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Background Chemotoxicity risk scores were developed to predict grade 3-5 chemotherapy toxicity in older women with early breast cancer. However, whether these toxicity risk scores are associated with clinically meaningful decline in patient health remains unknown. Methods In a prospective study of women aged 65 years and older with stage I-III breast cancer treated with chemotherapy, we assessed chemotoxicity risk using the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score (categorized as low, intermediate, and high). We measured patient health status before (T1) and after (T2) chemotherapy using a clinical frailty index (Deficit Accumulation Index, categorized as robust, prefrail, and frail). The population of interest was robust women at T1. The primary outcome was decline in health status after chemotherapy, defined as a decline in Deficit Accumulation Index from robust at T1 to prefrail or frail at T2. Multivariable logistic regression was used to examine the association between T1 CARG-BC score and decline in health status, adjusted for sociodemographic and clinical characteristics. Results Of the 348 robust women at T1, 83 (24%) experienced declining health status after chemotherapy, of whom 63% had intermediate or high CARG-BC scores. After adjusting for sociodemographic and clinical characteristics, women with intermediate (odds ratio = 3.14, 95% confidence interval = 1.60 to 6.14, P Conclusions In this cohort of older women with early breast cancer, higher CARG-BC scores before chemotherapy were associated with decline in health status after chemotherapy independent of sociodemographic and clinical risk factors.

Older adults with plasma cell disorders (PCDs) experience cognitive dysfunction that may be attributable to the disease and associated therapies. Yet, this has seldom been reported in the literature. Our objectives were to describe cognitive function (objective and patient-reported) in adults with PCDs and to explore clinical correlates of cognitive impairment.Participants completed a geriatric assessment between March 2018 and February 2020. Cognitive function was evaluated using two objective measures - Montreal Cognitive Assessment (MoCA, cutpoint26) and Blessed Orientation Memory Concentration Test (BOMC, cutpoint4) - and two patient-reported outcome (PRO) measures - Patient-Reported Outcomes Measurement Information System Cognitive Function (PROMIS-CF, cutpoint45) and European Organization for Research and Treatment of Cancer Cognitive Functioning subscale (EORTC-CF, cutpoint75). Spearman correlations examined relationships among these measures and log binomial regression was used to examine characteristics associated with cognitive impairment, as defined by the MoCA and PROMIS-CF measures.Among 86 participants with a mean age of 69 (range: 46-91), the prevalence of cognitive dysfunction was between 20% (BOMC) and 63% (MoCA). There was moderate correlation among objective measures (r = 0.51, p 0.0001), moderate to high correlation among PRO measures (r = 0.69, p 0.0001), but no correlation between objective and PRO measures. Factors associated with objective impairment included ≤ high school education (RR 1.46, p = 0.009), living alone (RR 1.42, p = 0.02), relapsed/refractory disease (RR 1.39, p = 0.04), empirically de-intensified induction therapy (RR 1.62, p = 0.008), frailty (RR 1.49, p = 0.04), and peripheral vascular disease (RR 1.54, p = 0.002). Factors associated with PRO impairment included social isolation (RR 3.43, p = 0.003), depression (RR 3.30, p = 0.004) and anxiety (RR 4.43, p = 0.0002), frailty (RR 3.60, p = 0.02), falls in the previous 6 months (RR 2.53, p = 0.02), and deficits in physical function (RR 4.44, p = 0.01). Older age was not associated with either objective or PRO impairment.Cognitive impairment, using objective and PRO screening measures, was relatively common in adults with PCDs. Cancer-related factors and medical comorbidities were associated with objective cognitive impairment whereas psychosocial and functional factors were associated with PRO impairment.

Previous work from our group and others has shown that patients with breast cancer can generate a T cell response against specific human epidermal growth factor 2 (HER2) epitopes. In addition, preclinical work has shown that this T cell response can be augmented by Ag-directed mAb therapy. This study evaluated the activity and safety of a combination of dendritic cell (DC) vaccination given with mAb and cytotoxic therapy. We performed a phase I/II study using autologous DCs pulsed with two different HER2 peptides given with trastuzumab and vinorelbine to a study cohort of patients with HER2-overexpressing and a second with HER2 nonoverexpressing metastatic breast cancer. Seventeen patients with HER2-overexpressing and seven with nonoverexpressing disease were treated. Treatment was well tolerated, with one patient removed from therapy because of toxicity and no deaths. Forty-six percent of patients had stable disease after therapy, with 4% achieving a partial response and no complete responses. Immune responses were generated in the majority of patients but did not correlate with clinical response. However, in one patient, who has survived >14 y since treatment in the trial, a robust immune response was demonstrated, with 25% of her T cells specific to one of the peptides in the vaccine at the peak of her response. These data suggest that autologous DC vaccination when given with anti-HER2–directed mAb therapy and vinorelbine is safe and can induce immune responses, including significant T cell clonal expansion, in a subset of patients.

PURPOSE Research studies have demonstrated that comprehensive geriatric assessment (CGA) improves outcomes in older adults with cancer treated with chemotherapy. We compared survival outcomes on older adults with advanced cancer before and after the initiation of a geriatric oncology service (GOS) in a single Japanese cancer center. METHODS This was a comparative study of two groups of consecutive patients 70 years and older with advanced cancer who were referred to medical oncology for first-line chemotherapy before (controls; n = 151, September 2015-August 2018) and after (GOS; n = 191, September 2018-March 2021) implementation of the GOS. When the treating physician requested a consultation from the GOS, a geriatrician and an oncologist performed CGA and provided recommendations for cancer treatment and geriatric interventions. Time to treatment failure (TTF) and overall survival (OS) were compared between the two groups. RESULTS The median age for all patients was 75 (range, 70-95) years, and 85% had GI cancers. In the GOS group, 82 patients received the CGA before a treatment decision and oncologic treatment plans were changed in 49 patients (60%). The overall implementation rate of the CGA-based geriatric interventions was 45%. Two hundred and eighty-two patients received chemotherapy (controls; n = 128 and GOS; n = 154), and 60 patients were treated with best supportive care only (controls; n = 23 and GOS; n = 37). Among patients receiving chemotherapy, TTF event rates for the GOS group compared with the control group were 5.7% versus 14% at 30 days ( P = .02) and 13% versus 29% at 60 days ( P = .001). The GOS group had longer OS than the control group with a hazard ratio of 0.64 (95% CI, 0.44 to 0.93; P = .02). CONCLUSION In this study, older adults with advanced cancer managed after the implementation of a GOS had improved survival outcomes compared with a historical control of patients.

Exercise has been shown to reduce fatigue in early breast cancer survivors (EBCS), though it is unclear if these results translate to community-based exercise settings. Mechanisms that influence changes in fatigue seen after exercise are also poorly understood. This study sought to evaluate the impact of community-based exercise and identify associations of fatigue in EBCS.Twenty-nine EBCS and 13 non-cancer controls (CON) enrolled. Pre/post-intervention measurements included measures of fitness/function, balance, and adherence/compliance as well as self-reported measures of fatigue, health-related quality of life (HRQOL), well-being, self-efficacy, and physical activity. Both groups participated in a supervised 16-week aerobic + resistance exercise intervention. A mixed model ANOVA and Cohen's D effect size assessed fatigue changes, and univariable linear regressions identified fatigue associations.Fatigue improved for EBCS (- 2.6, Cohen's D = 0.51) but not CON (0.0, Cohen's D = 0.02); no interaction effect was observed. Post-intervention fatigue in EBCS was associated with better QOL (RCommunity-based exercise appears beneficial for alleviating fatigue in EBCS. These improvements may be driven by parallel improvements in psychosocial outcomes and objectively measured functional outcomes.

OBJECTIVES: Findings from a brief geriatric assessment (GA) in a cohort of adults with multiple myeloma (MM) are presented, with particular attention to the utility of the GA in identifying important deficits in adults judged to have a normal Karnofsky Performance Status (KPS ≥ 80). MATERIALS AND METHODS: Adults age 18 and older with MM were recruited into an observational study from 2018 to 2020. A modified Cancer and Aging Research Group (CARG) GA was administered at enrollment. Enrollees also completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients Core 30 questionnaire (QLQ-C30), with subscales of physical, social, role, and cognitive functioning (range 0-100; higher values indicate better function). Data were analyzed using descriptive statistics for the full cohort and stratified by concurrent KPS (score < 80 vs ≥ 80). RESULTS: Among 89 adults, the mean age was 69.1 years, 68% were aged ≥ 65 years, and 70% were white. In this cohort, 78% had KPS ≥ 80. Among those with KPS ≥ 80, functional impairments (Timed Up and Go ≥ 14 seconds and dependence in ≥ 1 instrumental activity of daily living) were seen in 30% and 21%, respectively, with 11% reporting ≥ 1 fall in the prior 6 months. At least two GA-identified deficits were detected in 50% of the overall cohort and in 41% of those with KPS ≥ 80. Among those with KPS ≥ 80, self-reported physical impairment on EORTC QLQ-C30 was noted by 34%. CONCLUSION: Using a modified CARG GA and EORTC questionnaire, functional impairments were identified among adults considered to have a good performance status based on a KPS (≥ 80). Future studies should focus on using GA measures for therapy assignment and identifying opportunities for intervening upon GA-identified deficits.

Little is known regarding the predictive value of the Cancer and Aging Research Group (CARG) score, a validated chemotherapy toxicity prediction tool for older adults with cancer, for survival outcomes.This was a prospective observational study of patients ≥65 years old receiving first-line chemotherapy for advanced noncolorectal gastrointestinal cancer for which combination chemotherapy is the standard of care. Overall survival (OS), time to treatment failure (TTF), which was defined as the time from the start of first-line chemotherapy to the discontinuation of first-line chemotherapy for any reason, and toxicity were compared in 4 groups of patients: 1) non-high-risk (nHR) CARG score (10) and standard-intensity therapy (ST), 2) nHR score and reduced-intensity therapy (RT), 3) high-risk (HR) CARG score (≥10) and ST, and 4) HR score and RT.Fifty patients (median age, 71 years) were enrolled. The median OS in months was 19.7 in nHR/ST (n = 19) group, 12.7 in nHR/RT (n = 9) group, 4.5 in HR/ST (n = 12) group, and 3.9 in HR/RT (n = 10) group (log-rank test, P = .005). The median TTF in months was 9.1 in nHR/ST group, 2.5 in nHR/RT group, 2.3 in HR/ST group, and 3.0 in HR/RT group (log-rank test, P = .04). The CARG-score category was prognostic of OS (HR, 3.04; 95% confidence interval [CI], 1.59-5.83, P = .001) and TTF (HR, 2.60; 95% CI, 1.31-5.20, P = .007). The incidence of grade 3-5 toxicity was 68% in nHR/ST group, 33% in nHR/RT group, 92% in HR/ST group, and 70% in HR/RT group (Fisher exact test, P = .048).Risk-adapted chemotherapy based on the CARG-score may improve treatment outcomes.

BACKGROUND: Older adults are under-represented in cancer clinical trials. However, it remains unclear which types of trials under-enroll aging patients. We aimed to identify associations between trial characteristics and disparate enrollment of older adults onto trials sponsored by the Alliance for Clinical Trials in Oncology (Alliance). METHODS: Actual age ≥ 65 percentage and trial data were extracted from the Alliance closed study list. Each trial, based on its cancer type and years of enrollment, was assigned an expected age ≥ 65 percentage extracted from the Surveillance, Epidemiology, and End Results (SEER) US population-based database. Enrollment disparity difference (EDD), the difference between the expected age ≥ 65 percentage and the actual age ≥ 65 percentage, was calculated for each trial. Linear regression determined trial variables associated with larger EDDs and variables with an overall association p-value < 0.20 were included in a multivariable fixed-effects linear model. RESULTS: The median age of 66,708 patients across 237 trials was 60 years (range 18-102). The average actual age ≥ 65 percentage enrolled per trial was lower than each trial’s expected age ≥ 65 percentage average (39% vs. 58%; EDD 19, 95% CI 17.1-21.3%, p

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Purpose: Poor body composition metrics (BCM) are associated with inferior cancer outcomes; however, in early breast cancer (EBC), there is a paucity of evidence regarding the impact of BCM on toxicities. This study investigates associations between BCM and treatment-related toxicity in patients with EBC receiving anthracyclines and taxane–based chemotherapy.Experimental Design: Pretreatment computerized tomographic (CT) images were evaluated for skeletal muscle area (SMA), skeletal muscle density (SMD), and fat tissue at the third lumbar vertebrae. Skeletal muscle index (SMI = SMA/height2) and skeletal muscle gauge (SMG = SMI × SMD) were also calculated. Relative risks (RR) are reported for associations between body composition measures and toxicity outcomes, after adjustment for age and body surface area (BSA).Results: BCM were calculated for 151 patients with EBC (median age, 49 years; range, 23–75 years). Fifty patients (33%) developed grade 3/4 toxicity, which was significantly higher in those with low SMI (RR, 1.29; P = 0.002), low SMG (RR, 1.09; P = 0.01), and low lean body mass (RR, 1.48; P = 0.002). Receiver operating characteristic analysis showed the SMG measure to be the best predictor of grade 3/4 toxicity. Dividing SMG into tertiles showed toxicity rates of 46% and 22% for lowest versus highest tertile, respectively (P = 0.005). After adjusting for age and BSA, low SMG (P = 0.02), gastrointestinal grade 3/4 toxicities (RR, 6.49; P = 0.02), and hospitalizations (RR, 1.91; P = 0.05).Conclusions: Poor BCMs are significantly associated with increased treatment-related toxicities. Further studies are needed to investigate how these metrics can be used to more precisely dose chemotherapy to reduce treatment-related toxicity while maintaining efficacy. Clin Cancer Res; 23(14); 3537–43. ©2017 AACR.

Purpose: Severe skeletal muscle (SM) loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased toxicity. This study investigates SM measures in metastatic breast cancer (MBC) patients receiving first-line taxane-based chemotherapy and evaluates associations with treatment toxicity and other outcomes.Experimental Design: Using computerized tomography (CT) images taken for the evaluation of disease burden, skeletal muscle area (SMA), and density (SMD) were measured at the third lumbar vertebrae. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) ≤ 41. Skeletal muscle gauge (SMG) was created by multiplying SMI × SMD. Fisher exact tests, t tests, the Kaplan–Meier method, and Cox regression modeling were used.Results: MBC patients (N = 40), median age 55 (range, 34–80), 58% sarcopenic, median SMG 1296 AU (SD, 522). Grade 3–4 toxicity was found in 57% of sarcopenic versus 18% of non-sarcopenic patients (P = 0.02). Toxicity-related hospitalizations were also higher in sarcopenic patients (39% vs. 0%, P = 0.005) as were any adverse events—defined as any grade 3–4 toxicities, hospitalizations, dose reductions, or dose delay—(74% vs. 35%, P = 0.02). Low SMG was associated with grade 3–4 toxicity (P = 0.04), hospitalization (P = 0.01), and time to treatment failure (for progression or toxicity; P = 0.03). Low SMG had a borderline significant association with any adverse event (P = 0.06) and overall survival (P = 0.07).Conclusions: SM measures are associated with toxicity outcomes and survival in MBC patients receiving first-line taxane-based chemotherapy. Further studies are needed to explore how routinely obtained CT scans can be used to individualize dosing and improve treatment planning. Clin Cancer Res; 23(3); 658–65. ©2016 AACR.

PURPOSE This study determined whether an electronic version of the geriatric assessment is feasible in a multi-institutional, diverse setting. METHODs Ten sites within the Alliance for Clinical Trials in Oncology participated. Patients who had active cancer or a history of cancer and were 65 years of age or older were eligible. The geriatric assessment was completed with an electronic data capture system that had been loaded onto iPads. Feasibility was defined a priori as completion in at least 70% of patients either with or without help. To enhance racial diversity, the original sample size was later changed and augmented by 50% with the intention of increasing enrollment of older minority patients. RESULTS A total of one hundred fifty-four patients were registered with a median age of 72 years (range, 65-91 years). Forty-three (28%) identified themselves as African American or Black. One hundred forty-one patients (92%) completed the electronic geriatric assessment. Feasibility was observed across all subgroups, regardless of race, education, performance status, comorbidities, and cognition; 124 patients (81%) completed the geriatric assessment without help. Reasons for not completing the geriatric assessment are as follows: clinic visit did not occur (n = 6), no iPad connection to the Internet (n = 3), patient declined (n = 2), prolonged hospitalization (n = 1), and patient died (n = 1). Reasons for needing help, as reported by study personnel, were as follows: the patient preferred that research personnel ask the questions (n = 9), vision problem (n = 3), lack of comfort with the iPad (n = 2), questions were not clear (n = 1), less proficient in English (n = 1), and challenge in pressing the green button to go to the next question (n = 1). CONCLUSION The electronic geriatric assessment is feasible in a multi-institutional setting that includes a notable proportion of African American or Black patients.

PURPOSE: Residents of communities facing social vulnerability (eg, poverty) have limited access to clinical trials, leaving them susceptible to experiencing poor health outcomes. We examined the association between North Carolina county-level social vulnerability and available multiple myeloma (MM) trials. METHODS: Using a novel data linkage between ClinicalTrials.gov, the 2019 American Community Survey, and the Centers for Disease Control and Prevention's Social Vulnerability Index, we investigated at the county level (1) availability of MM trial sites and (2) the relationship between Social Vulnerability Index and MM trial site availability using logistic regression. RESULTS: Between 2002 and 2021, 229 trials were registered across 462 nonunique trial sites in 34 counties. Nearly 50% of trial sites were in academic medical centers, 80% (n = 372) of all trials were industry-sponsored, 60% (n = 274) were early-phase, and 50% (n = 232) were for patients with relapsed or refractory MM. Counties with low as opposed to high poverty rates had six times greater odds of having ≥ 1 MM trial sites (odds ratio [OR], 5.60; 95% CI, 1.85 to 19.64; P = .004). Counties with the lowest percentage of Black Indigenous Persons of Color and non-native English speakers had 77% lower odds (OR, 0.23; 95% CI, 0.07 to 0.69; P = .011) of having ≥ 1 trial sites. The effect remained significant after accounting for the presence of five academic medical centers (n = 95; OR, 0.18; 95% CI, 0.05 to 0.6; P = .008) and adjustment for metropolitan, suburban, or rural status (OR, 0.25; 95% CI, 0.07 to 0.81; P = .025). CONCLUSION: Counties with the lowest poverty rates had more MM trial sites, whereas those with the lowest percentage of Black Indigenous Persons of Color populations had fewer MM trial sites. Multilevel efforts are needed to improve the availability and access to trials for socially vulnerable populations.

Current guidelines recommend a comprehensive geriatric assessment (CGA) for the management of older adults with cancer. We evaluated the effect of CGA conducted by a geriatric oncology service (GOS) on the management of older adults with cancer. We also queried patients about their perceptions of the value of this process.This was a prospective quality assessment study of 498 consecutive older adults with cancer who were referred to the GOS from May 2020 through December 2021. Treating physicians requested a consultation and the GOS conducted a CGA and assessed patient preferences. The GOS provided recommendations on cancer treatment and geriatric interventions. Patient perspectives on the consultation were evaluated using collaboRATE and modified Patient Assessment of Care for Chronic Conditions (PACIC) subscales.A 10-item frailty index based on a CGA (FI-CGA-10) [Oncologist, 26, e1751 (2021)] in the 498 patients showed that 19% of patients were fit, 40% pre-frail, and 41% frail. Prior to CGA the intent of the proposed cancer treatment was curative in 56% (n = 280), life-extending in 40% (n = 201), and palliative in 3.4% (n = 17). After a CGA consultation, a cancer treatment decision was changed in 45% of patients. The intent of treatment after the CGA consultation was curative in 45%, life-extending in 34%, and palliative in 21%. At least one referral to relevant disciplines was recommended for 88% of patients and was implemented in 43%. As part of the GOS consultation educational support was provided to 97% of patients. Based on the collaboRATE and PACIC tools, patients perceived the GOS consultation positively and helpful for facilitating shared decision-making and patient-centered care.Our institutional experience demonstrated the valuable effect of the CGA consultation on oncologic decision-making and geriatric interventions in a patient-centered manner.

As part of ongoing efforts to meaningfully improve recruitment, enrollment, and accrual of older adults into cancer clinical trials, the National Cancer Institute (NCI) sponsored a workshop with experts across the country entitled Engaging Older Adults in the NCI Clinical Trials Network: Challenges and Opportunities. Three working groups, including Study Design, Infrastructure, and Stakeholders, were formed, who worked together to offer synergistic improvements in the system. Here, we summarize the workshop discussions of the Infrastructure Working Group, whose goal was to address infrastructural challenges, identify underlying resources, and offer solutions to facilitate accrual of older adults into cancer clinical trials. Based on preconference work and workshop discussions, four key recommendations to strengthen NCI infrastructure were proposed: 1) further centralize resources and expertise; 2) provide training for clinical research staff; (3) develop common data elements; and 4) evaluate what works and does not work. These recommendations provide a strategy to improve the infrastructure to enroll more older adults in cancer clinical trials.

Background: This study investigates whether high body mass index (BMI) in women diagnosed with early breast cancer (BC) is associated with patient-reported symptom severity during chemotherapy.Methods: Women with Stage I-III BC completed toxicity reports for 17 side effects during regularly scheduled chemotherapy infusions. Toxicity reports were compared in women with obesity (BMI >=30) versus no obesity (BMI Results: In a sample of 286 patients, Black women comprised 23% of the sample. The obesity rate was 76% among Black patients and 31% among White patients (pConclusions: Among women with early BC, patients with obesity reported higher chemotherapy toxicity as compared to patients without obesity; however, this did not result in differences in treatment completion.

BACKGROUND: Newer adjuvant treatment options for non-metastatic breast cancer have increased survival. There is a need to investigate whether demographic and clinical characteristics of women with hormone receptor-positive, human epidermal growth receptor 2-negative non-metastatic breast cancer (stages I-III) differentially influence treatment decisions in older (age 65 or older) versus younger patients (under age 65). METHODS: In a retrospective electronic medical record review, prevalence ratio with 95% confidence interval for treatment decisions in older vs younger patients was calculated using log binomial regression adjusted for race, stage, and total number of comorbidities. RESULTS: In a sample of 537 patients, 66% were age < 65 and 34% age ≥ 65. Older patients included a higher proportion of White women (85% vs 75%, P = .02), higher number of comorbidities (P ≤0.0001), and lower stage tumors (P = .0004). In multivariable analysis, age ≥ 65 was independently associated with fewer mastectomies (95% CI 0.65–0.96, P = .02), more lumpectomies (95% CI 1.05–1.42, P = .01), and less receipt of radiation treatment (95% CI 0.78–0.97, P = .01) and/or chemotherapy (95% CI 0.73–0.95, P = .006). In multivariate analysis, stage was independently significant for all treatment modalities, except endocrine therapy, and race was not. CONCLUSIONS: This study suggests that age, in addition to breast cancer stage, is a predictor of treatment modality, independent of race and number of comorbidities. Treatment modality reflects a combination of patient preference and clinician assessment of fitness for current standard of care.

Young adult cancer survivors experience frailty and decreased muscle mass at rates equivalent to much older noncancer populations, which indicate accelerated aging. Although frailty and low muscle mass can be identified in survivors, their implications for health-related quality of life are not well understood.Through a cross-sectional analysis of young adult cancer survivors, frailty was assessed with the Fried frailty phenotype and skeletal muscle mass in relation to functional and quality of life outcomes measured by the Medical Outcomes Survey Short-Form 36 (SF-36). z tests compared survivors with US population means, and multivariable linear regression models estimated mean SF-36 scores by frailty and muscle mass with adjustments made for comorbidities, sex, and time from treatment.Sixty survivors (median age, 21 years; range, 18-29) participated in the study. Twenty-five (42%) had low muscle mass, and 25 were either frail or prefrail. Compared with US population means, survivors reported worse health and functional impairments across SF-36 domains that were more common among survivors with (pre)frailty or low muscle mass. In multivariable linear modeling, (pre)frail survivors (vs nonfrail) exhibited lower mean scores for general health (-9.1; P = .05), physical function (-14.9; P .01), and overall physical health (-5.6; P = .02) independent of comorbid conditions.Measures of frailty and skeletal muscle mass identify subgroups of young adult cancer survivors with significantly impaired health, functional status, and quality of life independent of medical comorbidities. Identifying survivors with frailty or low muscle mass may provide opportunities for interventions to prevent functional and health declines or to reverse this process.Young adult cancer survivors age more quickly than peers without cancer, which is evidenced by a syndrome of decreased resilience known as frailty. The relationship between frailty (and one of its common components, decreased muscle mass) and quality of life among young adult cancer survivors was examined. Measuring decreased muscle mass and frailty identifies young survivors with poor quality of life, including worse general health, fatigue, physical function, and overall physical health, compared with nonfrail survivors. Interventions to address components of frailty (low muscle mass and weakness) may improve function and quality of life among young adult cancer survivors.

Background In this study, we explore recruitment, retention, and potential quality of life (QoL) and function benefits from a self-directed, home-based walking intervention in women during active treatment for metastatic breast cancer (MBC). Methods In this single-arm pilot study, women with stage IV BC wore an activity tracker (FitbitTM) to measure steps per week throughout the intervention study. Participants were asked to walk 150 min per week at a comfortable and safe pace. Patient-reported outcome measures (PRO) were collected at baseline and follow-up. Results Target recruitment of 60 patients was achieved. In 52 patients who completed all baseline measures, mean age was 55 (SD 11.1), 23% were pre-menopausal, and 19% non-White. Forty patients (77%) were retained at 3 months and 29 (56%) at 6 months. Baseline walking was the strongest predictor of retention at 3 months (P = .02). For 24 patients (46%) with analyzable Fitbit data at 3 months, mean steps/week rose from 19,175 to 31,306. Higher number of steps correlated with larger improvements FACT-G General well-being (FACT-G, rho = 0.55, P = .01), FACT-G Physical well-being (rho = 0.48, P = .03), and PROMIS Mental Health (rho = 0.55, P = .01). Conclusion Recruitment into a walking intervention is feasible (a priory target of N = 60) in women during treatment for MBC, but retention at 3 months follow-up fell short (77% versus a priori 80%), yet there were potential benefits in general and physical well-being and mental health. ClinicalTrials.gov Identifier NCT02682836.

Association between the CARG-BC score and clinical decline after adjuvant chemotherapy in fit older adults with breast cancer: Results from the Hurria Older PatiEnts (HOPE) Prospective Study Background: We previously developed and validated a risk prediction model for grade 3-5 chemotherapy toxicity in patients age ≥65 with early breast cancer, known as the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score. The CARG-BC score is calculated by combining eight clinical variables that classify patients as low, intermediate, and high risk for grade 3-5 chemotherapy toxicity. However, whether this score can also identify individuals most likely to experience a clinical decline after chemotherapy remains unknown. Here, we evaluated the association between the CARG-BC score and decline in health status. Methods: This is a pre-specified secondary analysis of the Hurria Older PatiEnts (HOPE) with Breast Cancer Study (NCT01472094). This multicenter, prospective cohort study gathered biological and clinical data from women ≥65 with stage I-III breast cancer scheduled to receive neo/adjuvant chemotherapy. Health status was measured pre- (≤14 days) and post-chemotherapy (≤30 days) using a Deficit Accumulation Index (DAI), derived from geriatric assessment data (Cohen et al Cancer 2017). The DAI categorized patients as robust (0.0< 0.2), prefrail (0.2< 0.35), or frail (≥0.35). Baseline clinical characteristics, blood biomarkers of inflammation (interleukin-6 [IL-6] and C-reactive protein [CRP]), and CARG-BC scores (classified as low [0-5], intermediate [6-11] or high [≥12]) were collected pre-chemotherapy. The population of interest was older women who were clinically fit (defined as robust per the DAI) pre-chemotherapy. The primary outcome was chemotherapy-induced decline in health status, a dichotomized (yes/no) variable defined as a decline in DAI from robust pre-chemotherapy to pre-frail or frail post-chemotherapy. Multivariable logistic regression was used to examine the association between baseline CARG-BC score and chemotherapy-induced decline in health status. Results: Of 392 women included in this analysis, 316 (80.6%) were clinically fit based on DAI assessment pre-chemotherapy. The median age was 70 (range 65-86), 61.7% had stage II or III disease, 31% had HR+/HER2+ disease, 22% had HR-/HER2- disease, 36% received an anthracycline, and 74% received prophylactic WBC growth factors. At baseline, 38.7% had low, 53.4% had intermediate, and 7.9% had high CARG-BC scores. Among the 316 clinically fit patients, 80 (25.3%) experienced a decline in health status at the end of chemotherapy. In univariate analysis, we observed that patients with high IL-6 (odds ratio [OR]=2.24, 95% CI: 1.32-3.79, p=0.003), high CRP (OR=1.84, 95%: CI 1.10-3.09, p=0.02), and intermediate (OR=3.29, 95% CI 1.72-6.29, p< 0.001) or high (OR=6.29, 95% CI 2.36-16.71, p< 0.001) CARG-BC scores were more likely to experience chemotherapy-induced decline in health status. After adjusting for IL-6 and CRP, patients with both intermediate (OR=3.25, 95% CI 1.68-6.27, p< 0.001) and high (OR=5.17, 95% CI 1.90-14.02, p=0.001) CARG-BC scores had significantly higher odds of experiencing chemotherapy-induced clinical decline as compared to patients with low CARG-BC scores. Conclusions: In this cohort of older women with early breast cancer who were clinically fit pre-chemotherapy, 25% experienced a decline in health status after neo/adjuvant chemotherapy. Women with an intermediate/high CARG-BC score prior to chemotherapy had 3-5-fold increased odds of experiencing chemotherapy-induced decline in health status independent of baseline clinical characteristics and biomarkers of inflammation. These findings may be useful to clinicians for predicting individual probability of chemotherapy-induced clinical decline and informing treatment decisions in older adults with early breast cancer. Table 1. Univariate and multivariable association of the CARG-BC score with chemotherapy-induced decline in health status. Multivariable analysis adjusted for baseline demographic, clinical, and inflammatory levels (IL-6 and CRP); *CARG-BC score is calculated using 8 independent predictors (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). The total CARG-BC risk score is the sum of each point derived from these 8 predictors. Each patient’s total CARG-BC score can then be classified into three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). Citation Format: Jingran Ji, Canlan Sun, Hyman B. Muss, Harvey J. Cohen, Mina S. Sedrak. PD6-01 Association between the CARG-BC score and clinical decline after adjuvant chemotherapy in fit older adults with breast cancer: Results from the Hurria Older PatiEnts (HOPE) Prospective Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD6-01.

Background: Previous studies have demonstrated poorer survival of Black women with breast cancer. We assessed whether race/ethnicity was associated with disease-free (DFS) and overall survival (OS) among women with breast cancer enrolled in clinical trials for early-stage breast cancer according to tumor subtype, age, and body mass index (BMI). Methods: 10,011 women enrolled in one of four adjuvant chemotherapy trials: CALGB 9741, CALGB 49907, CALGB 40101, or NCCTG N9831. 9918 participants had available DFS and/or OS data and were included in the analysis. Cox models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between race/ethnicity and DFS and OS. We compared Non-Hispanic (NH) Black (n=871), Hispanic (n=436), and other race participants (n=283) to NH Whites (n=7889). We assessed associations within strata of age group ( Results: In multivariable-adjusted models, NH Black patients under 50 years of age had worse DFS compared to NH White patients (HR: 1.34, 95% CI: 1.10-1.62) and worse OS (HR: 1.64, 95% CI: 1.30-2.07). The differences in DFS and OS persisted in patients ages 50 to Conclusions: Our results identified subgroups that may contribute to the observed disparities in survival between NH Black and NH White women with early-stage breast cancer. The greatest disparities are among individuals Support: U10CA180821 and U10CA180882; ClinicalTrials.gov Identifiers: NCT00003088, NCT00005970, NCT00024102, NCT00041119; https://acknowledgments.alliancefound.org Citation Format: Marla Lipsyc-Sharf, Karla V. Ballman, Jordan D. Campbell, Hyman B. Muss, Edith A. Perez, Lawrence N. Shulman, Lisa A. Carey, Ann H. Partridge, Erica T. Warner. Role of age, BMI, and tumor subtype in racial/ethnic disparities in breast cancer survival: A pooled analysis of four Alliance adjuvant clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 494.

TPS3640 Background: CRC is the 2nd most common cause of cancer death in the US, and nearly 60% of CRC cases occur among older adults. There is a critical unmet need to understand the underlying cause(s) of observed variability in chemotherapy toxicity (chemotoxicity) outcomes to minimize adverse outcomes and appropriately personalize therapy for older adults. Low muscle mass, known as myopenia, is prevalent in older adults with CRC (̃60%) and is associated with chemotoxicity and decreased overall survival (OS). However, little is known about trajectories of myopenia and underlying mechanisms of increased toxicities and decreased survival in myopenic patients. We address these gaps in a prospective cohort study, with the central goal of examining the role of myopenia in chemotoxicity in older adults with metastatic CRC undergoing 5-Fluouracil (5FU) based chemotherapy, and to explore the mediating influence of germline genetic variants and pharmacokinetics (PKs) in the association between myopenia and chemotherapy toxicity. Methods: This prospective cohort study is accruing through the Wake Forest NCI Community Oncology Research Program Research Base (WF NCORP) and funded by the NCI grants 2UG1CA189824 and K08CA234225. The study examines the impact of myopenia on chemotoxicity and OS in older adults with newly diagnosed metastatic CRC planning to receive systemic 5FU-based chemotherapy (either as monotherapy or in combination with oxaliplatin and/or irinotecan +/- biologics) (NCT03998202). All patients undergo the Cancer & Aging Resilience Evaluation and Life-Space Evaluation at baseline, 3 and 6 months. Standard of care Computed Tomography (CT) images will be obtained to assess muscle measures (skeletal muscle area/density) at the L3 cross-section. The primary outcome is grades 3 to 5 chemotoxicity measured up to 6 months after initiation of chemotherapy using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. We will assess the association of baseline myopenia and trajectories of myopenia with severe chemotherapy toxicities. Secondary outcome measures include OS at 1 year and chemotoxicities using the Patient Reported Outcomes (PRO) version of the CTCAE. The study also explores the mediating/moderating influence of genetic variation and altered PKs (n = 60) in the association between myopenia and chemotherapy toxicity. To date, the study has accrued 73 of the 300 targeted patients from 110 NCORP practices. Clinical trial information: NCT03998202.

12109 Background: Up to 75% of patients with breast cancer report cognitive decline following chemotherapy. There is no standard of care prevention or treatment of cognitive problems in these patients. This trial (NCT04033419) examines the feasibility of using memantine to prevent cognitive decline during chemotherapy for breast cancer. Methods: We enrolled patients with stage I-III breast cancer scheduled to receive neo/adjuvant chemotherapy. Participants completed a cognitive battery (4 traditional neuropsychological measures and 3 computerized tests) and surveys of self-reported cognition (PROMIS Cognitive Function Short Form 8a) and other neuropsychiatric symptoms at pre-treatment (baseline) and 4 weeks after the last cycle of chemotherapy (post-assessment). Memantine (10 mg BID) was initiated within 1 week of starting chemotherapy and continued until the post-assessment. Adherence and adverse event (AE) monitoring occurred every 2-3 weeks during chemotherapy infusion visits. We used descriptive statistics to evaluate recruitment, retention, and tolerability, adherence, and acceptability of memantine. To evaluate objective cognition, we standardized individual measures using population-based data and averaged them to calculate composite scores of 1) global cognition; 2) attention, working memory, and executive function; and 3) learning and memory. Improvement or decline was defined as ≥ 0.5 SD change between the two assessments. For self-reported cognition, established cutpoints were used to define clinically meaningful change. Results: Of 154 eligible patients approached, 56 (36%) enrolled. Of 51 who completed the baseline assessment and started memantine, 44 (86%) completed the post-assessment; 2 remain active. Among evaluable participants, 92% reported taking ≥ 90% of scheduled doses. Only 36% self-reported cognitive decline, while no change was reported in 57% and improvement in 7%. Decline in objective cognitive domains was observed in 7 - 14% (see Table). There were 7 ≥ grade 3 AEs 2 were possibly related to memantine (diarrhea and hypokalemia). Only 3 participants expressed worry about memantine and only 2 felt that taking memantine disrupted their lives. Conclusions: Our findings suggest that memantine is a safe and feasible intervention for chemotherapy-related cognitive decline and may ameliorate cognitive loss. Randomized controlled trials are needed to determine its preliminary efficacy. Clinical trial information: NCT04033419. [Table: see text]

12042 Background: Although breast cancer and breast cancer chemotherapy (chemo) have been linked to accelerated functional decline, it is not well understood whether this decline is driven by cancer itself or the combination of cancer and chemo. Here, we compared the change in functional status over time in older breast cancer survivors treated with and without chemo and age-matched women without cancer. Methods: Women age ≥65 with non-metastatic breast cancer (n = 538; 441 treated with chemo and 97 without chemo) and n = 100 non-cancer controls were prospectively evaluated at two timepoints: ≤14 days pre-chemo (baseline) and ≤30 days post-chemo (or matched times for non-chemo and non-cancer controls). At each timepoint, functional status was measured using instrumental Activities of Daily Living (iADL) scores. The primary endpoint was the proportion of patients with a decline in functional status (Yes/No, yes defined as ≥2-point decrease [minimal meaningful difference] in iADL scores between timepoints). Baseline demographic, functional, and clinical characteristics were compared between survivors treated with and without chemo and non-cancer controls using t and chi-squared tests. Among the 441 women treated with chemo, univariate and multivariable logistic regression analyses were performed to determine baseline risk factors associated with chemo-induced functional decline. Results: 10% of older survivors treated with chemo experienced a clinically meaningful decline in function as compared to 3% in the non-chemo and 4% in non-cancer control groups (p = 0.017). Across the 3 groups, there were no differences in median age, race/ethnicity, education, number of comorbidities, or baseline functional status (iADL, ADL, Timed Up and Go [TUG]). Among the 441 older survivors treated with chemo, greater age, higher BMI, more comorbidity, lower ADL score, and longer TUG were significantly associated with functional decline univariately. After multivariable analyses, age ≥78 (26% declined, odds ratio [OR] = 3.67, 95% CI 1.60-8.43) and BMI > 30 (16% declined, OR = 2.11, 95% CI 1.02-4.38) remained significantly associated with functional decline. Patients who were both ≥78 years old and obese (BMI > 30) had the highest odds of developing functional decline post-chemo (41% declined, OR = 8.43, 95% CI 2.48-28.63). Conclusions: In this study, older breast cancer survivors treated with chemo had a 3-fold increased incidence of clinically meaningful decline in functional status as compared to age-matched survivors not treated with chemo and those without cancer. Although these findings need to be replicated in larger studies, our results raise the possibility that accelerated functional decline may be driven by cellular damage from cytotoxic chemo. Further research is warranted to understand the impact of cancer and its treatment on older adults' functional status and underlying aging processes. Clinical trial information: NCT01472094.