Search

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.

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

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.

It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I–III) receiving current chemotherapy regimens and, in turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization. Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher’s exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White, p = .04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (p = .05) and diabetes (p = .05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White, p = .01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen. Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients.

PURPOSE: To assess potential disparities in guideline-concordant care delivery among women with early-stage triple-negative and HER2-positive breast cancer treated with breast conserving therapy. METHODS: Women ≥ 40 years old diagnosed with pT2N0M0 triple-negative or HER2-positive breast cancer treated with primary surgery and axillary staging between 2012 and 2017 were identified using the National Cancer Database (NCDB). The primary outcome was receipt of adjuvant systemic therapy and radiation concordant with current guidelines. Multivariable log-binomial regression was used to assess the prevalence of optimal therapy use across patient and cancer characteristics. Kaplan–Meier curves were used to assess 5-year overall survival. Multivariable Cox proportional hazards regression was used to compare the impact of optimal therapy on 5-year mortality. RESULTS: 11,785 women were included with 7,843 receiving optimal therapy. Receipt of optimal therapy decreased with age even after adjusting for comorbidities and cancer characteristics; other sociodemographic factors were not associated with differences in receipt of optimal therapy. Among patients who did not receive adjuvant systemic therapy, most were not offered the treatment (49%) or refused (40%). Overall 5-year survival was higher among women who received optimal therapy (89% [95% CI 88.0–89.3] vs. 66% [95% CI 62.9–68.5]). Patients who received suboptimal therapy were over twice as likely to die within 5 years of their diagnosis (adjusted HR 2.44, 95% CI 2.12–2.82). CONCLUSION: Age is the primary determinant of the likelihood of a woman to receive optimal adjuvant therapies in high-risk early-stage breast cancer. Patients who did not receive optimal therapy had significantly diminished survival.

PURPOSE Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer. METHODS Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated. RESULTS In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (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). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively ( P < .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity ( P < .01). CONCLUSION The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.

Myosteatosis (intramuscular adiposity) is predictive of chemotherapy toxicity in women undergoing adjuvant chemotherapy for breast cancer (BC). We evaluated a novel, user-friendly and cost-effective technique utilizing a Picture Archiving and Communication Systems (PACS) tool that is readily available in the electronic medical record (EMR), using skeletal muscle density (SMD) to detect myosteatosis and then compared PACS results with those derived from widely used body composition software (SliceOMatic, QC, Canada). Using retrospective data from a sample of women with early BC (Stage I-III) who had CT scan and received chemotherapy. Pearson correlation coefficients were used to compare SliceOMatic with PACS results. Associations of PACS results with chemotherapy-related adverse events were evaluated using multivariable (MV) log-binomial models adjusted for age, race, BMI, anthracycline-based therapy, and number of comorbidities. In 338 patients, mean age was 51, 32% were non-white, and 40% had obesity (BMI ≥ 30 kg/m2). Correlation of SMD using SliceOMatic whole muscle measurements with PACS psoas muscle was 0.76 (p

BACKGROUND This study investigates obesity and comorbidity in Black and White women with early breast cancer (stages I-III) and their potential impact on treatment decisions for patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) tumors. METHODS In this retrospective chart review, comparisons of frequencies for Black and White patients were calculated with the Fisher exact test. Log binomial regression was used to estimate prevalence ratios (PRs) with 95% confidence intervals for total and individual comorbidities, and multivariable modeling was used to estimate PRs adjusted for age and body mass index (BMI). RESULTS In a sample of 548 patients, 26% were Black, and 74% were White. Sixty-two percent of Black patients and 32% of White patients were obese (BMI ≥ 30 kg/m2 ; P < .0001). Seventy-five percent of Black patients and 87% of White patients had HR+ tumors (P = .001). Significant intergroup differences were seen for 2 or more total comorbidities (62% of Blacks vs 47% of Whites; P = .001), 2 or more obesity-related comorbidities (33% vs 10%; P < .0001), hypertension (60% vs 32%; P < .0001), diabetes mellitus (23% vs 6%; P < .0001), hypercholesterolemia or hyperlipidemia (28% vs 18%; P = .02), and hypothyroidism (4% vs 11%; P = .012). In women with HR+/HER2- tumors, there were no intergroup differences in treatment decisions regarding the type of surgery, chemotherapy regimen, radiation, or endocrine treatment despite significant differences in the prevalence of obesity and comorbidities. CONCLUSIONS This study documents significant disparities between Black and White women with early breast cancer with regard to high rates of obesity, overall comorbidities, and obesity-related comorbidities, and it highlights the prevalence of competing risks that may complicate outcomes in breast cancer.

BACKGROUND To the authors' knowledge, it is unknown whether patient-reported symptom severity and symptom interference with daily activities differ between younger (aged

Background Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single-item reports. Materials and Methods Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log-binomial regression. Cohen's kappa was used to assess agreement between patient- and clinician-reported symptoms. Results In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient-provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk [RR], 2.17; 95% confidence interval [CI], 1.36–3.45) and anxiety (RR, 1.48; 95% CI, 1.05–2.09). Conclusion Oncologists frequently underestimate patients’ depression and anxiety and should consider incorporating patient-reported outcomes to enhance monitoring of mental health symptoms. Implications for Practice In this sample of 256 patients with breast cancer, depression and anxiety, measured using single-item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient-reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients’ mental health symptoms. The use of patient-reported, single-item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients’ psychological health.

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.

This commentary provides an overview of four randomized clinical trials on the use of geriatric assessment to guide decisions and interventions for cancer care. These studies show the effect of geriatric interventions on oncological outcomes, including toxicity, quality of life, and survival.

There is great variability in life-expectancy, physical, cognitive, and functional domains in cancer patients of similar chronologic age. Nowhere is this more apparent than among middle-aged and older patients. However, even in younger patients of similar age, extensive exposure to environmental stressors can cause great variability in health status. A biomarker that would reflect biologic age and any and all health deficits in a cancer patient at a distinct point in time might help predict long term outcomes related to treatment, especially toxicity and overall survival. p16INK4a (hereafter referred to as p16) expression represents an ideal biomarker that reflects both cellular senescence and biologic aging. In murine models, p16 expression reflects biologic aging in almost all organs. Preliminary findings in patients with cancer support p16 measurement as a marker of physiologic aging and predictor of toxicity in patients treated with chemotherapy. This review describes the role of p16 in cell senescence, the methodology of p16 measurement in humans, preliminary studies of p16 in humans, and the potential clinical utility of p16 in guiding treatment for cancer patients.

Background Cellular senescence, measured by expression of the cell cycle kinase inhibitor p16INK4a , may contribute to accelerated aging in survivors of childhood, adolescent, and young adult cancer. The authors measured peripheral blood T-lymphocyte p16INK4a expression among pediatric and young adult cancer survivors, hypothesizing that p16INK4a expression is higher after chemotherapy and among frail survivors. Methods A cross-sectional cohort of young adult survivors and age-matched, cancer-free controls were assessed for p16INK4a expression and frailty. Newly diagnosed pediatric patients underwent prospective measurements of p16INK4a expression before and after cancer therapy. Frailty was measured with a modified Fried frailty phenotype evaluating sarcopenia, weakness, slowness, energy expenditure, and exhaustion. Results The cross-sectional cohort enrolled 60 survivors and 29 age-matched controls with a median age of 21 years (range, 17-29 years). The prospective cohort enrolled 9 newly diagnosed patients (age range, 1-18 years). Expression of p16INK4a was higher among survivors compared with controls (9.6 vs 8.9 log2 p16 units; 2-sided P = .005, representing a 25-year age acceleration in survivors) and increased among newly diagnosed patients from matched pretreatment to posttreatment samples (7.3-8.9 log2 p16 units; 2-sided P = .002). Nine survivors (16%) were frail and had higher p16INK4a expression compared with robust survivors (10.5 [frail] vs 9.5 [robust] log2 p16 units; 2-sided P = .055), representing a 35-year age acceleration among frail survivors. Conclusions Chemotherapy is associated with increased cellular senescence and molecular age in pediatric and young adult cancer survivors. Frail survivors, compared with robust survivors, exhibit higher levels of p16INK4a , suggesting that cellular senescence may be associated with early aging in survivors.

Body composition metrics as predictors of adverse events are a growing area of interest in oncology research. One barrier to the use of these metrics in clinical practice is the lack of standardized cut points for identifying patients with at-risk body composition profiles. We examined the association of chemotherapy adverse events with several body composition measures, using alternative cut points from published studies. This is a retrospective study of women diagnosed with early breast cancer (EBC). Axial computerized tomography (CT) images from lumbar L3 segments were analyzed for the following body composition measures: myosteatosis (low Skeletal Muscle Density/SMD), sarcopenia (low Skeletal Muscle Index/SMI), and high Visceral Adipose Tissue (VAT). Adverse events during chemotherapy were dose reduction, early treatment discontinuation, and hospitalization. Log-binomial modeling was used to evaluate associations between body composition measures at different cut points with adverse events, adjusting for age, race, Body Mass Index/BMI, and comorbidities. Relative risks were reported as the measure of association. In a sample of 338 women, mean age was 51, 14% were age 65 or older, 32% were non-white, 40% had obesity (/BMI ≥ 30 kg/m2), and mean number of comorbidities was 1.56. In multivariable analysis (MV), all three SMD cut points for myosteatosis had significant associations with total number of adverse events, as well as different cut points having significant associations with either dose reduction, early treatment discontinuation or hospitalization. SMI and VAT were not significant in the MV analysis; however, in some models, age and total comorbidities were significant for adverse events. Among CT-derived measures of body composition, myosteatosis determined at any of three SMD cut points was associated with total and individual adverse events during chemotherapy for early breast cancer.

12114Background: Cognitive decline related to cancer and its treatments is a common concern among patients receiving treatment for cancer. Routine cognitive screening in oncology practice has been ...

Introduction Cognitive impairment (CI) increases chemotherapy toxicity risk with need to understand this association utilizing publicly available short screening tools. We evaluated this utilizing a lower threshold on a short screening tool in older adults with cancer. Materials and methods We analyzed data from the Cancer and Aging Research Group (CARG) Chemotherapy Toxicity Risk tool (CARG score) development and validation cohorts (n = 703), which recruited adults age ≥ 65 with cancer from academic centers. Cognition was evaluated with the Blessed Orientation-Memory-Concentration test (BOMC). Patients with BOMC score ≥ 11 were excluded. Utilizing cut-points for older adults, we considered moderate BOMC scores (5-10) as potential CI. Logistic regression was used for analysis. Results Patient baseline characteristics included: mean age 73; 85% white; 63% college or higher education; 250 (36%) potential CI; 385 (55%) severe toxicity. Patients with potential CI were more likely non-white (p ≤ 0.01) and to have high school or lower education (p ≤ 0.01) and high CARG score (p = 0.04). Potential CI was associated with increased severe toxicity risk (OR = 1.54, p ≤ 0.01). After adjusting for CARG score, this association became nonsignificant (OR = 1.35; p = 0.08). Among patients with lower education (n = 258; 36.7%), potential CI remained associated with severe toxicity, even after adjusting for CARG score (OR = 1.87, p = 0.03). Conclusions Our findings suggest potential cognitive impairment, defined by BOMC score 5–10, in older adults with cancer and lower education is associated with increased severe toxicity risk. Future studies are needed to validate these findings. Healthcare providers should consider cognitive testing before treatment for these vulnerable patients.

Introduction: Sarcopenia and muscle composition are associated with treatment-related toxicities and adverse events in women with EBC (Shachar 2017). We investigated the relationship of muscle mass with other measures of body composition as well as comorbidities, physical function, fatigue, and quality of life. Methods: Women age 21 or older were enrolled in intervention studies (NCT02167932, NCT02328313) investigating home-based walking during chemotherapy for early breast cancer (stage I-III). Prior to the start of chemotherapy, patients completed the Short Physical Performance Battery (SPPB) and the Timed Up and Go (TUG) test. When available from staging, transverse views of computed tomography (CT) through L3 lumbar segments were analyzed using Slice-O-Matic software (Tomovision Quebec, Canada) to ascertain skeletal muscle area (SMA= -29 to +150 Hounsfield Units), skeletal muscle density (SMD= average attenuation of skeletal muscle in HU), skeletal muscle index (SMI= SMA/height2), and skeletal muscle gauge (SMG= SMI x SMD). BSA and BMI were calculated using standard formulas. Descriptive statistics (mean and standard deviation (SD)) were estimated and simple linear regression models were used to evaluate associations of body composition, function and quality of life and continuous muscle measures. Pearson correlation coefficients were estimated to assess the relationship between muscle metrics. Results: In 99 patients, mean age was 56 (SD 13), BMI was 30 (SD 7), 47% were obese (≥30 kg/m2), and 54% had stage III breast cancer. Mean SMI was 45.3 (SD. 8.5), 26% were sarcopenic (SMI 1512 Arbitrary Units]. For each additional comorbidity, mean SMD decreased by 1.91 (p=.003), mean BSA increased by 0.035 (p=.02), and mean BMI increased by 1.31 (p=.005). Lower SMD and SMG were seen for patients with TUG >14 seconds (-5.70, p=.04 and -325.4, p=.02, respectively). The mean SMD increased by 1.22 (p=.02) for each additional point on the SPPB scale. For the correlation between BMI and muscle matrices, there was a strong positive correlation for SMI (+0.648 p Citation Format: Gabriel F. P. Aleixo, Allison M Deal, Grant R Williams, Hyman B Muss, Kirsten A Nyrop, Ji Hye Park, Hyeon Yu, Shlomit S Shachar. Muscle measures, body composition, and function in patients with early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-73.

Introduction: Visceral adipose tissue (VAT) is correlated with lower overall survival and higher chemotherapy toxicity in women with breast cancer (Del Fabbro 2012, Feliciano 2019). In a sample of women scheduled for chemotherapy for early breast cancer (EBC) (stage I-III), we evaluate whether VAT or superficial adipose tissue (SAT) are associated with comorbidities, function, and clinically-used body metrics, Body Mass Index (BMI) and Body Surface Area (BSA).Methods: Women age 21 or older were enrolled in intervention studies (NCT02167932, NCT02328313) to encourage home-based walking during chemotherapy for EBC. Prior to chemotherapy initiation, patients had abdominal computerized tomography (CT) scans and completed Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) tests. Axial CT images were evaluated at the L3 level using Slice-O-Matic software (Tomovision Quebec, Canada). Superficial adipose tissue(SAT) was calculated from extra-muscular tissue with densities ranging from -190 to -30 Hounsfield Units (HU). Visceral adipose tissue (VAT) was calculated from non-subcutaneous tissue with densities from -150 to -50 HU, with values in cm2. BSA and BMI were calculated using standard formulas. Descriptive statistics(mean and standard deviation (SD)) were estimated and simple linear regression models were used to evaluate associations of comorbidities, function, and clinically-used body metrics and continuous adiposity measures. Pearson correlation coefficients were estimated to assess the relationship between adiposity measures.Results: In a sample of 99 women, mean age was56 (SD 13.1), BMI was 30 (SD 7), 47% were obese (≥30 kg/m2), and mean number of comorbidities was1.3 (SD 1.5).The mean VAT was 113.9 (SD 71.2), 50% had high VAT (>100 cm2), and the mean SAT was 294.2 (SD 71.2). For each additional comorbidity, mean VAT increased by 16.68, and SAT increased by 21.6. Both arthritis and high blood pressure were associated with higher VAT (+67.2 p14 seconds +57.87 (p=.004). For each additional point on the SPPB scale, the mean VAT decreased by 12.14(p=.002). For each additional comorbidity, BSA increased 0.035(p=.004) and BMI increased 1.31(p=.003). Strong positive correlations with VAT were seen for BSA (.697 p Citation Format: Gabriel F. P. Aleixo, Allison M Deal, Shlomit S Shachar, Hyman B Muss, Kirsten A Nyrop, Ji Hye Park, Hyeon Yu, Grant R Williams. Adiposity, comorbidities, and function in patients with early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-48.

OBJECTIVE For patients with HER2-positive breast cancer metastatic to brain, HER2-directed systemic therapies are increasingly used with stereotactic radiosurgery (SRS). These include monoclonal antibodies such as trastuzumab (H) and pertuzumab (P), antibody-drug conjugates such as ado-trastuzumab emtansine (T-DM1), and tyrosine kinase inhibitors such as lapatinib. Limited data exist regarding appropriate timing with SRS and outcomes of this treatment regimen. METHODS A single-institution retrospective review collected clinical data on patients with breast cancer metastatic to brain who were treated with SRS from 2009-2020. Statistical analyses were performed using the Kaplan-Meier method and chi-square statistic. RESULTS Of 82 patients with breast cancer metastatic to brain treated with SRS, 33 (40%) were HER2-positive, 18 of whom were hormone receptor-positive. At brain metastasis diagnosis, 15 patients (45%) had >1 intracranial metastasis (range 2-7), and the median brain metastasis maximal dimension was 2.0 cm. Fifteen patients had uncontrolled extracranial disease. After brain metastasis diagnosis, 9 patients (27%) were treated with systemic therapy first (T-DM1+/-HP, lapatinib+HP, chemotherapy+/-HP) followed by SRS at a median of 18.6 months after starting systemic therapy. Seven patients (21%) were treated with SRS first, followed by systemic therapy in 6 of these patients (multi-agent regimens, 4 including T-DM1 or lapatinib). Seventeen (52%) received concurrent systemic therapy and SRS (T-DM1+/-chemotherapy, lapatinib, HP, hormone therapy, chemotherapy). Median follow-up time was 21.1 months. Median overall survival was 24.8 months and not statistically different between treatment groups. Four patients (12%) developed symptomatic radionecrosis; 3 were on T-DM1 concurrent with SRS. CONCLUSION In this small patient sample, we noted favorable survival outcomes for patients with HER2-positive breast cancer metastatic to brain when treated with HER2-targeted therapies together with SRS. The sequence of systemic therapy and SRS does not appear to impact survival outcomes. Concurrent treatment with T-DM1 and SRS may be associated with higher rates of radionecrosis.

Following therapy, breast cancer survivors (BCS) have an increased risk of infections because of age and cancer dysregulation of inflammation and neutrophil functions. Neutrophil functions may be improved by exercise training, although limited data exist on exercise and neutrophil functions in BCS.Sixteen BCS [mean age: 56 (SD 11) years old] completed 16 weeks of community-based exercise training and a 45-minute acute bout of cycling before (Base) and after (Final) the exercise training program. Exercise training consisted of 3 x 40 – 60 minute mixed mode aerobic exercises, comprising 10 – 30 minutes aerobic and 30 minutes resistance training. At Base and Final, we took BCS blood samples before (PRE), immediately after (POST), and 1 hour after (1Hr) acute exercise to determine neutrophil counts, phenotype, bacterial killing, IL-6, and IL-8 levels. Eleven healthy, age- and physical activity levels-matched women (Control) completed the acute bout of exercise once as a healthy response reference. Resting Responses. BCS and Controls had similar Base PRE absolute neutrophil counts [mean (SD): 3.3 (1.9) v 3.1 (1.2) x 109/L, p=0.801], but BCS had lower bacterial phagocytosis [3991 (1233) v 4881 (417) MFI, p=0.035] and higher oxidative killing [6254 (1434) v 4709 (1220) MFI, p=0.005], lower CD16 [4159 (1785) v 7018 (1240) MFI, pClinical Trial RegistrationClinicalTrials.gov, identifier NCT03760536.

INTRODUCTION AND OBJECTIVE:Sarcopenia, or severe muscle wasting, has been well documented as a risk factor for mortality, complications, and non-home discharge disposition for patients with bladder...

Background Hospitalized older adults have significant geriatric deficits that may lead to poor outcomes. We conducted a randomized trial to investigate the effectiveness of providing clinicians with a real-time geriatric assessment (GA) report in nonelectively hospitalized older patients with cancer. Subjects, Materials, and Methods We developed a web-based software platform for administering a modified GA (Cancer 2005;104:1998–2005) to older (>70 years) nonelectively hospitalized patients with pathologically confirmed malignancy. Patients were randomized to have their GA report provided to their treating clinicians (Intervention arm) or not provided (Control arm). Results Our study included 135 patients, median age 76 years, 52% female, 75% white, 21% black, 79% greater than high school education, 59% married, and 17% living alone. All patients had at least one GA-identified deficit, including physical function deficits (90%), cognitive impairment (22%), >5 comorbidities (28%), polypharmacy (>9 medications; 38%), weight loss ≥10% in the past 6 months (40%), anxiety (32%), or depression (30%). There was no difference between the Intervention (6%) and Control arms (9%) in the proportion of patients who were referred by their clinical team for an intervention to address a deficit (p = .53). Conclusion Many older nonelectively hospitalized patients with cancer have geriatric deficits that are amenable to evidence-based interventions. Real-time GA reports provided to the care team prior to discharge did not influence provider referral for such interventions. There is a need for systems-level interventions to address deficits in this vulnerable patient population. Implications for Practice Geriatric deficits are common in hospitalized older adults with cancer and lead to poor outcomes. Addressing modifiable deficits represents an appealing way to improve outcomes. Widespread geriatrician consultation is impractical owing to resource and personnel constraints. This work tested whether prompt delivery of a mostly self-administered, web-based geriatric assessment report to clinicians improved referral rates for evidence-informed interventions. It confirmed frequent geriatric deficits and high readmission rates in this population but found that real-time geriatric assessment reporting did not influence provider referral for evidence-informed interventions on geriatric assessment identified deficits. These findings highlight the need for systems-level intervention to improve outcomes in this vulnerable patient population.

Background The selection of later-line treatment for older patients with AJCC (version 7) stage IV non-small cell lung cancer (NSCLC) remains controversial. Nanoparticle albumin-bound (nab)-paclitaxel is approved with carboplatin for the first-line treatment of patients with NSCLC and subgroup analysis of phase 3 data has suggested superior survival in older patients. Methods The authors conducted a phase 2 study of nab-paclitaxel in 42 patients aged ≥70 years who had been treated previously with a platinum doublet regimen; patients also could have received a PD-1 inhibitor. The primary endpoint of the current study was grade 3 to 5 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). In addition to response rate, progression-free survival (PFS), and overall survival (OS), geriatric assessments also were performed before and during treatment, associations between baseline sarcopenia and outcomes were explored, and changes in T lymphocyte p16 before and during treatment were measured. The authors also performed a retrospective subgroup analysis of 19 older patients who were treated with nab-paclitaxel as part of a larger, randomized, phase 2 study; data were not combined. Results The rate of grade 3 to 5 toxicities was 33.7%. The most common grade 3 to 5 toxicities were decreased white blood cell count (11.9%), neutropenia (9.5%), and fatigue (11.9%). The response rate was 34.2% (2.6% complete response rate and 31.6% partial response rate). The median PFS was 5.2 months and the median OS was 9.3 months. Adverse prognostic factors were common: 42% of patients were frail and 39% of patients were prefrail, whereas 21% had an Eastern Cooperative Oncology Group performance status of 2 and 27% were sarcopenic. Only frailty was found to be predictive of inferior survival. A subgroup analysis of 19 older patients treated with nab-paclitaxel alone in a prior trial demonstrated a response rate of 15.8%, a PFS of 4.2 months, and an OS of 13.6 months. Conclusions Fit and prefrail older patients with stage IV NSCLC should be considered for treatment with nab-paclitaxel after disease progression with doublet chemotherapy.

Background Despite data demonstrating the safety of omitting axillary surgery in older women with early-stage breast cancer, the incidence of axillary surgery remains high. It was hypothesized that the prevalence of nodal positivity would decrease with advancing age. Methods The National Cancer Data Base was used to construct a cohort of adult women with early-stage, clinically node-negative, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative breast cancer treated between 2013 and 2015. Multivariable logistic regression was used to assess the relationship between age and nodal positivity, and this was stratified by the axillary surgery category. Modified Poisson regression was used to estimate the proportion of women receiving adjuvant therapy according to age and nodal status. Results The incidence of axillary surgery among women aged 70 and older (n = 51,917) remained high nationwide (86%). There was a significant decrease in nodal positivity with advancing age in women with early-stage, ER+, clinically node-negative breast cancer from the youngest cohort up to patients aged 70 to 89 years, and this was independent of histologic subtype (ductal vs lobular), race, comorbidities, and socioeconomic factors. Overall, less than 10% of women aged 70 or older who underwent surgery had node-positive disease, regardless of axillary surgery type, and almost 95% of node-positive patients aged 70 or older were at pathological stage N1mi or N1. Conclusions Axillary surgery may be safely omitted for many older women with ER+, clinically node-negative, early-stage breast cancer. Nodal positivity declines with advancing age, and this suggests varied biology in older patients versus younger patients.

Weight gain after breast cancer (BC) diagnosis is a well-known phenomenon; however, it is not a universal phenomenon and identification of patients at highest risk for weight gain is needed. This study investigates weight trajectories in early BC patients at 2 years post-primary treatment, examining potential contributing factors such as age, race, and receipt of chemotherapy, anti-HER-2 therapy, and endocrine treatment (ET).A single institution cohort of newly diagnosed women age 21 and older with early breast cancer patients (Stage 0-3) were identified by retrospective chart review (diagnosis year 1995 to 2016). Log-binomial regression models for net weight changes at 2 years post-primary treatment including patient demographic, clinical, and treatment characteristics.The final sample of 625 patients included 29% who were non-White and 37% who were pre-menopausal at diagnosis. Body mass index (BMI) at diagnosis was calculated and found to be normal in 33% (BMI 18 to 25), overweight in 27% (BMI 25 to 30), and obese in 40% (BMI 30 and higher). At 2 years, compared to weight at diagnosis, 31% had lost 2 kg, 34% had stable weight ± 2 kg, and 35% had gained 2 kg. Factors associated with 2 kg weight gain were menopausal status (pre-menopausal HR 1.65, 95% CI 1.34-2.04, p .0001), receiving any chemotherapy (HR 1.36, 95% CI 1.04-1.77), and anthracycline-based chemotherapy followed by ET (HR 1.60, CI 1.01-2.45). Anti-HER-2 therapy and transition from pre- to post-menopausal during the 2-year study period were not significant factors in weight gain. In multivariate analysis, menopausal status remained the only significant variable related to weight gain when adjusted for treatment. For all treatment combinations, pre-menopausal women had significantly more weight gain.Weight gain, weight loss, and stable weight in women with early breast cancer vary greatly by treatment plan. However, pre-menopausal patients have the highest risk for weight gain.

Geriatric assessment (GA) is used in oncology to identify deficits in older patients with cancer that may affect treatment choice. We examine GA in 550 patients with early breast cancer, including both younger (

Background: The American Society of Clinical Oncology (ASCO) Position Statement on Obesity and Cancer notes that the oncology care team is in a unique position to initiate weight management convers...

Breast cancer is the most common cancer and leading cause of cancer death in women. Body composition parameters, especially those related to muscle, have become a growing focus of cancer research. In this review, we summarize the literature on breast cancer and muscle parameters as well as combine their outcomes for overall survival (OS), time to tumor progression (TTP), and chemotherapy toxicity in a meta-analysis. A systematic search of the literature for randomized controlled trials and observational studies was conducted on MEDLINE, Cochrane CENTRAL, and EMBASE through May 1, 2019. Two reviewers independently searched and selected. Meta-analysis was conducted using a random-effects model. The risk of bias was evaluated using the Newcastle–Ottawa quality assessment for cohorts and GRADE summary of findings tool from Cochrane. A total of 754 articles were screened from which 6 articles and one abstract were selected. Using skeletal muscle index (SMI), patients classified as sarcopenic had a 68% greater mortality risk compared to non-sarcopenic patients (HR 1.68 95% CI 1.09–2.59, 5 studies) (p = .02) (i2 = 70%). Low muscle density was not predictive of OS (HR 1.44 95% CI 0.77–2.68, 2 studies) (p = .25) (i2 = 87%). Patients with sarcopenia (56%) had more grade 3–5 toxicity compared to non-sarcopenic (25%) (RR 2.17 95% CI 1.4–3.34, 3 studies) (p = .0005) (i2 = 0%). TTP was nearly 71 days longer in advanced/metastatic patients classified as non-sarcopenic compared to patients with sarcopenia (MD − 70.75 95% CI − 122.32 to − 19.18) (p = .007) (i2 = 0%). Our synthesis of the literature shows that patients with sarcopenia have more severe chemotherapy toxicity as well as shorter OS and TTP, and that low muscle density is prognostic of OS for women with metastatic breast cancer. Our findings suggest that in clinical practice, body composition assessment is valuable as a prognostic parameter in breast cancer.

PURPOSE: The association between geriatric assessment (GA)–identified impairments and long-term health care use in older cancer survivors remains unknown. Our objective was to evaluate whether a GA performed at cancer diagnosis was predictive of hospitalizations and long-term care (LTC) use in older adult cancer survivors. METHODS: Older adults with GA performed between 3 months before through 6 months after diagnosis were included (N = 125). Patients with Medicare Parts A and B coverage and no managed care were identified. Hospitalizations and LTC use (skilled nursing or assisted living) were assessed up to 5 years postdiagnosis. GA risk measures were evaluated in separate Poisson models estimating the relative risk (RR) for hospital and LTC visits, adjusting for age and Charlson comorbidity score. RESULTS: The mean age of patients was 74 years, and the majority were female (80%) and white (90%). Breast cancer (64%) and early-stage disease (stages 0 to III, 77%) were common. Prefrail/frail status (RR, 2.5; P < .001), instrumental activities of daily living impairment (RR, 5.47; P < .001), and limitations in climbing stairs (RR, 2.94; P < .001) were associated with increased hospitalizations. Prefrail/frail status (RR, 1.86; P < .007), instrumental activities of daily living impairment (RR, 4.58; P < .001), presence of falls (RR, 6.73; P < .001), prolonged Timed Up and Go (RR, 5.45; P < .001), and limitations in climbing stairs (RR, 1.89; P < .005) were associated with LTC use. CONCLUSION: GA-identified impairments were associated with increased hospitalizations and LTC use among older adults with cancer. GA-focused interventions should be targeted toward high-risk patients to reduce long-term adverse health care use in this vulnerable population.

Establishing accurate estimates of physical activity at baseline is essential for interventions assessing the potential benefits of exercise in adults with cancer. This study compares self-reported physical activity with independent data from activity trackers in women with early breast cancer (BC) recruited into a “walking” intervention during chemotherapy. Baseline (pre-intervention) questions inquired about self-reported physical activity—number of walking days/week and minutes/day—in women who were initiating chemotherapy for Stage I–III BC. Activity trackers measured steps per day during the first full week of chemotherapy. Weighted Kappa statistic and Pearson correlation coefficients were used to evaluate agreement and association between self-reported and objectively tracked physical activity levels, respectively. Univariate analyses were conducted to identify variables that may influence congruence between the two measures. In a sample of 161 women, 77% were white, with mean age 56 years. Agreement between self-reported and objectively tracked physical activity was “fair” (kappa coefficient = 0.31), with most patients (59%) over-reporting their physical activity levels. There was weak correlation between the two measures (r = 0.24); however, correlation was strong in participants who were not married (r = 0.53) and/or living alone (r = 0.69). Objective methods for assessing physical activity (activity trackers, accelerometers) should be used as a complement to self-reported measures to establish credible activity levels for intervention studies seeking to increase physical activity and/or measure the impact of increased physical activity in women with breast cancer.

Our aim was to evaluate the prognostic impact of three inflammatory markers - neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) - on overall survival (OS) in older adults with cancer.Our sample includes 144 patients age ≥ 65 years with solid tumor cancer who completed a cancer-specific Geriatric Assessment (GA) from 2010 to 2014 and had pretreatment CBC with differential. NLR was dichotomized a previously reported cut-off value of 3.5, while PLR and LMR were dichotomized at the median. Cox proportional hazards models evaluated whether NLR, PLR and LMR were predictive of OS independent of covariates including a recently developed 3-item GA-derived prognostic scale consisting of (1) "limitation in walking several blocks", (2) "limitation in shopping", and (3) "≥ 5% unintentional weight loss in 6 months".Median age was 72 years, 53% had breast cancer, 27% had stage 4 cancer, 14% had Karnofsky Performance Status (KPS) 80, 11% received less intensive than standard treatment for stage, and 39% had NLR 3.5. In univariable analysis, higher NLR and PLR and lower LMR were significantly associated with worse OS. NLR remained a significant predictor of OS (HR = 2.16, 95% CI; 1.10-4.25, p = .025) after adjusting for cancer type, stage, age, KPS, treatment intensity, and the GA-derived prognostic scale.NLR 3.5 is predictive of poorer OS in older adults with cancer, independent of traditional prognostic factors and the GA-derived prognostic scale.

Background: While immunotherapy holds promise in the treatment of mTNBC, response rates (RR) in unselected patients (pts) are approximately 20%. Strategies to augment response to immunotherapy include depletion of regulatory T cells (Tregs). A single dose of cyclophosphamide (Cy) given prior to checkpoint inhibition achieved this goal in preclinical models of TNBC (Taylor et al., JCI, 2017). Thus, we designed a phase II study to evaluate this strategy in the clinical setting of mTNBC. Patients/Methods: In cycle 1 (C1), eligible pts with mTNBC received a single dose of Cy 300mg/m2 IV on day 1 (C1D1) followed by pembrolizumab 200mg IV on day 2 (C1D2), then every 3 weeks thereafter. The co-primary objectives were (1) progression free survival (PFS, null 1.9 mos vs. 2.9 mos, 80% power, alpha 0.05) and (2) reduction in Tregs in peripheral blood measured by flow cytometry. Secondary endpoints were response rate (RR), survival (OS), and RNA-based correlative endpoints. Results: 40 patients were evaluable for efficacy: mean age 54.5 yrs (33 – 82 yrs), 75% white, 22% black, 3% American Indian. All patients had received 1 prior line of chemotherapy in the metastatic setting; 29% received 5 or more prior lines. The most common grade 3 adverse events (AE's), all 5%, were neutropenia, anemia, elevated AST, and fatigue. Immune-related grade 3 AE's, all 3%, included colitis, dry mouth, pneumonitis. Overall RR was 21% (0 CR, 8 PR), 3 pts had stable disease. Median PFS was 1.8 months (mos) (95% CI 1.4–2.5) and OS was 6.3 mos (95% CI 2.8–8.4). There was a non-significant decrease in Tregs from C1D1 to C1D2 (-3.3%, p=0.19); but from C1D2 to C2D1, Tregs increased 21.7% (p=0.005). There was no association between changes in Tregs or number of prior lines of therapy with RR (p>0.09), while immune-related AE's were associated with response (p=0.02). Correlatives studies illustrate B cell immune gene signature expression and B cell receptor repertoire diversity were enriched in responders, while genes/pathways associated with neutrophils, anti-apoptosis, PI3K/AKT and down-regulation of MHC class 1 were associated with non-response. Conclusions: While pembroliuzumab plus Cy was well-tolerated among pts with mTNBC, efficacy was similar to historical control, likely due to minimal effect of Cy on Tregs. Correlative analyses illustrate that study of adaptive immune features, including B cell biology, is a promising strategy for understanding response to PD-1 inhibition in breast cancer. Further strategies to deplete Tregs in a more sustained manner are worthy of future exploration (NCT02768701). Citation Format: Anders CK, Moore D, Sambade M, Cuaboy L, Garrett A, Woodcock M, McKinnon K, Cowens K, Bortone D, Calhoun B, Carey L, Dees C, Jolly T, Muss H, Reeder-Hayes K, Kaltman R, Jankowitz R, Gudena V, Olajide O, Perou C, Vincent B, Serody J. LCCC 1525: A phase II study of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-05.

Background Women with obesity are at higher risk for high-grade and/or advanced-stage breast cancer in comparison with women without obesity. Many women with a high body mass index (BMI) at breast cancer diagnosis experience further weight gain during and after treatment. This study investigated Black and White patient perspectives on conversations with their oncologists about weight and weight management. Methods Focus groups using a virtual platform (Zoom) were conducted with women after primary treatment for stage I to III breast cancer who were 21 years or older and had a BMI ≥ 30 kg/m2 : 2 with Black women (n = 12) and 2 with White women (n = 14). Results Participants asked that their oncologists be "transparent" about weight gain as a potential side effect of their cancer treatment and how excess weight might affect their prognosis and survival. They asked to be "seen as an individual" to facilitate both person-centered and culturally appropriate conversations about behavioral changes needed for weight management. Participants urged clinicians to take the lead in initiating conversations about weight to underscore its importance in cancer care and survivorship. They welcomed actionable recommendations about nutrition and exercise from either the oncology clinician or a specialist. Participants offered specific suggestions on how clinicians could initiate weight-related conversations, beginning with questions eliciting patients' perspectives on their weight and lifestyle. Conclusions Many women with early-stage breast cancer and obesity have concerns about weight and weight gain and urge their oncologists to use an active and personalized approach in recommending and supporting efforts at weight management. Lay summary Focus group discussions with Black and White women with early-stage breast cancer and obesity have elicited patient perspectives on conversations with their oncologists about weight and weight management. Many patients have concerns about weight and weight gain and urge their oncologists to use an active and personalized approach in recommending and supporting efforts at weight management.

Background Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. Objectives The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. Methods Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14+CD16- and CD14+CD16+ monocytes using flow cytometry. Results Exercise training decreased IL-1ß+CD14+CD16- proportion (24.6%, p=0.016), IL-1ß+CD14+CD16- mean fluorescence intensity (MFI) (−9989, p=0.014), IL-1ß+CD14+CD16+ MFI (−11101, p=0.02), and IL-6+CD14+CD16- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14+CD16- (−63, p=0.002) and CD14+CD16+ (−18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14+CD16+ concentrations being decreased at 1 h post without changes in intracellular cytokine production. Conclusions Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production., Highlights • Acute exercise increased monocyte concentrations at 0 h after exercise, with a decrease in CD14+CD16+ monocytes only at 1 h. • Exercise training decreased IL-1β and IL-6 proportions while acute exercise reduced the TLR2 and TLR4 expression. • Anti-inflammatory effect of exercise may be partly explained by reduced pro-inflammatory cytokine production by monocytes.

Background Insufficient social support is associated with increased mortality among older adults. Lung cancer is primarily a disease of older adults and is the leading cause of all cancer deaths. We assessed the association of social support with outcomes among older adults with lung cancer. Materials and methods Adults age 65 and older with lung cancer with a completed geriatric assessment (GA) were assessed. Emotional social support (ES) and tangible (material, instrumental) support (TS) measures and patient characteristics were obtained from the GA. The electronic health record was used to extract clinical variables. Simple linear regression models evaluated the association between social support scales with patient and clinical factors. Results 79 adults were assessed. White race was positively associated with ES score (p=.04), while higher BMI (p=.03), depression (p=.03) and anxiety (p=.02) were associated with worse ES. Higher BMI was associated with higher/better TS score (p=.02) while living alone was associated with lower/worse TS score (p=.03). Completion of platinum-based doublet chemotherapy with immunotherapy as planned was associated with higher ES scores (p=.02) and higher TS scores (p=.02). Disease progression was associated with lower ES scores (p=.03). Conclusion Social support may influence clinical outcomes in older adults with lung cancer. As lung cancer often portends to poor prognosis, social support may be an important prognostic indicator.

PURPOSE: Hospitalizations during cancer treatment are costly, can impair quality of life, and negatively affect therapy completion. Our objective was to identify risk factors for unplanned hospitalization among older adults receiving chemotherapy. METHODS: This is a secondary analysis of a multisite cohort study (N = 750) of patients ≥ 65 years of age evaluated with a geriatric assessment (GA) to predict chemotherapy toxicity. The primary outcome of this analysis was unplanned hospitalizations during treatment; the secondary outcome was length of stay (LOS) of the first hospitalization. Independent variables included pretreatment GA measures, laboratory values, cancer type and stage, and treatment intensity characteristics. We used logistic regression to estimate the odds of hospitalization and generalized linear models for LOS in multivariable analyses. RESULTS: The sample median age was 72 years (range, 65-94 years); 59% had stage IV disease. At least one unplanned hospitalization occurred in 193 patients (25.7%) during receipt of chemotherapy. In multivariable analyses controlling for cancer type, the following baseline characteristics were significantly associated with increased odds of hospitalization: needing help bathing or dressing (odds ratio [OR], 1.8; 95% CI, 1.0 to 3.1), polypharmacy (≥ 5 meds) (OR, 1.6; 95% CI, 1.1 to 2.4), more comorbid conditions (OR, 1.1; 95% CI, 1.0 to 1.3), availability of someone to take them to the doctor (OR, 2.0; 95% CI, 1.0 to 4.1), CrCl < 60 mL/min (OR, 1.7; 95% CI, 1.1 to 2.4), and albumin < 3.5 g/dL (OR, 1.8; 95% CI, 1.2 to 2.8). In multivariable analyses, older age, self-reported presence of liver or kidney disease, living alone and depressive symptoms were associated with longer LOS. CONCLUSION: Readily available GA variables and laboratory data, but not age, were associated with unplanned hospitalizations among older adults receiving chemotherapy. If validated, these data can inform prediction models and the design of interventions to decrease unplanned hospitalizations.

BACKGROUND Evidence for exercise as an efficacious strategy to improve aerobic capacity of breast cancer survivors (BCS) has come largely from intervention studies conducted in laboratory settings. There is an increasing need to translate to community-type settings, but the efficacy of those interventions using gold standard evaluation is not well-established. AIM To investigate whether similar improvement in aerobic capacity (maximal oxygen consumption [VO2]) measured with gold standard testing can be achieved through a community-based setting in BCS. METHODS A peak cardiopulmonary exercise test (VO2peak), 6-min walk test (6MWT), and timed up and go test (TUG) were assessed pre- and post-16 wk of progressive intensity aerobic and strength training exercise at a community center. RESULTS The sample consisted of 31 early BCS (< 1 year since treatment completion) and 15 controls (CTLs). Both groups significantly improved VO2peak (+1.2 mL/kg/min; P = 0.030), 6MWT (+35 meters; P < 0.001), and TUG (-0.44 s; P < 0.01) following training. Both groups improved peak cycling power during the cardiopulmonary exercise test with BCS improving by +10 watts more than the CTLs (P = 0.020). Average exercise attendance was 71% (34 of 48 possible days), but compliant days averaged only 60% of total days for aerobic, and < 40% for strength in both groups. CONCLUSION Community-based exercise programs can be an effective strategy to improve aerobic capacity and physical function for early-stage BCS but potentially not to the same extent observed in laboratory-based randomized controlled trials. Further research is needed to explore barriers and facilitators of exercise engagement in community-based centers to maximize training benefits for adults with cancer.

Exercise may attenuate immunosenescence with aging that appears to be accelerated following breast cancer treatment, although limited data on specific cell types exists and acute and chronic exercise have been investigated independently in older adults. PURPOSE: To determine the mucosal associated invariant T (MAIT) cell response to acute exercise before (PRE) and after (POST) 16 weeks of exercise training in breast cancer survivors (BCS) and healthy older women (CON). METHODS: Age-matched BCS and CON performed 45 minutes of intermittent cycling at 60% peak power output wattage. Blood samples were obtained at rest, immediately (0h) and 1h after exercise to determine MAIT cell counts, frequency, and intracellular cytokine expression. RESULTS: At PRE, MAIT cell counts were greater in CON (137%) than BCS at 0h (46%, p

Over the past several decades, adult weight gain and excess weight have emerged as risk factors for cancers of the esophagus, pancreas, liver, colorectal, breast (postmenopausal), endometrium, and kidney, as well as probable evidence for cancers of the stomach (cardia), mouth/pharynx/larynx, gallbladder, ovary, and prostate. In the USA, overweight and obesity account for 55% of cancers in women and 24% in men. The evidence of risks, outcomes, and interventions is most developed in the literature pertaining to women with early breast cancer (Stage I–III). Primarily with the oncology clinician-patient relationship in mind, this chapter provides an overview of weight trajectories in women with early breast cancer, implications for prognosis and survival, nutrition and exercise for weight management, and the role of oncology clinicians. Lessons learned from the breast cancer population are illustrative for other types of cancers. Culturally sensitive, person-centered language about the importance of weight management in survivorship is essential to clinician-patient communication and other interventions to help adults with cancer to understand the importance of weight management and other benefits from exercise and a healthy diet. Equally important, but not within the scope of this chapter, is the urgency of lowering cancer risk and adverse outcomes through effective and widespread community-based obesity interventions.

Background In metastatic triple negative breast cancer (mTNBC), median progression-free survival (PFS) with chemotherapy alone is approximately 2–4 months1 and improvements with single agent checkpoint inhibitors (CI) are limited by modest response rates. Murine breast cancer models have demonstrated a role for intratumoral regulatory T cells (Tregs) in modulating response to CIs.2 A phase II clinical trial was conducted to test the hypothesis that a single, priming dose of cyclophosphamide prior to pembrolizumab would improve PFS in mTNBC. Here we present the correlative genomic and immunologic analyses from this study. Methods This trial (https://clinicaltrials.gov/ct2/show/NCT02768701) recruited 40 patients with largely pretreated mTNBC. Response was defined as >30% decrease in imaging-assessed disease burden. Clinical benefit was defined as treatment response or stable disease. Tumor specimens were collected prior to enrollment, and peripheral blood mononuclear cell (PBMC) samples taken prior to cyclophosphamide and before each cycle of pembrolizumab. RNA sequencing was performed on tumor samples for gene expression and immune repertoire reconstruction. Targeted sequencing of the T-cell beta chain, IG kappa, lambda and heavy chain (TRB, IGK, IGL, and IGH, respectively) on PBMCs captured the peripheral immune repertoire. Whole exome sequencing was performed on tumor samples with PBMCs serving as a matched normal. Results Of 40 patients enrolled, 31 patients had tumor RNA-seq and at least 15 had matched PBMC-derived immune chains capturing both pre and post treatment. When preliminary RNA-seq samples (n=22) revealed upregulation in B-cell receptor pathways and related gene signatures (figure 1), we updated our planned analysis to exclude tumor specimens collected from lymph nodes. In our final analysis, response to therapy (4 of 25, 16%) was associated in tumor RNA-Seq with gene pathways involving programmed cell death and MAPK activation, while non-responding tumors were enriched in G-protein signaling and inhibition of insulin secretion (figure 2a,b, table 1). Immune gene signatures related to NK cells and B-cell activation, signaling and interaction with T follicular helper cells,3–7 were associated with response (figure 2g). Pre-treatment immune repertoire measures demonstrated a significant association between increased peripheral IGH abundance and richness, and both future clinical benefit and response to therapy (figure 3a-d). Conclusions Response to CI therapy was associated with immunogenomic features of programmed cell death and B-cell activation. Pre-treatment circulating immunoglobulin diversity measures (high IGH abundance and IGH richness) also correlated with future response to therapy. Taken together, these data suggest that B-cell activity contributes significantly to response to CI therapy in mTNBC. Acknowledgements UNC Office of Clinical and Translational Research (OCTR), High Throughput Sequencing Facility (HTSF), and UNC Bioinformatics Core. We also thank the patients in this study and their families, without whom this study would not have been possible. Trial Registration Clinical Trials. gov: NCT02768701. Ethics Approval All patients provided written informed consent, and the study was approved by each institution’s institutional review board (No. NCT02768701). References Tutt A, Tovey H, Cheang MCU, et al. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med 2018;24(5):628–637. doi:10.1038/s41591-018-0009-7 Taylor NA, Vick SC, Iglesia MD, et al. Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer. J Clin Invest 2017;127(9):3472–3483. doi:10.1172/JCI90499 Hollern TFH B cell: Hollern DP, Xu N, Thennavan A, et al. B Cells and T Follicular Helper cells mediate response to checkpoint inhibitors in high mutation burden mouse models of breast cancer. Cell 2019;179(5):1191–1206.e21. doi:10.1016/j.cell.2019.10.028 Iglesia B cell: Iglesia MD, Vincent BG, Parker JS, et al. Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific breast and ovarian cancer. Clin Cancer Res 2014;20(14):3818–3829. doi:10.1158/1078-0432.CCR-13-3368 Fan IGG: Fan C, Prat A, Parker JS, et al. Building prognostic models for breast cancer patients using clinical variables and hundreds of gene expression signatures. BMC Med Genomics2011;4:3. Published 2011 Jan 9. doi:10.1186/1755-8794-4-3 Bindea: Bindea G, Mlecnik B, Tosolini M, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 2013;39(4):782–795. doi:10.1016/j.immuni.2013.10.003 Prat Claudin: Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 2010;12(5):R68. doi:10.1186/bcr2635

Caring for older patients with breast cancer presents unique clinical considerations because of preexisting and competing comorbidity, the potential for treatment-related toxicity, and the consequent impact on functional status. In the context of the COVID-19 pandemic, treatment decision making for older patients is especially challenging and encourages us to refocus our treatment priorities. While we work to avoid treatment delays and maintain therapeutic benefit, we also need to minimize the risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, myelosuppression, general chemotherapy toxicity, and functional decline. Herein, we propose multidisciplinary care considerations for the aging patient with breast cancer, with the goal to promote a team-based, multidisciplinary treatment approach during the COVID-19 pandemic and beyond. These considerations remain relevant as we navigate the “new normal” for the approximately 30% of breast cancer patients aged 70 years and older who are diagnosed in the United States annually and for the thousands of older patients living with recurrent and/or metastatic disease.

Objectives The agreement between clinician- and patient-reported toxicities and their association with poor tolerance to therapy were assessed in an older population receiving curative radiotherapy (RT). Materials and Methods Patients ≥ 65 years old with newly-diagnosed head and neck or lung cancer receiving curative RT ± chemotherapy were enrolled on a prospective, observational study. Agreement between clinician (CTCAEv4.02) and patient (PRO-CTCAE, EORTC QLQ-C30) report of toxicities were assessed at baseline, during treatment, and post-treatment. The association of clinician- and patient-reported symptoms with poor tolerance to therapy (defined as hospitalization, >3-day treatment delay, change in treatment regimen, or death) was assessed. Results Among 45 patients, median age was 71, 60% had head and neck cancer, and 47% received concurrent chemotherapy with RT. In comparing CTCAE vs PRO-CTCAE, there was good agreement at baseline except for fatigue, anorexia, and pain, where clinicians under-reported the severity. The discrepancy increased during treatment with clinicians reporting lower severity in ≥50% of matched pairs for 4/10 symptoms assessed. At follow-up, clinicians under-reported severity in ≥50% of pairs for 7/10 symptoms. CTCAE vs EORTC QLQ-C30 mirrored these findings. Patient-reported symptoms of nausea and dysphagia at 2 weeks and clinician-observed symptoms of nausea and dysphagia at 4 weeks were associated with poor tolerance to therapy. Conclusion Clinicians under-report toxicities during and after curative RT in older patients with head and neck or lung cancer. Select toxicities reported by patients early in treatment and clinicians later in treatment were associated with poor tolerance to cancer therapy, providing valuable complementary information.

Advances in breast cancer research are making treatment options increasingly effective and reducing mortality. Body composition is an example of a prognostic tool that can help personalize breast cancer treatments and further increase their effectiveness. In this study, we examine the association of several body composition measures with comorbidities, physical function, and quality of life. This study is a cross-sectional analysis of 99 women with early breast cancer scheduled for chemotherapy. Univariate regression models were used to identify significant associations of body composition metrics with patient demographics, clinical characteristics, measures of physical function, and patient-reported outcomes (PRO)s. Multivariable modeling was used to evaluate associations adjusted for age. Median age was 58 (range 24–83), 27% were non-white, and, 47% were obese (≥ 30 kg/m2). Increasing age was associated with lower Skeletal Muscle Density (SMD) (p = 0.0001), lower Skeletal Muscle Gauge (SMG) (p = 0.0005), and higher Visceral Adipose Tissue (VAT) (p 14 s), mean VAT was 57.87 higher (p = 0.004), SMD 5.70 lower (p = 0.04), and SMG 325.4 lower (p = 0.02). For each point of higher performance on the Short Physical Performance Battery (SPPB), VAT decreased 12.24 (p = 0.002) and SMD rose 1.22 (p = 0.02). In multivariable analysis adjusting for age, the association of TUG > 14 with higher VAT remained significant (p = 0.02). Suboptimal body composition prior to treatment is associated poor physical function and may be an indicator of clinical importance.

Diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) are aggressive non-Hodgkin’s lymphomas (NHLs) that evolve rapidly and are fatal if untreated [1]. While the majority of patients are ...

BACKGROUND. This study explores the incidence of patient‐reported major toxicity—symptoms rated “moderate,” “severe,” or “very severe”—for chemotherapy regimens commonly used in early breast cancer. PATIENTS AND METHODS. Female patients aged 21 years or older completed a validated Patient‐Reported Symptom Monitoring instrument and rated 17 symptoms throughout adjuvant or neoadjuvant chemotherapy. Fisher's exact tests compared differences in percentages in symptom ratings, and general linear regression was used to model the incidence of patient‐reported major toxicity. RESULTS. In 152 patients, the mean age was 54 years (range, 24–77), and 112 (74%) were white; 51% received an anthracycline‐based regimen. The proportion of patients rating fatigue, constipation, myalgia, diarrhea, nausea, peripheral neuropathy, and swelling of arms or legs as a major toxicity at any time during chemotherapy varied significantly among four chemotherapy regimens (p < .05). The mean (SD) number of symptoms rated major toxicities was 6.3 (3.6) for anthracycline‐based and 4.4 (3.5) for non‐anthracycline‐based regimens (p = .001; possible range, 0–17 symptoms). Baseline higher body mass index (p = .03), patient‐reported Karnofsky performance status ≤80 (p = .0003), and anthracycline‐based regimens (p = .0003) were associated with greater total number of symptoms rated major toxicities (alternative model: chemotherapy duration, p < .0001). Twenty‐six percent of dose reductions (26 of 40), 75% of hospitalizations (15 of 20), and 94% of treatment discontinuations (15 of 16) were in anthracycline‐based regimens. CONCLUSION. Capturing multiple toxicity outcomes throughout chemotherapy enables oncologists and patients to understand the range of side effects as they discuss treatment efficacies. Continuous symptom monitoring may aid in the timely development of interventions that minimize toxicity and improve outcomes. IMPLICATIONS FOR PRACTICE. This study investigated patient‐reported toxicities for 17 symptoms recorded prospectively during adjuvant and neoadjuvant chemotherapy regimens for early breast cancer. An analysis of four commonly used chemotherapy regimens identified significant differences among regimens in both individual symptoms and total number of symptoms rated moderate, severe, or very severe. Longer chemotherapy regimens, such as anthracycline‐based regimens followed by paclitaxel, had higher proportions of symptoms rated major toxicities. The inclusion of patient perspectives on multiple toxicity outcomes at the same time at multiple time points during chemotherapy has the potential for improving patient‐provider communication regarding symptom management, patient satisfaction, and long‐term clinical outcomes.

BACKGROUND. The aim of this meta‐analysis was to compare patient‐reported outcomes (PROs) between programmed death receptor‐1/programmed death‐ligand 1 (PD‐1/PD‐L1) inhibitors and standard‐of‐care therapy in patients with advanced cancer. METHODS. We searched randomized controlled trials (RCTs) comparing single‐agent PD‐1/PD‐L1 inhibitors (nivolumab, pembrolizumab, atezolizumab, avelumab, or durvalumab) with standard‐of‐care therapy in patients with advanced cancer reporting PROs with generic measures: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (QLQ‐C30) and the EuroQol Five Dimensions Questionnaire. The summary outcomes were changes in PROs from baseline to follow‐up within and between treatment groups and time to deterioration (TTD) in PROs based on clinically meaningful change. RESULTS. A total of 6,334 patients from 13 RCTs were included: six nivolumab, five pembrolizumab, and two atezolizumab trials. For the QLQ‐C30 global health status/quality of life, the pooled difference in mean change between treatment groups was 5.1 (95% confidence interval [CI], 3.3–6.9; p < .001) favoring PD‐1/PD‐L1 inhibitors. The pooled mean change from baseline in PD‐1/PD‐L1 inhibitors and controls was 0.1 (95% CI, −2.2, 2.5) and − 6.1 (95% CI, −8.4, −3.8), respectively. The TTD was significantly longer with PD‐1/PD‐L1 inhibitors, with a hazard ratio of 0.72 (95% CI, 0.55–0.93; p = .011). Similarly, significantly better outcomes were noted with PD‐1/PD‐L1 inhibitors on most of the other PRO measures. CONCLUSION. PD1/PD‐L1 inhibitors maintained health‐related quality of life to a greater degree and had less worsening in symptoms than standard‐of‐care therapy even though patients on these immune modulators were on treatment longer. The better PRO profile further supports the clinical benefit of this treatment strategy for advanced cancer. IMPLICATIONS FOR PRACTICE. We conducted a systematic review and meta‐analysis to compare patient‐reported outcomes (PROs) of programmed death receptor‐1/programmed death‐ligand 1 (PD‐1/PD‐L1) inhibitors and standard‐of‐care therapy in patients with advanced cancer. PD‐1/PD‐L1 inhibitors were associated with consistently smaller PRO score deterioration from baseline to follow‐up for different health‐related quality‐of‐life and symptoms scales. In addition, the time to deterioration in multiple PRO domains was significantly longer with PD‐1/PD‐L1 inhibitors. Taken together, these findings indicate that the patients treated with PD‐1/PD‐L1 inhibitors maintained health‐related quality of life to a greater degree and had less symptom burden compared with those treated with standard‐of‐care therapy.

Objectives To examine longitudinal symptoms, mobility and function, and quality of life (QOL) in adults newly diagnosed with acute leukemia. Sample & setting 55 adults undergoing induction chemotherapy at the University of North Carolina Lineberger Comprehensive Cancer Center and the Duke Cancer Institute. Methods & variables A prospective, longitudinal study with measures of mobility and function, global physical and mental health, cancer-related fatigue, anxiety, depression, sleep disturbance, pain intensity, and leukemia-specific QOL was conducted. Data were analyzed using descriptive statistics, linear mixed modeling, and one-way analysis of variance. Results 49 adults with acute leukemia completed assessments during hospitalizations. Global mental health and pain intensity did not change significantly. Global physical health significantly improved. Fatigue, anxiety, depression, and sleep disturbance decreased significantly. QOL increased significantly. Implications for nursing The significant decrease in anxiety and fatigue during hospitalization may be attributable to understanding of the disease process, familiarity with the staff, and ability to communicate concerns.