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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.

235 Background: The CARG tox score can predict risk of chemotherapy-related tox in older adults with cancer. GAIN can reduce tox vs standard of care (SOC) among these patients (pts); GAIN’s impact across CARG risk groups is unknown. Methods: A secondary analysis of the GAIN randomized clinical trial (NCT02517034) of pts aged ≥65 (solid tumor diagnosis, starting a new chemotherapy) was performed. Pts were randomized 2:1 to receive GAIN vs SOC and were categorized into low (0-5), medium (6-9), and high (10-20) risk groups according to CARG score. The primary outcome was incidence of grade 3-5 tox. Chi-square/Fisher’s exact tests were used to compare outcomes (GAIN vs SOC, stratified by risk groups). Log-rank tests were used to compare 1-year survival across risk groups. Results: This analysis included 600 pts: 26.5% low risk, 45.2% medium risk, 28.3% high risk. Table shows pt/treatment characteristics. For pts with low/medium risk scores, GAIN demonstrated a 14.0% (95% CI 4.1%-23.9%) reduction in tox vs SOC (p = 0.006). No significant reduction in tox was observed among pts with high risk scores (p = 0.86). One-year survival (GAIN vs SOC) for each risk group was 73.6% vs 67.4% (low risk), 68.5% vs 64.5% (medium risk), and 57.3% vs 61.7% (high risk), respectively (log-rank p = 0.10). Conclusions: Older adults with low/medium, but not high, CARG risk scores benefit from GAIN. Additional strategies may be needed to improve outcomes for pts with high CARG risk scores. Clinical trial information: NCT02517034. [Table: see text]

12042 Background: Although breast cancer and breast cancer chemotherapy (chemo) have been linked to accelerated functional decline, it is not well understood whether this decline is driven by cancer itself or the combination of cancer and chemo. Here, we compared the change in functional status over time in older breast cancer survivors treated with and without chemo and age-matched women without cancer. Methods: Women age ≥65 with non-metastatic breast cancer (n = 538; 441 treated with chemo and 97 without chemo) and n = 100 non-cancer controls were prospectively evaluated at two timepoints: ≤14 days pre-chemo (baseline) and ≤30 days post-chemo (or matched times for non-chemo and non-cancer controls). At each timepoint, functional status was measured using instrumental Activities of Daily Living (iADL) scores. The primary endpoint was the proportion of patients with a decline in functional status (Yes/No, yes defined as ≥2-point decrease [minimal meaningful difference] in iADL scores between timepoints). Baseline demographic, functional, and clinical characteristics were compared between survivors treated with and without chemo and non-cancer controls using t and chi-squared tests. Among the 441 women treated with chemo, univariate and multivariable logistic regression analyses were performed to determine baseline risk factors associated with chemo-induced functional decline. Results: 10% of older survivors treated with chemo experienced a clinically meaningful decline in function as compared to 3% in the non-chemo and 4% in non-cancer control groups (p = 0.017). Across the 3 groups, there were no differences in median age, race/ethnicity, education, number of comorbidities, or baseline functional status (iADL, ADL, Timed Up and Go [TUG]). Among the 441 older survivors treated with chemo, greater age, higher BMI, more comorbidity, lower ADL score, and longer TUG were significantly associated with functional decline univariately. After multivariable analyses, age ≥78 (26% declined, odds ratio [OR] = 3.67, 95% CI 1.60-8.43) and BMI > 30 (16% declined, OR = 2.11, 95% CI 1.02-4.38) remained significantly associated with functional decline. Patients who were both ≥78 years old and obese (BMI > 30) had the highest odds of developing functional decline post-chemo (41% declined, OR = 8.43, 95% CI 2.48-28.63). Conclusions: In this study, older breast cancer survivors treated with chemo had a 3-fold increased incidence of clinically meaningful decline in functional status as compared to age-matched survivors not treated with chemo and those without cancer. Although these findings need to be replicated in larger studies, our results raise the possibility that accelerated functional decline may be driven by cellular damage from cytotoxic chemo. Further research is warranted to understand the impact of cancer and its treatment on older adults' functional status and underlying aging processes. Clinical trial information: NCT01472094.

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.

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.

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 .

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.

10044Background: Older patients (pts) with cancer are at risk for depression and anxiety, which are often under-recognized. Participation in religious activities has been associated with better men...

11003Background: Although older adults represent the majority of patients with cancer, oncology nurses receive little training in the care of older patients. In an effort to bridge this knowledge g...

10009Background: Older adults with cancer facing decisions with competing health outcomes may favor maintaining quality of life (QOL), independence, or cognition over prolonging survival. The goal ...

e18672Background: By 2060, nearly a quarter of older adults in the US will identify themselves as Hispanic/Latino. We have previously developed a self-administered GA tool which can be used to iden...

Purpose To examine the independent roles of pre–hematopoietic cell transplantation (HCT) therapeutic exposures, transplantation-related conditioning, and comorbidities (pre- and post-HCT) in the development of late congestive heart failure (CHF) after HCT. Methods This was a nested case-control design. Individuals with late CHF (diagnosed ≥ 1 year after HCT) were identified from a cohort of 2,938 1+ year survivors who underwent transplantation at City of Hope National Medical Center, Duarte, CA. This cohort formed the sampling frame for selecting controls (without CHF) matched for age and year of HCT, donor source (allogeneic v autologous), and length of follow-up. Results Sixty patients with late CHF were identified; median age at HCT was 45.3 years (range, 16.6 to 68.6 years); median time to CHF was 3.0 years (range, 1.03 to 18.9 years); 68% received autologous HCT. Median ejection fraction was 36.9% (range, 15% to 53%). Compared with matched controls (n = 166), patients with late CHF received more cycles of pre-HCT chemotherapy (8.6 v 4.9 cycles; P < .01), had greater body mass index at HCT (28.4 v 26.2 kg/m2; P = .01), greater lifetime anthracycline exposure (285.3 v 175.6 mg/m2; P < .01), and were more likely to have multiple chronic comorbidities (30.0% v 13.9%; P < .01). Multivariable analysis revealed number of pre-HCT chemotherapy cycles (odds ratio [OR] = 1.2; P < .01), anthracycline dose ≥ 250 mg/m2 (OR = 3.2; P = .05), and two or more chronic comorbidities (OR = 4.3; P = .01) to be independently associated with late CHF. Conclusion Pre-HCT exposure to anthracyclines and presence of comorbidities are primarily responsible for the risk associated with late CHF after HCT. Conditioning-related therapeutic exposure does not contribute significantly to the risk. These results form the basis for identifying high-risk individuals for targeted surveillance, as well as developing preventive strategies in the form of aggressive management of comorbidities.

10036 Background: Hearing and visual impairment increase the risk of psychological, functional, and cognitive deficits in older adults. However, little is known about their impact in older patients (pts) with cancer. Methods: This is a cross-sectional analysis of 2 prospective studies of pts ≥65 with cancer (Hurria et al. JCO 2011 & 2016) which identified risk factors for chemotherapy (CT) toxicity. Relationships between self-reported hearing/visual impairment (fair, poor or deaf/blind) and the need for assistance in instrumental activities of daily living (IADL, i.e. shopping), or activities of daily living (ADL, i.e. bathing); anxiety; depression and cognitive deficit (>11 on Blessed OMC test) were assessed (adjusted for age, sex, race, education, cancer type/stage, comorbidity, falls & medication). Results: Among 750 pts (median age 72, range 65-94) with solid tumors (28% lung, 27% GI, 30% breast/GYN; 58% stage IV), 28% (n = 213) reported 1 impairment (61% hearing, 39% visual) and 7% (n = 55) both. On multivariate analysis, impaired hearing was associated with IADL dependency, anxiety and depression. Visual impairment was associated with IADL dependency, ADL limitation and depression. Impairment in both was associated with IADL dependency, anxiety, depression and cognitive deficit. Conclusions: Older pts with cancer and hearing/visual impairment are at higher risk of functional, psychological and cognitive deficits. Interventions aimed at improving vision and hearing of older adults with cancer should be studied. [Table: see text]

10573Background: The growing population of AYA cancer survivors is at high risk for HPV exposure, increasing risk for HPV-related cancers. Vaccination should protect survivors from HPV-related canc...

10511Background: CCS are at a 10-fold increased risk of CNS SNs. Cranial radiation (CRT) for primary cancer increases the risk; dose-risk relation with CRT is linear. The substantial burden of CNS SN-related morbidity presents an unmet need for identifying high-risk patients to guide targeted interventions. We present a risk prediction model to address this gap. Methods: CCS with CNS SNs (cases: n=82) matched to CCS without CNS SNs (controls: n=228; matched on primary cancer diagnosis (dx), year of dx, race/ethnicity and follow-up), contributed germline DNA for genotyping 43 previously published candidate genes (97 SNPs). Risk prediction models were derived sequentially: Base Model (age at primary cancer dx, gender), Clinical Model (Base Model + CRT [Y/No]), Final Model (Clinical Model + SNPs). Receiver operating characteristic analysis was used to evaluate predictive utility of Final Model in assessing CNS SN risk. Two risk groups were derived using predicted values (high risk: ≥0.1; low risk

10057Background: Older patients with cancer are at increased risk of hospitalizations during cancer treatment. Our objective was to identify risk factors for unplanned hospitalization among older a...

10036Background: Our study aims to evaluate the relationship between social support (SS) and chemotherapy-related toxicities (CRT) among older cancer patients. We hypothesized that patients with po...

e17537 Background: Effective management of ES/OS/RMS requires a multidisciplinary approach. Whether care at specialized centers (e.g., NCICCCs) affords a survival advantage across socioeconomic strata remains unstudied. Methods: We constructed a population-based cohort of 629 patients with newly diagnosed (dxed) ES/OS/RMS reported to Los Angeles cancer registry between 1998 and 2008. Multivariable Cox regression was used to determine impact of care at NCI sites (NCICCCs [all ages]; Children’s Oncology Group [COG] sites [

10066 Background: Identification of genetic variants that modify anth-card risk can facilitate targeted interventions. Methods: Discovery: Case-control approach used to conduct GWAS in non-Hispanic...

188 Background: Despite advances in therapy and supportive care, prognosis for certain cancers remains poor. Rigorous processes ensure quality of research, clinical care and education at NCICCC. However, impact of site of care on survival and access to NCICCC for vulnerable subpopulations (race/ethnicity, payor) remains unstudied. Methods: We constructed a population-based cohort of 53,618 patients diagnosed between 22y-65y with adult-onset cancers and reported to LA County cancer registry between 1998-2008. Geographic Information Systems (ArcGIS) was used for geospatial analysis. Results: Across multiple diagnoses, patients at NCICCC showed superior 5y overall survival (OS) as compared to those at community sites (Breast [n=31,770]: 89% vs. 86%, p 9 miles from nearest NCICCC (OR 0.5-0.9, p

6591 Background: Poorer outcome is documented among AYA (15-39y at diagnosis [dx]) with cancer as compared to younger (

123 Background: AYA (15-39yo) have not seen the same survival improvement as younger cancer patients with similar diagnoses (dx), leaving an AYA Gap. Treatment on pediatric trials is associated with superior survival in 15-21yo. However, impact of care at NCICCC for complex diseases with poor prognosis that require evidence-based care available at NCICCC (e.g. CNSt), remain unstudied. Methods: We constructed a cohort of 560 children (0-14yo) and 785 AYA with newly-dx CNSt, reported to the LA County (LAC) cancer registry between 1998 and 2008. While 82% of children (0-14y) and 65% of young AYA (15-18y) were treated at one of 3 NCICCC or 3 COG sites in LAC, only 17% of older AYA (19-39y) were treated at one of 3 NCICCC. We sought to determine the impact of NCICCC/COG on overall survival (OS) and barriers to access to care at NCICCC/COG in AYA with CNSt. Since distance to NCICCC/COG could serve as a barrier to accessing care, Geographic Information Systems were used to derive distance between patient’s residence to the nearest NCICCC/COG. Results: OS rates were uniformly good for children and AYA with grade 1 CNSt (96 vs. 89% at 5y, p=0.2) and uniformly poor for children and AYA with grade 3/4 CNSt (43 vs. 43% at 5y, p=0.6). Among patients with WHO grade 2 CNSt, AYA had worse outcome (HR=1.9, p12mi OR 0.5 , p=0.05) reduced likelihood to receive care at NCICCC. Conclusions: Population-based data reveal that receipt of care at NCICCC abrogates the inferior outcome in AYA with WHO grade 2 CNSt. Young AYA are less likely to use NCICCC than children, as are older AYA with low SES, public/ no insurance, or living > 5 miles from an NCICCC.

6537 Background: AYA (15-39y) have not seen survival improvement as in younger or older ages with similar cancer diagnoses, leaving an AYA Gap. Pediatric protocol use is associated with superior survival among 15-21y-olds, but impact of site of care for complex diseases with poor prognosis (such as CNSt) that require multidisciplinary, evidence-based care available at NCICCC, are unstudied. Methods: We constructed a cohort of 746 AYA with newly diagnosed CNSt, reported to the LA cancer registry from 1998-2008; 133 (18%) were treated at the 3 NCICCC in LA county. We examined clinical (WHO grade, diagnosis (dx) year, site of care) and demographic (age at dx, gender, SES, insurance, race/ethnicity) variables univariately; we included only those with p2y, n=493) to examine impact of care at NCICCC among AYA with aggressive disease (resulting in death within 2y from dx) vs. those who survived 2y from dx – representing disease likely amenable to new strategies for control. Results: 5y overall survival (OS) was 59% and did not differ by site of care (p=0.2). Multivariable analysis restricted to the first 2y revealed an increased risk of death among those with high WHO grade (HR 4.7, p

10004 Background: The strong dose-dependent association between anthracyclines and cardiomyopathy limits the therapeutic potential of this extremely effective class of agents, demanding identification of those at highest risk, such that anthracycline exposure may be tailored. Methods: In a two-stage design, we investigated host susceptibility to anthracycline-related cardiomyopathy in cancer survivors by using the ITMAT/Broad/CARe cardiovascular SNP-array to profile common SNPs in 2100 genes considered most relevant to de novo cardiovascular disease. All cases of cardiomyopathy fulfilled American Heart Association (AHA) criteria for cardiac compromise and were confirmed echocardiographically. Results: Using a matched case-control design (93 cases, 194 controls, all non-Hispanic white survivors of childhood cancer) we identified a common SNP rs2232228 in hyaluronan synthase (HAS3) gene that exerts a substantial modifying effect on anthracycline dose-dependent risk of cardiomyopathy. Among individuals with GG genotype, cumulative anthracycline exposure was not associated with cardiomypathy risk at any dose. Individuals with AA genotype, exposed to >250mg/m2 anthracyclines, had an 8.5-fold increased cardiomyopathy risk (95%CI, 2.0-35.6, p=0.004). Replication in an independent set of 76 patients (adult-onset and childhood cancer; all races) with anthracycline-related cardiomyopathy revealed the odds of cases with AA genotype in the high-dose anthracycline group to be 4.5-times higher (95%CI, 1.1-18.4, p=0.04). Hyaluronan (HA) – produced by HAS3 – is a ubiquitous component of extracellular matrix (ECM). ECM is involved in tissue remodeling; the extent of cardiac remodeling/repair after anthracycline-induced cardiac injury is possibly modulated by variability in HA production. Conclusions: The significant modifying effect of HAS3 genotype on the dose-dependent association between anthracycline and cardiomyopathy risk suggests that, upon confirmation in prospective studies, genotyping HAS3 may be considered when evaluating risk of anthracycline-related cardiomyopathy.

217 Background: AYAs (15-39y at diagnosis) with cancer have not seen the survival improvement evidenced by younger and older age groups with similar diagnoses, leaving an AYA Gap. While treatment on pediatric protocols is associated with superior survival in 15-21y, impact of site of care on survival for vulnerable AYA subpopulations (race/ethnicity) between 22-39y at diagnosis remains unstudied. Methods: Utilizing a cohort of 10,602 AYAs newly diagnosed between 22-39y with lymphoma, leukemia, brain tumors, melanoma, thyroid and GU cancers, and reported to the Los Angeles County cancer registry between 1998 and 2008, we aimed to determine the impact of receiving care at NCI Comprehensive Cancer Centers (NCICCC) on overall survival for AYAs, and disparities in survival by race/ethnicity. We further aimed to understand the role of SES and insurance status in accessing care at NCICCC. Multivariable analyses included race/ethnicity, age at diagnosis, SES, insurance status, primary cancer diagnosis and diagnosis year in the model. Results: A total of 904 (9%) patients received treatment at the 3 NCICCC (City of Hope, Jonsson Cancer Center, and Norris Cancer Center) in LA County. Ten-year overall survival (10y OS) was significantly worse for patients treated at non-NCICCC (81%) when compared with those treated at NCICCC (83%, p=0.02). Also, 10y OS was worse for African Americans (AA) (68%) vs. non-Hispanic whites (86%, p

9512 Background: AYAs (15-39y at diagnosis) with cancer have not seen the survival improvement evidenced by younger and older age groups with similar diagnoses, leaving an AYA Gap. While treatment on pediatric protocols is associated with superior survival in 15-21 year-olds, the impact of site of care on survival for vulnerable AYA subpopulations (age at diagnosis or race/ ethnicity) between 22-and 39y at diagnosis remains unstudied. Methods: We constructed a cohort of 10,727 patients newly diagnosed between the ages of 22- and 39y with lymphoma, leukemia, brain tumors, melanoma, thyroid and GU cancers, and reported to the LA County cancer registry between 1998 and 2008. Multivariable Cox regression analysis was conducted, and included race/ethnicity, age at diagnosis, SES, insurance status, primary cancer diagnosis and diagnosis year in the model; the analysis was stratified by site of care (NCICCC vs. non-NCICCC). Results: A total of 928 (9%) patients received treatment at the 3 NCICCCs (City of Hope, Jonsson Cancer Center and Norris Cancer Center) in LA County, and 9,799 received care elsewhere. Five-year overall survival (5y OS) was significantly worse for patients treated at non-NCICCC (87%) when compared with those treated at NCICCC (84%, p=0.02). In addition, 5y OS was worse for African Americans (71%) vs. non-Hispanic whites (89%, p

1592 Background: s-BC after conventional chest radiation for histologically distinct cancer is well-recognized, and has resulted in radiologic screening recommendations by American Cancer Society. However, risk of s-BC after TBI is not well-defined. Methods: We determined the risk of s-BC in 648 consecutive females transplanted for leukemia (ALL [19%], AML/MDS [57%], CML [24%]) between 1976 and 2008 with a post-HCT survival of ≥2 years. The study was restricted to leukemia to understand the role of TBI without the influence of pre-HCT chest radiation. Near-complete ascertainment of s-BC was assured by combining institutional follow-up with California Cancer Registry data. Results: Median age at HCT was 38 years (range, 0-71); 14% had received autologous HCT, 64% related and 22% unrelated donor HCT; 70% had received TBI for myeloablative conditioning. After 5,675 person-years of observation, 16 patients developed s-BC (14 after TBI). Median latency from HCT to s-BC was 16y (2-27). Median age at s-BC was 50y (29-66). Cumulative incidence of s-BC was 6% at 20y after HCT, contributed to largely by TBI (s-BC incidence after TBI: 5.7%). Among TBI-exposed, 8.6% were projected to develop s-BC by age 65y (1.6% among non-TBI-exposed, p=0.03). TBI-exposed patients were 2.4 times more likely to develop s-BC compared with general population (p=0.001); non-TBI exposed were not at increased risk (SIR=0.9, p=0.9). Multivariate analysis (adjusted for age at HCT, follow-up and primary diagnosis) revealed a 4.7-fold (p=0.068) increased risk of s-BC among TBI-exposed. Conclusions: Risk of s-BC after TBI as the sole source of radiation to breast is increased. Nearly 9% of those exposed to TBI will develop s-BC by age 65y. Identification of vulnerable sub-populations among the TBI-exposed patients is underway to create targeted screening strategies for early detection of s-BC.

8038 Background: Studies from the CALGB and IFM have suggested an increased incidence of SPM post ASCT in patients on lenalidomide maintenance. Patients with MM as well as patients post ASCT are inherently at higher risk of SPM. Therefore, assessment of risk factors associated with SPM would be useful in therapeutic decisions re preASCT therapy and post ASCTmaintenance. Methods: We conducted a retrospective cohort study of 841 consecutive MM patients who underwent at least one ASCT at City of Hope from 1989 to 2009. Sixty cases with 70 SPMs were identified. A nested case-control study was also conducted to understand the role of therapeutic exposures associated with SPMs. Controls were MM patients post ASCT matched by year of HCT (±5 years). Results: The median length of follow up was 3.3 yrs. (range 0.3-19.9). Median age at ASCT was 56 yrs (range 18-77). 62% had received a single autologous HCT, 27% tandem autologous HCT, 11% had received multiple HCTs (72 had a second allogeneic HCT)). The overall cumulative incidence of any SPM was 7.4% at 5 years and 15.9% at 10 years; the cumulative incidence of SPMs for patients >55 years approached 21.9% at 10 years. The cumulative incidence of MDS/AML was 1.8% and of solid tumors was 13.0%. Factors examined included age, race, sex, number and individual therapeutic exposures ( pre-ASCT, conditioning, and post-ASCT), disease status at ASCT. Multivariate Cox regression analysis revealed non-Hispanic whites (RR=2.4, 95% CI, 1.2-4.6, p=0.01) and older age (>55) at diagnosis of MM (RR=2.3, 95% CI, 1.3-4.1, p=0.004) to be associated with an increased risk of developing SPMs. Only cumulative thalidomide exposure (both pre-ASCT and post-ASCT) demonstrated a trend toward a positive association (OR=3.5, 95% CI, 0.6-19.4, p=0.15). Six patients (3 cases and 3 controls) were exposed to lenalidomide prior to development of SPM (OR=1.0, 95% CI, 0.14-7.10). Conclusions: This single institution analysis identified non-hispanic whites and older age to be associated with increased risk of developing SPM in pts post ASCT for MM. The trend towards increased risk with thalidomide exposure may be suggestive of a class effect from IMIDs that is not restricted to lenalidomide alone.

9042 Background: aHCT survivors are at risk for CHF due to exposure to cardiotoxic agents (pre-aHCT anthracyclines, chest radiation, aHCT conditioning). The magnitude of risk of CHF and risk factors are not defined, nor is the modifying effect of preventable causes, such as cardiovascular risk factors (CV RF). Methods: A retrospective cohort design was used to describe the cumulative incidence (CI) of CHF and examine the role of aHCT conditioning and sociodemographic factors. Next, a nested case-control approach was used to evaluate the role of pre-aHCT exposures and post-aHCT CV RF. Results: Eighty-one cases of CHF were observed in a cohort of 1,010 aHCT survivors transplanted at City of Hope between 1988 and 2002, followed for a median of 6.7 yrs (1-21). Median age at aHCT was 44.4 yrs (17-69); median time to CHF: 3.0 yrs (0.02-18.6); 40% were females; 71% non-Hispanic white; 68% underwent aHCT for lymphoma. CI of CHF was 7.8% at 10 yrs and 10.4% at 15 yrs post-aHCT. Female gender (Hazard Ratio [HR] 2.5...

9034 Background: Childhood cancer survivors are at risk for cardiac dysfunction (CD) due to exposure to anthracyclines and chest radiation. This risk is further compounded by cardiovascular (CV) ri...

6022 Background: Racial differences in prostate cancer-specific survival account for 50% of observed disparities in cancer survival between Caucasians and African Americans. These differences could...

9512 Background: Anthracycline-related cardiomyopathy is a well-recognized dose-limiting complication. Inter-individual variability in risk exists, potentially due to genetic susceptibility. Carbon...

9517 Background: The role of race and ethnicity in disease presentation and survival among children with NBL remains unclear. We investigated the relationship between race/ethnicity, NBL biology, a...

6615 Background: As hematopoietic cell transplantation (HCT) has increasingly become a curative option for many diseases, studying long-term complications has assumed critical importance. A major issue in conducting scientifically rigorous long-term follow up studies with large cohorts is the ability to track patients, and obtain informed consents. High participation rates are critical to avoid selection bias and ensure generalizability. Methods: A mass consenting process was implemented to obtain informed consents from 1056 City of Hope HCT patients transplanted during 1976–2006 who were one+ year survivors and alive in June 2007. This process involved mailing consent forms followed by phone calls. Patients were classified as consented, refused, or lost-to-follow-up (LTFU). Sociodemographic and clinical characteristics indicative of higher risks for refusal or LTFU were identified. Results: Study patients comprised 58% males, and 53% Caucasians. Median age at HCT was 34 years (0.6–73); median age at study initiation was 47 years (6–81); and median time from HCT to study initiation was 10 years (1–30). Primary diagnoses included acute/chronic leukemia (43%), Hodgkin/non-Hodgkin lymphoma (36%), multiple myeloma (9%), and other miscellaneous diagnoses (12%). Fifty percent received allogeneic HCT. At the end of the process, 46% consented, 17% refused, and 37% were LTFU. Compared to consented patients, males, Asians, and younger patients were more likely to refuse consent. Patients LTFU were more likely to have lower SES, a longer time since HCT, in addition to being males, Asians and younger at HCT (Table). Conclusions: This study demonstrates the critical need for maintaining up-to-date contact information on patients after HCT in order to obtain valid long-term follow-up data. It also describes the characteristics of the sub-population that are more likely to refuse or be LTFU, information necessary for planning targeted interventions in long-term follow-up initiatives. [Table: see text] No significant financial relationships to disclose.

6520 Background: A significant gap exists between Caucasians and African-Americans (AAs) in prostate cancer mortality, possibly due to sociodemographics, disease biology, or treatment. Furthermore, differential access to care at NCI-designated Comprehensive Cancer Centers (NCICCCs) conceivably contributes to this difference. Methods: Using data from the Los Angeles Cancer Surveillance Program, we studied the underlying causes of differences in mortality in 18,790 men (AAs: 4,211; Caucasians: 14,579) diagnosed with prostate cancer between 1998 and 2003, and followed until 2006. Three NCICCCs serve this area: USC-Norris, UCLA-Jonsson, and City of Hope. Results: Median age at diagnosis was 67.5 yrs; AAs were significantly more likely to have lower SES; carry no insurance; have distant disease; and be managed with “watchful waiting.” The overall and prostate-specific survival was significantly superior for patients treated at NCICCCs, and for Caucasians (Table). Multivariate analysis, after adjustment for sociodemographics, race, insurance, tumor-related factors, and treatment-modality, revealed that treatment at NCICCCs was associated with lower overall (HR=0.74, 95% CI=0.6–0.9) and prostate-specific mortality (HR=0.69, 95% CI=0.5–0.97). AAs were less likely to utilize NCICCCs (OR=0.42, 95%CI=0.4–0.5). Finally, adjustment for sociodemographic, tumor/treatment-related factors, and treatment site abrogated the racial difference in overall (HR=1.08, 95%CI=0.99–1.2) and prostate-specific (HR=1.11, 95%CI=0.9–1.3) mortality. Conclusions: Patients treated at NCICCCs have lower mortality compared with other facilities. AAs are less likely to utilize NCICCCs for prostate cancer. AAs and Caucasians have comparable overall and prostate-specific survival, after adjustment for sociodemographic, tumor/treatment-related factors, and treatment site. Future studies are needed to understand barriers and facilitators to utilization of NCICCCs for management of prostate cancer. [Table: see text] No significant financial relationships to disclose.

9510 Background: Patients undergoing HCT are at increased risk for chronic health conditions, including CHF. However, the independent roles of pre-HCT exposures, transplant-related conditioning, an...

10054 Background: Knowledge deficits regarding diagnosis and treatment history exist, and could impair childhood cancer survivors’ ability to seek and receive risk-based care (RBC). Specialized lon...

6608 Background: A third of long-term HCT survivors report severe or life-threatening chronic health conditions, placing significant demands on the healthcare system for a prolonged period of time....