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Purpose: We aimed to establish the MTD of the poly (ADP-ribose) (PAR) polymerase inhibitor, veliparib, in combination with carboplatin in germline BRCA1- and BRCA2- (BRCA)-associated metastatic breast cancer (MBC), to assess the efficacy of single-agent veliparib, and of the combination treatment after progression, and to correlate PAR levels with clinical outcome.Experimental Design: Phase I patients received carboplatin (AUC of 5–6, every 21 days), with escalating doses (50-20 mg) of oral twice-daily (BID) veliparib. In a companion phase II trial, patients received single-agent veliparib (400 mg BID), and upon progression, received the combination at MTD. Peripheral blood mononuclear cell PAR and serum veliparib levels were assessed and correlated with outcome.Results: Twenty-seven phase I trial patients were evaluable. Dose-limiting toxicities were nausea, dehydration, and thrombocytopenia [MTD: veliparib 150 mg po BID and carboplatin (AUC of 5)]. Response rate (RR) was 56%; 3 patients remain in complete response (CR) beyond 3 years. Progression-free survival (PFS) and overall survival (OS) were 8.7 and 18.8 months. The PFS and OS were 5.2 and 14.5 months in the 44 patients in the phase II trial, with a 14% RR in BRCA1 (n = 22) and 36% in BRCA2 (n = 22). One of 30 patients responded to the combination therapy after progression on veliparib. Higher baseline PAR was associated with clinical benefit.Conclusions: Safety and efficacy are encouraging with veliparib alone and in combination with carboplatin in BRCA-associated MBC. Lasting CRs were observed when the combination was administered first in the phase I trial. Further investigation of PAR level association with clinical outcomes is warranted. Clin Cancer Res; 23(15); 4066–76. ©2017 AACR.

Veliparib pharmacokinetics with geometric mean* and standard deviation (SD) plasma pharmacokinetic parameters during the phase I combination phase

Best response in phase I* and phase II

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

Purpose To determine whether older breast cancer survivors score lower on neuropsychological tests compared to matched non-cancer controls and to test the hypotheses that survivors who were APOE ε4 carriers would have the lowest cognitive performance, but that smoking history would decrease the negative effect of ε4 on cognition. Methods Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5 – 15 year survivors (N=328) and age and education matched non-cancer controls (N=160) were assessed at enrollment and at 8, 16 and 24 month follow ups with standard neuropsychological and psychological assessments. Blood for APOE genotyping was collected and smoking history was assessed at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or no chemotherapy and approximately 50% had a smoking history. Results After adjusting for age, cognitive reserve, depression and fatigue, breast cancer survivors scored significantly lower on all domains of cognitive function. A significant two-way interaction demonstrated that the negative effect of ε4 on cognitive performance was stronger among survivors. A significant three-way interaction supported the hypothesis that smoking history had a protective effect on cognitive function in ε4 carriers that was more pronounced in the controls than the survivors. Conclusions The results support the long-term cognitive impact of breast cancer diagnosis and treatments on older, disease-free survivors, particularly for ε4 carriers. The results also emphasize the importance of assessing smoking history when examining APOE and cognition and are an example of the complex interactions of age, genetics, health behaviors and disease history in determining cognitive function.

INTRODUCTION: Oncology nurses are key in caring for older adults with cancer, but few have received specialized training in gerontology. To address this, a geriatric oncology curriculum was developed for oncology nurses. MATERIALS & METHODS: The Geriatric Oncology Workshop (GrOW) was developed and delivered to oncology nurses (n = 387) from 2016 to 2019. Workshops were evaluated using: 1) Assessment of preparedness, comfort, and skills; 2) Knowledge gained; 3) Participant evaluations of workshop (4-point Likert-type scale); 4) Faculty evaluations (10-point Likert-type scale); and 5) Follow-up assessment of goals. Descriptive statistics (frequencies, proportions, medians, means) were used to describe participants and results. Paired t-test was used to evaluate participants’ knowledge gain, and linear mixed modeling was used to evaluate longitudinal changes in preparedness, comfort, and skill levels. RESULTS: Overall, 387 oncology nurses participated in GrOW. Participant-rated workshop evaluation means were 3.7 to 3.9. Overall, nurses had statistically significant increases in pre- to post- questionnaire scores of 18.8% (p < 0.001) in workshop 1, 26.8% (p < 0.001) in workshop 2, 24.9% (p < 0.001) in workshop 3, and 18.6% (p < 0.001) in workshop 4, with an overall mean of 22.4% (p < 0.001) knowledge gained for all four workshops. Nurses reported an increase in skill, comfort, and preparedness at 18 months for workshop 1, 2, and 3 and in skill and comfort at 12 months for workshop 4 (p < 0.01). Faculty evaluation scores ranged from 9.3 to 10.0. DISCUSSION: A geriatric oncology curriculum designed for oncology nurses can improve levels of evidence-based knowledge and provide more skill, comfort, and preparedness in caring for this population.

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.

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.

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

Cross-sectional studies suggest that falls are prevalent among older breast cancer survivors. However, fall risk in this population has not been comprehensively examined. Therefore, we compared fall risk in older women post-breast cancer diagnosis to fall risk before cancer diagnosis and to risk in cancer-free matched controls. Among 2019 women in the Women’s Health Initiative with localized breast cancer diagnosed at age ≥ 60 years with fall assessment data for 3 years pre-diagnosis and 3 years post-diagnosis, recurrent fall risk post-diagnosis was compared to risk in 2019 cancer-free controls matched by age, year of WHI entry, and baseline fall frequency. Generalized estimating equations under a logistic regression model were used to compare fall recurrence in breast cancer survivors and controls. Multi-variable models were adjusted for the matching factors, race/ethnicity, body mass index, and multiple chronic conditions. In breast cancer survivors aged 70.8 years (mean) at diagnosis, over the 3-year pre-diagnosis interval, recurrent falls were reported by 18.5%. Over the 3-year post-diagnosis interval, recurrent falls were reported by 21.8% of breast cancer survivors and 20.0% of controls over the same time period (P = 0.27). Recurrent fall risk did not differ between breast cancer survivors and control women (OR 1.07, 95% CI 0.92–1.25), even after multi-variable adjustment. In contrast to prior reports, older breast cancer survivors were not more likely to experience recurrent falls than age-matched counterparts. These findings underscore the need for incorporation of cancer-free control populations in survivorship studies to distinguish cancer sequelae from processes related to aging.

This article describes the qualitative analysis of goal achievement by oncology nurses who attended a gero-oncology course.Four annual programs were completed and included 140 teams of oncology nurses from cancer settings across the United States.Self-determination theory and achievement goal theory provided the conceptual framework for understanding what motivates people to achieve goals and how goals can measure outcomes. SMART goals were used to measure outcomes and barriers.Goal achievement at 18 months showed that 70% of developed goals were in process or completed. The top three goal categories were professional education, structure/team building, and resource development. Top barriers included time constraints and staffing shortages.Encouraging oncology nurses to set specific goals while attending an educational program supports successful integration of new knowledge in their practice setting.

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

Background Older adults (≥65 years) with gastrointestinal (GI) cancers who receive chemotherapy are at increased risk of hospitalization caused by treatment-related toxicity. Geriatric assessment (GA) has been previously shown to predict risk of toxicity in older adults undergoing chemotherapy. However, studies incorporating the GA specifically in older adults with GI cancers have been limited. This study sought to identify GA-based risk factors for chemotherapy toxicity–related hospitalization among older adults with GI cancers. Patients and Methods We performed a secondary post hoc subgroup analysis of two prospective studies used to develop and validate a GA-based chemotherapy toxicity score. The incidence of unplanned hospitalizations during the course of chemotherapy treatment was determined. Results This analysis included 199 patients aged ≥65 years with a diagnosis of GI cancer (85 colorectal, 51 gastric/esophageal, and 63 pancreatic/hepatobiliary). Sixty-five (32.7%) patients had ≥1 hospitalization. Univariate analysis identified sex (female), cardiac comorbidity, stage IV disease, low serum albumin, cancer type (gastric/esophageal), hearing deficits, and polypharmacy as risk factors for hospitalization. Multivariable analyses found that patients who had cardiac comorbidity (OR 2.48, 95% CI 1.13-5.42) were significantly more likely to be hospitalized. Conclusion Cardiac comorbidity may be a risk factor for hospitalization in older adults with GI cancers receiving chemotherapy. Further studies with larger sample sizes are warranted to examine the relationship between GA measures and hospitalization in this vulnerable population.

BACKGROUND Sleep disturbance and genetic profile are risks for cognitive decline in noncancer populations, yet their role in cancer-related cognitive problems remains understudied. This study examined whether sleep disturbance was associated with worse neurocognitive outcomes in breast cancer survivors and whether sleep effects on cognition varied by genotype. METHODS Newly diagnosed female patients (n = 319) who were 60 years old or older and had stage 0 to III breast cancer were recruited from August 2010 to December 2015. Assessments were performed before systemic therapy and 12 and 24 months later. Neuropsychological testing measured attention, processing speed, executive function, learning, and memory; self-perceived cognitive functioning was also assessed. Sleep disturbance was defined by self-report of routine poor or restless sleep. Genotyping included APOE, BDNF, and COMT polymorphisms. Random effects fluctuation models tested associations of between-person and within-person differences in sleep, genotype, and sleep-genotype interactions and cognition and controlled for age, reading level, race, site, and treatment. RESULTS One-third of the patients reported sleep disturbances at each time point. There was a sleep-APOE e4 interaction (P = .001) in which patients with the APOE e4 allele and sleep disturbances had significantly lower learning and memory scores than those who were APOE e4-negative and without sleep disturbances. There was also a sleep disturbance-COMT genotype interaction (P = .02) in which COMT Val carriers with sleep disturbances had lower perceived cognition than noncarriers. CONCLUSIONS Sleep disturbance was common and was associated with worse cognitive performance in older breast cancer survivors, especially those with a genetic risk for cognitive decline. Survivorship care should include sleep assessments and interventions to address sleep problems.

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.

BACKGROUND/OBJECTIVES Women diagnosed with breast cancer (BC) at an older age are less likely to undergo genetic cancer risk assessment and genetic testing since the guidelines and referrals are biased toward earlier age at diagnosis. Thus, we determined the prevalence and type of pathogenic cancer predisposition variants among women with a history of BC diagnosed at the age of 65 years or older vs younger than 65 years. DESIGN Prospective registration cohort. SETTING The Clinical Cancer Genomics Community Research Network, including 40 community-based clinics in the United States and 5 in Latin America. PARTICIPANTS Women with BC and genetic testing results. MEASUREMENTS Sociodemographic characteristics, clinical variables, and genetic profiles were compared between women aged 65 years and older and those younger than 65 years at BC diagnosis. RESULTS Among 588 women diagnosed with BC and aged 65 years and older and 9412 diagnosed at younger than 65 years, BC-associated pathogenic variants (PVs) were detected in 5.6% of those aged 65 years and older (n = 33) and 14.2% of those younger than 65 years (n = 1340) (P

Introduction Phase II clinical trials including geriatric assessment (GA) measures are critical for improving the evidence base for older adults with cancer. We assessed the efficacy and tolerability of nab-paclitaxel in older adults with metastatic breast cancer (MBC). Patients and Methods Patients aged ≥ 65 years with MBC and ≤ 1 previous line of chemotherapy received 100 mg of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle. A GA was completed pre-chemotherapy, and the validated Cancer and Aging Research Group (CARG) chemotherapy toxicity risk score was calculated. Relationships between tolerability (number of courses, hospitalizations, dose reductions, and toxicity) and risk score were assessed using general linear models, Student t tests, and the Fisher test. Response rate and progression-free survival were evaluated using the Kaplan-Meier method. Results Forty patients (mean age, 73 years; range, 65-87 years) were included. The median number of cycles was 6, 75% (n = 30) of patients had ≥ 1 dose hold, and 50% (n = 20) had ≥ 1 dose reduction. Fifty-eight percent (n = 23) had treatment-related ≥ grade 3 toxicities, and 30% (n = 12) were hospitalized owing to toxicity. Thirty-five percent (n = 14) responded, and the median progression-free survival was 6.5 months (95% confidence interval, 5.5 months to undefined). Patients with intermediate/high toxicity risk scores had higher risk of grade ≥ 3 toxicity than those with low risk scores (odds ratio, 5.8; 95% confidence interval, 1.3-33.1; P = .01). A higher mean risk score was associated with higher likelihood of dose reductions and hospitalizations. Conclusions Among older adults with MBC receiving weekly nab-paclitaxel, more than one-half experienced ≥ grade 3 chemotherapy toxicity. However, a GA-based risk score could predict treatment tolerability.

BACKGROUND Older patients with advanced cancer who are 100% certain they will be cured pose unique challenges for clinical decision making, but to the authors' knowledge, the prevalence and correlates of absolute certainty about curability (ACC) are unknown. METHODS Cross-sectional data were collected in a geriatric assessment trial. ACC was assessed by asking patients, "What do you believe are the chances that your cancer will go away and never come back with treatment?" Response options were 100% (coded as ACC), >50%, 50/50

Background: Response to neoadjuvant therapy is a predictor of progression-free and overall survival in HER2+. To decrease treatment associated toxicities in patients with HER2+ breast cancers we utilized a non-anthracycline regimen with pertuzumab (pert), trastuzumab (trast), and nab-paclitaxel (nab). Pre- neoadjuvant therapy biopsies were procured to evaluated possible biological predictors of pathologic complete response (pCR). Methods: Women with locally advanced HER2 positive breast cancers were recruited from our breast cancer clinics. After obtaining informed consent for this IRB-approved trial, patients were treated with 6 cycles of pertuzumab (day 1 every 21 days [d]), and weekly trastuzumab 2 mg/kg with and nab-paclitaxel 100 mg/m2. Formalin fixed paraffin embedded (FFPE) or frozen biopsies pre-NT and post-NT were collected, along with blood samples at pre-treatment, and at the end of study for correlative analysis. Results: Accrual is complete, with 42 of the 45 HER2+ patients assessed for pCR rate (3 too early to evaluate). The median age was 54 yrs (range 31-77 years). 12 patients were stage 3, 26 stage 2, and 1 stage 1 patient. The pCR rate was 64.2% (27/42), with 73.7% (14/19) in ER/PR negative patients and 56.5% (13/23) in ER/PR positive patients. The initial primary tumor size was similar for in those who achieved pCR and non-pCR patients (mean 4.1 cm vs 3.2 cm, respectively). Most patients required dose modifications. Grade 3 AEs reported included 6 patients with hypertension, 3 patients with hematological AEs, 3 patients with elevated LFTs, and 2 patients with diarrhea. Conclusions: This anthracycline-free regimen in HER2+ BC can achieve promising pCR response rates, with toxicities well-managed with dose modifications. Results of correlative analysis will be presented. Citation Format: Somlo G, Waisman J, Yuan Y, Kruper L, Frankel P, Jones V, Lusi T, Schmolze D, Yim J, Hurria A, Mortimer J. Pathologic complete response (pCR) in locally advanced HER2+ (HER2+) breast cancer (BC) treated with anthracycline-free neoadjuvant therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-18.

Background: Almost a quarter of older adults in the United States will identify themselves as Hispanic/Latino by 2060. Our group has previously developed and validated a self-administered geriatric assessment tool which can be used to identify functional, psychological, social and cognitive impairments among older patients with various types of cancer. Among English-speaking older adults, completing this tool using paper/pencil or a tablet takes a median of 15-21 minutes (min), with < 10% needing assistance to answer it (Hurria, JOP 2016). However, the utilization of this tool among Spanish-speaking older adults has not been tested. We assessed the feasibility of administering a translated and validated Spanish version of our geriatric assessment tool for older Hispanic women with breast cancer, and identified their preferred format (tablet or paper/pencil). Methods: Spanish-speaking women aged ≥ 65 years with a diagnosis of breast cancer completed the geriatric assessment twice on the same day. Patients were randomized into 3 groups: paper/pencil twice; tablet and paper/pencil in random order; and tablet twice. We assessed the proportion of patients requiring assistance to complete the geriatric assessment, the time needed to complete it, and the proportion of patients who thought the geriatric assessment was difficult/very difficult. Results: 140 older women with breast cancer completed the geriatric assessment twice and were evaluable. Mean age was 71.6 years (SD 5.8), 53% had ≤ 8th grade education, 43% were married, 45% were retired, 32% were homemakers, and 6% were employed. The participants came from 13 different Spanish-speaking countries, although 70% were born in Mexico. For 90%, Spanish was their primary language, and 75% spoke only in Spanish at home. Regarding computer skills, 64% of the patients said they had none. 39% (n = 54) were unable to complete the geriatric assessment on their own; mean time to complete the geriatric assessment was 29 min (range 8-90); and 28% (n = 39) thought the geriatric assessment was difficult/very difficult. The most common reasons for needing assistance were difficulty understanding questions (39%) and visual problems (31%). Patients with ≤ 8th grade education took longer to complete the geriatric assessment (mean 37.2 vs 29.4 min, p < 0.01), and more often needed help completing the assessment (51% vs 19%, p < 0.01) than those with ≥9th grade education. 53% of the participants preferred using a tablet to answer the geriatric assessment, while 47% preferred paper/pencil. Conclusions: A substantial proportion of Spanish-speaking older women with breast cancer required assistance to complete our self-administered geriatric assessment tool. This may be a consequence of the low educational level we found among this patient population. Tailoring assessments for diverse populations with particular attention to educational level is needed in multicultural settings. Citation Format: Soto-Perez-de-Celis E, Vazquez J, Kim H, Sun C-L, Somlo G, Yuan Y, Waisman JR, Mortimer JE, Kruper L, Taylor L, Patel NH, Moreno J, Charles K, Roberts E, Uranga C, Levi A, Katheria V, Paredero-Perez I, Mitani D, Hurria A. A self-administered geriatric assessment tool for Spanish-speaking older women with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-16-04.

Background: Alteration of PI3K/Akt/mTOR pathway is the most common genomic abnormality detected in triple negative breast cancer (TNBC). Everolimus acts synergistically with eribulin in inducing apoptosis in TNBC cell lines and xenografts in our preclinical study. This phase I trial was designed to test the safety and tolerability of combining eribulin and everolimus in patients (pts) with metastatic TNBC. Methods: The overall objective of this study was to describe the safety and toxicities of the combination. The secondary objective was to assess activity based on response rate (RR) and progression free survival (PFS). Eligibility criteria included pts with metastatic TNBC, ECOG 0-2, 0-3 lines of prior chemotherapy in metastatic setting, and prior treatment with anthracycline and/or taxane therapy. The study utilized the toxicity equivalence range (TEQR) design with a target equivalence range for dose-limiting toxicities (DLTs) of 0.20-0.35. The recommended phase 2 dose (RP2D) will be the dose closest to the target of 0.25 below 0.51 based on isotonic regression.Three dosing levels of the combinations were tested: level A1 (everolimus 5mg daily; eribulin 1.4 mg/m2 days 1, 8 every 3 weeks), level A2 (everolimus 7.5mg daily; eribulin 1.4 mg/m2, days 1, 8 every 3 weeks), level B1(everolimus 5mg daily; eribulin 1.1 mg/m2 days 1, 8 every 3 weeks). Nanostring RNA analysis and genomic mutation analysis were conducted in 16 pts with available tumor tissue. Results: A total of 27 pts were enrolled. Median age was 55 years (range 36-76). Two pts were ineligible due to HER2+ on repeat biopsy and were only included in the toxicity analysis. Dose level B1 (everolimus 5mg daily and eribulin 1.1 mg/m2 days 1, 8 every 3 weeks) was determined to be the RP2D doses. The DLTs were neutropenia, stomatitis and hyperglycemia. Across all cycles, 59% (16/27) had a ≥ Gr3 toxicity attributed to treatment at the possible or above level. 44% (12/27) had Gr3 heme-toxicities. The most common toxicities were ≥ Gr3 neutropenia (10 pts), Gr3 lymphopenia (6 pts) and ≥ Gr3 leukopenia (7 pts). 33% (9/27) had Gr3 non-heme toxicities. The most common were Gr3 stomatitis (3 pts), Gr3 hyperglycemia (3 pts) and Gr3 fatigue (5 pts). The median number of cycles completed was 4 (0-8). 68% (17/25) had a dose modification or hold, 14 of 25 (56%) were for eribulin and 15 of 25 (60%) were for everolimus. Of 25 eligible pts, 8 (32%) achieved a best response as partial response, 11 (44%) had stable disease and 6 (24%) had progression. 80% (20/25) experienced progression by RECIST or showed clinical progression, and the median time to progression was 2.7 mo (95% CI (2.2, 4.6)). At the time of this analysis, 16 participants had died, median OS was 6.3 mo (95% CI (5.3, undefined)). Two pts are still being followed on treatment. PI3K-Akt-mTOR pathway genes and mutations profiles were studied. Conclusion: Eribulin 1.1 mg/m2 days 1, 8 and everolimus 5mg daily was defined as the RP2D. Genomic analysis is currently underway to understand the molecular mechanisms of resistance. Citation Format: Yuan Y, Yost S, Blanchard S, Yin H, Li M, Robinson K, Tang A, Martinez N, Leong L, Somlo G, Tank Patel N, Waisman J, Portnow J, Hurria A, Luu T-H, Mortimer J. Phase I trial of eribulin and everolimus in patients with metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-18.

Background: Response to neoadjuvant therapy (NT) predicts progression-free and overall survival in triple negative breast cancer (TNBC). Carboplatin has shown efficacy in patients with TNBC. The current phase II prospective neoadjuvant trial was designed to decrease toxicities and improve efficacy. Methods: Patients with TNBC received carboplatin (carb) and nab-paclitaxel (nab). Pre-NT biopsies were procured to evaluate for biological predictors of pathological complete response (pCR). Newly diagnosed stage II-III patients with TNBC were treated with 4 cycles of carb (AUC 6, day 1 of 28 day cycle) and weekly nab 100 mg/m2 x 16. Targeted accrual goal is 70. RNA extracted from formalin fixed paraffin embedded (FFPE) biopsies pre-NT was tested for MammaPrint/BluePrint and custom Agilent full genome microarrays for gene expression (GE, by Agendia Inc). The raw gMeanSignal was log2 transformed and normalized to the 75thpercentile for GE analysis. Association between MammaPrint/ BluePrint results and pCR was tested by Fisher exact test. The linear model from R limma package was applied. Ingenuity Pathway Analysis (IPA) was applied to assess functional pathways associated with pCR. Cellular distribution by CIBERSORT analysis was carried out to estimate the abundance of 22 different cell types in each patient sample, and test whether the distribution of cell types is different between pCR and non-responders. Results: A total of 64 patients were enrolled. Two patients were deemed ineligible (Her2+), and three were too early, resulting in 59 patients evaluable for pathological response. The pCR rate was 47% (RCB0, 28/59). Eight patients had RCB I. RCB0 plus RCBI reached 61%. Sufficient quality RNA and DNA were available from the first 43 of 55 pts with TNBC. 44/59 (75%) required dose modifications (mostly hematologic), 5 patients had grade 3 peripheral neuropathy (PN), 3 had grade 2 PN, and 3 patients had grade 2 LFTs. In the 53 pts with GE assessment, pCR was inversely associated with luminal BluePrint type (p=0.04). With fold change >1.5 and p-value < 0.05, 36 genes were differentially expressed (DE) in TNBC. CIBERSORT analysis suggested that T-cell regulatory cells (TREGS) were associated with pCR in TNBC, and 5 cell types (plasma cells, TREGS, macrophage, dendritic cells and neutrophils) presented differently between all pCR and non-pCRs with P-value Conclusions: The combination of carboplatin and nab-paclitaxel given in the neoadjuvant setting reached a promising pCR rate of 47%. The MammaPrint non-luminal BluePrint subtype was predictive of pCR in TNBC. Preliminary analysis suggested that a 36-gene signature for TNBC was associated with pCR. CIBERSORT analysis revealed 5 cell types with different abundance between the pCR and non-responders, suggesting the need to target the tumor microenvironment. Citation Format: Yuan Y, Frankel P, Li M, Kruper L, Jones V, Treece T, Waisman J, Yim J, Tumyan L, Schmolze D, Hurria A, Yeon C, Mortimer J, Somlo G. Phase II trial of neoadjuvant carboplatin and nab-paclitaxel in patients with locally advanced triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-07.

Background:Obese postmenopausal women are at higher breast cancer risk potentially driven by hyperinsulinemia. However, reports of insulin level associations with breast cancer incidence and survival are inconsistent. Therefore, we examined associations among insulin resistance by homeostasis model assessment-insulin resistance (HOMA-IR) index and incident breast cancer, deaths from breast cancer, and deaths after breast cancer in postmenopausal women participating in the Women's Health Initiative (WHI). Patients and Methods:From the 161,808 postmenopausal women, aged 50-79 years, enrolled at 40 US clinical centers from 1993 through1998 in WHI clinical trials or the observational study, 22,837 with available fasting serum insulin and glucose by the same methodology and no prior breast cancer represent the current study population. The exposure was insulin resistance (HOMA-IR index) as [fasting insulin (qIU/ml) times fasting glucose (mg/dL) / 22.5. Survival by cause was determined by central medical record or death certificate review, enhanced by National Death Index queries. Breast cancers, initially ascertained by serial survey, were confirmed by medical record review. Associations between HOMA-IR quartiles and breast cancer outcomes were examined using Cox multi- variate proportional hazards models with results reported as hazard ratios (HR) and 95% confidence intervals. Results: At entry, women in the highest HOMA-IR quartile were more likely to be Black, have lower education level, have higher body mass index (BMI), higher waist circumference ≥ 88 cm and lower physical activity levels, but have lower calculated five-year breast cancer risk. After 18.1 years median follow-up from randomization with 1,148 incident breast cancers, breast cancer incidence was higher in women in the highest, compared to the lowest, HOMA-IR index quartile (HR 1.39 95% CI 1.14 -1.69, P = 0.0012). Of the women with incident breast cancer, 353 (31%) have died, with cause of death available on 334 (95% of cases) where breast cancer was the most common cause of death (33%); followed by cardiovascular disease (24%); and other cancers (13%). With median post-breast cancer diagnosis follow-up of 10.5 years, breast cancer mortality was examined from breast cancer diagnosis. No association was found between death from breast cancer and HOMA-IR. However, women with breast cancer in the highest HOMA-IR quartile, compared to women in the lowest, were significantly more likely to experience death after breast cancer from any cause (HR 1.45 95% CI 1.00 - 2.09, P = 0.0488) and were at somewhat higher risk of death from cardiovascular disease (HR 1.51 95% CI 0.67 - 3.41) and other causes (HR 1.93 95% CI 0.87-4.27). Conclusion:In postmenopausal women, higher insulin resistance is associated with higher breast cancer incidence and more deaths after breast cancer, likely due to insulin influence on several causes of death. However, deaths from breast cancer, even in this older postmenopausal population, remains a major factor limiting survival which needs to be addressed. The findings suggest insulin resistance represented a potential intervention target for postmenopausal women with early stage breast cancer. Citation Format: Chlebowski RT, Pan K, Mortimer J, Cespedes Feliciano EM, Gunter MJ, Hurria A, Rohan T, Vitolins MZ, Adams-Campbell L, Ho G, Cheng T-YD, Nelson R. Insulin resistance and breast cancer incidence and mortality in postmenopausal women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-10.

Through the National Institute on Aging's (NIA's) "Grants for Early Medical/Surgical Specialists" Transition to Aging Research (GEMSSTAR) U13 grant, the NIA and the American Geriatrics Society (AGS) developed three transdisciplinary research conferences with a focus on mentoring and leadership skills development. The NIA's GEMSSTAR program evolved from two earlier programs, the AGS' Dennis W. Jahnigen and the Association of Specialty Professors' T. Franklin Williams Career Development Scholars Awards. It supports the continued cultivation of the next generation of medical and surgical specialty researchers with an interest in aging research. The award requires both geriatrics and specialty mentoring and currently provides up to $150,000 a year in direct support to scholars. Additionally, the award requires that scholars have a professional development plan that is complementary to the GEMSSTAR award. The U13 conferences, focused on frailty, models of aging, and cognition, brought together GEMSSTAR scholars, former scholars, innovators, mentors, and leaders in aging research, the specialties, and geriatric medicine. This article describes the themes of each of the GEMSSTAR U13 conferences and highlights the lessons learned on mentoring, team science, aging research networks, and work-life balance. We plan to use these lessons to guide the support we provide to the growing group of emerging leaders who are poised to lead the transdisciplinary research network of the future. J Am Geriatr Soc 67:650-656, 2019.

The American Geriatrics Society convened a conference in Bethesda, Maryland, to explore models and studies of aging. This was the second of three conferences, supported by a U13 grant from the National Institute on Aging, to aid recipients of Grants for Early Medical/Surgical Specialists Transition to Aging Research (GEMSSTAR) in integrating geriatrics into their specialties. Recognizing that aging is the largest risk factor for multiple chronic diseases and age-related loss of resilience, the conference organizers focused scientific sessions on how targeting age-related mechanisms can delay, prevent, or reverse geriatric syndromes, age-related chronic diseases, and loss of resilience. The rationale for studying models of aging as well as study designs, strategies, and challenges of studying human aging were reviewed. This article provides a summary of the full conference report, Models and Studies of Aging: Report from the U13 Conference Series, and summarizes key take-home messages that were designed to support GEMSSTAR awardees in developing their research careers focused on aging research (see supplementary text for the full report). J Am Geriatr Soc 67:428-433, 2019.

Background To characterize functional trajectories in the year before and after a new cancer diagnosis among older adults and to identify risk factors for worsening disability post-diagnosis. Methods We identified 170 participants 70+ years with monthly assessments of thirteen basic, instrumental, and mobility activities and with a new cancer diagnosis from 1998 to 2014. A group-based trajectory model identified distinct functional trajectories based on a total disability score during the twelve months pre- and post-diagnosis. We evaluated associations between potential risk factors at the time of cancer diagnosis and worsening disability post-diagnosis, explored functional transitions from pre- to post-diagnosis and identified participants whose functional trajectories worsened. Results Three pre-diagnosis functional trajectories were identified among 170 participants (mean age at diagnosis: 83 years (range: 73–105 years): mild, moderate, and severe disability. Three post-diagnosis functional trajectories were identified among 158 non-decedents: mild, moderate, and severe disability. Most participants (93.9%) with severe disability pre-diagnosis had severe disability post-diagnosis. Risk factors independently associated with worsening disability post-diagnosis included moderate or severe disability pre-diagnosis (adjusted risk ratio, aRR: moderate: 2.96; 95%CI: 2.11–4.16; severe: 5.11; 95%CI: 3.07–8.52) vs. mild (reference), poor physical capability (aRR: 1.57; 95%CI: 1.07–2.30), and incurable stage (aRR:1.99; 95%CI: 1.41–2.80). 40% of participants with a mild or moderate disability trajectory pre-diagnosis transitioned to a worse functional trajectory post-diagnosis. Conclusion Older adults followed distinct functional trajectories in the twelve months before and after cancer diagnosis. Functional trajectory pre-diagnosis, poor physical capability, and incurable stage were independent risk factors for worsening disability post-diagnosis.

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

Introduction The relationship between cognitive function and frailty in older, long-term breast cancer survivors was examined. Materials and methods Breast cancer survivors who were diagnosed and treated at 60 years of age or above and were 5–15 year disease-free survivors and non-cancer controls matched on age and education were evaluated with neuropsychological tests and the Comprehensive Geriatric Assessment which was used to assess frailty based on a deficit accumulation frailty index (DAFI). Results Unadjusted regression analyses revealed that cancer survivors scored significantly lower on the Language (P = 0.015), Attention, Processing Speed, Executive Function (APE) (P = 0.015), and Learning and Memory (LM) (P = 0.023) domains compared to controls. However, only the LM domain remained significantly different (P = 0.002) in the adjusted analysis. Survivors had significantly higher DAFI scores compared to controls (p = 0.006) and significantly more survivors were categorized as pre-frail or frail (35%) compared to controls (23%, P = 0.009). Increasing frailty scores were associated with worse cognitive performance across all domains (all Ps ≤ 0.004). For the LM domain, there was a significant interaction (P = 0.019) between DAFI score and survivorship vs control status. Survivors demonstrated a significant linear decline in LM scores as DAFI scores increased, whereas controls demonstrated comparable scores between the robust and pre-frail DAFI groups, demonstrating decline in the frailty group only. Conclusion Older, long-term breast cancer survivors had lower cognitive performance and higher levels of frailty compared to controls. For the Learning and Memory domain, the decline in performance began in the pre-frail range for survivors, but not controls.

509 Background: Patient values toward treatment goals and competing health outcomes among adults with neuroendocrine tumors (NETs) are not well understood. The goal of this study was to identify NET patient values towards treatment goals and health outcomes. Methods: Patients with well-differentiated, grade 1/2, advanced NETs starting a new systemic therapy were recruited at a National Cancer Institute-designated cancer center. Patients completed four tools: 1) Health Outcomes Tool: ranks importance of four outcomes (survival, function, freedom from pain, freedom from symptoms); 2) Attitude Scale: identifies the extent to which patients agree with statements related to health outcomes; 3) Now versus Later Tool: ranks relative importance of quality of life (QOL) now, one year from now, and five years from now; and 4) Prognosis and Treatment Perceptions Questionnaire: identifies the amount of information patients prefer to receive about their disease and treatment, patient’s goal of treatment, physician’s goal of treatment (patient’s perception), and self-reported health status. Results: Sixty patients (50.0% ≥65 years) completed the questionnaires. Ninety-seven percent had stage IV disease. Primary tumor locations included gastrointestinal tract (41.7%), pancreas (30.0%), and lung (21.7%). Sixty percent of patients had received at least one prior systemic therapy. Only 30.0% of patients chose survival as their most important treatment outcome on the Health Outcomes Tool. The remaining 70.0% chose maintaining independence (46.7%), freedom from pain (11.7%), and freedom from symptoms (11.7%) as their most important health outcome. Similarly, on the Attitude Scale, 66.7% of patients agreed with: “I would rather live a shorter life than lose my ability to take care of myself”; 85.0% agreed with: “It is more important to me to maintain my thinking ability than to live as long as possible.” Ninety-three percent of patients agreed with: “I am willing to have side effects right now if it means I could have a better quality of life in the future.” Moreover, on the Now versus Later Tool, 48.3% of patients considered QOL one year in the future more important than their current QOL; 40.0% considered QOL five years in the future more important than their current QOL. On the Prognosis and Treatment Perceptions Questionnaire, only 30.0% of patients chose “To extend my life as long as possible” as their primary treatment goal, but 40.0% believed survival was their oncologist’s primary treatment goal. Furthermore, only 51.7% of patients believed they had the same treatment goal as their oncologist. Across all questionnaires, there were no significant differences between the responses of younger and older patients. Conclusions: NET patients value independence more than survival. More communication between NET patients and physicians is needed to ensure patient preferences and values are incorporated into treatment plans.

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.

Up to 85% of adult cancer survivors and 99% of adult survivors of childhood cancer live with an accumulation of chronic conditions, frailty, and/or cognitive impairments resulting from cancer and its treatment. Thus, survivors often show an accelerated development of multiple geriatric syndromes and need therapeutic interventions. To advance progress in this area, the National Cancer Institute convened the second of 2 think tanks under the auspices of the Cancer and Accelerated Aging: Advancing Research for Healthy Survivors initiative. Experts assembled to share evidence of promising strategies to prevent, slow, or reverse the aging consequences of cancer and its treatment. The meeting identified research and resource needs, including geroscience-guided clinical trials; comprehensive assessments of functional, cognitive, and psychosocial vulnerabilities to assess and predict age-related outcomes; preclinical and clinical research to determine the optimal dosing for behavioral (eg, diet, exercise) and pharmacologic (eg, senolytic) therapies; health-care delivery research to evaluate the efficacy of integrated cancer care delivery models; optimization of intervention implementation, delivery, and uptake; and patient and provider education on cancer and treatment-related late and long-term adverse effects. Addressing these needs will expand knowledge of aging-related consequences of cancer and cancer treatment and inform strategies to promote healthy aging of cancer survivors.

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.

Cancer is a disease of aging, and oncologists are faced with the challenge of providing evidence-based treatment to a growing number of older adults with cancer. Cancer and aging share common biologic and cellular mechanisms, and older adults have age-related changes in all organ systems that decrease the tolerance to both cancer and its treatments. Presently, generic scales and chronologic age are used to determine a treatment course, assess eligibility for clinical trials, and predict treatment toxicity and survival. However, these parameters offer a poor reflection of the functional status of older patients and should not be the main factor guiding decision making. In contrast, the geriatric assessment is a multidimensional diagnostic evaluation aimed at providing a comprehensive overview of an older patient's functional status, cognition, comorbidities, psychological status, social functioning, and nutritional status. Although this comprehensive evaluation is able to identify important areas of vulnerability for which targeted interventions can be applied, it is not commonly taught in oncology training or used in oncology practice. In this chapter, we discuss the fundamental science behind the geriatric assessment, and review the clinical applications of a geriatric assessment-based approach to the prevention and treatment of cancer in older adults.

As part of the ongoing efforts to address the lack of clinical research on older adults with cancer, the American Society of Clinical Oncology (ASCO) and the US Food and Drug Administration cosponsored a public workshop on geriatric oncology in November 2017. The goals were to review progress, build collaborations across stakeholders, and generate new action items for increasing the evidence base for treating older adults with cancer. It built on previous work of the Institute of Medicine, ASCO, and the U13 Conferences convened by the Cancer and Aging Research Group, the National Cancer Institute, and the National Institute of Aging between 2010 and 2015. The workshop drew a diverse group of presenters, panelists, and attendees, including academic and clinical oncologists, regulators, other government officials, representatives from industry, and patient advocacy groups. Attendees at the workshop were tasked with proposing next steps to address the lack of evidence on treating older adults with cancer. Based on the workshop discussions, four new action items to move the field forward were developed: 1) increase enrollment of older adults in clinical trials, 2) collect more information on older adults enrolled on clinical trials, 3) expand the use of real-world data in research on older adults, and 4) strengthen collaboration between stakeholders to develop advocacy and policy solutions. These action items, alongside the previous ASCO, Institute of Medicine, and U13 recommendations, provide a strategy for improving the evidence base for treating older adults with cancer and ensuring all patients with cancer receive high-quality, evidence-based care.

One-third of breast cancer (BC) cases worldwide occur in women aged 65 years and older, with 10 to 15% overexpressing the human epidermal growth factor receptor 2 (HER2). Although several HER2-targeted therapies have been developed, the lack of data regarding their use in older patients hampers evidence-based decision-making for this population.We review current evidence on the efficacy and safety of HER2-targeted therapies in older adults with BC, focusing on approved therapies such as trastuzumab, lapatinib, pertuzumab, ado-trastuzumab-emtansine, and neratinib. Additionally, we discuss drugs under development to target the HER2-receptor, and to overcome resistance to existing therapies. Finally, we highlight the cardiotoxicity of HER2-targeted drugs among older adults.Older adults are underrepresented in trials of HER2-targeted therapies in BC. We propose strategies to increase recruitment of older adults in clinical trials in order to increase the evidence base to treat this growing population.

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.

Background Most oncology trainees are not taught about the needs of older patients, who make up the majority of patients with cancer. Training of health care providers is critical to improve the care of older adults with cancer. There is no consensus about which geriatric oncology (GO) competencies are important for medical oncology trainees. Our objective was to identify GO competencies medical oncology trainees should acquire during training. Materials and Methods A modified Delphi consensus of experts in oncology medical education and GO was conducted. Experts categorized at what training stage proposed competencies should be attained: internal medicine, oncology, or GO training. Consensus was obtained if two thirds of experts agreed on the training stage at which the competency should be attained. Results A total of 78 potential competencies were identified, of which 35 (44.9%) proposed competencies were felt to be appropriate to be acquired during oncology training. The majority of the identified competencies pertained to prescribing of systemic therapy (n = 12) and psychosocial and supportive care (n = 13). No competencies related to geriatric assessment were identified for acquisition during oncology training. Conclusion Experts in oncology education and geriatric oncology agreed upon a set of GO competencies appropriate for oncology trainees. These results provide the foundation for developing a GO curriculum for medical oncology trainees and will hopefully lead to better care of older adults with cancer. Implications for Practice The aging population will drive the projected rise in cancer incidence. Although aging patients make up the majority of patients diagnosed with cancer, oncologists rarely receive training on how to care for them. Training of health care providers is critical to improving the care of older adults with cancer. The results of this study will help form the foundation of developing a geriatric oncology curriculum for medical oncology trainees.

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.

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Purpose The purpose of this study was to evaluate longitudinal changes in brain gray matter density (GMD) before and after adjuvant chemotherapy in older women with breast cancer. Methods We recruited 16 women aged ≥ 60 years with stage I–III breast cancers receiving adjuvant chemotherapy (CT) and 15 age- and sex-matched healthy controls (HC). The CT group underwent brain MRI and the NIH Toolbox for Cognition testing prior to adjuvant chemotherapy (time point 1, TP1) and within 1 month after chemotherapy (time point 2, TP2). The HC group underwent the same assessments at matched intervals. GMD was evaluated with the voxel-based morphometry. Results The mean age was 67 years in the CT group and 68.5 years in the HC group. There was significant GMD reduction within the chemotherapy group from TP1 to TP2. Compared to the HC group, the CT group displayed statistically significantly greater GMD reductions from TP1 to TP2 in the brain regions involving the left anterior cingulate gyrus, right insula, and left middle temporal gyrus (pFWE(family-wise error)-corrected pFWE-corrected pFWE-corrected Conclusions Our findings indicate that GMD reductions were associated with adjuvant chemotherapy in older women with breast cancer. Future studies are needed to understand the clinical significance of the neuroimaging findings. This study is registered on ClinicalTrials.gov (NCT01992432).

Early-stage non-small cell lung cancer (NSCLC) is on the rise due to the implementation of screening guidelines for patients at risk for developing lung cancer. It is anticipated that as the US population continues to age, there will be a higher percentage of medically inoperable early-stage lung cancer patients. For this reason, noninvasive ablative therapies are necessary. Stereotactic body radiation therapy (SBRT) is an effective modality in addressing early-stage NSCLC. SBRT consists of high-dose radiation delivered over 3-5 treatments. Several randomized trials comparing surgery to SBRT in early-stage operable patients have unfortunately closed early due to poor accrual. However, a recent pooled analysis from 2 randomized trials (StereoTActic Radiotherapy and Radiosurgery Or Surgery for operable Early-stage non-small cell Lung cancer) comparing surgery to SBRT did show comparable local control and overall survival rates between surgery and SBRT, offering a very effective, noninvasive modality for older adult patients with early-stage NSCLC. In this review, we summarize the role of SBRT in early-stage NSCLC, in particularly applied to the older adult population.

BACKGROUND Hearing and visual impairments are common among community-dwelling older adults, and are associated with psychological, functional, and cognitive deficits. However, to the authors' knowledge, little is known regarding their prevalence among older patients with cancer. METHODS The current study was a secondary analysis combining 2 prospective cohorts of adults aged ≥65 years with solid tumors who were receiving chemotherapy. The authors assessed the association between patient-reported hearing and/or visual impairment (defined as fair/poor grading by self-report) and physical function, instrumental activities of daily living (IADLs), anxiety, depression, and cognition. Descriptive analyses were conducted to summarize patient and treatment characteristics. One-way analysis of variance and chi-square tests were conducted as appropriate to examine differences between patients with and without sensory impairments. Logistic regression was used to analyze associations between sensory impairments and outcomes. RESULTS Among 750 patients with a median age of 72 years who had solid tumors (29% with breast/gynecological tumors, 28% with lung tumors, and 27% with gastrointestinal tumors), approximately 18% reported hearing impairment alone, 11% reported visual impairment alone, and 7% reported dual sensory impairment. Hearing impairment was associated with IADL dependence (odds ratio [OR], 1.9), depression (OR, 1.6), and anxiety (OR, 1.6). Visual impairment was associated with IADL dependence (OR, 1.9), poor physical function (OR, 1.9), and depression (OR, 2.5). Dual impairment was associated with IADL dependence (OR, 2.8), anxiety (OR, 2.3), depression (OR, 2.5), and cognitive impairment (OR, 3.2). CONCLUSIONS Sensory impairment is common among older adults with cancer. Patients with sensory impairment are more likely to have functional, psychological, and cognitive deficits. Interventions aimed at improving the vision and hearing of older adults with cancer should be studied. Cancer 2018. © 2018 American Cancer Society.

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

Older adults represent the majority of patients diagnosed with cancer, yet the evidence base used to guide therapy for this growing segment of the population is limited compared with data available for younger adults. Information is particularly limited for adults commonly seen in practice, including those over age 75 and those with comorbidity or frailty. Efforts have been underway to raise awareness of this substantial gap in evidence and identify strategies to build an evidence base for older adults. Recently, the ASCO and the U.S. Food and Drug Administration convened a public workshop to address this issue. There is a need for innovative trial design to test the efficacy and tolerability of therapies among generalizable older adult populations. Incorporation of endpoints such as functional independence and quality of life as well as investigation of geriatric assessment–based treatment allocation strategies will be needed to individualize care planning. Strategies to increase trial enrollment need to be emphasized, including modernizing eligibility criteria, addressing patient and provider barriers to clinical trial enrollment, and consideration of incentives for patients, providers, and sponsors. Finally, investigation of real-world data and incorporation of patient-reported outcomes into the drug-development process may provide opportunities to build evidence related to treatment benefit and tolerance with an emphasis on the patient experience among older adults in diverse treatment settings.