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574 Background: Omission of axillary surgery is appropriate in some patients with clinically node-negative (cN0), HR+ ESBC; however, there are no pre-operative tools to predict pathologic node positivity (pN+) in these women. We propose a clinically validated predictive model to inform treatment decisions regarding axillary evaluation. Methods: We constructed a cohort of adult women with ESBC (clinical T1/T2, N0, M0) diagnosed 2012-2016, who underwent lumpectomy or mastectomy and lymph node surgery without neoadjuvant therapy using the National Cancer Database breast cancer dataset. The dataset was non-randomly split into training (2012-2015) and testing (2016) for development and validation. Stepwise logistic regression was used to identify predictors of pathologic node positivity (pN0 vs pN+) in the training dataset. Potential predictors included: age, race, ethnicity, comorbidity score, histologic type, clinical T, ER positivity, PR positivity, HER2 positivity, and grade. Predictor variables required a bivariate p-value 1.5) and adding together the values for each included variable. LNPS was treated as a linear variable for prediction in validation dataset. Results: 423,068 women were included (2012-2015: 334,778; 2016: 88,290). Pathologic node positivity was 17% in 2012-2015 and 2016. All variables were included in the final stepwise model. Strong predictors were age, histologic type, clinical T, and grade. Scores ranged from 0-11. In the validation dataset, predicted pN+ by LNPS was very similar to actual pN+ (Table). A 1-point increase in LNPS was associated with a 3.3% increase in absolute risk of pN+. Conclusions: A novel lymph node prediction score can be used in HR+ cT1-T2 cN0 breast cancers to estimate the probability of pN+ and guide decisions regarding axillary surgical evaluation. [Table: see text]

Background: Older adults with breast cancer receiving neo/adjuvant chemotherapy are at increased risk for toxicity and dose reductions, often leading to decreased relative dose intensity (dRDI < 85%) and potentially compromised chemotherapy benefits. Identifying which older patients are projected to have dRDI with standard regimens could help to optimize systemic treatment delivery and completion. Methods: We prospectively enrolled patients aged ≥ 65 who were starting neo/adjuvant chemotherapy for HER2-negative, stage I-III breast cancer. Geriatric assessment and clinical variables were captured at baseline. Chemotherapy regimen, dosing, and treatment-related modifications (reductions, delays, discontinuation) were also captured. RDI was calculated as the ratio of actual dose delivered to intended dose. Our primary outcome was dRDI, which we defined as RDI < 85% (associated with poorer survival, Bonadonna et al. NEJM 1995). Bivariate logistic regression for dRDI was performed to elucidate the relationship with baseline factors. Stepwise regression was used to identify the significant factors that are independently associated with dRDI. Results: Of 323 patients (median age 69, range 65-86), 216 had HR+/HER2- breast cancer and 107 had triple negative breast cancer (TNBC). Patients were treated with taxotere and cyclophosphamide [TC] (47%), anthracycline-based regimens (46%), and cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] (7%). Overall, the mean RDI was 90.1% (median 100%, range 16.7%-100%), and 69 patients (21%) had dRDI (i.e. RDI 70, higher stage (II/III), use of non-TC regimens (anthracycline-based or CMF), abnormal liver function, KPS < 90, poor physical function, lack of social support, and cardiac conditions were associated with reduced RDI. Multivariate stepwise regression identified that anthracycline-based or CMF regimens (28% dRDI, OR=3.34, 95% CI 1.77-6.29), age >70 (27% dRDI, OR = 2.01, 95% CI 1.11-3.63), abnormal liver function (41% dRDI, OR = 2.50, 95% CI 1.10-5.66), and KPS < 90 (48% dRDI, OR = 4.31, 95% CI 2.06-9.03) were significantly associated with dRDI. dRDI was significantly associated with grade 3 or higher toxicities, hospitalization, dose reduction, dose delay, and early discontinuation of chemotherapy (all p < 0.001). Conclusion: Among older patients receiving neo/adjuvant chemotherapy for HER2-negative early-stage breast cancer, those aged > 70, treated with anthracycline or CMF regimens, with abnormal liver functions, and KPS < 90 were at substantially higher risk for reduced RDI (actual/planned dose) likely due to increased rates of toxicities, hospitalizations, dose modifications, and/or early treatment discontinuation. Future targeted supportive care interventions and/or alternative treatment regimens are needed to improve the delivery of chemotherapy in older patients who are predicted to have dRDI and better understand whether dRDI impacts outcomes in this population. Citation Format: Mina S Sedrak, Can-Lan Sun, Allison Magnuson, Hyman Muss, Rachel Freedman, Cary P Gross, William P Tew, Heidi Klepin, Tanya M Wildes, Efrat Dotan, Tracey O'Connor, Harvey J Cohen, Heeyoung Kim, Vani Katheria, Reena Jayani, Anait Arsenyan, Abrahm Levi, Kemeberly Charles, Arti Hurria, William Dale. Factors associated with decreased relative dose intensity in older adults with early-stage breast cancer receiving chemotherapy [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 PD10-10.

The evidence that body composition parameters influence multiple cancer outcomes is rapidly expanding. Excess adiposity deposits in muscle tissue, termed myosteatosis, can be detected in CT scans through variations in the density of muscle tissues (Hounsfield Units). Patients with similar muscle mass but different amounts of intramuscular adipose infiltration have increased chemotherapy toxicity, time to tumor progression and other adverse outcomes among different cancer types. Our review examines the impact of myosteatosis on overall survival (OS) in patients with cancer.A systematic search of the literature was conducted on PubMed/ MEDLINE, Cochrane CENTRAL, and EMBASE. Meta-analysis was conducted using a random-effects model. Risk of bias was evaluated using the Newcastle-Ottawa Quality assessment for cohort studies, funnel plot (publication bias), and GRADE summary of findings tool from Cochrane.A total of 4880 articles were screened from which 40 articles selected, including 21,222 patients. The overall mean proportion of patients with myosteatosis was 48 % (range 11-85 %). Using skeletal muscle density (SMD), patients classified as having myosteatosis had 75 % greater mortality risk compared to non-myosteatosis patients (HR 1.75 95 % CI 1.60-1.92, 40 studies) (p.00001) (i2 = 62 %). Specifically, myosteatosis was prognostic for worse OS in patients with gynecological, renal, periampullary/pancreatic, hepatocellular, gastroesophageal, and colorectal carcinoma, and lymphomas.Our analysis of the literature shows that cancer patients with myosteatosis have shorter survival. Our findings suggest that in oncological practice, muscle density assessment is valuable as a prognostic parameter.

PURPOSE: In older women, breast cancer and its treatment can have profound impact on their physical, mental, and social health, especially in frail patients. This study evaluated the association between frailty and long-term health-related quality of life (HRQOL) in older women undergoing breast cancer treatment. METHODS: Using the Carolina Senior Registry (CSR), participants with breast cancer were contacted to complete a follow-up HRQOL questionnaire (median 4 years). Baseline Geriatric Assessment (GA) variables were used to calculate the Carolina Frailty Index (CFI) and categorize participants as robust, pre-frail, or frail. Outcomes included HRQOL domains of physical function, social roles, fatigue, depression, anxiety, pain, and sleep disturbance assessed using PROMIS(®) instruments. Regression modeling compared outcomes between frailty groups using adjusted mean differences (AMD). RESULTS: Of 190 eligible patients, 63 completed follow-up HRQOL survey. Mean age was 70 years (range 65–86) and 91% were white. Based on the CFI, 49 (78%) patients were robust, 11 (18%) pre-frail, and 3 (5%) frail. After controlling for age and cancer stage, patients identified as pre-frail/frail reported worse physical function (AMD −9.2, p

Few older cancer patients are enrolled in cancer clinical trials. This article assesses whether the development and conduct of older‐patient‐specific trials is justified, comparing outcomes of patients enrolled in trials purposely designed for older cancer patients versus age‐unspecified trials., Background. Less than 3% of older patients with cancer are enrolled in clinical trials. To reverse this underrepresentation, we compared older patients enrolled with older‐patient‐specific trials, defined as those designed for older patients with cancer, with those enrolled in age‐unspecified trials. Materials and Methods. We focused on individual patient data from those ≥65 years (younger patients excluded) and included all Alliance phase III adjuvant breast cancer trials from 1985–2012. Results. Among 2,277 patients, 1,014 had been enrolled to older‐patient‐specific and 1,263 to age‐unspecified trials. The median age (range) in the older‐patient‐specific trials was 72 (65–89) years compared with 68 (65–84) years in the cohort of older patients in age‐unspecified trials; p < .0001. A greater percentage of patients 75 years or older had enrolled in older‐patient‐specific trials compared with the cohort of age‐unspecified trials: 26% versus 6% (p < .0001). Median overall survival (OS) was 12.8 years (95% confidence interval [CI], 11.9–13.7) and 13.5 years (95% CI, 12.9–14.1) for older‐patient‐specific and age‐unspecified trials, respectively. OS was comparable (hazard ratio [HR], 1.08; 95% CI, 0.92–1.28; p = .34; referent: age‐unspecified trials), after adjusting for age, estrogen receptor status, tumor size, and lymph node status. Similar findings were reached for recurrence‐free survival. A lower rate of grade 3–5 adverse events (hematologic and nonhematologic) was reported in older‐patient‐specific trials (43% vs. 58%; p < .0001). Sensitivity analysis with chemotherapy only trials and subset analysis, adjusted for performance score, yielded similar OS results. Conclusion. Older‐patient‐specific trials appear to address this underrepresentation of older patients with ostensibly comparable outcomes. Clinical trial identification numbers. NCT00003088 (CALGB 9741); NCT00024102 (CALGB 49907); NCT00068601 (CALGB 40401); NCT00005970 (NCCTG N9831) Implications for Practice. This work underscores the importance of clinical trials that focus on the recruitment of older patients with cancer.

Objectives The Mental Health Index (MHI) is widely used as a measure of mental health status, but has not been evaluated in the geriatric oncology population. This study evaluated the MHI-17 in a geriatric oncology population, to establish validity and scoring rules. Materials and Methods The Carolina Senior Registry ( NCT01137825 ) was used to obtain data for 686 patients with cancer 65 and older who completed the MHI-17. The 17-item patient-reported measure produces one total score summing across four domains: anxiety, depression, positive affect, and sense of belonging. Cronbach's alpha (α), confirmatory factor analyses (CFA), item-response theory (IRT) analyses, and differential item functioning (DIF) analyses were used to evaluate internal consistency and validity. Results and Discussion The revised MHI retained the 13 best-fitting items from the MHI-17 and resulted in a final model that included two subscales: anxiety (four items, RMSEA 0.11; CFI 0.99; TLI 0.98) and depression (9 items, RMSEA 0.10; CFI 0.96; TL 0.95). IRT analyses of the four anxiety items indicated good fit (RMSEA 0.08) and precise measurement of adults with poor mental health, and the nine depression items also fit well (RMSEA 0.05). No meaningful differences were found by sex, education, or treatment stage. Scores were developed to provide meaningful norms. The new MHI-13 is a shorter, more accurate way to assess mental health in older adults with cancer and most importantly allows clinicians to separately identify anxiety and/or depression - a clinically important distinction as treatment differs among these two types of mental health impairment.

Objectives The impact of occupational therapy (OT) and physical therapy (PT) on functional outcomes in older adults with cancer is unknown. Design Two-arm single-institution randomized controlled trial of outpatient OT/PT. Setting Comprehensive cancer center with two off-site OT/PT clinics. Participants We recruited adults 65 years and older with a recent diagnosis or recurrence of cancer within 5 years, with at least one functional limitation as identified by a geriatric assessment. Participants were randomized to OT/PT or usual care. Intervention Rehabilitation consisted of individualized OT and PT that addressed functional activities and strength/endurance needs. Measurements Primary outcome was functional status as measured by the Nottingham Extended Activities of Daily Living scale. Secondary outcomes were Patient-Reported Outcomes Measurement Information System-Global Mental Health (GMH) and Global Physical Health (GPH), ability to participate in Social Roles (SR), physical function, and activity expectations and self-efficacy (Possibilities for Activity Scale [PActS]). Results Among those recruited (N = 63), only 45 patients (71%) were evaluable due to loss of follow-up and/or nonreceipt of intervention. The median age was 74 years; 53% were female, and 91% were white. Overall, 30% patients had hematologic malignancies, 30% breast cancer, and 16% colorectal cancers. A total of 65% were in active treatment; 49% had stage 3 or 4 disease. At follow-up, both OT/PT (P = .02) and usual care (P = .03) groups experienced a decline in functional status. PActS scores between groups (P = .04) was significantly improved in the intervention group. GMH and SR met criteria for minimally important clinical difference favoring the intervention, but not statistical significance. Several barriers were noted in the implementation of the intervention program: recruitment, concerns about cost, distance, scheduling, and limited treatment provided. Conclusion OT/PT may positively influence activity expectations and self-efficacy. Future research needs to address significant barriers to implementation to increase use of OT/PT services and access to quality care. J Am Geriatr Soc 67:953-960, 2019.

Purpose: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM. Patients and methods: Eligible patients had progressive HER2 + BCBM. The primary endpoint was intracranial response rate (RR); secondary objectives were CNS clinical benefit rate (CBR), extracranial RR, time to progression (TTP), overall survival (OS), and targeted sequencing of tumors from enrolled patients. A two-stage design distinguished intracranial RR of 5% versus 20%. Results: 32 patients were evaluable for toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was 27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2–5). OS was 12.2 mos (95% CI 0.6–20.2). Grade 3–4 toxicities included neutropenia (41%), anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2 amplification was higher in BCBM compared to primary BC; ERBB2 amplification in the primary BC trended toward worse OS. Conclusion: While intracranial RR to ETV was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar to historical control. No new toxicity signals were observed. Further analysis of the genomic underpinnings of BCBM to identify tractable prognostic and/or predictive biomarkers is warranted. Clinical Trial: (NCT01305941).

Introduction. Fatigue is a distressing symptom for adults with acute leukemia, often impeding their ability to exercise. Objectives. 1) Examine effects of a 4-week mixed-modality supervised exercise program (4 times a week, twice a day) on fatigue in adults with acute leukemia undergoing induction chemotherapy. 2) Evaluate effects of exercise program on cognition, anxiety, depression, and sleep disturbance. 3) Evaluate effect of intervention on adherence to exercise. Methods. 17 adults (8 intervention, 9 control), aged 28-69 years, newly diagnosed with acute leukemia were recruited within 4 days of admission for induction treatment. Patient-reported outcomes (PROs) (fatigue, cognition, anxiety, depression, sleep disturbance, mental health, and physical health) and fitness performance-based measures (Timed Up and Go [TUG], Karnofsky Performance Status, and composite strength scoring) were assessed at baseline and at discharge. Changes in PRO and performance-based physical function measures from baseline to time of discharge were compared between groups using Wilcoxon Rank Sum tests. Results. With PROMIS (Patient-Reported Outcomes Measurement Information System) Fatigue, we found a median change in fatigue (−5.95) for the intervention group, which achieved a minimally important difference that is considered clinically relevant. Intervention group reduced their TUG performance by 1.73 seconds, whereas the control group remained fairly stable. A concerning finding was that cognition decreased for both groups during their hospitalization. 80% adherence of visits completed with a mean of 6 sessions attended per week. Conclusions. Our study provides information on the impact of exercise on symptomatology, with focus on fatigue and other psychosocial variables in acute leukemia.

OBJECTIVE To describe associations of functional, psychosocial, medical, and socio-demographic factors with performance on a cognitive screening test in chemotherapy naive patients with breast cancer. METHODS Women with breast cancer were recruited between 2009 and 2018. The Blessed Orientation Memory Concentration Test (BOMC) was administered prior to chemotherapy. Associations between baseline BOMC and functional (Karnofsky Self-Reported Performance Rating Scale (KPS), Time Up and Go Test (TUG), Medical Outcomes Study (MOS) Physical Function, Instrumental Activities of Daily Living (IADL)), psychosocial (Mental Health Inventory-13, MOS Social Activity Limitation and Social Support Survey), medical, and socio-demographic variables were assessed using linear regression analysis. RESULTS In a sample of 331 women with breast cancer, the mean age was 65.2 years and 68.6% were 65 and older. Mean BOMC score was 3.60 on a scale from 0 (best) to 28 (worst). After controlling for demographic factors, worse BOMC screening test results were associated with KPS

Mixed results have been reported regarding whether older cancer patients are at a greater risk for chemotherapy‐induced neuropathy. This article further evaluates the age‐based risk of this adverse event., Purpose. A few previous studies report a direct relationship between older age and chemotherapy‐induced neuropathy. This study further evaluated this adverse event's age‐based risk. Methods. CALGB 40101 investigated adjuvant paclitaxel (80 mg/m2 once per week or 175 mg/m2 every 2 weeks) in patients with breast cancer and served as a platform for the current study that investigated age‐based differences in neuropathy. Grade 2 or worse neuropathy, as per Common Terminology Criteria for Adverse Events version 4, was the primary endpoint; patients were assessed at baseline, every 6 months for 2 years, and then annually for 15 years. Results. Among these 1,881 patients, 230 were 65 years of age or older, 556 were 55–64 years, and 1,095 were younger than 55; 1,226 neuropathy events (commonly grade 1 or 2) were reported in 65% of the cohort. The number of grade 2 or worse events was 63 (27%), 155 (28%), and 266 (24%) within respective age groups (p = .14). In univariate analysis, only motor neuropathy had a higher age‐based incidence: 19 (8%), 43 (8%), and 60 (5%), respectively (p = .04); in multivariate analyses, this association was no longer statistically significant. Other endpoints, such as time to onset of neuropathy (time from trial enrollment to neuropathy development) and time to improvement (time from maximal grade sensory neuropathy to a one‐category improvement), showed no statistically significant age‐based differences. In contrast, obesity was associated with neuropathy, and every 2‐week paclitaxel was associated with trends toward neuropathy. Conclusion. Although paclitaxel‐induced neuropathy is common, older age is not an independent risk factor. Clinical trial identification number. NCT00041119 (CALGB 40101). Implications for Practice. Age alone is not an independent risk factor for paclitaxel‐induced neuropathy.

BACKGROUND: In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer. METHODS: CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade ≥3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined. RESULTS: One hundred thirteen (58%) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade ≥3 adverse events were hypertension (26%), pain (20%), and proteinuria (7%). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age ≥65 years (p

Introduction Time-to-treatment-failure (TTF) is the interval from chemotherapy initiation to premature discontinuation. We evaluated TTF based on age. Methods Pooled analyses were conducted with first-line chemotherapy trials for advanced NSCLC (CALGB 9730, 30203, and 30801). Comparisons among patients who were 65 years and older and 70 years and older were performed for TTF (primary endpoint), reasons for early chemotherapy cessation, grade 3+ adverse events, and overall survival. Results Among 1006 patients, 460 (46%) were older than 65 years of age. One hundred forty-five older patients (32% of this age cohort) completed all six planned chemotherapy cycles as did 170 (32%) younger patients. Median TTF was 2.9 months (95% confidence interval: 2.7– 3.2) in older patients and 3 months (95% confidence interval: 2.9–3.5) in younger patients; adjustment for performance status and stratification by chemotherapy by trial yielded no statistically significant age-based difference in TTF. However, reasons for early chemotherapy cessation differed between age groups (multivariate p = 0.004). Older patients were less likely to discontinue from cancer progression (41% versus 55%) and more likely from toxicity or patient choice (16% and 15%, respectively) compared to younger patients (13% and 6%, respectively). Older patients were more likely to experience grade 3+ adverse events (86% versus 79%) with no statistically significant difference in survival. An age cutpoint of 70+ years showed no difference in TTF, a lower trend of early cessation due to cancer progression, and somewhat shorter older patient survival. Conclusions TTF was comparable between older and younger patients; but different, age-based, and potentially modifiable reasons account for it.

Triple-negative breast cancer, which affects about 10% of older women with breast cancer, represents a major treatment challenge in this population. Treatment decisions for these patients can best be made based on geriatric assessment, estimated life expectancy, whether the treatment goal is prolonged survival or palliation, the potential benefits and toxicities of a specific treatment, and the patient's personal goals for treatment. Treatment outcomes for healthy older and younger women are similar, but great challenges exist in managing the vulnerable and frail patient. The cornerstone of therapy for early-stage triple-negative breast cancer is local therapy (surgery and radiation) and, for most patients, adjuvant chemotherapy. In the management of metastatic triple-negative breast cancer, all therapy is palliative and chemotherapy is the treatment of choice. Since all treatment modalities in older patients-especially chemotherapy-can affect physical and mental function, a geriatric assessment is key in selecting the most appropriate treatment strategy. Many older patients (older than 70 years) are poor candidates for state-of-the-art therapy, and some who have substantial comorbidities not related to breast cancer may opt for palliative and hospice care. In this review, we will discuss the role of geriatric assessment, alternative treatment modalities for older women with triple-negative breast cancer, and other special considerations for this patient population.

Background The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457–3465] for treatment decisions in older adults. Materials and Methods This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS Results Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS Conclusion Older patients with cancer with a high CTRS who receive combination chemotherapy have an exceedingly high rate of severe toxicity and hospitalization. Implications for Practice The potential utility of the chemotherapy toxicity risk score (CTRS) in old adults with advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3–4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (

BACKGROUND: Falls in older adults with cancer are common, yet factors associated with fall-risk are not well-defined and may differ from the general geriatric population. This study aims to develop and validate a model of factors associated with prior falls among older adults with cancer. METHODS: In this cross-sectional secondary analysis, two cohorts of patients aged ≥65 with cancer were examined to develop and validate a model of factors associated with falls in the prior 6 months. Potential independent variables, including demographic and laboratory data and a geriatric assessment (encompassing comorbidities, functional status, physical performance, medications and psychosocial status), were identified. A multivariate model was developed in the derivation cohort using an exhaustive modeling approach. The model selected for validation offered a low Akaike Information Criteria value and included dichotomized variables for ease of clinical use. This model was then applied in the validation cohort. RESULTS: The development cohort (N=498) had a mean age of 73 (range 65-91). Nearly one-fifth (18.2%) reported a fall in the prior 6 months. The selected model comprised 9 variables involving functional status, objective physical performance, depression, medications and renal function. The AUC of the model was 0.72 (95% confidence intervals 0.65-0.78). In the validation cohort (N=250), the prevalence of prior falls was 23.6%. The AUC of the model in the validation cohort was 0.62 (95% confidence intervals 0.51-0.71). CONCLUSION: In this study, we developed and validated a model of factors associated with prior falls in older adults with cancer. Future study is needed to examine the utility of such a model in prospectively predicting incident falls.

Purpose MA.17R was a Canadian Cancer Trials Group–led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor as adjuvant therapy for hormone receptor–positive breast cancer. Quality of life (QOL) was a secondary outcome measure of the study, and here, we report the results of these analyses. Methods QOL was measured using the Short Form-36 (SF-36; two summary scores and eight domains) and menopause-specific QOL (MENQOL; four symptom domains) at baseline and every 12 months up to 60 months. QOL assessment was mandatory for Canadian Cancer Trials Group centers but optional for centers in other groups. Mean change scores from baseline were calculated. Results One thousand nine hundred eighteen women were randomly assigned, and 1,428 women completed the baseline QOL assessment. Compliance with QOL measures was > 85%. Baseline summary scores for the SF-36 physical component summary (47.5 for letrozole and 47.9 for placebo) and mental component summary (55.5 for letrozole and 54.8 for placebo) were close to the population norms of 50. No differences were seen between groups in mean change scores for the SF-36 physical and mental component summaries and the other eight QOL domains except for the role-physical subscale. No difference was found in any of the four domains of the MENQOL Conclusion No clinically significant differences were seen in overall QOL measured by the SF-36 summary measures and MENQOL between the letrozole and placebo groups. The data indicate that continuation of aromatase inhibitor therapy after 5 years of prior treatment in the trial population was not associated with a deterioration of overall QOL.

BACKGROUND National guidelines recommend that patients with a cancer diagnosis engage in regular physical activity to reduce cancer-related fatigue, maintain quality of life and physical function, and improve overall prognosis and survival. This study investigates oncology provider communications about physical activity during routine clinic visits with patients with early-stage breast, colon, or prostate cancer. METHODS This study used a retrospective chart review for documentation of inquiries or recommendations pertaining to physical activity in clinician notes and after-visit patient summaries. RESULTS In a 1-month period, 55 oncology providers had 361 encounters (clinic visits) with early-stage cancer patients. Thirty-five percent of these encounters included a provider communication about “physical activity,” “exercise,” or “activity.” Encounters with a medical oncologist resulted in a physical activity communication 55% of the time, whereas encounters with other clinician specialties did so 20% of the time (P

The American Society of Clinical Oncology (ASCO) convened a subcommittee to develop recommendations on improving the evidence base for treating older adults with cancer in response to a critical need identified by the Institute of Medicine. Older adults experience the majority of cancer diagnoses and deaths and make up the majority of cancer survivors. Older adults are also the fastest growing segment of the US population. However, the evidence base for treating this population is sparse, because older adults are underrepresented in clinical trials, and trials designed specifically for older adults are rare. The result is that clinicians have less evidence on how to treat older adults, who represent the majority of patients with cancer. Clinicians and patients are forced to extrapolate from trials conducted in younger, healthier populations when developing treatment plans. This has created a dearth of knowledge regarding the risk of toxicity in the average older patient and about key end points of importance to older adults. ASCO makes five recommendations to improve evidence generation in this population: (1) Use clinical trials to improve the evidence base for treating older adults with cancer, (2) leverage research designs and infrastructure for generating evidence on older adults with cancer, (3) increase US Food and Drug Administration authority to incentivize and require research involving older adults with cancer, (4) increase clinicians' recruitment of older adults with cancer to clinical trials, and (5) use journal policies to improve researchers' reporting on the age distribution and health risk profiles of research participants.

Falls in older adults are common. Screening for falls is quick, simple, and important because falls increase the risk of morbidity and mortality in older patients with cancer. The aim of this study was to evaluate oncology providers' recognition of and response to falls in older patients with cancer.From a sample of older patients with cancer who completed a geriatric assessment blinded to oncology providers, we identified patients who self-reported falls within the past 6 months. Their history and physical and/or clinic notes completed by an oncology provider were reviewed for the following: documentation of falls, gait assessment, referral to geriatrics or physical and/or occupational therapy, and measurement of 25-hydroxy vitamin D level.In our sample of older patients with cancer who reported at least one recent fall (N = 125), the average age was 72 years (range, 65 to 93 years), 78% were female, and 62% had a breast cancer diagnosis. Chart reviews showed that 13 (10%) had falls documented, 25 (20%) had a gait assessment, eight (6%) were referred, and 21 (17%) had vitamin D level measured.We found that only 10% of older patients with cancer who self-reported a recent fall had appropriate medical record documentation. Oncologists are often the primary care providers for older patients and are largely unfamiliar with the frequency and impact of falls in this population. There is a need to increase awareness of falls prevalence and consequences among oncology providers in order to provide timely interventions to reduce the risks associated with falls.

Background. Geriatric assessment (GA) is an important tool for management of older cancer patients; however, GA research has been performed primarily in the outpatient setting. The primary objective of this study was to determine feasibility of GA during an unplanned hospital stay. Secondary objectives were to describe deficits found with GA, to assess whether clinicians recognized and addressed deficits, and to determine 30-day readmission rates. Materials and Methods. The study was designed as an extension of an existing registry, “Carolina Senior: Registry for Older Patients.” Inclusion criteria were age 70 and older and biopsy-proven solid tumor, myeloma, or lymphoma. Patients had to complete the GA within 7 days of nonelective admission to University of North Carolina Hospital. Results. A total of 142 patients were approached, and 90 (63%) consented to participation. All sections of GA had at least an 83% completion rate. Overall, 53% of patients reported problems with physical function, 63% had deficits in instrumental activities of daily living, 34% reported falls, 12% reported depression, 31% had ≥10% weight loss, and 12% had abnormalities in cognition. Physician documentation of each deficit ranged from 20% to 46%. Rates of referrals to allied health professionals were not significantly different between patients with and without deficits. The 30-day readmission rate was 29%. Conclusion. GA was feasible in this population. Hospitalized older cancer patients have high levels of functional and psychosocial deficits; however, clinician recognition and management of deficits were poor. The use of GA instruments to guide referrals to appropriate services is a way to potentially improve outcomes in this vulnerable population. Implications for Practice: Geriatric assessment (GA) is an important tool in the management of older cancer patients; however, its primary clinical use has been in the outpatient setting. During an unplanned hospitalization, patients are extremely frail and are most likely to benefit from GA. This study demonstrates that hospitalized older adults with cancer have high levels of functional deficits on GA. These deficits are under-recognized and poorly managed by hospital-based clinicians in a tertiary care setting. Incorporation of GA measures during a hospital stay is a way to improve outcomes in this population.

Background Studies point to a direct association between social support and better cancer outcomes. This study examined whether baseline social support is associated with better survival and fewer chemotherapy-related adverse events in older, early-stage breast cancer patients. Methods This study is a pre-planned secondary analysis of CALGB 49907/Alliance A171301, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in breast cancer patients 65 years of age or older. A subset reported on the extent of their social support with questionnaires that were completed 6 times over 2 years. Results The median age of this 331-patient cohort was 72 years (range: 65, 90); 179 (55%) were married, and 210 (65%) lived with someone. One hundred forty-five patients (46%) described a social network of 0–10 people; 110 (35%) of 11–25; and 58 (19%) of 26 or more. The Medical Outcomes Study (MOS) social support survey revealed that the median scores (range) for emotional/informational, tangible, positive social interaction, and affectionate social support were 94 (3, 100), 94 (0, 100), 96 (0, 100), and 100 (8, 100), respectively. Social support scores appeared stable over 2 years and higher (more support) than in other cancer settings. No statistically significant associations were observed between social support and survival and adverse events in multivariate analyses. However, married patients had smaller tumors, and those with arthritis reported less social support. Conclusion Although social support did not predict survival and adverse events, the exploratory but plausible inverse associations with larger tumors and arthritis suggest that social support merits further study. Copyright © 2015 John Wiley & Sons, Ltd.

Breast cancer is a disease of aging. The average age at diagnosis is 61, and the majority of deaths occur after age 65. Caring for older women with breast cancer is a major challenge, as many have coexisting illness that can preclude optimal breast cancer treatment and which frequently have greater effect than the breast cancer itself. Older patients with cancer should be screened or have a brief geriatric assessment to detect potentially remediable problems not usually assessed by oncologists (e.g., self-care, falls, social support, nutrition). Older women with early-stage breast cancer should be treated initially with surgery unless they have an exceedingly short life expectancy. Primary endocrine therapy should be considered for patients who have hormone receptor–positive tumors and a very short life expectancy, an acute illness that delays surgery, or tumors that need to be downstaged to be resectable. Sentinel node biopsy should be considered for patients in whom it might affect treatment decisions. Breast irradiation after breast-conserving surgery may be omitted for selected older women, especially for those with hormone receptor–positive early-stage breast cancer that are compliant with adjuvant endocrine therapy. The majority of older women with stage I and II breast cancer have hormone receptor–positive, HER2-negative tumors, and endocrine therapy provides them with optimal systemic treatment. If these patients have life expectancies exceeding at least 5 years, they should be considered for genetic assays to determine the potential value of chemotherapy. Partnering care with geriatricians or primary care physicians trained in geriatrics should be considered for all vulnerable and frail older patients.

Background: In CALGB-49907 (NEJM 2009;360:2055), older patients (pts) with ESBC were randomized to standard adjuvant chemo (AC or CMF versus capecitabine). The objective of this secondary QoL analysis is to assess if pts’ BL chemo preference (CP, defined as high or low), is associated with the following during and after completion of chemo: self and professional-reported toxicity, changes in mental health, function, QoL, recurrence-free (RFS) and overall (OS) survival. Patients and Methods: Of 633 trial pts 350 participated in the QoL substudy; 145/350 pts completed the BL assessment regarding CP. CP was measured by asking the amount of benefit women would require to choose adjuvant chemo in a hypothetical situation, irrespective of chemo agents. Women who chose chemo for an increase in OS of ≤12 months (mo) were designated as high chemo preference (HCP) and those who chose >12 mo were designated low chemo preference (LCP). CP associations were evaluated with: BL perception of self-health and perceived QoL on chemo; patient reported outcomes (PROs), changes in function and QoL (based on EORTC-QLQ-C30); anxiety and depression (Hospital Anxiety and Depression Scale); observed grade 3-5 adverse events (AEs) by NCI common toxicity criteria (CTC v2.0). Pts were assessed at midtreatment and at 1, 12, 18 and 24 mo post-treatment. Chi-square tests, t-tests, and Cox models were used for categorical, continuous, and time-to-event variables, respectively. Results: The demographic and tumor characteristics of women (median age 71) who provided CP at BL were not different from women in the QoL subset or from non-QoL pts. 68/145 (47%) women had a HCP. CP groups did not differ based on age, surgery type, tumor and nodal stage, hormone receptor status, performance status, chemo assignment, education, marital or employment status except the LCP group had a higher proportion of white women (95% vs. 78%, p=0.004). At BL, there were no differences in perception of self-health based on CP but women with LCP predicted QoL on chemo to be worse than women with HCP (p=0.006) and reported greater nausea/vomiting. Mid-treatment, LCP pts reported worse nausea/vomiting, financial worries, and cancer symptoms. Post-treatment, LCP pts had worse constipation (at 1 mo) and financial worries (at 24 mo). There were no differences based on CP for dyspnea, pain, fatigue, insomnia, anxiety or depression at any timepoint. Mid-treatment, LCP women reported lower QoL and worse social, emotional and physical function compared to HCP women. These scores were not significantly different after treatment completion. LCP women had significantly higher rates of grade 3-5 AEs (53 vs. 34%, p=0.02) during treatment but these did not persist post-therapy. CP was not significantly associated with OS (HR =0.75, p=0.36) or RFS (HR=0.94, p=0.84). Conclusions: LCP at BL was associated with lower QoL, worse physical symptoms, AEs and function mid-therapy, but not mental health. Mid-therapy declines in women with LCP largely reversed post-therapy. This information may be useful for oncology professionals to counsel older ESBC pts with LCP receiving adjuvant chemo. Citation Format: Ajeet Gajra, Linda McCall, Hyman B Muss, Harvey J Cohen, Aminah Jatoi, Karla V Ballman, Ann H Partridge, Linda Sutton, Barbara A Parker, Gustav Magrinat, Jaqueline M Lafky, Arti Hurria. Association of patient preference for adjuvant chemotherapy (chemo) at baseline (BL) with toxicity, mental health, function, quality of life (QoL) and survival in older women with early stage breast cancer (ESBC) [CALGB 49907 Alliance] [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-07.

Background Serious infections related to the anti-HER2 monoclonal antibody trastuzumab has been reported in clinical trials. It is not yet clear whether trastuzumab increases infection risk or not. We performed a systematic review and meta-analysis to assess the risk of infections associated with trastuzumab. Patients and methods We searched PubMed and the ASCO online database of meeting abstracts up to January 2014 for relevant clinical trials. Eligible studies included randomized controlled trials (RCTs) of trastuzumab for breast cancer patients that reported adequate safety data for grade 3-4 infection, febrile neutropenia, neutropenia, or leukopenia. Grade3 and 4 infection is defined as "IV antimicrobial agents, interventional radiology or operative intervention indicated" and "life-threatening consequences (e.g., septic shock)", respectively. The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated. RRs and summary incidence were calculated using random-or fixed-effects models depending on the heterogeneity of included studies. Prespecified exploratory subgroup analyses were performed according to treatment setting (neoadjuvant or adjuvant vs. metastatic setting) and therapy used with trastuzumab (combination vs. best supportive care (BSC) or single agent therapy) with regard to the RRs. Results A total of 10,094 patients from 13 trials of trastuzumab were included. The use of trastuzumab was associated with an increased risk of high-grade infection (RR, 1.21; 95% CI, 1.07-1.37; P=0.002) and febrile neutropenia (RR, 1.28; 95% CI, 1.08-1.52; P=0.004). The incidence of grade 3-4 infection and febrile neutropenia related to trastuzumab and control was 8.5% (95% CI 4.5-15.4%) vs. 6.9% (95% CI 4.0–11.6%) and 12.0% (95% CI, 8.1-17.4%) vs. 9.9% (95% CI, 6.6-14.6%), respectively. There was no significant increase in a risk of high-grade neutropenia (RR, 1.07; 95% CI, 0.98-1.68; P=0.15) or leukopenia (RR, 1.07; 95% CI, 0.94-1.23; P=0.31) in patients receiving trastuzumab. The results of exploratory subgroup analyses were shown in table1. RR of high-grade infection and febrile neutropenia according to treatment setting and therapy used with trastuzumab.High-grade infectionFebrile neutropeniaNo. of trialsRR (95%CI)PNo. of trialsRR (95%CI)PTreatment settingNeoadjuvant/Adjuvant setting71.21 (1.06-1.38)0.00461.27 (1.06-1.52)0.008Metastatic setting61.21 (0.82-1.79)0.3431.38 (0.79-2.42)0.26Therapy used with trastuzumabCombination therapy71.18 (1.04-1.35)0.0161.27 (1.06-1.52)0.008BSC/Single agent therapy71.47 (1.02-2.12)0.0431.38 (0.79-2.42)0.26BSC, best supportive care; RR, relative risk Conclusions Treatment with trastuzumab is associated with a 1.21-fold increased risk of high-grade infection and a 1.28-fold increased risk of febrile neutropenia compared with control. In order to obtain the maximum therapeutic benefit from trastuzumab, clinicians should be aware of the increased infection risk and perform careful monitoring especially when it is used with combination chemotherapy in the neoadjuvant and adjuvant setting. Citation Format: Tomohiro Funakoshi, Maya Suzuki, Hyman B Muss. Risk of infectious complications in breast cancer patients treated with trastuzumab: A meta-analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-12-03.

Background Colorectal cancer (CRC) diagnosis and treatment can have substantial detrimental impacts on health related quality of life (HRQOL) and physical function. This is especially true for older CRC patients and is of paramount concern in chemotherapy treatment decision making; yet, few studies to date have focused on understanding and managing fatigue in older CRC patients. We present the design of a study to evaluate the feasibility and impact of a home-based, self-directed physical activity intervention on fatigue in older CRC patients receiving adjuvant chemotherapy treatment. Secondary aims pertain to intervention impact on HRQOL, physical function, and self-efficacy for managing fatigue. Methods/design Multi-site, randomized controlled trial of physical activity intervention compared to usual care in a sample of older adults undergoing adjuvant chemotherapy for CRC. Forty CRC patients will be recruited and study questionnaires/assessments will be performed at baseline, 3 months, and after completion of adjuvant chemotherapy. The primary outcome is a comparison of the change in fatigue from baseline to 3 months between Intervention and Control arms. We will also compare changes in engagement in physical activity, HRQOL, physical function, and self-efficacy. Exploratory analyses will compare Intervention and Control arms with regard to changes in muscle mass and a biomarker aging that is known to increase during chemotherapy (p16 INK4a ). Discussion If positive, findings from this pilot study would suggest the potential for improving the care of older persons with CRC undergoing adjuvant chemotherapy through a home-based physical activity intervention to manage fatigue, HRQOL, and physical function. Trial Registration : NCT02191969

Previous studies have documented use of health care services by oncology patients in the Emergency Department (ED), but little is known about the utilization of health services of patients with acute leukemia after induction therapy. The aim of this study was to examine chief reasons for ED and hospital use by patients newly diagnosed with acute leukemia patients after induction therapy up to one year after discharge. A retrospective, longitudinal study of all visits to the ED or unplanned hospital admissions at a single institution for patients with acute leukemia was conducted. Inclusion criteria were patients ≥18 years of age at time of diagnosis, a confirmed diagnosis of AML or ALL, and received and discharged from induction treatment between 2007 and 2010. Donabedian's structure-process-outcome framework guided this study examining health services utilization and assessing patient outcomes. 80 patients met the inclusion criteria; 52 had AML and 28 had ALL; median age was 48 (range: 18-76) and 29% (n=23) were non-Caucasian. 70% (n=56) were discharged from induction in remission. 81% (n=65) had at least 1 ED or hospitalization event, and 44% (n=35) had 2 or more events. Of 137 events in 65 patients, the most common reason was neutropenic fever/infection (55%), bleeding (12%), and GI problems (11%). Mean number of events for ALL was 2.43 compared to 1.33 for AML patients (p=0.02), and 2.23 for

Background. We investigated whether a brief geriatric assessment (GA) would identify important patient deficits that could affect treatment tolerance and care outcomes within a sample of older cancer patients rated as functionally normal (80%–100%) on the Karnofsky performance status (KPS) scale. Methods. Cancer patients aged ≥65 years were assessed using a brief GA that included both professionally and patient-scored KPS and measures of comorbidity, polypharmacy, cognition, function, nutrition, and psychosocial status. Data were analyzed using descriptive statistics and multivariable logistic regression. Results. The sample included 984 patients: mean age was 73 years (range: 65–99 years), 74% were female, and 89% were white. GA was conducted before (23%), during (41%), or after (36%) treatment. Overall, 54% had a breast cancer diagnosis (n = 528), and 46% (n = 456) had cancers at other sites. Moreover, 81% of participants (n = 796) had both professionally and self-rated KPS ≥80, defined as functionally normal, and those patients are the focus of analysis. In this subsample, 550 (69%) had at least 1 GA-identified deficit, 222 (28%) had 1 deficit, 140 (18%) had 2 deficits, and 188 (24%) had ≥3 deficits. Specifically, 43% reported taking ≥9 medications daily, 28% had decreased social activity, 25% had ≥4 comorbidities, 23% had ≥1 impairment in instrumental activities of daily living, 18% had a Timed Up and Go time ≥14 seconds, 18% had ≥5% unintentional weight loss, and 12% had a Mental Health Index score ≤76. Conclusion. Within this sample of older cancer patients who were rated as functionally normal by KPS, GA identified important deficits that could affect treatment tolerance and outcomes.

Background. Limited data are available regarding outcomes in elderly head and neck cancer patients. This retrospective study was designed to characterize head and neck cancer in geriatric patients. Patients and Methods. This study included all patients in a large university-based tumor registry who were diagnosed with head and neck cancer from January 1, 1990, to December 31, 2005. Patients aged ≥70 years at the time of diagnosis were defined as older. Overall survival and progression-free survival were censored at 60 months. Survival differences were compared using the log-rank test. Hazard ratios were estimated using a Cox proportional hazards model, adjusting for potential confounders. Results. Of 1,598 patients identified, 1,166 patients were aged Conclusion. This study highlights the need for better understanding of the factors affecting head and neck cancer outcomes in elderly patients. Information about life expectancy in elderly head and neck cancer patients may help guide treatment decisions.

Background Our ability to optimize the care of older adults with cancer and comorbid illnesses is insufficient because most clinical trials lack systematic measurement. The primary purpose of this study was to evaluate the association between patient-reported comorbidity and all-cause mortality using various comorbidity scoring algorithms. Materials and Methods The Carolina Senior Registry was linked with the North Carolina Central Cancer Registry to obtain mortality data. Comorbidity was assessed using the patient-reported Older Americans Resources and Services Questionnaire subscale that assesses 13 specific conditions and the degree to which each impairs activities. Multivariable Cox proportional hazard regression models were used to evaluate the association between comorbidities and all-cause mortality. Results The study sample included 539 patients; the median age was 72 years, 72% were female, and 47% had breast cancer. Overall, 92% reported ≥1 comorbid condition, with a mean of 2.7 conditions (range 0–10), with arthritis and hypertension the most common (52% and 50%, respectively). Approximately 60% reported a functional limitation related to comorbidity. After adjusting for time from diagnosis to geriatric assessment, age, cancer type, and stage, the risk of death increased by 5% for each unit increase in comorbidity burden score (adjusted hazard ratio [HR] = 1.05, 95% confidence interval [CI]: 1.01–1.10) and 12% for each comorbid condition impacting function (HR = 1.12, 95% CI: 1.02–1.23). Conclusion Comorbid conditions in older adults with cancer are highly prevalent and associated with all-cause mortality, particularly those conditions that impair function. Routine comorbidity assessment should be included in clinical trials and can be measured via a simple one-page patient-reported questionnaire. Implications for Practice In order to optimize and personalize the care of older adults with cancer, systematic measurement of comorbidities is necessary in both clinical trials and routine practice. Patient-reported comorbid conditions in older adults with cancer are highly prevalent and are associated with increased risk of all-cause mortality, particularly for those conditions that impair function. Comorbidity can be systematically measured via a one-page patient-reported questionnaire and should be incorporated into future clinical trials and considered for use in oncology clinics to aid in assessing older adults with cancer.

Great heterogeneity exists in the ability of adults with cancer to tolerate chemotherapy. Variability in body composition may affect rates of metabolism of cytotoxic agents and contribute to the variable chemotherapy toxicity observed. The objective of this exploratory study was to examine the association of low skeletal muscle, commonly known as sarcopenia, on the pharmacokinetics (PKs) of 5-fluorouracil (5FU) in patients receiving FOLFOX for colorectal cancer. We performed a secondary analysis of a completed multicenter trial that investigated PK-guided 5FU dosing in patients receiving mFOLFOX6 +/− bevacizumab for colorectal cancer. Cycle 1 PK samples were obtained 2–44 h after the start of the 5FU infusion (steady state). No significant differences in first cycle 5FU area-under-the-concentration-time-curve (AUC) were found between sarcopenic and non-sarcopenic patients (17.3 vs. 19.3 AUC, p = 0.43). Patients with grade 3/4 toxicity had a higher dose of 5FU per kg lean body mass (LBM) (105 vs. 93 mg/kg, p = 0.06), most notably for hematological toxicities (110 vs. 94 mg/kg, p = 0.002); however, no correlation between the dose/LBM and 5FU AUC was found. Although our results did not confirm the impact of low skeletal muscle on PKs of 5FU, further research exploring the impact of body composition on chemotherapy PKs and related toxicities is warranted with the potential for alternative dosing strategies in sarcopenic patients to reduce unnecessary toxicities while maintaining efficacy.

OBJECTIVE Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions. PATIENTS AND METHODS We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004-2014. Toxicity was assessed per the NCI-CTCAE (version 3-5). Probabilities of experiencing grade three or four hematologic and non-hematologic toxicities were modeled as a function of clinical and disease-related factors using logistic regression. RESULTS 1199 patients (409 age ≥ 65; 790 age

Objective Actual weight-based (AWB) chemotherapy dosing is recommended for obese patients in the 2012 ASCO Clinical Practice Guideline. CALGB 49907, which utilized ABW-based adjuvant chemotherapy dosing, was a phase 3 trial in women age ≥ 65 years with early stage breast cancer, providing the opportunity to examine impact of such dosing on toxicities and outcome in older patients with breast cancer. Materials and Methods Adverse event data were available for 615 of 633 enrolled patients. Objectives were to assess grade ≥ 3 hematologic/non-hematologic toxicities by treatment arm, age, study entry BSA/BMI, and relapse-free (RFS) and overall survival (OS) by BSA/BMI. Results The 615 patients were sub-grouped by BSA (quartiles) and standard BMI categories, with BMI underweight/normal weight categories combined. Overall, grade ≥ 3 non-hematologic and hematologic toxicities occurred in 39.8% and 28.3% of patients, respectively. There were no significant differences in grade ≥ 3 toxicities among BSA quartiles. However, more grade ≥ 3 hematologic toxicities occurred in the underweight/normal weight BMI subgroup compared to overweight/obese subgroups (p = 0.048). Type of chemotherapy and age had no impact on toxicity occurrence by BSA/BMI categories. RFS was superior in the 25th–50th BSA percentile patients in univariate analysis (p = 0.042), as was OS in both univariate and multivariate analyses (p = 0.007, p = 0.009, respectively). No differences in RFS or OS were found by BMI categories. Conclusion Obesity was not correlated with adverse relapse or survival outcome, and grade ≥ 3 toxicities were not greater with ABW-based dosing. This supports safety and efficacy of ABW-based dosing as per the 2012 ASCO clinical practice guideline. ClinicalTrials.gov Identifier: NCT00024102 (49907).

Purpose: Musculoskeletal events (MEs) resulting from breast cancer treatment can significantly interfere with the quality of life (QOL) of older adults. We evaluated the incidence of MEs in women 65 years and older who had surgery and adjuvant chemotherapy for breast cancer, and the impact of treatment on MEs and arm function. Patients and methods: Patient-reported data in Alliance/CALGB 49907 were collected using the EORTC QLQ-BR23 and physician-reported adverse events to characterize self-reported MEs and incidence of lymphedema. EORTC QLQ-BR23 items related to musculoskeletal events were analyzed in this study and data collected at study entry (post-operative) and 12 and 24 months post-entry. Results: Lymphedema, arm function, and ME data were available for 321 patients. One or more MEs were reported by 87% (median number = 3) and 64% (median number = 1) of patients post-operatively and at 24 months. At 24 months 2% had persistence of six MEs. Seventy-four percent experienced at least ���3/6 types of MEs over the 24-month period. Detection of lymphedema at any time during the study was noted in 7.5% of the patients and appeared to be associated with the type of chemotherapy given: CMF 16.4%, capecitabine 5.8%, and AC 4%. Mastectomy and axillary node dissection were associated with the most MEs. LROM correlated with poorer arm function at all time periods. Conclusion: Potentially debilitating MEs occur in three-fourths of elderly women undergoing standard therapy for breast cancer. Emphasis should be placed on prevention, identification, and treatment of these MEs to improve QOL.

To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older").Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (1 year); midpoint (1-3 years); and late discontinuation (3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates.Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p 0.001), considering covariates, but cognition was not related to discontinuation in the other periods.Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

A geriatric assessment (GA) assesses functional age of older patients with cancer and is a well-established tool predictive of toxicity and survival. The objective of this study was to investigate the prognostic value of individual GA items.546 patients with cancer ≥ 65 years completed GA from 2009 to 2014 and were followed for survival status for a median of 3.7 years. The GA consisted of function, nutrition, comorbidity, cognition, psychological state, and social activity/support domains. GA items with p 0.05 in univariable analyses for overall survival (OS) were entered into multivariable stepwise selection procedure using a Cox proportional hazards model. A prognostic scale was constructed with significant GA items retained in the final model.Median age was 72 years, 49% had breast cancer, and 42% had stage 3-4 cancer. Three GA items were significant prognostic factors, independent of traditional factors (cancer type, stage, age, and Karnofsky Performance Status): (1) "limitation in walking several blocks", (2) "limitation in shopping", and (3) "≥ 5% unintentional weight loss in 6 months". A three-item prognostic scale was constructed with these items. In comparison with score 0 (no positive items), hazard ratios for OS were 1.85 for score 1, 2.97 for score 2, and 8.67 for score 3. This translated to 2-year estimated survivals of 85%, 67%, 51% and 17% for scores of 0, 1, 2 and 3, respectively.This three-item scale was a strong independent predictor of survival. If externally validated, this could be a streamlined tool with broader applicability.

Background: Older adults are often exposed to multiple medications, some of which could be inappropriate or have the potential to interact with each other. Older cancer patients may be at increased risk for medication-related problems due to exposure to cancer-directed treatment. Methods: We described patterns of potentially inappropriate medication (PIM) use and potential drug–chemotherapy interactions among adults age 66+ years diagnosed with stage I–III breast, stage II–III colon, and stage I to II lung cancer. Within the Surveillance, Epidemiology, and End Results–Medicare database, patients had to have Medicare Part D coverage with 1+ prescription in the diagnosis month and Medicare Parts A/B coverage in the prior 12 months. We estimated monthly prevalence of any and cancer-related PIM from 6 months pre- to 23 months postcancer diagnosis and 12-month period prevalence of potential drug–chemotherapy interactions. Results: Overall, 19,318 breast, 7,283 colon, and 7,237 lung cancer patients were evaluated. Monthly PIM prevalence was stable prediagnosis (37%–40%), but increased in the year following a colon or lung cancer diagnosis, and decreased following a breast cancer diagnosis. Changes in PIM prevalence were driven primarily by cancer-related PIM in patients on chemotherapy. Potential drug–chemotherapy interactions were observed in all cohorts, with prevalent interactions involving hydrochlorothiazide, warfarin, and proton-pump inhibitors. Conclusions: There was a high burden of potential medication-related problems among older cancer patients; future research to evaluate outcomes of these exposures is warranted. Impact: Older adults diagnosed with cancer have unique medication management needs. Thus, pharmacy specialists should be integrated into multidisciplinary teams caring for these patients. Cancer Epidemiol Biomarkers Prev; 27(1); 41–49. ©2017 AACR.

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.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.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.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.

The aging of the Canadian population represents the major risk factor for a projected increase in cancer incidence in the coming decades. However, the evidence base to guide management of older adults with cancer remains extremely limited. It is thus imperative that we develop a national research agenda and establish a national collaborative network to devise joint studies that will help to accelerate the development of high-quality research, education, and clinical care and thus better address the needs of older Canadians with cancer. To begin this process, the inaugural meeting of the Canadian Network on Aging and Cancer was held in Toronto, 27 April 2016. The meeting was attended by 51 invited researchers and clinicians from across Canada, as well as by international leaders in geriatric oncology from the United States and France. The objectives of the meeting were to (1) review the present landscape of education, clinical care, and research in the area of cancer and aging in Canada; (2) identify issues of high research priority in Canada within the field of cancer and aging; (3) identify current barriers to geriatric oncology research in Canada and develop potential solutions; (4) develop a Canadian collaborative multidisciplinary research network between investigators to improve health outcomes for older adults with cancer; (5) learn from successful international efforts to stimulate the geriatric oncology research agenda in Canada. In the present report, we describe the education, clinical care, and research priorities that were identified at the meeting.

Tools to estimate survival, such as ePrognosis ( http://eprognosis.ucsf.edu/carey2.php ), were developed for general, not cancer, populations. In older patients with breast cancer, accurate overall survival estimates would facilitate discussions about adjuvant therapies. Secondary analyses were performed of data from two parallel breast cancer studies (CALGB/Alliance 49907/NCT000224102 and CALGB/Alliance 369901/NCT00068328). We included patients (n = 971) who were age 70 years and older with complete baseline quality of life data (194 from 49907; 777 from 369901). Estimated versus observed all-cause two-year mortality rates were compared. ePrognosis score was calculated based on age, sex, and daily function (derived from EORTC QLQ-C30). ePrognosis scores range from 0 to 10, with higher scores indicating worse prognosis based on mortality of community-dwelling elders and were categorized into three groups (0–2, 3–6, 7–10). Observed mortality rates were estimated using Kaplan–Meier methods. Patient mean age was 75.8 years (range 70–91) and 73% had stage I–IIA disease. Most patients were classified by ePrognosis as good prognosis (n = 562, 58% 0–2) and few (n = 18, 2% 7–10) poor prognosis. Two-year observed mortality rates were significantly lower than ePrognosis estimates for patients scoring 0–2 (2% vs 5%, p = 0.001) and 3–6 (8% vs 12%, p = 0.01). The same trend was seen with scores of 7–10 (23% vs 36%, p = 0.25). ePrognosis tool only modestly overestimates mortality rate in older breast cancer patients enrolled in two cooperative group studies. This tool, which estimates non-cancer mortality risk based on readily available clinical information may inform adjuvant therapy decisions but should be validated in non-clinical trial populations.

Background Discordance in hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status between primary tumors and metastatic sites for breast cancer is well established. However, it is uncertain which patient-related factors lead to biopsy when metastases are suspected and whether having a biopsy impacts survival. Methods The medical charts of metastatic breast cancer (MBC) patients diagnosed January 2000-August 2014 were retrospectively reviewed. A biopsy was defined as a procedure where tissue was obtained and assessed for both HR and HER2. Both bivariate and multivariate analyses were performed to assess patient characteristics related to biopsy and whether having a biopsy was associated with improved survival. Results Of 409 patients suspected of having MBC, 165 (40%) had a biopsy, and 34% of these had discordant HR or HER2 status when compared to the initial diagnosis. In multivariate analysis, having a biopsy was associated with: recurrence in years 2010–2014, disease-free interval of > =3 years, stage 0-IIA at presentation, suspected locoregional recurrence, being HR+/HER2-, or missing HR/HER2 at diagnosis. A similar multivariate analysis revealed that having a biopsy was associated with improved survival (HR = 0.67, p = 0.002). The association of biopsy and improved survival was noted in specific subgroups: patients with missing HR and HER2 data at initial diagnosis (p = 0.001), those without metastases in liver, lung or brain (p = 0.001), and being younger than 70 years old at recurrence (p

Background Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. Methods PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016. Eligible studies included randomized controlled trials (RCTs) comparing single-agent U.S. Food and Drug Administration-approved PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) with chemotherapy in cancer patients reporting any all-grade (1-4) or high-grade (3-4) adverse events (AEs), all- or high-grade treatment-related symptoms, hematologic toxicities and immune-related AEs, treatment discontinuation due to toxicities, or treatment-related deaths. The summary incidence, relative risk, and 95% confidence intervals were calculated. Results A total of 3,450 patients from 7 RCTs were included in the meta-analysis: 4 nivolumab, 2 pembrolizumab, and 1 atezolizumab trials. The underlying malignancies included were non-small cell lung cancer (4 trials) and melanoma (3 trials). Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, any all- and high-grade AEs, and treatment discontinuation. There was an increased risk of all-grade rash, pruritus, colitis, aminotransferase elevations, hypothyroidism, and hyperthyroidism, and all- and high-grade pneumonitis with PD1/PD-L1 inhibitors. Conclusion PD-1/PD-L1 inhibitors are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for PD-1/PD-L1 inhibitors. The Oncologist 2017;22:470-479 IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare summary toxicity endpoints and clinically relevant adverse events between programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy. PD1/PD-L1 inhibitors were associated with a lower risk of treatment-related symptoms (fatigue, anorexia, nausea, diarrhea, constipation, and sensory neuropathy) but a higher risk of immune-related adverse events (AEs). Summary toxicity endpoints favor PD1/PD-L1 inhibitors (any all- and high-grade AEs and treatment discontinuation). PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. In addition to efficacy data from trials, our findings provide useful information for clinicians for well-balanced discussions with their patients on the risks and benefits of treatment options for advanced cancer.

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

Nearly half of all women diagnosed with breast or ovarian cancer are age 65 years or older with the number of women diagnosed expected to increase as the population ages and life expectancy improves. Older women are less likely to be offered standard cancer treatments, are more likely to develop higher toxicity, and have higher mortality. Chronologic age should not be the only factor used for making treatment decisions. Functional dependence, organ function, comorbidity, polypharmacy, social support, cognitive and/or psychosocial factors, overall life expectancy, and patient's goals of care are equally vital and should be assessed before and during treatment. In this review, current evidence and treatment guidelines for older women with breast or ovarian cancer are outlined.

Purpose. Breast cancer (BC) is a disease of aging and the number of older BC patients in the U.S. is rising. Immunohistochemical data show that with increasing age, the incidence of hormone receptor-positive tumors increases, whereas the incidence of triple-negative tumors decreases. Few data exist on the frequency of molecular subtypes in older women. Here, we characterize the incidence and outcomes of BC patients by molecular subtypes and age. Patients and Methods. Data from 3,947 patients were pooled from publicly available clinical and gene expression microarray data sets. The PAM50 algorithm was used to classify tumors into five BC intrinsic subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like. The association of age and subtype with recurrence-free survival (RFS), overall survival, and disease-specific survival (DSS) was assessed. Results. The incidence of luminal (A, B, and A+B) tumors increased with age (p < .01, p < .0001, and p < .0001, respectively), whereas the percentage of basal-like tumors decreased (p < .0001). Among patients 70 years and older, luminal B, HER2-enriched, and basal-like tumors were found at a frequency of 32%, 11%, and 9%, respectively. In older women, luminal subtypes had better outcomes than basal-like and HER2-enriched subtypes. After controlling for subtype, treatment, tumor size, nodal status, and grade, increasing age had no impact on RFS or DSS. Conclusion. More favorable BC subtypes increase with age, but older patients still have a substantial percentage of high-risk tumor subtypes. After accounting for tumor subtypes, age at diagnosis is not an independent prognostic factor for outcome.