The relationship between body composition and left ventricular performance in women with breast, lymphoma, or sarcoma cancer.

BACKGROUND: To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma. METHODS: Women underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change. RESULTS: Women (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047). CONCLUSIONS: These results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet. TRIAL REGISTRATION: DETECTIV_NCT01719562, WF99112, & WF97415-NCT02791581.

Clinicians' Perspectives on the Telehealth Serious Illness Care Program for Older Adults With Myeloid Malignancies: Single-Arm Pilot Study.

BACKGROUND: Serious illness conversations may help patients avoid unwanted treatments. We previously piloted the telehealth Serious Illness Care Program (SICP) for older adults with acute myeloid leukemia and myelodysplastic syndrome. OBJECTIVE: In this study, we aimed to understand the experience of the telehealth SICP from the clinician's perspective. METHODS: We studied 10 clinicians who delivered the telehealth SICP to 20 older adults with acute myeloid leukemia or myelodysplastic syndrome. Quantitative outcomes included confidence and acceptability. Confidence was measured using a 22-item survey (range 1-7; a higher score is better). Acceptability was measured using an 11-item survey (5-point Likert scale). Hypothesis testing was performed at α=.10 (2-tailed) due to the pilot nature and small sample size. Clinicians participated in audio-recorded qualitative interviews at the end of the study to discuss their experience. RESULTS: A total of 8 clinicians completed the confidence measure and 7 clinicians completed the acceptability measure. We found a statistically significant increase in overall confidence (mean increase of 0.5, SD 0.6; P=.03). The largest increase in confidence was in helping families with reconciliation and goodbye (mean 1.4, SD 1.5; P=.04). The majority of clinicians agreed that the format was simple (6/7, 86%) and easy to use (6/7, 86%). Clinicians felt that the telehealth SICP was effective in understanding their patients' values about end-of-life care (7/7, 100%). A total of three qualitative themes emerged: (1) the telehealth SICP deepened relationships and renewed trust; (2) each telehealth SICP visit felt unique and personal in a positive way; and (3) uninterrupted, unrushed time optimized the visit experience. CONCLUSIONS: The telehealth SICP increased confidence in having serious illness conversations while deepening patient-clinician relationships. TRIAL REGISTRATION: ClinicalTrials.gov NCT04745676; https://www.clinicaltrials.gov/study/NCT04745676.

Phase III Randomized, Placebo-Controlled Clinical Trial of Donepezil for Treatment of Cognitive Impairment in Breast Cancer Survivors After Adjuvant Chemotherapy (WF-97116).

PURPOSE: To test efficacy of donepezil, a cognitive enhancer, to improve memory in breast cancer survivors who report cancer-related cognitive impairment 1-5 years postchemotherapy. PATIENTS AND METHODS: Adult female BCS exposed to ≥4 cycles of adjuvant chemotherapy 1-5 years before enrollment who reported cancer-related cognitive impairment were eligible. Participants, enrolled at sites affiliated with the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base, were randomly assigned to receive 5 mg of donepezil once daily for 6 weeks titrated to 10 mg once daily for 18 weeks or placebo. Cognition and self-report cognitive functioning was assessed at baseline, 12, 24 (end of intervention), and 36 (washout) weeks postrandomization. Mixed-effects repeated measures analysis of covariance models were used to assess treatment differences in immediate recall (primary outcome) on the Hopkins Verbal Learning Test-Revised (HVLT-R) and other cognitive domains (secondary outcomes) with covariates of treatment, time, time by treatment interaction, baseline outcome level, age stratification, and an unstructured covariance matrix to account for within participant correlation over time. RESULTS: Two hundred seventy-six BCS from 87 NCORP practices (mean age, 57.1, standard deviation [SD], 10.5) who were at a mean of 29.6 months (SD, 14.2) postchemotherapy were randomly assigned to donepezil (n = 140) or placebo (n = 136). At 24 weeks, treatment groups did not differ on HVLT-R scores (donepezil mean = 25.98, placebo = 26.50, P = .32). There were no statistically significant differences between treatments at 12, 24, or 36 weeks for attention, executive function, verbal fluency, processing speed, or self-reported cognitive functioning. Endocrine therapy and menopausal status did not affect results. CONCLUSION: BCS 1-5 years after completing chemotherapy with documented memory problems, randomly assigned to 24 weeks of 5-10 mg of donepezil once daily, did not perform differently at the end of treatment on tests of memory, other cognitive functions, or subjective functioning than those randomly assigned to placebo.

A scoping review of racial, ethnic, socioeconomic, and geographic disparities in the outcomes of older adults with cancer.

INTRODUCTION: Cancer health disparities are widespread. Nevertheless, the disparities in outcomes among diverse survivors of cancer ages 65 years and older ("older") have not been systematically evaluated. METHODS: We conducted a scoping review of original research articles published between January 2016 and September 2023 and indexed in Medline (Ovid), Embase, Scopus, and CINAHL databases. We included studies evaluating racial, ethnic, socioeconomic disadvantaged, geographic, sexual and gender, and/or persons with disabilities disparities in treatment, survivorship, and mortality among older survivors of cancer. We excluded studies with no a priori aims related to a health disparity, review articles, conference proceedings, meeting abstracts, studies with unclear methodologies, and articles in which the disparity group was examined only as an analytic covariate. Two reviewers independently extracted data following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines. RESULTS: After searching and removing duplicates, 2573 unique citations remained and after screening 59 articles met the inclusion criteria. Many investigated more than one health disparity, and most focused on racial and ethnic (n = 44) or socioeconomic (n = 25) disparities; only 10 studies described geographic disparities, and none evaluated disparities in persons with disabilities or due to sexual and gender identity. Research investigating disparities in outcomes among diverse older survivors of cancer is increasing gradually-68% of eligible articles were published between 2020 and 2023. Most studies focused on the treatment phase of care (n = 28) and mortality (n = 26), with 16 examined disparities in survivorship, symptoms, or quality of life. Most research was descriptive and lacked analyses of potential underlying mechanisms contributing to the reported disparities. CONCLUSION: Little research has evaluated the effect of strategies to reduce health disparities among older patients with cancer. This lack of evidence perpetuates cancer inequities and leaves the cancer care system ill equipped to address the unique needs of the rapidly growing and increasingly diverse older adult cancer population.

Functional decline in older breast cancer survivors treated with and without chemotherapy and non-cancer controls: results from the Hurria Older PatiEnts (HOPE) prospective study.

PURPOSE: This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both. METHODS: We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference). RESULTS: Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001). CONCLUSION: In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS: The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes. CLINICAL TRIAL: NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study.

Strategies to Assess and Manage Frailty among Patients Diagnosed with Primary Malignant Brain Tumors.

OPINION STATEMENT: Frailty refers to a biologic process that results in reduced physiologic and functional reserve. Patients diagnosed with primary malignant brain tumors experience high symptom burden from tumor and tumor-directed treatments that, coupled with previous comorbidities, may contribute to frailty. Within the primary malignant brain tumor population, frailty is known to associate with mortality, higher healthcare utilization, and increased risk of postoperative complications. As such, methods to assess and manage frailty are paramount. However, there is currently no clear consensus on how to best assess and manage frailty throughout the entirety of the disease trajectory. Given the association between frailty and health outcomes, more research is needed to determine best practice protocols for the assessment and management of frailty among patients diagnosed with primary malignant brain tumors.

Exercise and inflammatory cytokine regulation among older adults with myeloid malignancies.

Tumor necrosis factor (TNF)α is a major regulator of inflammation. However, the epigenetic regulation of TNFα in the context of an exercise intervention among older adults with cancer is understudied. In this exploratory analysis, we used data from a single-arm mobile health (mHealth) exercise intervention among older adults with myeloid malignancies to 1) assess changes in TNFα promoter methylation, TNFα mRNA expression, serum TNFα and other related-cytokine levels after intervention; and 2) assess correlations between blood markers and exercise levels. Twenty patients were included. From baseline to post-intervention, there was no statistical changes in TNFα promoter methylation status at seven CpG sites, TNFα mRNA expression, and serum TNFα levels. Effect sizes, however, were moderate to large for several CpG sites (-120, -147, -162, and -164; Cohen's d = 0.44-0.75). Median serum TNFα sR1 levels increased (83.63, IQR 130.58, p = 0.06; Cohen's d = 0.18) but not the other cytokines. Increases in average daily steps were correlated with increases in TNFα promoter methylation at CpG sites -147 (r = 0.48; p = 0.06) and -164 (r = 0.51; p = 0.04). Resistance training minutes were negatively correlated with TNFα promoter methylation at CpG site -120 (r = -0.62; p = 0.02). All effect sizes were moderate to large. In conclusion, after a mHealth exercise intervention, we demonstrated changes with moderate to large effect sizes in several CpG sites in the TNFα promoter region. Exercise levels were correlated with increases in TNFα promoter methylation. Larger exercise trials are needed to better evaluate TNFα regulation to inform interventions to augment TNFα regulation in order to improve outcomes in older adults with cancer.

Cardiovascular health assessment in routine cancer follow-up in community settings: survivor risk awareness and perspectives.

BACKGROUND: Guidelines recommend cardiovascular risk assessment and counseling for cancer survivors. For effective implementation, it is critical to understand survivor cardiovascular health (CVH) profiles and perspectives in community settings. We aimed to (1) Assess survivor CVH profiles, (2) compare self-reported and EHR-based categorization of CVH factors, and (3) describe perceptions regarding addressing CVH during oncology encounters. METHODS: This cross-sectional analysis utilized data from an ongoing NCI Community Oncology Research Program trial of an EHR heart health tool for cancer survivors (WF-1804CD). Survivors presenting for routine care after potentially curative treatment recruited from 8 oncology practices completed a pre-visit survey, including American Heart Association Simple 7 CVH factors (classified as ideal, intermediate, or poor). Medical record abstraction ascertained CVD risk factors and cancer characteristics. Likert-type questions assessed desired discussion during oncology care. RESULTS: Of 502 enrolled survivors (95.6% female; mean time since diagnosis = 4.2 years), most had breast cancer (79.7%). Many survivors had common cardiovascular comorbidities, including high cholesterol (48.3%), hypertension or high BP (47.8%) obesity (33.1%), and diabetes (20.5%); 30.5% of survivors received high cardiotoxicity potential cancer treatment. Less than half had ideal/non-missing levels for physical activity (48.0%), BMI (18.9%), cholesterol (17.9%), blood pressure (14.1%), healthy diet (11.0%), and glucose/ HbA1c (6.0%). While > 50% of survivors had concordant EHR-self-report categorization for smoking, BMI, and blood pressure; cholesterol, glucose, and A1C were unknown by survivors and/or missing in the EHR for most. Most survivors agreed oncology providers should talk about heart health (78.9%). CONCLUSIONS: Tools to promote CVH discussion can fill gaps in CVH knowledge and are likely to be well-received by survivors in community settings. TRIAL REGISTRATION: NCT03935282, Registered 10/01/2020.

Falls prechemotherapy and toxicity-related hospitalization during adjuvant chemotherapy for breast cancer in older women: Results from the prospective multicenter HOPE trial.

BACKGROUND: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer. METHODS: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates. RESULTS: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003). CONCLUSIONS: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.

Treating acute myelogenous leukemia in patients aged 70 and above: Recommendations from the International Society of Geriatric Oncology (SIOG).

Acute myeloid leukemia (AML) treatment is challenging in older patients. There is a lack of evidence-based recommendations for older patients ≥70, a group largely underrepresented in clinical trials. With new treatment options being available in recent years, recommendations are needed for these patients. As such the International Society of Geriatric Oncology (SIOG) assembled a task force to review the evidence specific to treatment and outcomes in this population of patients ≥70 years. Six questions were selected by the expert panel in domains of (1) baseline assessment, (2) frontline therapy, (3) post-remission therapy, (4) treatment for relapse, (5) targeted therapies, and (6) patient reported outcome/function and enhancing treatment tolerance. Information from current literature was extracted, combining evidence from systematic reviews/meta-analyses, decision models, individual trials targeting these patients, and subgroup data. Accordingly, recommendations were generated using a GRADE approach upon reviewing current evidence by consensus of the whole panel. It is our firm recommendation and hope that direct evidence should be generated for patients aged ≥70 as a distinct group in high need of improvement of their survival outcomes. Such studies should integrate information from a geriatric assessment to optimize external validity and outcomes.

Geriatric Assessment in Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogenous disease that affects mostly older adults with varying baseline health and functional status. Treatment options have expanded for older adults, ranging from less intensive chronic therapies to intensive induction strategies with curative intent. Despite this, outcomes remain poor with advancing age due to underlying disease biology and variability in treatment tolerance. Reliance on chronological age alone, however, increases risks of both over- and under-treatment. Strategies to better characterize fitness in the context of therapy are needed to optimize decision-making and enhance clinical trial design. SUMMARY: Geriatric assessment (GA) is a series of validated tools that evaluate multiple health and functional domains of an older adult including physical function, comorbidities, cognition, nutrition, psychological health, and social support. While studies of GA in AML remain limited, current evidence shows that it is feasible to perform GA among older adults starting therapy for AML. GA measures including those assessing physical function, cognition, and mood are associated with mortality and toxicity in both intensive and less intensive treatment settings. KEY MESSAGES: In this review, we discuss the existing evidence to support use of GA in AML and highlight implications for clinical practice and future research.

Determining treatment tolerance and fitness for intensive chemotherapy in older adults with AML: a call to action.

ABSTRACT: Determining fitness for intensive chemotherapy in an older adult with acute myeloid leukemia (AML) is an unanswered age-old question. Geriatric assessment captures any variation in multidimensional health, which can influence treatment tolerance. A prospective study is necessary to validate fitness criteria, determine whether geriatric assessment-based fitness performs superiorly to other criteria, and what components of geriatric assessment are associated with treatment tolerance. A validation study should enroll diverse patients from both academic and community centers and patients receiving intensive and lower-intensity chemotherapy. Geriatric assessment should include at minimum measures of comorbidity burden, cognition, physical function, and emotional health, which in previous smaller studies have shown to be associated with mortality in AML. These assessments should be completed before or within a few days of initiation of chemotherapy to reduce the influence of chemotherapy on the assessment results. Treatment tolerance has been measured by rates of toxicities in patients with solid malignancies; however, during the initial treatment of AML, rates of toxicities are very high regardless of treatment intensity. Early mortality, frequently used in previous studies, can provide a highly consequential and easily identifiable measure of treatment tolerance. The key end point to assess treatment tolerance, thus, should include early mortality. Other end points may include decline in function and quality of life and treatment modifications or cessation due to toxicities. Validating fitness criteria can guide treatment selection and supportive care interventions and are crucial to guide fitness-based trial eligibility, inform the interpretation of trial results, and facilitate drug labeling.

Telehealth serious illness care program for older adults with hematologic malignancies: a single-arm pilot study.

ABSTRACT: Older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) feel shocked and bewildered when diagnosed. Serious illness conversations (SICs) may increase disease understanding and preparations for the future. However, SICs often happen late, in part because of clinician-perceived patient discomfort. Telehealth may promote patient comfort by allowing SICs to take place at home. This study assesses the feasibility and usability of a telehealth-delivered Serious Illness Care Program (SICP) for older adults with AML and MDS. We conducted a single-arm pilot study including 20 older adults with AML and MDS. Feasibility was measured using retention rate, with >80% considered feasible. Usability was measured using telehealth usability questionnaire (TUQ; range, 1-7): >5 considered usable. We collected other outcomes including acceptability and disease understanding and conducted post-visit qualitative interviews to elicit feedback. Hypothesis testing was performed at α = 0.10 owing to the pilot nature and small sample size. Retention rate was 95% (19/20); mean TUQ scores were 5.9 (standard deviation [SD], 0.9) and 5.9 (SD, 1.1) for patients and caregivers, respectively. We found the SICP to be acceptable. The majority of patients found the SICP to be very or extremely worthwhile (88.2%; 15/17), and reported it increased closeness with their clinician (75.0%; 12/16). After their visit, patient estimates of curability, and overall life expectancy aligned more closely with those of their clinicians. In qualitative interviews, most patients said that they would recommend this program to others (89.5%, 17/19). This study demonstrated that delivery of the telehealth SICP to older patients with AML and MDS is feasible, usable, and acceptable. This trial is registered at www.clinicaltrials.gov as #NCT04745676.

The Association Between an Electronic Health Record (EHR)-Embedded Frailty Index and Patient-Reported Outcomes Among Patients with Metastatic Non-Small-Cell Lung Cancer on Immunotherapy: A Brief Report.

Background: While frailty is a well-established predictor of overall mortality among patients with metastatic non-small cell lung cancer (mNSCLC), its association with patient-reported outcomes is not well-characterized. The goal of this study was to examine the association between an electronic frailty index (eFI) score and patient-reported outcome measures along with prognostic awareness among patients with mNSCLC receiving immunotherapy. Methods: In a cross-sectional study, patients with mNSCLC who were on immunotherapy completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) and the National Cancer Institute Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). We utilized bivariate analyses to compare quality of life, symptoms, supportive services, and prognostic awareness among 3 groups defined by e-frailty status. Results: Sixty patients (mean age 62.5 years, 75% Caucasian, 60% women) participated. Most patients were pre-frail (68%), with 13% being frail and 18% non-frail. Pre-frail and frail patients had significantly lower physical function scores (mean 83.9 fit vs 74.8 pre-frail vs 60.0 frail, P = .04) and higher rates of self-reported pain (75% frail vs 41.5% pre-frail vs 18.2% fit; P = .04) compared to non-frail patients. We found no differences in palliative referral rates. Conclusion: Pre-frail and frail mNSCLC patients identified by the eFI have higher rates of pain and physical functional impairments than non-frail patients. These findings highlight the importance of emphasizing preventive interventions targeting social needs, functional limitations, and pain management, especially among pre-frail patients to reduce further decline.

Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update.

PURPOSE: To update the ASCO guideline (2018) on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy. METHODS: An Expert Panel conducted a systematic review to identify relevant randomized clinical trials (RCTs), systematic reviews, and meta-analyses from January 2016 to December 2022. RESULTS: A total of 26 publications met eligibility criteria and form the evidentiary basis for the update. RECOMMENDATIONS: The Expert Panel reiterates its overarching recommendation from the prior guideline that geriatric assessment (GA), including all essential domains, should be used to identify vulnerabilities or impairments that are not routinely captured in oncology assessments for all patients over 65 years old with cancer. Based on recently published RCTs demonstrating significantly improved clinical outcomes, all older adults with cancer (65+ years old) receiving systemic therapy with GA-identified deficits should have GA-guided management (GAM) included in their care plan. GAM includes using GA findings to inform cancer treatment decision-making as well as to address impairments through appropriate interventions, counseling, and/or referrals. A GA should include high priority aging-related domains known to be associated with outcomes in older adults with cancer: physical and cognitive function, emotional health, comorbid conditions, polypharmacy, nutrition, and social support. Clinical adaptation of the GA based on patient population, resources, and time is appropriate.The Panel recommends the Practical Geriatric Assessment as one option for this purpose (https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/practice-patients/documents/2023-PGA-Final.pdf; https://youtu.be/jnaQIjOz2Dw; https://youtu.be/nZXtwaGh0Z0).Additional information is available at www.asco.org/supportive-care-guidelines.

Assessment of an embedded primary care-derived electronic health record (EHR) frailty index (eFI) in older adults with acute myeloid leukemia.

INTRODUCTION: Assessing frailty is integral to treatment decision-making for older adults with acute myeloid leukemia (AML). Prior electronic frailty indices (eFI) derive from an accumulated-deficit model and are associated with mortality in older primary care populations. We evaluated use of an embedded eFI in AML by describing baseline eFI categories by treatment type and exploring associations between eFI categories, survival, and treatment received. MATERIALS AND METHODS: This was a retrospective study of subjects ≥60 years old with new AML treated at an academic medical center from 1/2018-10/2020. The eFI requires ≥2 ambulatory visits over two years and uses demographics, vitals, ICD-10 codes, outpatient labs, and available functional information from Medicare Annual Wellness Visits. Frailty was defined as fit (eFI ≤ 0.10), pre-frail (0.10 < eFI ≤ 0.21), and frail (eFI > 0.21). Chemotherapy was intensive (anthracycline-based) or less-intensive (hypomethylating agent, low dose cytarabine +/- venetoclax). Therapy type, pre-treatment characteristics, and chemotherapy cycles were compared by eFI category using chi-square and Fisher's exact tests and ANOVA. Median survival was compared by eFI category using log-rank tests stratified by therapy type. RESULTS: Among 166 older adults treated for AML (mean age 74 years, 61% male, 85% Caucasian), only 79 (48%) had a calculable eFI score before treatment. Of these, baseline eFI category was associated with treatment received (fit (n = 31): 68% intensive, 32% less intensive; pre-frail (n = 38): 37% intensive, 63% less intensive; frail (n = 10): 0% intensive, 100% less intensive; not calculable (n = 87): 48% intensive, 52% less-intensive; p < 0.01). The prevalence of congestive heart failure and secondary AML differed by frailty status (p < 0.01). Median survival did not differ between eFI categories for intensively (p = 0.48) or less-intensively (p = 0.09) treated patients. For those with less-intensive therapy who lived ≥6 months, eFI category was not associated with the number of chemotherapy cycles received (p = 0.97). The main reason for an incalculable eFI was a lack of outpatient visits in our health system prior to AML diagnosis. DISCUSSION: A primary care-derived eFI was incalculable for half of older adults with AML at an academic medical center. Frailty was associated with chemotherapy intensity but not survival or treatment duration. Next steps include testing adaptations of the eFI to the AML setting.

Patient preferences, regret, and health-related quality of life among older adults with acute myeloid leukemia: A pilot longitudinal study.

INTRODUCTION: Acute myeloid leukemia (AML) is associated with poor outcomes and is generally incurable. Therefore, understanding preferences of older adults with AML is critical. We sought to assess whether best-worst scaling (BWS) can be used to capture attributes considered by older adults with AML when making initial treatment decisions and longitudinally, as well as assess changes in health-related quality of life (HRQoL) and decisional regret over time. MATERIALS AND METHODS: In a longitudinal study for adults ≥60 years with newly diagnosed AML, we collected: (1) attributes of treatment most important to patients using BWS, (2) HRQoL using EQ-5D-5L, (3) decisional regret using the Decisional Regret Scale, and (4) treatment worthiness using the "Was it worth it?" questionnaire. Data was collected at baseline and over six months. A hierarchical Bayes model was used to allocate percentages out of 100%. Due to small sample size, hypothesis testing was performed at α = 0.10 (2-tailed). We analyzed how these measures differed by treatment choice (intensive vs. lower intensity treatment). RESULTS: Mean age of patients was 76 years (n = 15). At baseline, the most important attributes of treatment to patients were response to treatment (i.e., chance that the cancer will respond to treatment; 20.9%). Compared to those who received lower intensity treatment (n = 7) or best supportive care (n = 2), those who received intensive treatment (n = 6) generally ranked "alive one year or more after treatment" (p = 0.03) with higher importance and ranked "daily activities" (p = 0.01) and "location of treatment" (p = 0.01) with less importance. Overall, HRQoL scores were high. Decisional regret was mild overall and lower for patients who chose intensive treatment (p = 0.06). DISCUSSION: We demonstrated that BWS can be used to assess the importance of various treatment attributes considered by older adults with AML when making initial treatment decisions and longitudinally throughout treatment. Attributes of treatment important to older patients with AML differed between treatment groups and changed over time. Interventions are needed to re-assess patient priorities throughout treatment to ensure care aligns with patient preferences.

Exercise and epigenetic ages in older adults with myeloid malignancies.

BACKGROUND: Older adults with myeloid malignancies are susceptible to treatment-related toxicities. Accelerated DNAm age, or the difference between DNA methylation (DNAm) age and chronological age, may be used as a biomarker of biological age to predict individuals at risk. In addition, cancer treatment can also lead to accelerated DNAm age. Exercise is a promising intervention to reduce or prevent functional, psychological, and cognitive impairments in older patients with myeloid malignancies, yet there is little evidence of the effects of exercise on DNAm age. We explored (1) the associations of accelerated DNAm age with physical, psychological, and cognitive functions at baseline; (2) changes in DNAm age from baseline to post-intervention; and (3) the associations of changes in accelerated DNAm age with changes in functions from baseline to post-intervention. METHODS: We enrolled older patients with myeloid malignancies to a single-arm pilot study testing a mobile health (mHealth) exercise intervention that combines an exercise program (EXCAP©®) with a mobile application over 2 cycles of chemotherapy (8-12 weeks). Patients completed measures of physical, psychological, and cognitive functions and provided blood samples for analyses of DNAm age at baseline and post-intervention. Paired t-tests or Wilcoxon signed rank tests assessed changes in DNAm ages, and Spearman's correlation assessed the relationships between accelerated ages and functions. RESULTS: We included 20 patients (mean age: 72 years, range 62-80). Accelerated GrimAge, accelerated PhenoAge, and DunedinPACE were stable from baseline to post-intervention. At baseline, DunedinPACE was correlated with worse grip strength (r = -0.41, p = 0.08). From baseline to post-intervention, decreases in accelerated GrimAge (r = -0.50, p = 0.02), accelerated PhenoAge (r = - 0.39, p = 0.09), and DunedinPace (r = - 0.43, p = 0.06) were correlated with increases in distance walked on 6-min walk test. Decreases in accelerated GrimAge (r = - 0.49, p = 0.03), accelerated PhenoAge (r = - 0.40, p = 0.08), and DunedinPace (r = - 0.41, p = 0.07) were correlated with increases in in grip strength. CONCLUSIONS: Among older adults with myeloid malignancies receiving chemotherapy, GrimAge and PhenoAge on average are stable after a mHealth exercise intervention. Decreases in accelerated GrimAge, accelerated PhenoAge, and DunedinPACE over 8-12 weeks of exercise were correlated with increased physical performance. Future trials assessing the effects of exercise on treatment-related toxicities should evaluate DNAm age. Trial registration Clinicaltrials.gov identifier: NCT04981821.

Endometrial cancer survivors' perceptions of their cardiovascular disease risk (results from WF-1804CD AH-HA).

OBJECTIVE: Despite considerable burden of cardiovascular disease (CVD), data on endometrial cancer survivors' CVD perceptions are lacking. We assessed survivors' perspectives on addressing CVD risk during oncology care. METHODS: This cross-sectional analysis utilized data from an ongoing trial of an EHR heart health tool (R01CA226078 & UG1CA189824) conducted through the NCI Community Oncology Research Program (NCORP, WF-1804CD). Endometrial cancer survivors post-potentially curative treatment were recruited from community practices and completed a pre-visit baseline survey, including American Heart Association Simple 7 CVD factors. Likert-type questions assessed confidence in understanding CVD risk, CVD risk perception, and desired discussion during oncology care. Medical record abstraction ascertained data on CVD and cancer characteristics. RESULTS: Survivors (N = 55, median age = 62; 62% 0-2 years post-diagnosis) were predominately white, non-Hispanic (87%). Most agreed/strongly agreed heart disease poses a risk to their health (87%) and oncology providers should talk to patients about heart health (76%). Few survivors reported smoking (12%) but many had poor/intermediate values for blood pressure (95%), body mass index (93%), fasting glucose/A1c (60%), diet (60%), exercise (47%) and total cholesterol (53%). 16% had not seen a PCP in the last year; these survivors were more likely to report financial hardship (22% vs 0%; p = 0.02). Most reported readiness to take steps to maintain or improve heart health (84%). CONCLUSIONS: Discussions of CVD risk during routine oncology care are likely to be well received by endometrial cancer survivors. Strategies are needed to implement CVD risk assessment guidelines and to enhance communication and referrals with primary care. Clinical Trials #: NCT03935282.