excision and ATM-mediated DNA repair.

Inhibition of heat shock protein 90 (HSP90) leads to inappropriate processing of proteins involved in cell survival pathways. We found that HSP90 inhibitor, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG), is synergistic with radiation for non-small cell lung cancer cell lines, NCI-H460 and A549. To establish the optimal schedule for this combination, cells were radiated before, after, or simultaneously with DMAG, and survival was scored by clonogenic assay. The sequence of DMAG administration was critical for synergy with radiation, and pretreatment for 16 h led to maximal synergy. Similar radiosensitization was observed in isogenic cells in which expression of wild-type p53 was silenced by RNA interference, although p53 loss rendered cells overall less radiosensitive. The mechanistic basis for synergy was studied by Western blotting, cell cycle analysis, alkaline comet assay, and direct measurement of the activities of key base excision repair enzymes. Regardless of schedule of administration, DMAG led to degradation of proteins involved in activation of cell survival pathways after radiation, which did not explain the differences in the schedule of administration observed in clonogenic assays. In addition to previously reported decrease in activation of ATM, pretreatment with DMAG blocked activation of base excision repair machinery and activity of key enzymes, apurinic/apyrimidinic endonuclease, and DNA polymerase-beta. Similarly, pretreatment with specific apurinic/apyrimidinic endonuclease inhibitor, CRT0044876, reproduced the effects of DMAG. Thus, administration of HSP90 inhibitors before radiation is critical for optimizing their use as radiosensitizers.

Frailty in Hematologic Malignancy.

PURPOSE OF REVIEW: Older adults with hematologic malignancy are a growing demographic. Estimating risk of chemotherapy toxicity based on age alone is an unreliable estimate of quality of life, functional capacity, or risk of treatment complications. RECENT FINDINGS: Dedicated geriatric assessment tools can aid the clinician in identifying geriatric syndromes such as frailty, resulting in improved prognostication to decrease morbidity and mortality. Frailty is not synonymous with individual performance status and is dynamic. Establishing the patient goals, values, and preferences is central to the consideration of malignant hematology decision process. Careful considerations of available data on the patient's prognosis based on estimated life expectancy, geriatric assessment data, and age-specific cancer mortality, with and without treatment, can reconcile the risks and benefits. Assessments of frailty can aid the clinical feasibility and burden of the treatment to the patient and family in the context of each patient's unique needs.