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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: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. METHODS: Individual-level data was pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36-months after. Cognitive performance was assessed with objective (working memory, processing speed and executive functions) and subjective tests and physical, emotional and functional well-being was also assessed. RESULTS: One hundred and sixty-seven (M age = 67.3 years) women, with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36-months. Measures of well-being improved from prior to systemic therapy to 12-months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. CONCLUSION: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.

PurposeOlder cancer survivors required medical care during the COVID-19 pandemic despite infection risks, but there are limited data on medical care in this age group. Methods. We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors ages 60-98 from five US regions (n=321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included self-reported interruptions in ability to see doctors, receive treatment or supportive therapies, or fill prescriptions. Logistic regression models evaluated bivariate and multivariate associations between care disruptions and education, medical, psychosocial and COVID-19-related factors. Multivariate models included age, county COVID-19 rates, comorbidity and post-diagnosis time. Results. There was a high response rate (n=262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were significantly higher with more education (OR 1.23 per one-year increase, 95% CI 1.09-1.39, p =0.001) and greater depression (OR 1.04 per one-point increase in CES-D score, CI 1.003-1.08, p=0.033); tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99 per one-point increase, p=0.012). There was a trend for associations between disruptions and comorbidity (unadjusted OR 1.13 per 1 added comorbidity, 95% CI 0.99-1.29, p=0.07). Adjusting for covariates, only higher education (p=0.001) and tangible social support (p=0.006) remained significantly associated with having care disruptions. Conclusions. Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.

Introduction Treatment burden is emerging as an important patient-centered outcome for older adults with cancer who concurrently manage geriatric conditions. Our objective was to evaluate the contribution of geriatric conditions to treatment burden in older adults with non-muscle invasive bladder cancer (NMIBC). Methods We identified 73,395 Medicare beneficiaries age 66+ diagnosed with NMIBC (Stage Results At baseline, 64% had multimorbidity and median 3 conditions (IQR 0–5). Prevalence of other geriatric conditions ranged from 5.9%–15.2%. Adjusted mean health system contact was 8.9 days (95% CI 8.6–9.2). Multimorbidity had the largest effect size (adjusted mean 11.8 contact days (95% CI 8.3–8.8)). Each additional chronic condition conferred a 13% increased average number of health system contact (adjusted IRR 1.132, 95% CI 1.129–1.135). Regardless of number of chronic conditions, rural patients consistently had more treatment burden than urban counterparts. Discussion In this population-based cohort of older NMIBC patients, multimorbidity and rurality were strongly associated with treatment burden in the year following NMIBC diagnosis. These findings highlight the need for interventions that reduce treatment burden due to geriatric conditions among the growing population of older adults with cancer, particularly in rural areas.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Background The coronavirus disease 2019 (COVID‐19) pandemic has had wide‐ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic. Methods The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web‐based or telephone COVID‐19 survey, between May 27 and September 11, 2020. Mixed‐effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies–Depression [CES‐D] scale) from before to during the pandemic in survivors versus controls and to test survivor‐control differences in the associations between changes in loneliness and changes in mental health, including depression (CES‐D, excluding the loneliness item), anxiety (the State‐Trait Anxiety Inventory), and perceived stress (the Perceived Stress Scale). Models were adjusted for age, race, county COVID‐19 death rates, and time between assessments. Results Loneliness increased from before to during the pandemic (0.211; P = .001), with no survivor‐control differences. Increased loneliness was associated with worsening depression (3.958; P < .001) and anxiety (3.242; P < .001) symptoms and higher stress (1.172; P < .001) during the pandemic, also with no survivor‐control differences. Conclusions Cancer survivors reported changes in loneliness and mental health similar to those reported by women without cancer. However, both groups reported increased loneliness from before to during the pandemic that was related to worsening mental health, suggesting that screening for loneliness during medical care interactions will be important for identifying all older women at risk for adverse mental health effects of the pandemic., Older breast cancer survivors and matched noncancer controls experienced similar increases in loneliness from before to during the COVID‐19 pandemic. Women who reported increased loneliness also experienced worsening depression and anxiety symptoms and higher stress during the pandemic.

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.

Background We evaluated deficit accumulation and how deficits affected cognition and physical activity among breast cancer survivors and non-cancer controls. Methods Newly diagnosed nonmetastatic survivors (n = 353) and matched non-cancer controls (n = 355) ages 60-98 years without neurological impairments were assessed presystemic therapy (or at enrollment for controls) from August 2010 to December 2016 and followed for 36 months. Scores on a 42-item index were analyzed in growth-mixture models to determine deficit accumulation trajectories separately and combined for survivors and controls. Multilevel models tested associations between trajectory and cognition (FACT-Cog and neuropsychological tests) and physical activity (IPAQ-SF) for survivors and controls. Results Deficit accumulation scores were in the robust range, but survivors had higher scores (95% confidence intervals [CI]) than controls at 36 months (0.18, 95% CI = 0.16 to 0.19, vs 0.16, 95% CI = 0.14 to 0.17; P = .001), and averages included diverse deficit trajectories. Survivors who were robust but became frailer (8.8%) had similar baseline characteristics to those remaining robust (76.2%) but experienced a 9.6-point decline self-reported cognition (decline of 9.6 vs 3.2 points; P = .04) and a 769 MET minutes per week decline in physical activity (P < .001). Survivors who started and remained prefrail (15.0%) had self-reported and objective cognitive problems. At baseline, frail controls (9.5%) differed from robust controls (83.7%) on deficits and self-reported cognition (P < .001). Within combined trajectories, frail survivors had more sleep disturbances than frail controls (48.6% [SD = 17.4%] vs 25.0% [SD = 8.2%]; P = .05). Conclusions Most survivors and controls remained robust, and there were similar proportions on a frail trajectory. However, there were differences in deficit patterns between survivors and controls. Survivor deficit accumulation trajectory was associated with patient-reported outcomes. Additional research is needed to understand how breast cancer and its treatments affect deficit accumulation.

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.

Unintentional falls and breast cancer are common among older women, but the associations between them are understudied. We aimed to identify factors associated with falls in older women with breast cancer. We retrospectively reviewed clinical records of older women with breast cancer at Duke Medical Center who had completed the Senior Adult Oncology Program geriatric assessment. Characteristics were compared between women had had at least one fall in the past year and those who did not. Pearson’s Chi-square tests and t tests were used for comparison of groups’ characteristics. Logistic regression determined factors associated with falling. We identified 425 women, age 76.2 years (range 65–89 years), at the time of the assessment. 118 (27.8%) women reported a fall in the prior year. Age, race, ethnicity, and time since diagnosis (all p > 0.05) were similar between groups. In univariate analyses, metastatic disease (p = 0.023) and history of endocrine therapy (p = 0.042) were more common among women who fell. Women who fell had lower systolic (p = 0.001), diastolic (p

Objectives The goal of this study was to evaluate the relationship between social support (SS) and grade 3–5 chemotherapy-related toxicities among older adults with cancer. Methods This is a secondary analysis of a prospective longitudinal study of patients aged 65+ with solid cancer which led to the development of a predictive model for grade 3–5 chemotherapy-related toxicity (the Cancer and Aging Research Group [CARG] Chemotherapy Toxicity Risk Score). SS was measured by a modified version of Medical-Outcome Study-Social Support Survey and grade 3–5 hematological and non-hematological toxicities were captured and graded using CTCAE version 3.0. Patients were categorized into those with poor (SS score ≤ 75) and good SS (score of 76–100). Multivariate polychotomous logistic regression was used to examine the associations between SS and chemotherapy-related toxicity with adjustment for the CARG Toxicity Risk Score. Results Compared to patients with good SS, those with poor SS were less likely to have grade 3–5 toxicity, especially for non-hematological toxicity (adjusted OR = 0.52, p = .02). Patients who did not have someone to take them to the doctor “most” or “all of the time” were less likely to have grade 3–5 non-hematological toxicity compared to patients who had someone to take them to the doctor most or all of the time (adjusted OR = 0.32, p = .02). Conclusion Our study showed that patients with poor SS, especially those with less availability of someone to take them to doctors were less likely to have a documented grade 3–5 non-hematological toxicity.

BACKGROUND Little is known about longitudinal symptom burden, its consequences for well-being, and whether lifestyle moderates the burden in older survivors. METHODS The authors report on 36-month data from survivors aged ≥60 years with newly diagnosed, nonmetastatic breast cancer and noncancer controls recruited from August 2010 through June 2016. Symptom burden was measured as the sum of self-reported symptoms/diseases as follows: pain (yes or no), fatigue (on the Functional Assessment of Cancer Therapy [FACT]-Fatigue scale), cognitive (on the FACT-Cognitive scale), sleep problems (yes or no), depression (on the Center for Epidemiologic Studies Depression scale), anxiety (on the State-Trait Anxiety Inventory), and cardiac problems and neuropathy (yes or no). Well-being was measured using the FACT-General scale, with scores from 0 to 100. Lifestyle included smoking, alcohol use, body mass index, physical activity, and leisure activities. Mixed models assessed relations between treatment group (chemotherapy with or without hormone therapy, hormone therapy only, and controls) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. RESULTS All groups reported high baseline symptoms, and levels remained high over time; differences between survivors and controls were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormone therapy-exposed survivors versus controls (P

ObjectiveThis study aimed to develop a blood test for the prediction of pre-eclampsia (PE) early in gestation. We hypothesised that the longitudinal measurements of circulating adipokines and sphingolipids in maternal serum over the course of pregnancy could identify novel prognostic biomarkers that are predictive of impending event of PE early in gestation.Study designRetrospective discovery and longitudinal confirmation.SettingMaternity units from two US hospitals.ParticipantsSix previously published studies of placental tissue (78 PE and 95 non-PE) were compiled for genomic discovery, maternal sera from 15 women (7 non-PE and 8 PE) enrolled at ProMedDx were used for sphingolipidomic discovery, and maternal sera from 40 women (20 non-PE and 20 PE) enrolled at Stanford University were used for longitudinal observation.Outcome measuresBiomarker candidates from discovery were longitudinally confirmed and compared in parallel to the ratio of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) using the same cohort. The datasets were generated by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays.ResultsOur discovery integrating genomic and sphingolipidomic analysis identified leptin (Lep) and ceramide (Cer) (d18:1/25:0) as novel biomarkers for early gestational assessment of PE. Our longitudinal observation revealed a marked elevation of Lep/Cer (d18:1/25:0) ratio in maternal serum at a median of 23 weeks’ gestation among women with impending PE as compared with women with uncomplicated pregnancy. The Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting impending event of PE with superior sensitivity (85% vs 20%) and area under curve (0.92 vs 0.52) from 5 to 25 weeks of gestation.ConclusionsOur study demonstrated the longitudinal measurement of maternal Lep/Cer (d18:1/25:0) ratio allows the non-invasive assessment of PE to identify pregnancy at high risk in early gestation, outperforming the established sFlt-1/PlGF ratio test.

BackgroundMaintenance of function during cancer treatment is important to older adults. Characteristics associated with pretreatment life-space mobility and changes during non-small cell lung cancer (NSCLC) treatment remain unknown.MethodsThis mixed methods cohort study recruited adults age ≥65 with advanced NSCLC starting palliative chemotherapy, immunotherapy, and/or targeted therapy from a Comprehensive Cancer Center, Veterans Affairs, and safety-net clinic. Patients completed geriatric assessments including Life-Space Assessment (LSA) pretreatment and at 1, 2, 4, and 6 months after treatment initiation. LSA scores range from 0 to 120 (greater mobility); LSA

Animal models suggest POCD may be caused by brain monocyte influx. To study this in humans, we developed a flow cytometry panel to profile CSF samples collected before and after major non-cardiac surgery in in 5 patients age ≥ 60 years who developed POCD and 5 matched controls who did not. We detected 12,654±4895 cells/10 ml CSF sample (mean±SD). Patients who developed POCD showed an increased CSF monocyte/lymphocyte ratio and MCP-1 receptor downregulation on CSF monocytes 24 hours after surgery. These pilot data demonstrate that CSF flow cytometry can be used to study mechanisms of postoperative neurocognitive dysfunction. CLINICAL TRIAL NUMBER AND REGISTRY URL: , https://clinicaltrials.gov/ct2/show/NCT01993836 (This manuscript describes a nested case-control study, performed within the larger cohort study, .)

Observational data have shown that some cancer survivors develop chronic conditions like frailty, sarcopenia, cardiac dysfunction, and mild cognitive impairment earlier and/or at a greater burden than similarly aged individuals never diagnosed with cancer or exposed to systemic or targeted cancer therapies. In aggregate, cancer- and treatment-related physical, cognitive, and psychosocial late- and long-term morbidities experienced by cancer survivors are hypothesized to represent accelerated or accentuated aging trajectories. However, conceptual, measurement, and methodological challenges have constrained efforts to identify, predict, and mitigate aging-related consequences of cancer and cancer treatment. In July 2018, the National Cancer Institute convened basic, clinical, and translational science experts for a think tank titled “Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.” Through the resulting deliberations, several research and resource needs were identified, including longitudinal studies to examine aging trajectories that include detailed data from before, during, and after cancer treatment; mechanistic studies to elucidate the pathways that lead to the emergence of aging phenotypes in cancer survivors; long-term clinical surveillance to monitor survivors for late-emerging effects; and tools to integrate multiple data sources to inform understanding of how cancer and its therapies contribute to the aging process. Addressing these needs will help expand the evidence base and inform strategies to optimize healthy aging of cancer survivors.

OBJECTIVES To examine the association between self-reported vision impairment (VI), hearing impairment (HI), and dual-sensory impairment (DSI), stratified by dementia status, on hospital admissions, hospice use, and healthcare costs. DESIGN Retrospective analysis. SETTING Medicare Current Beneficiary Survey from 1999 to 2006. PARTICIPANTS Rotating panel of community-dwelling Medicare beneficiaries, aged 65 years and older (N = 24 009). MEASUREMENTS VI and HI were ascertained by self-report. Dementia status was determined by self-report or diagnosis codes in claims data. Primary outcomes included any inpatient admission over a 2-year period, hospice use over a 2-year period, annual Medicare fee-for-service costs, and total healthcare costs (which included information from Medicare claims data and other self-reported payments). RESULTS Self-reported DSI was present in 30.2% (n = 263/871) of participants with dementia and 17.8% (n = 4112/23 138) of participants without dementia. In multivariable logistic regression models, HI, VI, or DSI was generally associated with increased odds of hospitalization and hospice use regardless of dementia status. In a generalized linear model adjusted for demographics, annual total healthcare costs were greater for those with DSI and dementia compared to those with DSI without dementia ($28 875 vs $3340, respectively). Presence of any sensory impairment was generally associated with higher healthcare costs. In a model adjusted for demographics, Medicaid status, and chronic medical conditions, DSI compared with no sensory impairment was associated with a small, but statistically significant, difference in total healthcare spending in those without dementia ($1151 vs $1056; P

Objective:To determine the relationship between affective measures and cognition before and after non-cardiac surgery in older adults.Methods:Observational prospective cohort study in 103 surgical patients age ≥ 60 years old. All participants underwent cognitive testing, Center for Epidemiologic Studies-Depression, and State Anxiety Inventory screening before and 6 weeks after surgery. Cognitive test scores were combined by factor analysis into 4 cognitive domains, whose mean was defined as the continuous cognitive index (CCI). Postoperative global cognitive change was defined by CCI change from before to after surgery, with negative CCI change indicating worsened postoperative global cognition and vice versa.Results:Lower global cognition before surgery was associated with greater baseline depression severity (Spearman’s r = −0.30, p = 0.002) and baseline anxiety severity (Spearman’s r = −0.25, p = 0.010), and these associations were similar following surgery (r = −0.36, p < 0.001; r = −0.26, p = 0.008, respectively). Neither baseline depression or anxiety severity, nor postoperative changes in depression or anxiety severity, were associated with pre- to postoperative global cognitive change.Conclusions:Greater depression and anxiety severity were each associated with poorer cognitive performance both before and after surgery in older adults. Yet, neither baseline depression or anxiety symptoms, nor postoperative change in these symptoms, were associated with postoperative cognitive change.

Background Cancer-related cognitive decline (CRCD) has been linked to apolipoprotein E (APOE) gene ε4 polymorphisms. APOE ε4 polymorphisms are also the strongest genetic risk for late-onset Alzheimer disease (AD), whereas ε2 polymorphisms protect against AD. However, the effects of ε2 polymorphisms on CRCD have not been evaluated. Methods We evaluated nonmetastatic breast cancer survivors (n = 427) and matched noncancer controls (n = 407) ages 60-98 years assessed presystemic therapy from August 2010 to December 2017 with annual follow-up to 24 months. Neuropsychological assessment measured attention, processing speed, executive function, and learning and memory. Linear mixed-effects models tested the effects of having an ε2 allele (vs none) on longitudinal cognitive domain z scores by treatment group (chemotherapy with or without hormonal therapy, hormonal therapy, and control) controlling for covariates; participants with ε2/ε4 genotype were excluded. Sensitivity analyses examined effects of other covariates and any ε4 positivity. Results There was an interaction with genotype for attention, processing speed, and executive functioning domain scores (Beta = 0.32, 95% confidence interval = 0.00 to 0.65); the chemotherapy group with an ε2 allele had higher scores at baseline and maintained higher scores over time compared with those without an ε2 allele, and this protective effect was not seen for other groups. There was no effect of ε2 on learning and memory domain scores. Conclusions APOE ε2 polymorphisms may protect against CRCD in older breast cancer survivors receiving chemotherapy. With replication, this information could be useful for survivorship care and informing future studies of possible links to AD and defining mechanisms of protection.

ObjectivesThe aim of this study was to develop a single blood test that could determine gestational age and estimate the risk of preterm birth by measuring serum metabolites. We hypothesised that serial metabolic modelling of serum analytes throughout pregnancy could be used to describe fetal gestational age and project preterm birth with a high degree of precision.Study designA retrospective cohort study.SettingTwo medical centres from the USA.ParticipantsThirty-six patients (20 full-term, 16 preterm) enrolled at Stanford University were used to develop gestational age and preterm birth risk algorithms, 22 patients (9 full-term, 13 preterm) enrolled at the University of Alabama were used to validate the algorithms.Outcome measuresMaternal blood was collected serially throughout pregnancy. Metabolic datasets were generated using mass spectrometry.ResultsA model to determine gestational age was developed (R2=0.98) and validated (R2=0.81). 66.7% of the estimates fell within ±1 week of ultrasound results during model validation. Significant disruptions from full-term pregnancy metabolic patterns were observed in preterm pregnancies (R2=−0.68). A separate algorithm to predict preterm birth was developed using a set of 10 metabolic pathways that resulted in an area under the curve of 0.96 and 0.92, a sensitivity of 0.88 and 0.86, and a specificity of 0.96 and 0.92 during development and validation testing, respectively.ConclusionsIn this study, metabolic profiling was used to develop and test a model for determining gestational age during full-term pregnancy progression, and to determine risk of preterm birth. With additional patient validation studies, these algorithms may be used to identify at-risk pregnancies prompting alterations in clinical care, and to gain biological insights into the pathophysiology of preterm birth. Metabolic pathway-based pregnancy modelling is a novel modality for investigation and clinical application development.

Context Testosterone treatment of hypogonadal men improves their hemoglobin, but the mechanism is not understood. Objective To investigate possible mechanisms by which testosterone stimulates erythropoiesis in hypogonadal older men with unexplained or iron-deficiency anemia. Design The Anemia Trial of The Testosterone Trials, a placebo-controlled study in older, hypogonadal men. Setting Twelve academic medical centers. Participants A total of 95 hypogonadal men (testosterone < 275 ng/mL) ≥65 years with anemia (hemoglobin < 12.7 g/dL). They were classified as having unexplained (n = 58) or iron deficiency anemia (n = 37). Intervention Testosterone or placebo gel for 1 year. Main Outcome Measures Markers of iron metabolism during the first 3 months of treatment. Results Testosterone replacement significantly (P < 0.001) increased hemoglobin in the 58 men who had unexplained anemia (adjusted mean difference 0.58 g/dL; 95% confidence interval, 0.31-0.85). Testosterone replacement tended to increase hemoglobin in the 37 men who had iron deficiency (0.38 g/dL; −0.19, 0.95), but the response was more variable and not statistically significant (P = 0.19). In men with unexplained anemia, testosterone replacement suppressed hepcidin (−8.2 ng/mL; −13.7, −2.7; P = 0.004) and ferritin (−19.6 µg/L; −32.8, −6.3; P = 0.004), but in men with iron deficiency, testosterone replacement did not. The decrease in hepcidin was moderately correlated with the increase in hemoglobin in the men with unexplained anemia (correlation coefficient −0.35, P = 0.01) but not in those with iron deficiency anemia (correlation coefficient −0.07, P = 0.73). Conclusions Testosterone replacement of older hypogonadal men with unexplained anemia stimulates erythropoiesis associated with increased iron mobilization. This effect appears to be attenuated by iron deficiency.

Outcomes in pediatric patients with ventricular assist devices (VADs) for advanced heart failure (HF) are improving, but the risk of associated morbidity and mortality remains substantial. Few data exist on the involvement of pediatric palliative care (PPC) in this high-risk patient population. We aimed to characterize the extent of palliative care involvement in the care of patients requiring VAD placement at our institution. Single-center retrospective chart review analyzing all VAD patients at a large pediatric center over a 4 year period. Timing and extent of palliative care subspecialty involvement were analyzed. Between January 2014 and December 2017, 55 HF patients underwent VAD implantation at our institution. Pediatric palliative care utilization steadily increased over consecutive years (2014

Background Prior comparisons of chemotherapy adverse events (AEs) by age and performance status (PS) are limited by the traditional maximum grade approach, which ignores low-grade AEs and longitudinal changes. Materials and Methods To compare fatigue and neuropathy longitudinally by age ( Results Older patients had on average a 0.17-point (95% confidence interval [CI], 0.00–0.34; p = .049) higher mean fatigue grade longitudinally compared with younger patients. PS 2 was associated with earlier development of grade ≥2 fatigue (hazard ratio [HR], 1.56; 95% CI, 1.07–2.27; p = .02). For neuropathy, older age was associated with earlier development of grade ≥2 neuropathy (HR, 1.41; 95% CI, 1.00–1.97; p = .049). Patients with PS 2 had a 1.30 point lower neuropathy AUC (95% CI, −2.36 to −0.25; p = .02) compared with PS 0–1. In contrast, maximum grade analyses only detected a higher percentage of older adults with grade ≥3 fatigue and neuropathy at some point during treatment. Conclusion Our comparison of complementary but distinct aspects of chemotherapy toxicity identified important longitudinal differences in fatigue and neuropathy by age and PS that are missed by the traditional maximum grade approach. Clinical trial identification number: NCT00003117 (CALGB 9730) Implications for Practice The traditional maximum grade approach ignores persistent low-grade adverse events (AEs) and changes over time. This toxicity over time analysis of fatigue and neuropathy during chemotherapy for advanced non-small cell lung cancer demonstrates how to use longitudinal methods to comprehensively characterize AEs over time by age and performance status (PS). We identified important longitudinal differences in fatigue and neuropathy that are missed by the maximum grade approach. This new information about how older adults and patients with PS 2 experience these toxicities longitudinally may be used clinically to improve discussions about treatment options and what to expect to inform shared decision making and symptom management.

Necrotizing Enterocolitis (NEC) is associated with prematurity, enteral feedings, and enteral dysbiosis. Accordingly, we hypothesized that along with nutritional variability, metabolic dysfunction would be associated with NEC onset. Methods: We queried a multicenter longitudinal database that included 995 preterm infants (&lt, 32 weeks gestation) and included 73 cases of NEC. Dried blood spot samples were obtained on day of life 1, 7, 28, and 42. Metabolite data from each time point included 72 amino acid (AA) and acylcarnitine (AC) measures. Nutrition data were averaged at each of the same time points. Odds ratios and 95% confidence intervals were calculated using samples obtained prior to NEC diagnosis and adjusted for potential confounding variables. Nutritional and metabolic data were plotted longitudinally to determine relationship to NEC onset. Results: Day 1 analyte levels of alanine, phenylalanine, free carnitine, C16, arginine, C14:1/C16, and citrulline/phenylalanine were associated with the subsequent development of NEC. Over time, differences in individual analyte levels associated with NEC onset shifted from predominantly AAs at birth to predominantly ACs by day 42. Subjects who developed NEC received significantly lower weight-adjusted total calories (p &lt, 0.001) overall, a trend that emerged by day of life 7 (p = 0.020), and persisted until day of life 28 (p &lt, 0.001) and 42 (p &lt, 0.001). Conclusion: Premature infants demonstrate metabolic differences at birth. Metabolite abnormalities progress in parallel to significant differences in nutritional delivery signifying metabolic dysfunction in premature newborns prior to NEC onset. These observations provide new insights to potential contributing pathophysiology of NEC and opportunity for clinical care-based prevention.

Objective To investigate the relationships between self-reported and objectively measured cognitive function prior to systemic therapy and subsequent well-being outcomes over 24 months in older breast cancer survivors. Methods Data were from 397 women aged 60 to 98 diagnosed with non-metastatic breast cancer in the Thinking and Living with Cancer Study recruited from 2010-2016. Cognitive function was measured at baseline (following surgery, prior to systemic therapy) using neuropsychological assessments of attention, processing speed, and executive function (APE), learning and memory (LM), and the self-reported FACT-Cog scale. Well-being was measured using the FACT-G functional, physical, social, and emotional well-being domain scales at baseline and 12 and 24 months later, scaled from 0 (low) to 100 (high). Linear mixed-effects models assessed the relationships between each of baseline APE, LM, and FACT-Cog quartiles with well-being scores over 24 months, adjusted for confounding variables. Results At baseline, older survivors in the lowest APE, LM, and FACT-Cog score quartiles experienced poorer global well-being than those in the highest quartiles. At 24 months, older survivors tended to improve in well-being, and there were no differences according to baseline APE or LM scores. At 24 months, mean global well-being was 80.3 (95% CI: 76.2-84.3) among those in the lowest vs 86.6 (95% CI: 83.1-90.1) in the highest FACT-cog quartile, a clinically meaningful difference of 6.3 points (95% CI: 1.5-11.1). Conclusions Among older breast cancer survivors, self-reported, but not objective cognitive impairments, were associated with lower global well-being over the first 2 years of survivorship.

Ceramides and dihydroceramides are sphingolipids that present in abundance at the cellular membrane of eukaryotes. Although their metabolic dysregulation has been implicated in many diseases, our knowledge about circulating ceramide changes during the pregnancy remains limited. In this study, we present the development and validation of a high-throughput liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for simultaneous quantification of 16 ceramides and 10 dihydroceramides in human serum within 5 mins by using stable isotope-labeled ceramides as internal standards (ISs). This method employs a protein precipitation method for high throughput sample preparation, reverse phase isocratic elusion for chromatographic separation, and Multiple Reaction Monitoring (MRM) for mass spectrometric detection. To qualify for clinical applications, our assay was validated against the FDA guidelines: the Lower Limit of Quantitation (LLOQ as low as 1 nM), linearity (R2>0.99), precision (Coefficient of Variation90%), stability (>85%), and carryover (

Low transferrin saturation (TSAT) or reduced serum ferritin level are suggestive of iron deficiency but the relationship between iron parameters and outcomes has not been systematically evaluated in older adults with heart failure (HF) and anemia.We identified a multicenter cohort of adults age ≥ 65 years with HF and incident anemia (hemoglobin13 g/dL [men] or 12 g/dL [women]) between 2005 and 2012. Patients were included if ferritin (ng/mL) and TSAT (%) were evaluated within 90 days of incident anemia. HF hospitalizations and all-cause death were ascertained from electronic health records.Among 4103 older adults with HF and incident anemia, 47% had TSAT20% and the median (IQR) ferritin was 126 (53, 256) ng/mL. In multivariable analyses, compared with TSAT ≥20%, patients with TSAT20% were at increased risk of HF hospitalization for serum ferritin100 ng/mL (adjusted HR [aHR] 1.40, 95% CI:1.16-1.70) and 100-300 ng/mL (aHR 1.24, 95% CI:1.01-1.52) but not for a ferritin300 ng/mL (aHR 0.89, 95% CI 0.65-1.23). In addition, TSAT20% was independently associated with an increased risk of all-cause death regardless of serum ferritin level (100 ng/mL: aHR 1.42, 95% CI:1.20-1.68; 100-300 ng/mL: aHR 1.18, 95% CI:1.00-1.38;300 ng/mL: aHR 1.33, 95% CI:1.06-1.69).Among older adults with HF and incident anemia who had iron studies tested, nearly half had a TSAT20%, which was independently associated with higher rates of morbidity and death.

BACKGROUND Platinum and etoposide with thoracic radiation followed by prophylactic cranial irradiation constitute the standard treatment for limited-stage small cell lung cancer (LS-SCLC). Many patients with LS-SCLC are elderly with comorbidities. METHODS Individual patient data were collected from 11 phase 2 or 3 trials for LS-SCLC conducted by the National Clinical Trials Network and activated from 1990 to 2010. The primary endpoint was overall survival (OS); the secondary endpoints were progression-free survival (PFS), the rate of severe adverse events, and off-treatment reasons. The outcomes were compared for patients 70 years old or older (elderly patients) and patients younger than 70 years (younger patients). RESULTS Individual patient data from 1049 younger patients (81%) and 254 elderly patients (19%) were analyzed. In the multivariate model, elderly patients, in comparison with younger patients, had worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.18-1.63; median OS for elderly patients, 17.8 months; OS for younger patients, 23.5 months) and worse PFS (HR, 1.19; 95% CI, 1.03-1.39; median PFS for elderly patients, 10.6 months; median PFS for younger patients, 12.3 months). Elderly patients, in comparison with younger patients, experienced more grade 5 adverse events (8% vs 3%; P < .01) and more grade 3 or higher dyspnea (11% vs 7%; P = .03) but less grade 3 or higher esophagitis/dysphagia (14% vs 19%; P = .04) and less grade 3 or higher vomiting (11% vs 17%; P = .01). Elderly patients completed treatment less often, discontinued treatment because of adverse events and patient refusal more frequently, and died during treatment more frequently. CONCLUSIONS Elderly patients with LS-SCLC have worse PFS and OS and more difficulty in tolerating therapy. Future trials should incorporate assessments of elderly patients, novel monitoring of adverse events, and more tolerable radiation and systemic therapies.

This study sought to define the role of first-line platinum-based doublet chemotherapy in older patients with non-small cell lung cancer (NSCLC).We analyzed three first-line NSCLC trials: CALGB 9730, CALGB 30203, and CALGB 30801, which tested carboplatin and paclitaxel; carboplatin and gemcitabine; and carboplatin with either pemetrexed or gemcitabine, respectively. Overall survival was the primary endpoint. Age-based comparisons with a cutpoint of 65 years were performed with Cox proportional hazards models with adjustments for sex, tumor histology, cancer stage, chemotherapy, and smoking history and after stratifying by performance score. Secondary endpoints were grade 3-5 adverse events, chemotherapy cycles completed, and whether toxicity prompted chemotherapy discontinuation.730 patients were included; 337 (46%) were 65+ years of age. No statistically significant difference in survival was observed for older (≥65) versus younger patients (HR = 1.096; 95% CI = (0.94, 1.28); p = 0.25). A trend emerged with increased odds of a grade 3-5 adverse event for patients ≥65 years versus65 years (OR = 1.52; 95% CI = (0.99, 2.31); p = 0.05). The proportion of completed chemotherapy cycles was marginally lower in older patients (difference = -5%; 95% CI = (-9, 0.2); p = 0.06) for those ≥65 years versus65 years, but no statistically significant difference occurred in the rate of chemotherapy discontinuation for toxicity (OR = 1.4; 95% CI = (0.85, 2.19); p = 0.21) for patients ≥65 years versus65 years. A cutpoint of 70 years yielded similar results.These findings support carboplatin doublet-based chemotherapy in select older patients with advanced NSCLC.

Objectives To analyze self-reported changes in physical function in older women with breast cancer receiving adjuvant chemotherapy. Design Secondary analysis of the Cancer and Leukemia Group B (CALGB) 49907 prospective randomized clinical trial. Setting CALGB institutions in the United States. Participants Women aged 65 and older with Stage I to III breast cancer enrolled in CALGB 49907 who had physical function data from before and after receipt of adjuvant chemotherapy (N=256; mean age 71.5, range 65-85). Measurements Participants were administered the physical function subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire before chemotherapy, at the end of chemotherapy, and 12 months after chemotherapy initiation. Functional decline was defined as a more than 10-point decrease from baseline at each time point. Resilience was defined as return to within 10 points of baseline. Multivariable regression was used to examine pretreatment characteristics associated with physical function changes. Results Of 42% of participants who had physical function decline from before to the end of chemotherapy, 47% recovered by 12 months (were resilient). Almost one-third experienced functional decline from before chemotherapy to 12 months later. Pretreatment fatigue was a risk factor for functional decline from before to the end of chemotherapy (P=.02). Risk factors for functional decline at 12 months included pretreatment dyspnea (P=.007) and being unmarried (P=.01). Conclusion Functional decline was common in older women receiving adjuvant chemotherapy for breast cancer in a clinical trial. Although half recovered their physical function, one-third had a clinically meaningful decline at 12 months. Strategies are needed to prevent functional decline in older adults receiving chemotherapy. J Am Geriatr Soc 67:920-927, 2019.

BACKGROUND The current study assessed the feasibility of a mentored home-based vegetable gardening intervention and examined changes in health-related outcomes among breast cancer survivors (BCS). METHODS BCS were randomized to either a year-long vegetable gardening intervention to begin immediately or a wait-list control. Master Gardeners mentored participants in planning, planting, and maintaining 3 seasonal gardens over the course of 1 year. Participant accrual, retention, and satisfaction rates of ≥80% served as feasibility (primary outcome) benchmarks. Secondary outcomes (ie, vegetable consumption, physical activity, performance and function, anthropometrics, biomarkers, and health-related quality of life) were collected at baseline and post-intervention (1-year follow-up) using subjective and objective measures. RESULTS The trial surpassed all feasibility benchmarks at 82% of targeted accrual, 95% retention, and 100% satisfaction (ie, experience ratings of "good to excellent" and willingness to "do it again"). Compared with the controls, intervention participants reported significantly greater improvements in moderate physical activity (+14 vs -17 minutes/week) and demonstrated improvements in the 2-Minute Step Test (+22 vs + 10 steps), and Arm Curl (+2.7 vs + 0.1 repetitions) (P values

BACKGROUND: Chemotherapy preference refers to a patient’s interest in receiving chemotherapy. This study examined whether chemotherapy preference was associated with toxicity, efficacy, quality of life (QoL), and functional outcomes during and after completion of adjuvant chemotherapy in older women with breast cancer. METHODS: This study is a secondary analysis of CALGB 49907, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in patients age 65 years or older with breast cancer. A subset of 145 patients completed a questionnaire to describe chemotherapy preference pre-treatment. The association of this pre-treatment preference with the patient’s perception of self-health, predicted and actual QoL, patient- and professional-reported toxicity, mental health, self-rated function, and survival was studied during and after treatment. RESULTS: The median age of patients was 71 years and 47% had a high preference for chemotherapy. On baseline demographics, the low preference group had a higher proportion of white patients (95% vs. 78%, p=0.004). Before treatment, low chemotherapy preference was associated with greater nausea/vomiting (p=0.008). Mid-treatment, low preference was associated with lower QoL, worse social, emotional and physical function (all p≤0.02) and worse nausea/vomiting, cancer symptoms and financial worries (all p

This article describes a web‐based survey of the Alliance for Clinical Trials in Oncology membership, including physicians, nurses, patient advocates, project managers, statisticians, leadership, and administrative staff. The goal of the survey was to identify new strategies to effect change in accrual for older patients with cancer by eliciting the opinions of a national sample of the oncology clinical research workforce and patient advocates who participate in high‐impact cancer clinical research., Background. There are multiple known individual‐ and practice‐level barriers to enrollment of older patients with cancer to clinical trials, but little is known about how the clinical research workforce feels about potential higher‐level strategy changes aimed to promote increased enrollment of older patients. Subjects, Materials, and Methods. We invited all 11,351 Alliance for Clinical Trials in Oncology (“Alliance”) members to participate in an anonymous, web‐based survey to examine awareness of current accrual patterns for older patients to clinical trials, to ascertain consensus on how to tackle enrollment challenges, and to provide the impetus for high‐level changes to improve clinical trial accrual of older patients with cancer. Results. During the period from February 28, 2017, to June 16, 2017, 1,146 Alliance members participated (response rate = 10%), including a national diverse sample of physicians, nurses, administrative/clinical research staff, and patient advocates with representation from community, academic, and rural sites. Overall, one third felt that >50% of clinical trial enrollees should be age ≥65, and 64.9% felt the Alliance could improve upon enrollment of older patients. The four most commonly ranked strategies to improve enrollment of older patients were creating more dedicated trials for this population (36.3%), minimizing exclusion criteria focused on comorbidity (35.5%), developing independent strategies for those aged ≥65 and for those aged ≥70 (33.2%), and requiring that most/all Alliance trials have a specific expansion cohort of older patients (30.0%). Conclusion. We anticipate that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials. Implications for Practice. This survey of the Alliance for Clinical Trials membership sought opinions on potential, large‐scale, national strategies to improve accrual of older adults with cancer. Consensus was found around multiple strategies, including creating more dedicated trials for older patients, developing less stringent eligibility criteria, and mandating expansion cohorts of older patients within broader Alliance trials. It is anticipated that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials.

Importance The practice of oncology will increasingly involve the care of a growing population of individuals with midlife and late-life cancers. Managing cancer in these individuals is complex, based on differences in biological age at diagnosis. Biological age is a measure of accumulated life course damage to biological systems, loss of reserve, and vulnerability to functional deterioration and death. Biological age is important because it affects the ability to manage the rigors of cancer therapy, survivors' function, and cancer progression. However, biological age is not always clinically apparent. This review presents a conceptual framework of life course biological aging, summarizes candidate measures, and describes a research agenda to facilitate clinical translation to oncology practice. Observations Midlife and late-life cancers are chronic diseases that may arise from cumulative patterns of biological aging occurring over the life course. Before diagnosis, each new patient was on a distinct course of biological aging related to past exposures, life experiences, genetics, and noncancer chronic disease. Cancer and its treatments may also be associated with biological aging. Several measures of biological age, including p16INK4a, epigenetic age, telomere length, and inflammatory and body composition markers, have been used in oncology research. One or more of these measures may be useful in cancer care, either alone or in combination with clinical history and geriatric assessments. However, further research will be needed before biological age assessment can be recommended in routine practice, including determination of situations in which knowledge about biological age would change treatment, ascertaining whether treatment effects on biological aging are short-lived or persistent, and testing interventions to modify biological age, decrease treatment toxic effects, and maintain functional abilities. Conclusions and relevance Understanding differences in biological aging could ultimately allow clinicians to better personalize treatment and supportive care, develop tailored survivorship care plans, and prescribe preventive or ameliorative therapies and behaviors informed by aging mechanisms.

Purpose Concurrent chemoradiotherapy is standard treatment for patients with stage III non–small-cell lung cancer. Elderly patients may experience increased rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy. Patients and Methods Individual patient data were collected from 16 phase II or III trials conducted by US National Cancer Institute–supported cooperative groups of concurrent chemoradiotherapy alone or with consolidation or induction chemotherapy for stage III non–small-cell lung cancer from 1990 to 2012. Overall survival (OS), progression-free survival, and AEs were compared between patients age ≥ 70 (elderly) and those younger than 70 years (younger). Unadjusted and adjusted hazard ratios (HRs) for survival time and CIs were estimated by single-predictor and multivariable frailty Cox models. Unadjusted and adjusted odds ratio (ORs) for AEs and CIs were obtained from single-predictor and multivariable generalized linear mixed-effect models. Results A total of 2,768 patients were classified as younger and 832 as elderly. In unadjusted and multivariable models, elderly patients had worse OS (HR, 1.20; 95% CI, 1.09 to 1.31 and HR, 1.17; 95% CI, 1.07 to 1.29, respectively). In unadjusted and multivariable models, elderly and younger patients had similar progression-free survival (HR, 1.01; 95% CI, 0.93 to 1.10 and HR, 1.00; 95% CI, 0.91 to 1.09, respectively). Elderly patients had a higher rate of grade ≥ 3 AEs in unadjusted and multivariable models (OR, 1.35; 95% CI, 1.07 to 1.70 and OR, 1.38; 95% CI, 1.10 to 1.74, respectively). Grade 5 AEs were significantly higher in elderly compared with younger patients (9% v 4%; P < .01). Fewer elderly compared with younger patients completed treatment (47% v 57%; P < .01), and more discontinued treatment because of AEs (20% v 13%; P < .01), died during treatment (7.8% v 2.9%; P < .01), and refused further treatment (5.8% v 3.9%; P = .02). Conclusion Elderly patients in concurrent chemoradiotherapy trials experienced worse OS, more toxicity, and had a higher rate of death during treatment than younger patients.

BACKGROUND A nocebo is an inert substance associated with adverse events. Although previous studies have examined the positive (placebo) effects of such inert substances, few have examined negative (nocebo) adverse event profiles, particularly in older patients who have higher morbidity and can experience frequent and severe adverse events from cancer therapy. METHODS This study focused on placebo/nocebo-exposed patients who participated in 2 double-blind, placebo-controlled, cancer therapeutic studies, namely, North Central Cancer Therapy Group trial NCCTG 97-24-51 and American College of Surgeons Oncology Group trial Z9001, with the goal of reporting the comparative, age-based adverse event rates, as reported during the conduct of these trials. RESULTS Among the 446 patients who received only placebo/nocebo and who were the focus of the current report, 161 were aged ≥65 years at the time of respective trial entry, and 5234 adverse events occurred. Unadjusted adverse event rates did not differ significantly between patients aged ≥65 years and younger patients (rate ratio, 1.01; 99% confidence interval, 0.47-2.02), and the findings were similar findings for grade 2 or worse adverse events and for all symptom-driven adverse events (for example, pain, loss of appetite, anxiety). Adjustment for sex, ethnicity, baseline performance score, and individual trial resulted in no significant age-based differences in adverse event rates. Similar findings were observed with an age threshold of 70 years. CONCLUSIONS Adverse events are equally common in older and younger cancer patients who are exposed to nocebo and thus require the same degree of clinical consideration regardless of age. Cancer 2017;123:4193-4198. © 2017 American Cancer Society.

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years ( v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population.

Malignant gliomas remain incurable with a poor prognosis despite of aggressive treatment. We have been studying the development of brain tumors in a glioma rat model, where rats develop brain tumors after prenatal exposure to ethylnitrosourea (ENU), and there is a sizable interval between when the first pathological changes are noted and tumors become detectable with MRI. Our aim to define a molecular timeline through proteomic profiling of the cerebrospinal fluid (CSF) such that brain tumor commitment can be revealed earlier than at the presymptomatic stage. A comparative proteomic approach was applied to profile CSF collected serially either before, at and after the time MRI becomes positive. Elastic net (EN) based models were developed to infer the timeline of normal or tumor development respectively, mirroring a chronology of precisely timed, "clocked", adaptations. These CSF changes were later quantified by longitudinal entropy analyses of the EN predictive metric. False discovery rates (FDR) were computed to control the expected proportion of the EN models that are due to multiple hypothesis testing. Our ENU rat brain tumor dating EN model indicated that protein content in CSF is programmed even before tumor MRI detection. The findings of the precisely timed CSF tumor microenvironment changes at presymptomatic stages, deviation from the normal development timeline, may provide the groundwork for the understanding of adaptation of the brain environment in tumorigenesis to devise effective brain tumor management strategies.

Adults aged 85 years and older, the "oldest old," are the fastest-growing age group in the United States, yet relatively little is known about their cancer burden. Combining data from the National Cancer Institute, the North American Association of Central Cancer Registries, and the National Center for Health Statistics, the authors provide comprehensive information on cancer occurrence in adults aged 85 years and older. In 2019, there will be approximately 140,690 cancer cases diagnosed and 103,250 cancer deaths among the oldest old in the United States. The most common cancers in these individuals (lung, breast, prostate, and colorectum) are the same as those in the general population. Overall cancer incidence rates peaked in the oldest men and women around 1990 and have subsequently declined, with the pace accelerating during the past decade. These trends largely reflect declines in cancers of the prostate and colorectum and, more recently, cancers of the lung among men and the breast among women. We note differences in trends for some cancers in the oldest age group (eg, lung cancer and melanoma) compared with adults aged 65 to 84 years, which reflect elevated risks in the oldest generations. In addition, cancers in the oldest old are often more advanced at diagnosis. For example, breast and colorectal cancers diagnosed in patients aged 85 years and older are about 10% less likely to be diagnosed at a local stage compared with those diagnosed in patients aged 65 to 84 years. Patients with cancer who are aged 85 years and older have the lowest relative survival of any age group, with the largest disparities noted when cancer is diagnosed at advanced stages. They are also less likely to receive surgical treatment for their cancers; only 65% of breast cancer patients aged 85 years and older received surgery compared with 89% of those aged 65 to 84 years. This difference may reflect the complexities of treating older patients, including the presence of multiple comorbidities, functional declines, and cognitive impairment, as well as competing mortality risks and undertreatment. More research on cancer in the oldest Americans is needed to improve outcomes and anticipate the complex health care needs of this rapidly growing population.

BackgroundThe clinical features of Kawasaki disease (KD) overlap with those of other paediatric febrile illnesses. A missed or delayed diagnosis increases the risk of coronary artery damage. Our computer algorithm for KD and febrile illness differentiation had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 94.8%, 70.8%, 93.7% and 98.3%, respectively, in a single-centre validation study. We sought to determine the performance of this algorithm with febrile children from multiple institutions across the USA.MethodsWe used our previously published 18-variable panel that includes illness day, the five KD clinical criteria and readily available laboratory values. We applied this two-step algorithm using a linear discriminant analysis-based clinical model followed by a random forest-based algorithm to a cohort of 1059 acute KD and 282 febrile control patients from five children’s hospitals across the USA.ResultsThe algorithm correctly classified 970 of 1059 patients with KD and 163 of 282 febrile controls resulting in a sensitivity of 91.6%, specificity of 57.8% and PPV and NPV of 95.4% and 93.1%, respectively. The algorithm also correctly identified 218 of the 232 KD patients (94.0%) with abnormal echocardiograms.InterpretationThe expectation is that the predictive accuracy of the algorithm will be reduced in a real-world setting in which patients with KD are rare and febrile controls are common. However, the results of the current analysis suggest that this algorithm warrants a prospective, multicentre study to evaluate its potential utility as a physician support tool.

Advanced heart failure in children is characterized by dynamic clinical trajectories, uncertainty of prognosis, and intermittent need for difficult decision-making, often related to novel therapeutic interventions with uncertain impact on quality of life. This review will examine the current role of palliative care to support this unique population.Pediatric heart failure patients commonly die in ICUs with high burden of invasive therapies together with end of life care needs. In addition, several studies advocate for integration of palliative care early in disease trajectory, not only focused on end of life care. Many advocate for the core tenets of palliative care (symptom management, communication of prognosis, and advanced care planning) to be provided by the primary cardiology team, with consultation by pediatric palliative care specialists. There is also a consensus that palliative care training should be incorporated into pediatric advanced heart disease training programs.Palliative care is an important component of pediatric heart failure care. Research and quality improvement efforts are needed to determine the most effective palliative care interventions for children with advanced heart disease. Provision of palliative care is an essential component of training for pediatric heart failure and transplant specialists.

PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician’s choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer–specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor–negative patients (HR, 0.66; P = .02), but not among hormone receptor–positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease. Competing risks in this older population dilute overall survival benefits.

Background Older patients with non-small cell lung cancer (NSCLC) are often not prescribed standard therapy. It is important to know which older patients would be candidates for aggressive therapy based on their prognosis, and to develop a model that can help determine prognosis. Methods Data on older patients (≥70 years) enrolled on 38 NCI cooperative group trials of advanced NSCLC from 1991 to 2011 were analyzed. Multivariable Cox PH model was built with a stepwise selection. We derived a prognostic score using the estimated Cox PH regression coefficient. We then calculated the area under receiver operating characteristic (ROC) curve of survival in the testing set. Results The final analysis included 1467 patients, who were randomly divided into a training (n = 963) and a testing set (n = 504). The prognostic risk score was calculated as: 3 (if male) + 3 (if PS = 1) + 8 (if PS = 2) + 11 (if initial stage = IV) + 4 (if weight loss). Patients were classified into two prognostic groups: good (0–8) and poor (≥9). The median survival in the two groups in the testing set were 13.15 (95% CI, 10.82–15.91) and 8.52 months (95% CI, 7.5–9.63), respectively. The model had area under the 1-year and 2-year ROCs (0.6 and 0.65, respectively) that were higher than existing models. Conclusions Male gender, poor performance status, distant metastases and recent weight loss predict for poor overall survival (OS) in older patients with advanced NSCLC. This study proposes a simple prognostic model for older adults with advanced NSCLC.

Cancer, its treatment, and associated adverse effects may accelerate the functional aging of cancer survivors. In the current study, the authors used geriatric assessment (GA) to compare the functional age of long-term cancer survivors with that of similarly aged women without a cancer history, and to examine whether functional age influences all-cause mortality differently between these 2 groups.Participants included 1723 cancer survivors and 11,145 age-matched, cancer-free women enrolled in the Iowa Women's Health Study in 1986 who completed the 2004 questionnaire (at ages 73-88 years). GA domain deficits included ≥2 physical function limitations, ≥2 comorbidities, poor general health, poor mental health, and underweight. The risk of all-cause mortality was estimated for deficits in each GA domain between 4 groups based on the cross-classification of the presence and/or absence of cancer history and GA domain deficit (the referent group was cancer-free women without a GA deficit).Both cancer history and GA domain deficits significantly predicted 10-year mortality for all GA domains. Cancer survivors without deficits had a 1.3-fold to 1.4-fold risk of mortality, similar to the 1.1-fold to 1.7-fold risk noted among cancer-free women with deficits (all P .05). Cancer survivors with deficits were found to have the highest mortality risk for 4 of 5 domains (hazard ratio range, 1.6-2.0). Mortality risk increased with the increasing number of GA deficits, which was greater in cancer survivors compared with cancer-free women.Even without GA deficits, cancer survivors appear to have an excess risk of death compared with women without cancer, and these deficits add to mortality risk. Interventions are needed to maintain or improve functional/physiological capacity as women age, especially in cancer survivors.

Aims Limited data exist on the epidemiology, evaluation, and prognosis of otherwise unexplained anaemia of the elderly in heart failure (HF). Thus, we aimed to determine the incidence of anaemia, to characterize diagnostic testing patterns for potentially reversible causes of anaemia, and to evaluate the independent association between incident anaemia and long-term morbidity and mortality. Methods and results Within the Cardiovascular Research Network (CVRN), we identified adults age ≥65 years with diagnosed HF between 2005 and 2012 and no anaemia at entry. Incident anaemia was defined using World Health Organization (WHO) haemoglobin thresholds ( Conclusion Among older adults with HF, incident anaemia is common and independently associated with substantially increased risks of morbidity and mortality. Additional research is necessary to clarify the value of routine evaluation and treatment of potentially reversible causes of anaemia.

Background: Physical resilience, the ability to resist decline and maintain functional status despite a stressor such as chemotherapy, is a central aspect of successful aging. Understanding clinical and biological factors associated with resilience in older women receiving chemotherapy for early breast cancer may facilitate the development of targeted interventions to maintain an individual’s robustness.Methods: Women age ≥65 (N=406) with Stage I-III breast cancer who were part of a clinical study of neo/adjuvant chemotherapy in older women were recruited from 16 sites (NCT01472094, R01AG037037). The Deficit Accumulation Index (DAI), a continuous score (0-1) calculated based on 51-items from geriatric assessment data (Cohen et al Cancer 2017), was measured before and after receipt of chemotherapy. DAI was categorized as robust (0.0 12 weeks, and 74% received primary prophylaxis with WBC growth factors. Among these 324 robust older women, 253 (78%) remained robust (resilient) at the end of chemotherapy, 63 (19%) became prefrail, and 8 (3%) became frail. In univariate analyses, patients treated with anthracycline (OR=0.63, p=0.09), planned duration of treatment > 12 weeks (OR=0.56, p=0.04), elevated IL-6 ≥2.7 pg/ml (OR=0.59, p=0.05), elevated CRP ≥4.3 μg/ml (OR=0.57, p=0.04), elevated D-dimer ≥0.7 μg/ml (OR=0.61, p=0.07), or at least one elevated biomarker (OR=0.18, p Conclusions: In this cohort of older women with early breast cancer who were robust prior to initiation of chemotherapy, 22% became prefrail or frail at end of treatment. Resilience to chemotherapy was related to inflammatory and coagulation biomarkers. Further research is needed to examine the mechanism underlying why some older women are resilient and retain their robustness after receiving treatment, whereas others experience decline, and further explore the role of inflammation/coagulation in this phenomenon. Table 1. Multivariable associations between baseline blood biomarkers and resilienceResilient (n=253) No. %Non-resilient (n=71) No. %Multivariable OR (95%CI)P value# of elevated biomarkers*064 (25)4 (6)1.00190 (36)29 (41)0.16 (0.05-0.55)0.004255 (22)22 (31)0.14 (0.04-0.49)0.002344 (17)16 (23)0.14 (0.04-0.51)0.003No elevated biomarker64 (25)4 (6)1.00At least one elevated189 (75)67 (94)0.15 (0.04-0.49)0.002*Biomarkers were defined as elevated using the entire cohort median value as cut off points (IL-6 ≥2.7 pg/ml, CRP ≥4.3 μg/ml, and D-dimer ≥0.7 μg/ml). Combined effects of biomarkers were examined by creating a four-level categorical combination variable: 0=all three biomarkers are Citation Format: Mina S Sedrak, Canlan Sun, Hyman Muss, Rachel A. Freedman, Allison Magnuson, Cary P. Gross, William P. Tew, Heidi D. Klepin, Tanya M. Wildes, Efrat Dotan, Tracey O'Connor, Mary Ann Fenton, Ruby Sharma, Andrew Chapman, Cynthia Owusu, Selina Chow, Heeyoung Kim, Vani Katheria, Mark LaBarge, William Dale, Saro Armenian, Susan Neuhausen, Harvey J. Cohen. Inflammation and coagulation biomarkers associated with physical resilience in older women receiving chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-03.

Ceramides and dihydroceramides are sphingolipids that present in abundance at the cellular membrane of eukaryotes. Although their metabolic dysregulation has been implicated in many diseases, our knowledge about circulating ceramide changes during the pregnancy remains limited. In this study, we present the development and validation of a high-throughput liquid chromatography-tandem mass spectrometric method for simultaneous quantification of 16 ceramides and 10 dihydroceramides in human serum within 5 min. by using stable isotope-labeled ceramides as internal standards. This method employs a protein precipitation method for high throughput sample preparation, reverse phase isocratic elusion for chromatographic separation, and Multiple Reaction Monitoring for mass spectrometric detection. To qualify for clinical applications, our assay has been validated against the FDA guidelines for Lower Limit of Quantitation (1 nM), linearity (R2>0.99), precision (imprecision 90 %), stability (>85 %), and carryover (