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Our objective was to assess distress levels in female breast cancer patients as a function of race, ethnicity, and preferred language. We hypothesized minority patients and non-English screen-takers would report higher distress levels compared to English screen-takers and non-Hispanic whites. We conducted a retrospective observational study of female breast cancer patients at an NCI designated cancer center from 2009 to 2016 who were administered a validated biopsychosocial distress screening questionnaire. Self-reported data on race and ethnicity was collected. A total of 3,156 patients were included in the analysis; mean age of 56.3 (SD 12.25) years. The racial/ethnic cohort distribution included 54% non-Hispanic white (NHW), 19% Hispanic, 16% Asian, 7% Black/African American, and 4% other. On multivariable analysis only Hispanic patients were significantly more likely to report overall distress compared to NHW (OR [1.39; CI [1.03-1.87; p=0.03). Asians were significantly less likely to report distress in the functional domain (OR 0.71, CI [0.58-0.88]; p=0.002), while Black patients were significantly more likely to report highest distress levels in the physical (OR 1.53, CI [1.11-2.12]; p=0.01) domain. Hispanic Spanish screen-takers reported significantly more distress compared to Hispanic English screen-takers across all four domains of distress (p

Chemotherapy may impair cognition and contribute to accelerated aging. The purpose of this study was to assess the effects of chemotherapy on the connectivity of the default mode network (DMN) in older women with breast cancer. This prospective longitudinal study enrolled women aged ≥ 60 years with stage I–III breast cancer (CTx group) and matched healthy controls (HC group). Study assessments, consisting of resting-state functional MRI (rs-fMRI) and the Picture Sequence Memory (psm) test for episodic memory from the NIH Toolbox for Cognition, were obtained at baseline and within one month after the completion of chemotherapy for the CTx group and at matched intervals for the HC group. Two-sample t-test and FDR multiple comparison were used for statistical inference. Our analysis of the CTx group (N = 19; 60–82 years of age, mean = 66.6, SD = 5.24) compared to the HC group (N = 14; 60–78 years of age, mean = 68.1, SD = 5.69) revealed weaker DMN subnetwork connectivity in the anterior brain but stronger connectivity in the posterior brain at baseline. After chemotherapy, this pattern was reversed, with stronger anterior connectivity and weaker posterior connectivity. In addition, the meta-level functional network connectivity (FNC) among the DMN subnetworks after chemotherapy was consistently weaker than the baseline FNC as seen in the couplings between anterior cingulate cortex (ACC) and retrosplenial (rSplenia) region, with ΔFNC(‘ACC’,’rSplenia’)=-0.14, t value=-2.44, 95 %CI=[-0.27,-0.10], pFDR

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.

Background The number of patients undergoing autologous haematopoietic cell transplant (HCT) is growing, but little is known about the factors that predict adverse outcomes. Low muscle mass and obesity are associated with disability and premature mortality in individuals with non‐malignant diseases and may predict outcomes after autologous HCT. Methods This was a retrospective cohort study of 320 patients who underwent autologous HCT for Hodgkin or non‐Hodgkin lymphoma between 2009 and 2014. Sarcopenia {skeletal muscle index male

Objectives Oncologists can be one of the major barriers to older adult's participation in research. Multiple studies have described academic clinicians' concerns for not enrolling older adults onto trials. Although the majority of older adults receive their cancer care in the community, few studies have examined the unique challenges that community oncologists face and how they differ from oncologist-related barriers in academia. Methods Semi-structured interviews were conducted by telephone or face-to-face with 44 medical oncologists (24 academic-based and 20 community-based) at City of Hope from March to June 2018. Interviews explored oncologists' perceptions of barriers to clinical trial enrollment of older adults with cancer. Data were analyzed using qualitative content analysis. Results Of the 44 participants, 36% were women and 68% were in practice for >10 years. Among the entire sample, stringent eligibility criteria (n = 20) and oncologist concerns for treatment toxicities (n = 15) were the most commonly cited barriers. Compared to academic oncologists, community oncologists more often cited patient attitudes, beliefs, and understanding (n = 9 vs. n = 2) and caregiver burden (n = 6 vs. n = 0). In contrast, compared to community oncologists, academic oncologists more often cited oncologist bias (n = 10 vs. n = 3) and insufficient time/support (n = 4 vs. n = 1). Conclusions Differences in perceptions among academic and community oncologists about trials suggest that barriers are multifaceted, complex, and vary by practice setting. Interventions to increase trial accrual among older adults with cancer may benefit from being tailored to address the unique barriers of different practice settings.

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.

IMPORTANCE: Although geriatric assessment–driven intervention improves patient-centered outcomes, its influence on chemotherapy-related toxic effects remains unknown. OBJECTIVE: To assess whether specific geriatric assessment–driven intervention (GAIN) can reduce chemotherapy-related toxic effects in older adults with cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial enrolled 613 participants from a National Cancer Institute–designated cancer center between 2015 and 2019. Patients were 65 years and older with a solid malignant neoplasm, were starting a new chemotherapy regimen, and completed a geriatric assessment. Patients were followed up until chemotherapy completion or 6 months after initiation, whichever occurred first. Data analysis was done by intention-to-treat principle. INTERVENTIONS: Patients were randomized (2:1) to either the GAIN (intervention) or standard of care (SOC) arm. In the GAIN arm, a geriatrics-trained multidisciplinary team composed of an oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist reviewed geriatric assessment results and implemented interventions based on prespecified thresholds built into the geriatric assessment’s domains. In the SOC arm, geriatric assessment results were sent to treating oncologists for consideration. MAIN OUTCOMES AND MEASURES: The primary outcome was incidence of grade 3 or higher chemotherapy-related toxic effects (graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). Secondary outcomes included advance directive completion, emergency department visits, unplanned hospitalizations, average length of stay, unplanned hospital readmissions, chemotherapy dose modifications, and early discontinuation. Overall survival analysis was performed up to 12 months after chemotherapy initiation. RESULTS: Among the 605 eligible participants for analysis, median (range) age was 71 (65-91) years, 357 (59.0%) were women, and 432 (71.4%) had stage IV disease. Cancer types included gastrointestinal (202 [33.4%]), breast (136 [22.5%]), lung (97 [16.0%]), genitourinary (91 [15.0%]), gynecologic (54 [8.9%]), and other (25 [4.1%]). Incidence of grade 3 or higher chemotherapy-related toxic effects was 50.5% (95% CI, 45.6% to 55.4%) in the GAIN arm and 60.6% (95% CI, 53.9% to 67.3%) in the SOC arm, resulting in a significant 10.1% reduction (95% CI, −1.5 to −18.2%; P = .02). A significant absolute increase in advance directive completion of 28.4% with GAIN vs 13.3% with SOC (P

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.

The use of social media has been explored as a potential strategy to improve enrollment in cancer clinical trials. However, significant barriers to implementation of this recruitment approach remain, including investigator reluctance to use social media for patient recruitment.1,2 We conducted a survey study to assess the prevalence of and attitudes toward the use of social media in clinical trial recruitment among cancer investigators.

Objective The tolerability and efficacy of targeted therapy in older adults with cancer has not been adequately studied. Neratinib is a novel HER1, HER2, HER4 tyrosine kinase inhibitor that has recently been granted FDA approval for treatment of breast cancer. The major toxicity of neratinib is diarrhea, which affects up to 90% of patients. This phase II trial evaluates the safety and tolerability of neratinib in adults ≥60. Methods Patients aged 60 or older with histologically proven metastatic breast cancer and HER2 amplification (defined by ASCO/CAP guideline) or HER2/HER3 activating mutation were enrolled to receive neratinib at 240 mg daily in 28-day cycles. The association between tolerability, defined as dose reduction and number of completed courses, and log2 Cancer and Aging Research Group (CARG) toxicity risk score was assessed using a Student's t-test and linear regression, respectively. Response rate, progression free survival, and overall survival were also evaluated. Results 25 patients were enrolled with median age of 66 (range 60–79). Seventy-six percent of patients were white, 16% Asian, and 8% African-American. Seventy-six percent were patients with hormone receptor (HR) positive metastatic breast cancer (MBC) and 24% were patients with HR negative MBC. Median number of prior lines of metastatic therapy were 3 (range 0–11). 20/25 (80%) had worst grade toxicities ≥2. A total of 9/25 (36%) had grade 3 toxicities including 5/20 (20%) diarrhea, 2/20 (8%) vomiting, and 2/20 (8%) abdominal pain. There were no grade 4 or 5 toxicities. A total of 9/25 (36%) had dose reduction, and 2/25 (8%) discontinued therapy due to toxicity. The association between dose reductions and CARG toxicity score reached borderline statistical significance suggesting a trend with participants with higher CARG toxicity risk scores being more likely to require a dose modification (p = 0.054). 1/25 (4%) had a partial response, 11/25 (44%) had stable disease, 12/25 (48%) had progression of disease, and 1/25 (4%) was not assessed. Median progression free survival (PFS) was 2.6 months (95% CI [2.56–5.26]), and median overall survival (OS) was 17.4 months (95% CI [10.3, NA]). Conclusions Neratinib was safe in this population of older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer (BC). Higher CARG toxicity risk score may be associated with greater need for dose adjustments. Future studies are needed to confirm this finding.

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).

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.

Purpose Survivors of childhood cancer treated with cranial radiation therapy are at risk for subsequent CNS tumors. However, significant interindividual variability in risk suggests a role for genetic susceptibility and provides an opportunity to identify survivors of childhood cancer at increased risk for these tumors. Methods We curated candidate genetic variants from previously published studies in adult-onset primary CNS tumors and replicated these in survivors of childhood cancer with and without subsequent CNS tumors (82 participants and 228 matched controls). We developed prediction models to identify survivors at high or low risk for subsequent CNS tumors and validated these models in an independent matched case-control sample (25 participants and 54 controls). Results We demonstrated an association between six previously published single nucleotide polymorphisms (rs15869 [ BRCA2], rs1805389 [ LIG4], rs8079544 [ TP53], rs25489 [ XRCC1], rs1673041 [ POLD1], and rs11615 [ ERCC1]) and subsequent CNS tumors in survivors of childhood cancer. Including genetic variants in a Final Model containing age at primary cancer, sex, and cranial radiation therapy dose yielded an area under the curve of 0.81 (95% CI, 0.76 to 0.86), which was superior ( P = .002) to the Clinical Model (area under the curve, 0.73; 95% CI, 0.66 to 0.80). The prediction model was successfully validated. The sensitivity and specificity of predicting survivors of childhood cancer at highest or lowest risk of subsequent CNS tumors was 87.5% and 83.5%, respectively. Conclusion It is possible to identify survivors of childhood cancer at high or low risk for subsequent CNS tumors on the basis of genetic and clinical information. This information can be used to inform surveillance for early detection of subsequent CNS tumors.

Cancer‐related therapy is increasingly administered in the outpatient setting, resulting in increased dependence on caregivers suggest to provide physical and emotional support to patients. This article describes differences in patient versus caregiver assessments of patient health, considering caregiver perceptions of the patient's health and abilities compared to that reported by the patient., Background. As patients age, caregivers increasingly provide essential support and patient information. We sought to determine if patient‐caregiver assessments of patient health differ and if differences contribute to burden in caregivers of older adults with cancer. Materials and Methods. One hundred patients, aged ≥65, and their caregivers independently assessed patient function, comorbidity, nutrition, social activity, social support, and mental health. Caregivers completed the Caregiver Strain Index (CSI). Patient‐caregiver assessments were compared using the Wilcoxon signed rank test and paired t test. Association between caregiver burden and differences between patient‐caregiver assessments was examined using generalized linear regression. Results. Median patient age was 70 (range 65–91) and 70% had advanced disease. Sixty percent of patients reported requiring help with instrumental activities of daily living (IADLs); most had good social support (median Medical Outcomes Study [MOS]‐Social Support Survey score 92) and mental health (median Mental Health Inventory score 85). Caregivers were a median age of 66 (range 28–85), 73% female, 68% spousal caregivers, and 79% lived with the patient. Caregivers rated patients as having poorer physical function (more IADLs dependency [p = .008], lower Karnofsky Performance Status [p = .02], lower MOS‐Physical Function [p

Breast cancer is a disease associated with aging. Before initiation of chemotherapy, an assessment of functional reserve is needed; however, simple performance assessment scores may not reflect the diverse nature of physical function and risk of toxicity among older adults. The focus of this article is on understanding the association between pre‐chemotherapy biomarkers (IL‐6, CRP, and D‐dimer) and measures of physical function., Background. Pro‐inflammatory and coagulation factors serve as biomarkers of aging and functional reserve. The purpose of this study was to determine if pro‐inflammatory (interleukin‐6 [IL‐6], C‐reactive protein [CRP]), and coagulation (D‐dimer) factors were associated with pre‐chemotherapy functional status in women with stage I–III breast cancer. Patients and Methods. Prior to chemotherapy initiation in patients with stage I–III breast cancer, the following was captured: IL‐6, CRP, D‐dimer blood levels, and physical function measures including activities of daily living (ADL, subscale of Medical Outcomes Study Physical Health); instrumental activities of daily living (IADL, subscale of the Older Americans Resources and Services Program); Timed Up and Go (TUG); physician‐rated Karnofsky Performance Status (KPS); and self‐rated KPS. The association of these biomarkers with physical function measures was evaluated. Results. One hundred sixty patients (mean age 58.3 years, range 30–81 years) with stage I–III breast cancer (stages I [n = 34; 21.5%], II [n = 88; 55.7%], III [n = 36; 22.8%]) were enrolled. The group with poorest physical function (defined by ADL

Background: Adolescents and young adults (AYA; 15–39 years) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) experience inferior survival when compared with children. Impact of care at NCI-designated Comprehensive Cancer Centers (CCC) or Children's Oncology Group sites (COG) on survival disparities remains unstudied. Methods: Using the Los Angeles cancer registry, we identified 1,870 ALL or AML patients between 1 and 39 years at diagnosis. Cox regression analyses assessed risk of mortality; younger age + CCC/COG served as the referent group. Logistic regression was used to determine odds of care at CCC/COG, adjusting for variables above. Results: ALL outcome: AYAs at non-CCC/COG experienced inferior survival (15–21 years: HR = 1.9, P = 0.005; 22–29 years: HR = 2.6, P < 0.001; 30–39 years: HR = 3.0, P < 0.001). Outcome at CCC/COG was comparable between children and young AYAs (15–21 years: HR = 1.3, P = 0.3; 22–29 years: HR = 1.2, P = 0.2) but was inferior for 30- to 39-year-olds (HR = 3.4, P < 0.001). AML outcome: AYAs at non-CCC/COG experienced inferior outcome (15–21 years: HR = 1.8, P = 0.02; 22–39 years: HR = 1.4, P = 0.06). Outcome at CCC/COG was comparable between children and 15- to 21-year-olds (HR = 1.3, P = 0.4) but was inferior for 22- to 39-year-olds (HR = 1.7, P = 0.05). Access: 15- to 21-year-olds were less likely to use CCC/COG than children (P < 0.001). In 22- to 39-year-olds, public/uninsured (ALL: P = 0.004; AML Conclusions: Poor survival in AYAs with ALL and AML is mitigated by care at CCC/COG. Barriers to CCC/COG care include public/uninsured, and African American/Hispanic race/ethnicity. Impact: Care at CCC/COG explains, in part, inferior outcomes in AYAs with ALL and AML. Key sociodemographic factors serve as barriers to care at specialized centers. Cancer Epidemiol Biomarkers Prev; 26(3); 312–20. ©2017 AACR.

Impact of treatment site on disparities in outcome among adolescent and young adults with Hodgkin lymphoma

Objective Older adults with cancer are at higher risk for costly and potentially dangerous hospital readmissions. Identifying risk factors for readmission in this population is important for future prevention of readmission. Materials and methods Hospital discharges among patients ≥ 65 years with solid tumors on non-surgical services from 2006-2011 were reviewed in this matched case-control study. We abstracted patient/cancer characteristics; functional status; fall risk; chemotherapy line; comorbidities; laboratory values; discharge parameters; and miscellaneous information (Do Not Resuscitate Order, pain scores) from medical records. Conditional logistic regression was used for univariate and multivariable analysis. Results This analysis included 184 case-patients readmitted within 30 days after discharge from the index admission and 184 sex- and age-matched control-patients discharged from index admission within three months of the cases with no readmission. Cases and controls had no differences in terms of primary cancer type, treatment, and index admission reason. Cases were more likely to have abnormal hemoglobin, albumin, sodium, and SGOT on discharge. Compared to those with ≤1 abnormal laboratory test, patients with 2 or more abnormal test results were 3 times more likely to be readmitted within 30 days. Conclusion This study demonstrated that older adults with cancer who had at least 2 abnormal laboratory results (hemoglobin, albumin, sodium, and SGOT) at discharge were 3 times more likely to be readmitted within 30 days compared to those with ≤1 abnormal results. These laboratory values may be predictive of the risk of readmission, and should be monitored before discharge to potentially prevent readmission.

Background Nutritional status can directly affect morbidity and mortality in older adults with cancer. This study evaluated the association between pretreatment body mass index (BMI), albumin level, and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors. Methods This was a secondary analysis of a prospective, multicenter study involving chemotherapy-treated patients 65 years old or older. Geriatric assessment, BMI, albumin level, and UWL data were collected before treatment. Multivariable logistic regression models evaluated the associations between nutritional factors and the risk of grade 3 or higher (grade 3+) chemotherapy toxicity. Results Seven hundred fifty patients with a median age of 72 years (range, 65-94 years) and mostly stage IV disease were enrolled. The median pretreatment BMI and albumin values were 26 kg/m2 (range, 15.1-52.1 kg/m2 ) and 3.9 mg/dL (range, 1.0-5.0 mg/dL), respectively. Nearly 50% of the patients reported UWL, with 17.6% reporting >10% UWL. Multivariable analysis revealed no association between >10% UWL and a risk for grade 3+ chemotherapy toxicity (adjusted odds ratio [AOR], 0.87; P = .58). Multivariable analysis showed a trend toward an association between a BMI ≥ 30 kg/m2 and a decreased risk of grade 3+ chemotherapy toxicity (AOR, 0.65; P = .06), whereas a low albumin level (≤3.6 mg/dL) was associated with a higher risk of grade 3+ chemotherapy toxicity (AOR, 1.50; P = .03). An analysis of the joint effect of BMI and albumin demonstrated the lowest risk of grade 3+ chemotherapy toxicity among patients with high BMIs (≥30 kg/m2 ) and normal albumin levels (AOR, 0.41; P = .008). Conclusions Among older adults with solid tumors, higher BMIs and normal albumin levels are associated with a lower risk of grade 3+ chemotherapy toxicity. Additional research is warranted to define the clinical significance of nutritional markers and to inform future interventions.

Objective Our goal was to identify pathogenic variants (PV) associated with germline cancer predisposition in an unselected cohort of older breast cancer survivors. Older patients with cancer may also be at higher risk for clonal hematopoiesis (CH) due to their age and chemotherapy exposure. Therefore, we also explored the prevalence of PVs suggestive of CH. Methods We evaluated 44 older adults (65 years or older) diagnosed with breast cancer who survived at least two years after diagnosis from a prospective study, compared to healthy controls over the age of 65 (n = 36). DNA extracted from blood samples and a multi-gene panel test was used to evaluate for common hereditary cancer predisposition and CH PVs. Fisher's exact test was used to compare PV rates between groups. Results Eight PVs in ATM, BRCA2 (x2), PALB2, RAD51D, BRIP1, and MUTYH (x2) were identified in 7 of 44 individuals with breast cancer (15.9%, 95% CI: 7–30%), whereas none were identified in healthy controls (p = .01). Results remained statistically significant after removal of MUTYH carriers (p = .045). PVs indicative of CH (ATM, NBN, and PPM1D [x2]) were identified in three of 27 individuals with breast cancer who received chemotherapy and in one healthy control. Conclusion Moderate-risk and later disease onset high-risk hereditary cancer predisposition PVs were statistically significantly enriched in our survivorship cohort compared to controls. Because age- and chemotherapy-related CH are more frequent in this population, care must be taken to differentiate potential CH PVs from germline cancer predisposition PVs.

Background: Survivors of Hodgkin lymphoma (HL) in childhood have an increased risk of subsequent malignant neoplasms (SMNs). Herein, the authors extended the follow-up of a previously reported Late Effects Study Group cohort and identified patients at highest risk for SMNs to create evidence for risk-based screening recommendations. Methods: The standardized incidence ratio was calculated using rates from the Surveillance, Epidemiology, and End Results program as a reference. The risk of SMN was estimated using proportional subdistribution hazards regression. The cohort included 1136 patients who were diagnosed with HL before age 17 years between 1955 and 1986. The median length of follow-up was 26.6 years. Results: In 162 patients, a total of 196 solid SMNs (sSMNs) were identified. Compared with the general population, the cohort was found to be at a 14-fold increased risk of developing an sSMN (95% confidence interval, 12.0-fold to 16.3-fold). The cumulative incidence of any sSMN was 26.4% at 40 years after a diagnosis of HL. Risk factors for breast cancer among females were an HL diagnosis between ages 10 years and 16 years and receipt of chest radiotherapy. Males treated with chest radiotherapy at age

We evaluated the feasibility, reliability, and validity of a Spanish-language self-administered geriatric assessment (GA) in older (age ≥ 65) Spanish-speaking women with breast cancer in the United States. Eligible participants (n = 181) were recruited and randomized. Feasibility was defined as the participant’s unassisted GA completion rate, completion time, and perception on ease of completion. Reliability and validity were assessed using Spearman’s correlation coefficients. Two-sided p &lt, 0.05 was considered significant. Ninety-eight percent of participants (n = 177) completed the GA at least once. Median age was 70 years (range: 65–95) and 55% had ≤8th grade education. Forty-one percent (n = 73) were unable to complete the GA unassisted, median completion time was 28 min (range 8–90), and 77% (n = 136) rated the GA as “easy”/“very easy”. Patients with ≤8th grade education took longer to complete the GA (30 vs. 25 min, p = 0.0036) and needed more assistance (59% vs. 19%, p &lt, 0.001) than those with ≥9th grade education. Test–retest reliability was high (≥0.82) for all domains except social activity (0.73). Validity among similar scales was found. The self-administered GA is a feasible, reliable, and valid tool for Spanish-speaking older women with breast cancer. Tailoring GA tools to the patients’ educational level is important when implementing tools in multicultural environments.

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

BACKGROUND Frailty has been suggested as a construct for oncologists to consider in treating older cancer patients. Therefore, the authors assessed the potential of creating a deficit-accumulation frailty index (DAFI) from a largely self-administered comprehensive geriatric assessment (CGA). METHODS Five hundred patients aged ≥65 years underwent a CGA before receiving chemotherapy. A DAFI was constructed, resulting in a 51-item scale, and cutoff values were examined for patients in the robust/nonfrail (cutoff value, 0.0

52 Background: Older adults with cancer often have age-associated vulnerabilities and challenges, especially during hospitalization. Geriatric assessment (GA) can help identify such vulnerabilities, generate recommendations, and guide the choice of interventions. Recently, GA-driven interventions have been shown to decrease chemotherapy toxicity among older adults with cancer in the outpatient setting. However, few studies have examined its role in the inpatient setting. Our purpose was to evaluate the feasibility of GA-driven interventions among hospitalized older adults with cancer. Methods: Hospitalized patients, age 75+, with a solid tumor malignancy were eligible. Each patient completed a GA while hospitalized at T1 (Timepoint 1) and one-month post discharge T2 (Timepoint 2). An Advanced Practice Nurse (APN) reviewed the T1 GA, provided targeted care utilizing GA results and implemented interventions based on predefined triggers built into the GA’s various domains. An APN also completed follow-up visits by phone at 1 week and 1 month post discharge. The primary outcome was feasibility, defined as the percentage of participants who received GA-guided interventions and was pre-specified as successful if > 80% were given recommendations. A secondary outcome of the study was to capture unplanned readmissions within 1 month post discharge. Results: Between 9/19/2017 and 5/3/2019, 49 patients were eligible and 40 were enrolled, an 82% participation rate. The median age was 80.5 years (range 75-88), 58% male, 63% Non-Hispanic white, 18% Hispanic, 15% Asian, 70% > a high school education, 73% married/partner, and 48% had stage IV cancer. Most common cancer types: GI (28%), GU (23%), lung (20%). All 40 patients (100%) had ≥ 1 predefined trigger in the GA generating interventions and completed ≥ 2 follow-up visits with the APN. In total, 857 interventions were recommended, and the mean number of interventions generated per patient was 11. The top 4 interventions were Occupational Therapy/Physical Therapy (n = 66), Social Work (n = 52), Nutrition (n = 39), and Pharmacy (n = 36). Overall 89% of GA-guided interventions were implemented. Unplanned hospital readmission was low with only one patient readmitted within 30 days (3%). Conclusions: Among hospitalized adults over age 75 with cancer, using GA to identify vulnerability, and provide GA-driven multidisciplinary interventions is feasible. Further studies are warranted to examine the impact of GA-driven interventions on outcomes among hospitalized older adults with cancer.

2024 Background: With movement towards value-based care, institutions seek ways to reduce costs by decreasing inpatient stays. A multidisciplinary approach to supportive care, especially when provided early, is one way to realize value-based care. We assess the impact of pre-admission versus post-admission involvement of an Integrated Supportive Care Model (ICSM) on inpatient length of stay (LOS) at a NCI-designated cancer center. Methods: Data was collected from 2014 to 2016 at City of Hope. The Integrated Supportive Care Model at City of Hope includes: palliative care, psychiatry, psychology, interventional pain, social work, child-life, distress screening, and couples program. “Pre-admission” was defined as seeing at least one service prior to hospital admission; “Post-admission” defined as seeing at least one service during admission. “Short LOS” for hematology patients was categorized as ≤ 14 days and for oncology patients as ≤ 3 days. Continuous LOS between patients receiving an ISCM intervention pre- and post-admission was compared using Kruskal-Wallis test. Univariate and multivariable logistic regression was done to examine association between involvement of ISCM pre- and post-admission and categorical LOS. P-values < 0.05 were considered statistically significant. Results: 1,627 (809 with hematologic malignancy, 818 with oncologic malignancy) patients with only one hospitalization during the study time were included. For hematology patients, involvement with the ISCM pre-admission was associated with shorter LOS ( ≤ 14 days) compared with involvement post-admission (29.3 vs 11.1%, multivariable OR = 4.08, P < 0.001). Median LOS for hematology patients who participated in the ISCM pre-admission was shorter than those who received ISCM services post-admission (21 vs. 22 days, p = 0.049). Similarly, for oncology patients, ISCM involvement pre-admission was associated with shorter LOS ( ≤ 3 days) compared to involvement post-admission (91.4% vs 8.6%, multivariable OR = 3.74, P < 0.001). Median LOS for oncology patients who received an ISCM intervention pre-admission was shorter than those who received an ISCM intervention post-admission (2 vs. 6 days, p < 0.001). Conclusions: In hematologic and oncologic malignancies, use of an ISCM prior to patient’s first hospitalization is associated with significantly shorter LOS compared with those who received ISCM services during the hospital stay. This suggests efforts should be made to include an ISCM early in the trajectory of illness, prior to first hospitalization.

12010 Background: Geriatric assessment (GA) can predict chemotherapy (chemo) toxicity in older adults (age ≥65) with cancer. However, evidence regarding the effect of GA-driven intervention (GAIN) on the incidence of chemo toxicity has been limited. Therefore, we conducted a randomized controlled trial evaluating the impact of GAIN vs. standard of care (SOC) on chemo toxicity in older adults with cancer. Methods: Patients (pts) age ≥65, diagnosed with a solid malignancy, and starting a new chemo regimen at City of Hope were eligible (NCT02517034). In a 2:1 ratio, 600 pts were randomly assigned to either GAIN (n = 398) or SOC (n = 202) arms. All pts completed a baseline GA prior to chemo. In the GAIN arm, a multidisciplinary team led by a geriatric oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist, reviewed GA results and implemented interventions based on predefined triggers built into the GA’s various domains. In the SOC arm, GA results were sent to treating oncologists to use at their discretion. Pts were followed until either end of chemo or 6 months after start of chemo, whichever occurred first. The primary endpoint was incidence of grade 3-5 chemo-related toxicity (NCI CTCAE v.4.0). Secondary endpoints included advance directive (AD) completion, emergency room (ER) visits, hospitalizations, and average length of stay (ALOS). Chi-square and Fisher’s exact tests were used to compare the categorical outcomes, and Kruskal-Wallis test was used to compare the ALOS between arms. Results: Pt characteristics were balanced between arms. Median age was 71 (range 65-91). Cancer types included: 33% gastrointestinal, 23% breast, 16% lung, 15% genitourinary, and 13% other. Most (71%) had stage IV disease. The incidence of grade 3-5 chemo-related toxicity was 50.5% (95% CI: 45.6-55.4%) in the GAIN arm and 60.4% (95% CI: 53.7-67.1%) in the SOC arm (p = 0.02). Compared to SOC, the GAIN arm had a reduction of 9.9% (95% CI: 1.6-18.2%) in chemo-related toxicity. At the end of study, AD completion increased 24.1% in the GAIN arm vs. 10.4% in the SOC arm (p < 0.001). No significant differences in ER visits (27.4% vs. 30.7%), hospitalizations (22.1% vs. 19.3%), or ALOS (median 4.8 vs. 5.0 days) were observed between the GAIN and SOC arms, respectively. Conclusions: Integration of multidisciplinary GA-driven interventions reduced grade 3-5 chemo-related toxicity and improved AD completion in older adults with cancer. GA-driven interventions should be included as a part of cancer care for all older adults. Clinical trial information: NCT02517034 .

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.

Background: In elderly patients with lung cancer, race/ethnicity is associated with not receiving treatment; however, little attention has been given to nonelderly patients (aged ≤65 years) with a range of disease stages and histologies. Nonelderly patients with lung cancer have superior survival at NCI-designated Comprehensive Cancer Centers (CCCs), although the reasons remain unknown. Patients and Methods: A retrospective cohort study was conducted in 9,877 patients newly diagnosed with small cell or non–small cell lung cancer (all stages) between ages 22 and 65 years and reported to the Los Angeles County Cancer Surveillance Program registry between 1998 and 2008. Multivariable logistic regression examined factors associated with nontreatment. Results: In multivariable analysis, race/ethnicity was associated with not receiving cancer treatment (black: odds ratio [OR], 1.22; P=.004; Hispanic: OR, 1.17; P=.04), adjusting for patient age, sex, disease stage, histology, diagnosis year, distance to treatment facility, type of facility (CCC vs non-CCC), and insurance status. With inclusion of socioeconomic status (SES) in the model, the effect of race/ethnicity was no longer significant (black: OR, 1.02; P=.80; Hispanic: OR, 1.00; P=1.00). Factors independently associated with nontreatment included low SES (OR range, 1.37–2.15; PPPPConclusions: In nonelderly patients with lung cancer, SES was associated with nontreatment, mitigating the effect of race/ethnicity. Patients were also at higher odds of nontreatment if they did not have private insurance or received cancer care at a non-CCC facility. These findings highlight the importance of understanding how both patient-level factors (eg, SES, insurance status) and facility-level factors (eg, treatment facility) serve as barriers to treatment of nonelderly patients with lung cancer.

As the number of older adults in the U.S. increases, so too will the incidence of cancer and cancer-related cognitive impairment (CRCI). However, the exact underlying biological mechanism for CRCI is not yet well understood. We utilized susceptibility-weighted imaging with quantitative susceptibility mapping, a non-invasive MRI-based technique, to assess longitudinal iron deposition in subcortical gray matter structures and evaluate its association with cognitive performance in women age 60+ with breast cancer receiving adjuvant chemotherapy and age-matched women without breast cancer as controls. Brain MRI scans and neurocognitive scores from the NIH Toolbox for Cognition were obtained before chemotherapy (time point 1) and within one month after the last infusion of chemotherapy for the patients and at matched intervals for the controls (time point 2). There were 14 patients age 60+ with breast cancer (mean age 66.3 ± 5.3 years) and 13 controls (mean age 68.2 ± 6.1 years) included in this study. Brain iron increased as age increased. There were no significant between- or within- group differences in neurocognitive scores or iron deposition at time point 1 or between time points 1 and 2 (p 0.01). However, there was a negative correlation between iron in the globus pallidus and the fluid cognition composite scores in the control group at time point 1 (r = -0.71; p 0.01), but not in the chemotherapy group. Baseline iron in the putamen was negatively associated with changes in the oral reading recognition scores in the control group (r = 0.74, p 0.01), but not in the chemotherapy group. Brain iron assessment did not indicate cancer or chemotherapy related short-term differences, yet some associations with cognition were observed. Studies with larger samples and longer follow-up intervals are warranted.

Background Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy. Methods Women aged ≥ 60 years with stage I–III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled. All participants underwent neuropsychological testing with the US National Institutes of Health (NIH) Toolbox for Cognition and brain magnetic resonance imaging (MRI) prior to chemotherapy, and again around one month after the last infusion of chemotherapy. Brain volumes were measured using Neuroreader™ software. Longitudinal changes in brain volumes and neuropsychological scores were analyzed utilizing linear mixed models. Results A total of 16 patients with breast cancer (mean age 67.0, SD 5.39 years) and 14 age-matched and sex-matched healthy controls (mean age 67.8, SD 5.24 years) were included: 7 patients received docetaxel and cyclophosphamide (TC) and 9 received chemotherapy regimens other than TC (non-TC). There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group pre-chemotherapy (p > 0.05). Exploratory hypothesis generating analyses focusing on the effect of the chemotherapy regimen demonstrated that the TC group had greater volume reduction in the temporal lobe (change = − 0.26) compared to the non-TC group (change = 0.04, p for interaction = 0.02) and healthy controls (change = 0.08, p for interaction = 0.004). Similarly, the TC group had a decrease in oral reading recognition scores (change = − 6.94) compared to the non-TC group (change = − 1.21, p for interaction = 0.07) and healthy controls (change = 0.09, p for interaction = 0.02). Conclusions There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group; however, exploratory analyses demonstrated a reduction in both temporal lobe volume and oral reading recognition scores among patients on the TC regimen. These results suggest that different chemotherapy regimens may have differential effects on brain volume and cognition. Future, larger studies focusing on older adults with cancer on different treatment regimens are needed to confirm these findings. Trial registration ClinicalTrials.gov, NCT01992432. Registered on 25 November 2013. Retrospectively registered.

Background: Adolescents and young adults (AYA: 15–39 years) with acute lymphoblastic leukemia (ALL) have inferior survival when compared with children (1–14 years). An approach is lacking that includes both patients enrolled and not enrolled in clinical trials, and includes the contribution of health care delivery, treatment, and clinical prognosticators. Methods: We assembled a retrospective cohort of ALL patients diagnosed between 1–39 years (AYA: n = 93; child: n = 91) and treated at a single institution between 1990 and 2010, irrespective of clinical trial enrollment. We modeled relapse risk (i) during therapy and (ii) after completing therapy. Results: On-therapy relapse: AYA experienced an increased risk of on-therapy relapse versus children (HR, 10.5; P = 0.004). In multivariable analysis restricted to AYA, independent predictors of relapse included lack of clinical trial enrollment (HR, 2.6, P = 0.04) and nonwhite race/ethnicity (HR, 2.2; P = 0.05). Relapse after completing therapy: When compared with children, AYA experienced an increased risk of relapse after completing therapy (HR, 7.7; P < 0.001). In multivariable analysis restricted to AYA, longer therapy (months of maintenance: HR, 0.7; P < 0.001; months of consolidation: HR, 0.8; P = 0.03) protected against relapse. Conclusions: Among AYA, aspects of health care delivery (clinical trial enrollment, nonwhite race/ethnicity) are associated with relapse during therapy, and aspects of treatment (shorter duration of maintenance and consolidation) are associated with relapse after completing therapy. Impact: These findings highlight the importance of clinical trial enrollment and therapy duration (maintenance, consolidation) in ensuring durable remissions in AYA ALL. Future studies encompassing health care delivery, treatment, and biology are needed. Cancer Epidemiol Biomarkers Prev; 27(10); 1133–41. ©2018 AACR.

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.

Objectives Older adults with cancer in developing countries face challenges accessing healthcare due to a lack of personnel and infrastructure. A decline in physical activity (defined as a decrease in the number of daily steps) may be a novel method for the timely detection of toxicity in older adults receiving chemotherapy in resource-constrained settings. Materials and Methods In this feasibility study, patients aged ≥ 65 years starting first-line chemotherapy for solid tumors were given a smartphone with a pedometer application. Daily steps were monitored daily for one cycle. If a ≥ 15% decrease from baseline was identified, the patient was called and the presence of toxicity assessed. The intervention would be feasible if ≥ 75% of the subjects recorded steps for ≥ 75% of the planned chemotherapy days. Results Forty patients (median age 73; 57% [N = 23] female) were included. Seventy percent (N = 28) had stage III-IV disease with 45% (N = 18) gastrointestinal, 23% (N = 9) breast, and 32% (N = 13) other malignancies. Mean pre-treatment daily steps was 3111 (Standard Deviation [SD] 1731), and median follow-up was 21 days (range 2–28). Despite having limited exposure to mobile technology, most (93%) patients used the smartphone appropriately, and 85% found it easy to use. Sixty percent of patients (N = 24) had toxicities managed over the phone, 27.5% (N = 10) were sent for urgent medical attention and 15% (N = 6) were hospitalized. Conclusion Using smartphones to monitor older adults with cancer receiving chemotherapy in a resource-constrained setting is feasible and acceptable. A decrease in the number of daily steps was common and helped to identify chemotherapy toxicity.

BACKGROUND Rigorous processes ensure quality of research and clinical care at National Cancer Institute-designated comprehensive cancer centers (NCICCCs). Unmeasurable elements of structure and process of cancer care delivery warrant evaluation. To the authors' knowledge, the impact of NCICCC care on survival and access to NCICCCs for vulnerable subpopulations remain unstudied. METHODS The current study's population-based cohort of 69,579 patients had newly diagnosed adult-onset (aged 22-65 years) cancers reported to the Los Angeles County cancer registry between 1998 and 2008. Geographic information systems were used for geospatial analysis. RESULTS With regard to overall survival across multiple diagnoses, patients not receiving their first planned treatment at NCICCCs experienced poorer outcomes compared with those treated at NCICCCs; differences persisted on multivariable analyses after adjusting for clinical and sociodemographic factors (hepatobiliary: hazard ratio [HR], 1.5; 95% confidence interval [95% CI], 1.4-1.7 [P 9 miles from the nearest NCICCC (OR range, 0.5-0.7 [P

Purpose Cognitive impairment is well-recognized after myeloablative allogeneic hematopoietic cell transplantation (HCT). However, cognitive functioning after reduced-intensity allogeneic or autologous HCT remains unclear. Methods A total of 477 HCT recipients (236 autologous, 128 reduced-intensity allogeneic, 113 myeloablative allogeneic) underwent standardized neuropsychologic testing before HCT and at 6 months and 1, 2, and 3 years after HCT. Ninety-nine frequency-matched healthy controls underwent testing at commensurate time points. Primary outcomes of the study were practice effect–adjusted domain-specific T scores and global deficit scores. Piecewise generalized estimating equation models were used to compare groups and to identify associated variables and post-HCT trends of cognitive impairment. Results Median age was 52 years (range, 18 to 74 years) for HCT recipients and 55 years (range, 19 to 73 years) for controls. Post-HCT scores were comparable between controls and autologous and reduced-intensity HCT recipients. Myeloablative HCT recipients had significantly lower ( P < .001) post-HCT scores than controls for executive function, verbal speed, processing speed, auditory memory, and fine motor dexterity. Pre-HCT to 6 months post-HCT scores did not change after reduced-intensity HCT but declined significantly for fine motor dexterity ( P < .001) after myeloablative HCT. However, pre-HCT to 3 years post-HCT scores declined significantly ( P < .003) in reduced-intensity HCT recipients for executive function, verbal fluency, and working memory. Older age, male sex, and lower education, income, and cognitive reserve were associated with post-HCT cognitive impairment. At 3 years post-HCT, global cognitive impairment was present in 18.7% of autologous and 35.7% of allogeneic HCT recipients. Conclusion Myeloablative allogeneic HCT recipients showed significant cognitive decline compared with healthy controls. Reduced-intensity allogeneic HCT recipients showed evidence of delayed decline. Cognitive functioning in autologous HCT recipients generally was spared. The study identified vulnerable subpopulations that could benefit from targeted interventions.

Background Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity. Chemotherapy efficacy depends on relative dose intensity (RDI), and an RDI

Purpose Cancer survivors are at high risk for human papillomavirus (HPV)-related morbidities; we estimated the prevalence of HPV vaccine initiation in cancer survivors versus the US population and examined predictors of noninitiation. Methods Participants included 982 cancer survivors (9 to 26 years of age; 1 to 5 years postcompletion of therapy); we assessed HPV vaccine initiation, sociodemographic and clinical characteristics, and vaccine-specific health beliefs; age-, sex-, and year-matched US population comparisons were from the National Immunization Survey-Teen and the National Health Interview Survey (2012-2015). Results The mean age at the time of the study was 16.3 ± 4.7 years; the mean time off therapy was 2.7 ± 1.2 years; participants were 55% male and 66% non-Hispanic white; 59% had leukemia/lymphoma. Vaccine initiation rates were significantly lower in cancer survivors versus the general population (23.8%; 95% CI, 20.6% to 27.0% v 40.5%; 95% CI, 40.2% to 40.7%; P < .001); survivors were more likely to be HPV vaccine–naïve than general population peers (odds ratio [OR], 1.72; 95% CI, 1.41 to 2.09; P < .001). Initiation in adolescent survivors (ages 13 to 17 years) was 22.0% (95% CI, 17.3% to 26.7%), significantly lower than population peers (42.5%; 95% CI, 42.2% to 42.8%; P < .001). Initiation in young adult survivors and peers (ages 18 to 26 years) was comparably low (25.3%; 95% CI, 20.9% to 29.7% v 24.2%; 95% CI, 23.6% to 24.9%). Predictors of noninitiation included lack of provider recommendation (OR, 10.8; 95% CI, 6.5 to 18.0; P < .001), survivors’ perceived lack of insurance coverage for HPV vaccine (OR, 6.6; 95% CI, 3.9 to 11.0; P < .001), male sex (OR, 2.9; 95% CI, 1.7 to 4.8; P < .001), endorsement of vaccine-related barriers (OR, 2.7; 95% CI, 1.6 to 4.6; P < .001), and younger age (9 to 12 years; OR, 3.7; 95% CI, 1.8-7.6; P < .001; comparison, 13 to 17 years). Conclusion HPV vaccine initiation rates in cancer survivors are low. Lack of provider recommendation and barriers to vaccine receipt should be targeted in vaccine promotion efforts.

Cyclin D1 (CCND1), an intracellular cell-cycle regulatory protein with checkpoint function, can promote cell proliferation or induce growth arrest and apoptosis depending on the cellular context. We hypothesized that the direction of the association between the (CCND1) G870A-polymorphism and breast cancer risk may be modified by dietary and genetic factors influencing the oxidant-antioxidant balance, such as a dietary pattern with a high intake of n-6 fatty acids and a low intake of n-3 fatty acids, or a genetic profile that is deficient in glutathione S-transferases. We tested our hypothesis in a case-control study nested into the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63 000 Chinese men and women. Genomic DNA collected from 258 incident cases of breast cancer and 670 female cohort controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 genes using fluorogenic 5′-nuclease assay. Unconditional logistic regression models were used to assess the effects with adjustment for potential confounders. All statistical tests were two-sided. The heterozygous CCND1 GA genotype significantly reduced the breast cancer risk in all subjects (OR = 0.67, 95% CI 0.45-0.99) when compared with the GG genotype. The association was restricted to women with a high (above median value) intake level of n-6 fatty acids (OR = 0.51, 95% CI 0.30-0.87), a low (below median value) intake level of the antagonistic marine n-3 fatty acids (OR = 0.54, 95% CI 0.32-0.93) or a total lack of the antioxidative GSTM1 (OR = 0.44, 95% CI 0.25-0.80) or GSTT1 genes (OR = 0.46, 95% CI 0.24-0.87). The effects were consistently stronger in cases with advanced disease. The AA genotype did not affect breast cancer risk. The results of this study are compatible with the hypothesis that the oxidant-antioxidant balance in cells is an important determinant of the direction of the cyclin D1 effect, leading either to cell proliferation or cell death

Cyclin D1 (CCND1) regulates cellular decision between proliferation and growth arrest. Despite the functional relevance of the CCND1 A870G single nucleotide polymorphism (SNP) published results on its association with colorectal cancer (CRC) were inconsistent. We examined the association between this CCND1 genotype and CRC in the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63 000 Chinese men and women. We explored the hypothesis that inconsistency regarding the CCND1/CRC association may be attributable to the modifying effect of additional CRC risk factors. Since GSTM1/GSTT1 genotype and dietary isothiocyanate (ITC) intake had previously been identified as CRC risk factors in this cohort, we now explored if they influenced the CCND1/CRC association. In a nested case-control study within the Singapore Cohort, genomic DNA collected from 300 incident CRC cases and 1169 controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 polymorphisms. Unconditional logistic regression was used to assess genotype effects on cancer risk. No main effect of CCND1 was observed, yet the CCND1 effect was influenced by ITC intake and GST genotypes. The presence of at least one CCND1 A-allele was associated with increased risk among low dietary ITC consumers (intake below median value for the cohort) with a high-activity GST profile (≥2 of the 3 GST genotypes classified non-null or high-activity) [odds ratio (OR) = 2.05; 95% confidence interval (CI), 1.10-3.82]. In contrast, the presence of at least one A-allele was associated with a decreased risk among all remaining subjects (OR = 0.56; 0.36-0.86) (P for interaction = 0.01). Recent studies indicate that ITCs inhibit cell proliferation and cause apoptosis through pro-oxidant properties. The results of our current study on CRC and those of our previous breast cancer study are compatible with the notion of oxidative stress in target cells as important determinant of direction and magnitude of the CCND1 effect

Primary care physicians (PCPs) may be involved in the evaluation of solitary pulmonary nodules (SPNs) detected through lung cancer screening. Little is known about their perspectives on the management or the referral of SPN. Using the American Medical Association's Physician Masterfile, we randomly surveyed 1384 PCPs between January and October 2015 with an 18% response rate. A subset analysis was performed on SPN management and referral practices of PCP. These results and those relating to practice characteristics were compared between family practice and internal medicine physicians. Responders and nonresponders did not differ by demographic characteristics. A total of 137 (55.5%) PCPs reported feeling confident in managing the workup of imaging-detected SPN. However, only 53 PCPs (21.3%) were inclined to manage the evaluation and follow-up of SPN. There was no significant difference between family practice and internal medicine physicians with regard to years in practice, size of practice, or referral to specialists. Family practitioners and internists similarly disagreed or were neutral to self-managing SPN (P = 0.60). Internists were twice as likely to express confidence as family practitioners (odds ratio 1.95, 95% confidence interval 1.09-3.48). Among all PCPs, 75.4% would refer management of these patients to a pulmonologist, 28.9% to a surgeon, and 24.2% to an oncologist. Confidence did not predict lung cancer screening practices. Although more than half of PCPs expressed confidence in the workup of SPN, most preferred referral to specialists. Additional research is needed to understand barriers to PCP management of incidental SPN in the effort to facilitate lung cancer screening.

INTRODUCTION: Lung cancer screening with low-dose computed tomography (LDCT) is recommended by the U.S. Preventive Services Task Force (USPSTF) in high-risk patients, but a minority of eligible people is screened. It is not clear whether knowledge of USPSTF recommendations among primary care physicians (PCP) impacts utilization of LDCT. METHODS: A randomly selected sample of 1384 primary care physicians in Los Angeles County was surveyed between January and October 2015, using surveys sent by mail, fax, and email. The response rate was 18% (n=250). Training background, years in practice, practice type, and respondent demographics were collected. We analyzed results based on the response to a question on whether the USPSTF recommends the use of LDCT to screen high-risk individuals for lung cancer. RESULTS: 117 (47%) PCPs responded that the USPSTF recommends LDCT for LCS. Of PCPs who were aware of USPSTF recommendations, 97% responded that CT was effective at reducing lung cancer mortality among individuals meeting eligibility criteria, compared with 90% who were unaware of guidelines (p=0.02). A larger proportion of PCPs aware of guidelines ordered LDCT (71% vs. 38%, p

11520 Background: We tested the hypothesis that candidate genetic variants are associated with cognitive impairment in BMT recipients for HM, and that inclusion of genetic variants improves the performance of a risk prediction model that includes only clinical and demographic characteristics. Methods: We used standardized tests to assess cognitive function in 277 adult BMT recipients at City of Hope (COH). Global Deficit Score (GDS) ≥0.50 was used as indicator of cognitive impairment. Generalized estimating equation models and logic regression were used to identify single-SNP and gene-level associations with cognitive impairment post-BMT. Three risk prediction models were developed in the COH cohort using elastic net regression: Base Model (sociodemographics); Clinical Model (Base Model + clinical characteristics, therapeutic exposures and baseline cognitive reserve); Combined Model (Clinical + Genetic Model). The Genetic Model included significant SNPs in blood brain barrier, telomere homeostasis and DNA repair identified from single- and gene-level analyses. Models were validated in an independent cohort of long-term BMT survivors (BMTSS) with (n = 141) and without (n = 258) memory problems. Results: Training set (COH): The cohort included 58.5% males; 68.6% non-Hispanic whites; 46.6% allogeneic BMT recipients; median age at BMT: 51.6y. The mean area under the receiver operating characteristic curve (AUC) was: Base Model: 0.69 (95%CI: 0.63-0.75); Clinical Model: 0.77 (95%CI: 0.71-0.83); Combined Model: 0.89 (95%CI: 0.84-0.92). Test set (BMTSS): Median age at BMT was 45y; 53.5% were males; 88.4% non-Hispanic whites. Testing the models in BMTSS yielded mean AUC of 0.57 (95%CI: 0.49-0.63) in the Clinical Model and 0.72, (95%CI: 0.65-0.78) in the Combined Model. Conclusions: These findings provide evidence on the utility of a validated risk prediction tool that incorporates genetic factors that could identify BMT recipients at risk for cognitive impairment, providing opportunities for targeted interventions.

11556 Background: Anxiety and depression are associated with decreased quality of life, treatment adherence, and survival in patients with cancer. Mental Health Inventory (MHI-17) is a validated screening tool for psychological well-being, but cut points for older adults with cancer are unknown. The goal of this study is to identify cut points on MHI-17 Anxiety (MHI-A) and Depression (MHI-D) subscales which correlate with patient-reported anxiety and depression in older adults with cancer. Methods: This is a secondary analysis of baseline data from a randomized controlled trial in adults aged 65+ with solid tumors starting chemotherapy. At baseline, patients completed MHI-17. MHI-A and MHI-D were calculated (range 0-100; higher scores represent better mental health). Self-reported anxiety was obtained from single-item Linear Analog Scale Assessment (0-5 = low, 6-10 = high). Self-reported depression was obtained from Yale Depression Screen, “Do you often feel sad or depressed?” The association of MHI-A and MHI-D with the patient-reported outcomes was analyzed using logistic regression. Youden’s index was used to determine the optimal cut points for MHI-A and MHI-D for identifying patients with high anxiety and depression. Results: 458 patients (median age 71 (range 65-91), 57% female, 55% non-Hispanic white) were included in this analysis. The most common cancer types were: GI (31%), breast (19%), GU (18%), and pulmonary (16%); 75% had stage IV cancer. Twenty-four percent (N = 110) reported high anxiety and 21% (N = 97) depression. Median scores for MHI-A and MHI-D were 75 (range 0-100) and 80 (range 0-100). The optimal cut point for high anxiety on MHI-A was 65; this had an accuracy of 76.1%, a sensitivity of 71.8%, and a specificity of 77.5%. The optimal cut point for depression on MHI-D was 70; this had an accuracy of 80.1%, a sensitivity of 80.4%, and a specificity of 79.8%. Conclusions: The current study identified optimal cut points for MHI-Anxiety and MHI-Depression subscales to identify older adults with cancer starting chemotherapy with self-reported anxiety and depression. In the absence of patient-reported anxiety and depression, these cut points could be used to identify older patients with cancer at risk for poor mental health.