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PURPOSE To describe the risk of late mortality, subsequent malignant neoplasms (SMNs), and chronic health conditions (CHCs) in survivors of neuroblastoma diagnosed in infancy by treatment era and exposures. METHODS Among 5-year survivors of neuroblastoma in the Childhood Cancer Survivor Study diagnosed age < 1 year between 1970 and 1999, we examined the cumulative incidence of late (> 5 years from diagnosis) mortality, SMN, and CHCs (grades 2-5 and 3-5). Multivariable Cox regression models estimated hazard ratios (HRs) and 95% CIs by decade and treatment (surgery-alone v chemotherapy with or without surgery [C ± S] v radiation with or without chemotherapy ± surgery [R ± C ± S]) among survivors and between survivors and 5,051 siblings. RESULTS Among 1,397 eligible survivors, the 25-year cumulative incidence of late mortality was 2.1% (95% CI, 1.3 to 3.9) with no difference by treatment era. Among 990 participants who completed a baseline survey, fewer survivors received radiation in more recent eras (51.2% 1970s, 20.4% 1980s, and 10.1% 1990s; P < .001). Risk of SMN was elevated only among individuals treated with radiation-containing regimens compared with surgery alone (HR[C ± S], 3.2 [95% CI, 0.9 to 11.6]; HR[R ± C ± S], 5.7 [95% CI, 1.2 to 28.1]). In adjusted models, there was a 50% reduction in risk of grade 3-5 CHCs in the 1990s versus 1970s (HR, 0.5 [95% CI, 0.3 to 0.9]; P = .01); individuals treated with radiation had a 3.6-fold risk for grade 3-5 CHCs (95% CI, 2.1 to 6.2) versus those treated with surgery alone. When compared with siblings, risk of grade 3-5 CHCs for survivors was lowest in the most recent era (HR[1970s], 4.7 [95% CI, 3.4 to 6.5]; HR[1980s], 4.6 [95% CI, 3.3 to 6.4]; HR[1990s], 2.5 [95% CI, 1.7 to 3.9]). CONCLUSION Neuroblastoma survivors treated during infancy have a relatively low absolute burden of late mortality and SMN. Encouragingly, risk of CHCs has declined in more recent eras with reduced exposure to radiation therapy.

e22023 Background: Survivors of childhood cancer with history of radiation therapy (RT) to the head/neck/chest are at increased risk for stroke. Children’s Oncology Group Guidelines recommend carotid ultrasound (CU) when clinically indicated or 10 years after RT ≥ 40Gy to the neck. Yet, the use of CU has not been previously described. Methods: 8,693 survivors of childhood cancer (median age at diagnosis 8.0 years, range 0-20; median age at evaluation 37.4, range 18-65) diagnosed between 1970-1999 were asked if they had ever had a CU. Cardiovascular disease (CVD) was defined as any of the following: stroke, congestive heart failure, hypertension, myocardial infarction, coronary heart disease, or arrythmia. Prevalence ratios (PR) were calculated; age and sex-adjusted multivariable Poisson regression models evaluated factors associated with CU. Results: 4.9% (427) of survivors had a history of stroke and 28% (2,442) had a history of any CVD. Of these, 40.0% (171) with a history of stroke and 28.6% (748) with any CVD had CU. Comparatively, 14.6% (1,404) without a stroke and 11.1% (798) without any CVD had a CU (both p40Gy RT to the neck have never had a CU, suggesting that greater awareness of guidelines is needed.[Table: see text]

Purpose Infection-related outcomes associated with asplenia or impaired splenic function in survivors of childhood cancer remains understudied. Methods Late infection-related mortality was evaluated in 20,026 5-year survivors of childhood cancer (diagnosed < 21 years of age from 1970 to 1999; median age at diagnosis, 7.0 years [range, 0 to 20 years]; median follow-up, 26 years [range, 5 to 44 years]) using cumulative incidence and piecewise-exponential regression models to estimate adjusted relative rates (RRs). Splenic radiation was approximated using average dose (direct and/or indirect) to the left upper quadrant of the abdomen (hereafter, referred to as splenic radiation). Results Within 5 years of diagnosis, 1,354 survivors (6.8%) had a splenectomy and 9,442 (46%) had splenic radiation without splenectomy. With 62 deaths, the cumulative incidence of infection-related late mortality was 1.5% (95% CI, 0.7% to 2.2%) at 35 years after splenectomy and 0.6% (95% CI, 0.4% to 0.8%) after splenic radiation. Splenectomy (RR, 7.7; 95% CI, 3.1 to 19.1) was independently associated with late infection-related mortality. Splenic radiation was associated with increasing risk for late infection-related mortality in a dose-response relationship (0.1 to 9.9 Gy: RR, 2.0; 95% CI, 0.9 to 4.5; 10 to 19.9 Gy: RR, 5.5; 95% CI, 1.9 to 15.4; ≥ 20 Gy: RR, 6.0; 95% CI, 1.8 to 20.2). High-dose alkylator chemotherapy exposure was also independently associated with an increased risk of infection-related mortality (RR, 1.9; 95% CI, 1.1 to 3.4). Conclusion Splenectomy and splenic radiation significantly increase risk for late infection-related mortality. Even low- to intermediate-dose radiation exposure confers increased risk, suggesting that the spleen is highly radiosensitive. These findings should inform long-term follow-up guidelines for survivors of childhood cancer and should lead clinicians to avoid or reduce radiation exposure involving the spleen whenever possible.

10044 Background: Survival rates for neuroblastoma vary widely based on risk group. Therapies have evolved over the past four decades to de-intensify treatment for individuals with low/intermediate risk disease and intensify therapy for those with high risk disease. Risk stratification is predicted to result in differential outcomes in late morbidity and mortality; the magnitude of these differences has not been well studied. Methods: We evaluated late mortality, subsequent malignant neoplasms (SMN) and chronic health conditions (CHC) graded according to CTCAE v4.03 among 491 5-year CCSS survivors of neuroblastoma diagnosed 1987-1999 at ≥1 year of age. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n=182]; intermediate [n=70]; high [n=239]). Standardized mortality ratios (SMR) and standardized incidence ratios (SIR) of SMN were calculated using rates from NCHS and SEER, respectively. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for CHC compared to 1,029 CCSS siblings. Results: Among survivors (48% male; median age 22 years, range 7-42; median follow-up 19 years, range 5-29), 80.4% with low risk disease were treated with surgery alone, while 77.8% with high risk disease received surgery, radiation, chemotherapy ± transplant. The 15-year cumulative incidence of all-cause mortality was 9.2% (CI: 7.1-11.4), with a recurrence-related mortality of 7.3% (CI: 5.3-9.3) and SMN-related mortality of 0.3% (CI: 0-0.7). All-cause mortality was significantly higher in all risk groups: (low, SMR=5.8 [CI: 2.6-13.0]; intermediate, SMR=5.7 [CI: 1.4-23.5]; high, SMR=38.6 [CI: 27.9-53.5]). The risk of SMN was elevated among high risk survivors (SIR=25.1, CI: 16.7-37.6), but did not differ from the US population for survivors of low or intermediate risk disease. Table describes the HR of CHCs (grades 1-5 and 3-5) in survivors, by risk group, as compared with siblings, as well as categories of CHCs for which survivors were at increased risk. Conclusions: Long-term survivors of neuroblastoma have a high risk of late morbidity and mortality; risk is particularly pronounced among survivors of high risk disease. Vigilant lifelong medical surveillance will be required for this relatively young population as they age.[Table: see text]

10017 Background: Racial, ethnic, and socioeconomic disparities are documented in outcomes for childhood cancer survivors. Understanding whether childhood cancer modifies established disparities in cardiovascular risk factors (CVRFs) in the general population would inform strategies to reduce health inequities among survivors. Methods: The CCSS is a retrospectively constructed cohort with prospective follow-up consisting of 25,579 five year survivors of childhood cancer diagnosed between 1970 and 1999. We estimated the incidence of self-reported Common Terminology Criteria for Adverse Events (CTCAE) grade >2 CVRFs (hypertension, diabetes, dyslipidemia, and obesity) and multiple (>2) CVRFs among survivors. Multivariable Poisson regression estimated the rate ratios (RR) of CVRFs by race/ethnicity, adjusted for key treatment exposures and sociodemographics. Results: Within the CCSS cohort, there were 20,416 non-Hispanic White (NHW), 1625 non-Hispanic Black (NHB), and 2043 Hispanic survivors with the cumulative incidence estimates of each CVRF at age 40 displayed in Table. Survivors who self-reported “Other” or mixed race were excluded for this analysis (n=1495). NHB survivors were more likely to report hypertension (unadjusted RR 1.3; 95% Confidence Interval [CI] 1.0-1.6), diabetes (RR 1.6; 95% CI 1.0-2.4), obesity (RR 1.6; 95% CI 1.4-1.9), and multiple CVRF (RR 1.3; 95% CI 1.2-1.5), whereas Hispanic survivors were more likely to report diabetes (RR 1.7; 95% CI 1.2-2.4), obesity (RR 1.4; 95% CI 1.2-1.5), and multiple CVRFs (RR 1.1; 95% CI 1.0-1.3) compared with NHW survivors. These observed disparities in risks of CVRFs remained nearly unchanged even after adjustment for sociodemographic factors (age, sex, household income, education, marital status, employment, and insurance) and treatment exposures (Yes/No for anthracyclines, alkylators, and chest radiation). Conclusions: NHB and Hispanic adult survivors demonstrate a higher burden of CVRF compared with NHW survivors, particularly diabetes and obesity. The associated morbidity of these conditions and established increase they incur in risk of more severe cardiovascular disease emphasizes the need for interventions to mitigate CVRFs to promote health equity among these survivors.[Table: see text]

10015 Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for obesity and cardiovascular (CV) disease. Exposure to cranial radiotherapy (CRT) increases risks. We tested whether a weight loss intervention that was successful in the general population could result in weight loss or improvements CV risk factors for ALL survivors. Methods: Obese and overweight 5-year ALL survivors diagnosed < age 21 from CCSS were randomized to a 24-month remotely delivered diet/physical activity intervention or self-directed weight loss (control), stratified by CRT. The intervention emphasized a low calorie DASH diet and physical activity via an app, a website, and weekly coach calls. The primary endpoint was difference in weight loss after 24 months, using an intent-to-treat analysis. Secondary endpoints: differences in changes in blood pressure, cholesterol, and triglycerides. Analyses were performed using linear mixed effects; the study was designed to detect a difference of 2.75 kg. Results: Of 358 survivors (59% female, 91% White non-Hispanic, median age 37, IQR: 33-43), 181 were randomized to the intervention and 177 to control. Baseline mean (SD) weight was 98.6 kg (24.0) for intervention and 94.9 kg (20.3) for controls. 55 (30%) of intervention participants were adherent beyond one year. At 12 months, after controlling for CRT, sex, race/ethnicity, and age, the adjusted mean (SE) change in weight from baseline was -1.83kg (0.7) for intervention and -0.16kg (0.64) for control participants. At 24 months, the adjusted mean (SE) change in weight was -0.36kg (0.78) for intervention and +0.18kg (0.66) for control participants with the average difference of -0.54 kg (95%CI: -2.5,1.5, p=0.59) between the arms. A small proportion had at least 5% weight loss at 24 months (intervention 24%; control 17%). No significant differences in CV risk factors were observed. Conclusions: A 24-month phone and app/web-based diet and physical activity intervention that was successful for weight loss in the general population did not result in greater weight loss or improvement in CV risk factors among adult survivors of childhood ALL. Reduced adherence to the intervention beyond 12 months, or lack of ALL survivor-specific tailoring, may account for these findings. Clinical trial information: NCT02244411. [Table: see text]

10515 Background: Survivors of childhood cancer exposed to cardiotoxic therapies are at increased risk of heart disease. Hypertension, dyslipidemia, and diabetes are modifiable cardiovascular risk factors (CVRFs) that synergistically increase this risk. Therefore, we aimed to determine the prevalence of and predictors associated with CVRF underdiagnosis and undertreatment in this population. Methods: CCSS participants at increased risk of heart disease due to prior cancer therapy were enrolled in an ongoing randomized intervention trial (NCT03104543) to improve CVRF identification and treatment. Participants completed a baseline survey (CVRF status, lifestyle habits, attitudes towards healthcare), anthropometry, and blood draw. Blood pressure, low density lipoprotein, triglyceride, glucose and Hgb A1c were measured and classified as normal/abnormal per standard clinical criteria. Multivariable logistic regression estimated odds ratios (OR [95% confidence intervals]) associated with predictors and risk of CVRF underdiagnosis and undertreatment. Results: As of January 2020, 522 participants (43% male) were available for analysis (47% response), with a median age 38y (range 20-65) and 28y (18-49) from original cancer treatment (75% anthracycline, 47% chest radiation). With mean measured BMI 27.3±6.5 kg/m2, self-reported prevalence rates were hypertension 27%, dyslipidemia 33%, and diabetes 9%. While 90% of participants had a routine check-up ≤2y ago, 58% had a measured CVRF in the abnormal range. Specifically, among previously undiagnosed participants, we observed rates of abnormal blood pressure (26%), lipids (17%), and glucose tolerance (27%). Among those with pre-existing hypertension, dyslipidemia, and diabetes, 11%, 49%, and 54%, respectively, had measurements outside of the usual therapeutic target range. In multivariable analysis, BMI ≥25 kg/m2 (vs < 25) was associated with risk of underdiagnosis (OR 1.8 [1.2-2.8]). For undertreatment, significant adverse factors included older age ( > 35 vs ≤35y: OR 2.5 [1.2-5.1]), BMI ≥30 kg/m2 (vs < 25: OR 3.3 [1.7-6.4]), and greater perceived reliance on others for healthcare decisions (OR 1.7 [1.2-2.4]). Those with greater health-related self-efficacy were less likely to be undertreated (OR 0.5 [0.3-0.96]). Conclusions: CVRF underdiagnosis and undertreatment among childhood cancer survivors at increased risk of heart disease was common. Greater awareness among survivors and primary care providers and more aggressive control of CVRFs may mitigate this risk.

401 Background: HD carboplatin is an essential part of curative salvage high-dose chemotherapy (HDCT) for GCT. Although ototoxicity is a known side effect of HD carboplatin, data on severity and characteristics of HL in this population are limited. Methods: Eligible patients (pts) received salvage HD carboplatin for GCT at our center from 1993-2017 and had audiograms pre- and post-HDCT. All pts were planned for 3 sequential cycles of HD carboplatin; some had audiograms after each cycle. HL severity was classified by ASHA criteria (slight: 15-24dB; mild: 25-40dB; moderate: 41-55dB; moderately severe: 56-70dB; severe: 71-90dB; profound: >90dB). Change in hearing threshold at each frequency (0.25 – 8 kHz) was analyzed by clinical and treatment variables using the Wilcoxon rank-sum test. The proportion of pts recommended for hearing aids was also recorded. Results: Of 115 pts (median age 31, 77% nonseminoma), 96 received TI-CE and 19 received TI-TIC on a clinical trial (Feldman CGUC 2015). Pts varied by prior cisplatin exposure (77% with ≤4 vs 23% with 5-9 cycles) and number of HD carboplatin cycles (89% had 3, 10% had 2, and 2% had 1). Carboplatin AUC was 21 in 23%, 24 in 75%, and 28 in 3%. Moderate to profound HL was present in 23% pre-HD carboplatin vs 82% post, preferentially at high frequencies (Table). Of 89 pts with normal to mild HL at baseline, 78% developed moderate or worse HL post-HD carboplatin, including 61% with moderately severe or severe HL. Higher AUC (24 vs 21) and number of HD carboplatin cycles were associated with greater HL with HD carboplatin whereas prior cisplatin exposure was not. Due to moderate or severe HL in the vital speech frequency range (2 – 4kHz), 20 (17%) pts were recommended for hearing aids post-HD carboplatin. Conclusions: In the largest series to detail ototoxicity in pts receiving salvage HD carboplatin for GCT, we show HL, particularly at high frequencies, is a major dose-dependent toxicity. Most pts will have at least moderate high frequency HL after HD carboplatin with approximately 1 in 6 recommended for hearing aids. [Table: see text]

Purpose Survivors of Hodgkin lymphoma (HL) are at increased risk of treatment-related cardiovascular (CV) events; whether exercise modifies this risk is unknown. Methods Survivors of HL (n = 1,187; median age, 31.2 years) completed a questionnaire evaluating vigorous-intensity exercise behavior. CV events were collected in follow-up questionnaires and graded according to Common Terminology Criteria for Adverse Events (version 4.03). The primary end point was incidence of any major (grade 3 to 5) CV event. Poisson regression analyses were used to estimate the association between exercise exposure (metabolic equivalent [MET] hours/week−1) and risk of major CV events after adjustment for clinical covariates and cancer treatment. Results Median follow-up was 11.9 years (range, 1.7 to 14.3 years). Cumulative incidence of any CV event was 12.2% at 10 years for survivors reporting 0 MET hours/week−1 compared with 5.2% for those reporting ≥ 9 MET hours/week−1. In multivariable analyses, the incidence of any CV event decreased across increasing MET categories (Ptrend = .002). Compared with survivors reporting 0 MET hours/week−1, the adjusted rate ratio for any CV event was 0.87 (95% CI, 0.56 to 1.34) for 3 to 6 MET hours/week−1, 0.45 (95% CI, 0.26 to 0.80) for 9 to 12 MET hours/week−1, and 0.47 (95% CI, 0.23 to 0.95) for 15 to 21 MET hours/week−1. Adherence to national vigorous intensity exercise guidelines (ie, ≥ 9 MET hours/week−1) was associated with a 51% reduction in the risk of any CV event in comparison with not meeting the guidelines (P = .002). Conclusion Vigorous exercise was associated with a lower risk of CV events in a dose-dependent manner independent of CV risk profile and treatment in survivors of HL.

10058 Background: Contemporary cancer protocols have incorporated modifications to minimize cardiotoxic exposures and preserve long-term health. We investigated the impact of these changes on late cardiac outcomes in a large cohort of adult survivors of childhood cancer. Methods: Congestive heart failure (CHF), myocardial infarction (MI), valvular disease, pericardial disease, and arrhythmias were graded by the National Cancer Institute’s Common Terminology Criteria for Adverse Events among 23,462 five-year cancer survivors [6,193 (26%) treated in the 1970s, 9,363 (40%) in the 1980s, and 7,906 (34%) in the 1990s] and 5,057 siblings. Cumulative incidence and 95% confidence intervals (95% CI) were estimated by treatment decade. Adjusted multivariable subdistribution hazard models were used to estimate hazard ratios (HR) and 95% CI for cardiac outcomes by decade. Mediation analysis examined risks with and without cardiotoxic exposures. Results: For survivors [median age 6 years (range: 0-21) at diagnosis, 28 years (8.2-58) at follow-up], cardiac radiation (RT) exposure declined from 77% of those treated in the 1970s to 55% and 40% in the 1980s and 1990s. Anthracycline exposure increased from 28% to 50% to 64%. The 20-year cumulative incidence of CHF (0.69% for those treated in 1970s, 0.74% in the 1980s, 0.54% in the 1990s) and MI (0.38%, 0.24%, 0.19%) declined in more recent treatment eras (p < 0.01). This change was not seen for valvular disease (0.06%, 0.06%, 0.05%), pericardial disease (0.04%, 0.02%, 0.03%) or arrhythmias (0.08%, 0.09%, 0.13%). Compared to survivors diagnosed in the 1970s, the risk of CHF, MI, and valvular disease decreased in the 1980s and 1990s, but only significantly for MI (HR 0.64 95% CI 0.47-0.89 and 0.52 95% CI 0.32-0.83). The overall MI risk was attenuated by adjustment for cardiac RT exposure (HR 0.94 95% CI 0.80-1.11), mostly among Hodgkin lymphoma (HL) survivors (HR 0.82 95% CI 0.69-0.98 [unadjusted for RT]; 1.03 95% CI 0.83-1.28 [adjusted for RT]). Conclusions: Reductions in exposure to cardiotoxic cancer therapies have resulted in declines in adverse cardiac outcomes, particularly for the RT-associated risk of myocardial infarction among HL survivors.

10051 Background: Infants with neuroblastoma typically have low-risk disease with excellent survival. Therapy has been de-intensified over time to minimize late effects, however the impact on survivors’ risk of late mortality, subsequent malignant neoplasms (SMN), and chronic health conditions (CHC) is unclear. Methods: We evaluated late mortality, SMNs and CHCs (graded according to CTCAE v4.03), overall and by diagnosis era, among 990 5-year neuroblastoma survivors diagnosed at < 1 year of age between 1970-1999. Cumulative mortality, standardized mortality ratios (SMR), and standardized incidence ratios (SIR) of SMNs were estimated using the National Death Index and SEER rates, respectively. Cox proportional hazards estimated hazard ratios (HR) and 95% confidence intervals (CI) for CHC, compared to 5,051 CCSS siblings. Results: Among survivors (48% female; median attained age: 24 years, range 6-46), there was increased treatment with surgery alone across the 1970s, 1980s and 1990s (21.5%, 35.3%, 41.1%, respectively), but decreased treatment with combination surgery + radiation (22.5%, 5.3%, 0.3%, respectively) and surgery + radiation + chemotherapy (28.7%, 14.7%, 9.3%, respectively). The 20-year cumulative mortality was 2.3% (95% CI, 1.4-3.8), primarily due to SMNs (SMRSMN= 10.0, 95% CI, 4.5-22.3). The 20-year cumulative incidence of SMN was 1.2% (95% CI, 0.3-3.2), 2.5% (95% CI, 1.3-4.4), and zero for those diagnosed in the 1970s, 1980s, and 1990s, respectively. SIR was highest for renal SMNs (SIR 12.5, 95% CI, 1.7-89.4). Compared to siblings, survivors were at increased risk for grade 1-5 CHC (HR 2.1, 95% CI, 1.9-2.3) with similar HR across eras (HR1970s= 1.9, 95% CI, 1.6-2.2; HR1980s= 2.2, 95% CI, 1.9-2.6; HR1990s= 2.0, 95% CI, 1.7-2.4). The HR of severe, disabling, life-threatening and fatal CHC (grades 3-5) decreased in more recent eras (HR1970s= 4.7, 95% CI, 3.4-6.6; HR1980s= 4.4, 95% CI, 3.2-6.2; HR1990s= 2.9, 95% CI, 2.0-4.3). Conclusions: Survivors of infant neuroblastoma remain at increased risk for late mortality, SMN, and CHCs many years after diagnosis. However, the risk of grade 3-5 CHCs has declined in more recent eras, likely reflecting de-intensification of therapy.

e21525 Background: Cholecystectomy (CCY) is among the most common operations performed in the developed world and is offered as a cure for symptomatic gallbladder disease. Whether survivors of childhood cancer undergo CCY at a higher rate than the general population is unknown. Methods: We identified 5-year survivors diagnosed between 1970 and 1999 who self-reported late (> 5 years after cancer diagnosis) CCY. Rates of CCY were determined among the entire cohort and in association with various risk factors and treatment exposures. Adjusted rate ratios (ARR) were estimated with multivariable piecewise exponential models. Results: Among 24,248 survivors (median follow-up 22.3, interquartile range [IQR] 16.2-30.1 years) and 5,038 siblings (median follow-up 26.4, IQR 19.3-33.7 years), the unadjusted cumulative incidence of CCY at age 50 was 7.2% (n = 757) in survivors and 6.5% (n = 168) in siblings. After adjusting for age, sex and race/ethnicity, survivors underwent CCY at higher rates compared to siblings (ARR = 1.3, 95% CI = 1.1-1.5). Relative to siblings, acute lymphoblastic leukemia survivors underwent CCY at a higher rate (ARR = 1.6, 95% CI = 1.3-2.0), all other diagnoses were not independently associated with higher rates of CCY. Among survivors, risk factors for late CCY included female sex, increasing body mass index (BMI) class, exposure to platinum agents and total body irradiation (TBI) (Table). Conclusions: CCY is performed more commonly among childhood cancer survivors relative to siblings. In addition to known risk factors for gallbladder disease, cancer treatment exposures may further enhance risk for CCY. Awareness and education regarding this observation may ensure timely diagnosis and treatment of symptomatic disease. [Table: see text]

10513Background: Adult survivors of childhood cancer are at risk for adverse psychological outcomes. Whether exercise can attenuate this risk is unknown. Methods: Using a longitudinal design, 6199 ...

10564Background: Childhood cancer survivors exposed to abdominal radiotherapy (abdRT) are at increased risk for diabetes mellitus (DM). We examined the association between DM risk and pancreatic ra...

131 Background: Radiotherapy is a well-known risk factor for non-melanoma skin cancer (NMSC), but whether diagnosis, histologic features, or natural history of NMSC after radiotherapy resemble those observed in the general population is unknown. This study aims to describe clinical findings, histology, and management of NMSC on the skin of childhood cancer survivors previously treated with radiotherapy. Methods: A retrospective chart review (2000-2017) was performed including adult survivors of childhood cancer referred to the Adult Long-Term Follow-Up Program or the dermatology service at Memorial Sloan Kettering Cancer Center. Data was obtained from electronic medical records, including demographics, histologic subtype and treatment received for NMSC (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)). Clinical features were assessed with clinical images. Results: 960 (mean age 40 years, SD ± 13) patients were assessed for the diagnosis of BCC/SCC after radiotherapy for cancer. The mean age of cancer diagnosis was 15 years (range: birth-39 years). The most common primary diagnosis was Hodgkin lymphoma. 82 patients developed NMSC; 67 of these developed NMSC in the field of prior radiotherapy. 283 in-field lesions were counted, of which 275 were BCC and 8 were SCC. Of the 275 BCC, 261 (95%) were primary lesions and 14 (5%) were recurrent lesions. All SCC were primary lesions. Based on clinical images, 30% of BCC were clinically pigmented; the most common presentation was macule (46%). The mean intervals for BCC and SCC from time of radiotherapy to diagnosis of the first in-field lesion were 24 years (range, 2-44 years) and 32 years (range, 14-46 years), respectively. Histologically, superficial subtype was most prevalent in the BCC subgroup, comprising 47% of all cases. Mohs surgery was the most common therapy (43% of BCC cases; 37% of SCC cases). Conclusions: Among survivors of childhood and young adult cancer, BCC was the most prevalent NMSC. Most of BCC arising in sites of prior radiotherapy for cancer treatment were of low-risk histologic subtype and had low rates of recurrence. An expanded role for topical therapy may be appropriate, but further research is needed.

LBA10500 Background: Modifications in childhood cancer treatments in recent decades have contributed to reductions in late mortality among 5-year survivors. We used the recently expanded CCSS cohort to investigate whether these changes have also reduced the incidence of chronic disease. Methods: We evaluated the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, CTCAE grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999. We calculated the 15-year cumulative incidence of chronic health conditions by decade of cancer diagnosis and compared risk across decades using Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Among 23,601 survivors, median age 28 years (range 5-63), 21 years from diagnosis (5-43), the 15-year cumulative incidence of grade 3-5 conditions decreased from 12.7% in survivors diagnosed in the 1970s to 10.1% and 8.8% in those diagnosed in the 1980s and 1990s (per 10 years, HR 0.84 [95% CI = 0.80-0.89]). The association with diagnosis decade was attenuated (HR 0.92 [0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk. Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR 0.57 [0.46-0.70]), Hodgkin lymphoma (HR 0.75 [0.65-0.85]), astrocytoma (HR 0.77 [0.64-0.92]), non-Hodgkin lymphoma (HR 0.79 [0.63-0.99]), and acute lymphoblastic leukemia (HR 0.86 [0.76-0.98]). Decreases were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% v. 1990s:1.6%; HR 0.66 [0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% v. 1990s: 1.6%; HR 0.85 [0.76-0.96]). Significant reductions were also found for gastrointestinal (HR 0.80 [0.66-0.97]) and neurological conditions (HR 0.77 [0.65-0.91]), but not cardiac or pulmonary conditions. Conclusions: Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but have also reduced the incidence of serious chronic morbidity in this population.

10563 Background: Asplenia or hyposplenism can develop in survivors of childhood cancer following splenectomy or radiotherapy exposure to the left upper quadrant of the abdomen (LUQ). Knowledge regarding long-term infection related outcomes for these survivors is limited. Methods: Infection related late mortality (sepsis, meningitis or pneumonia) was evaluated in 20,805 5-year survivors (diagnosed

10569 Background: Childhood cancer survivors have excess risk of second malignant neoplasms, but data are limited in Asian populations. We established a nationwide retrospective cohort of childhood cancer survivors in Taiwan to study the risk of second malignant neoplasms in the population. Methods: Children and adolescents diagnosed with cancer before age 21 years between 1990 and 2011 were identified from the Taiwan Cancer Registry, the national cancer registry in Taiwan. One-year survivors of childhood cancer were ascertained through data linkage with the national death registry. Survivors were followed up through December 2012. Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of second malignant neoplasms were calculated. Results: A total of 186 second malignant neoplasms occurred among 15,263 1-year survivors of childhood cancer after a mean follow-up time of 8.0 years (SIR = 5.4, 95% confidence interval [CI] = 4.6-6.2; AER = 12.4 per 10,000 person-years). The most common types of second malignant neoplasms were gastrointestinal cancers (n = 37), leukemia (n = 28), endocrine cancers (n = 18), and brain cancer (n = 17). Cancers in the liver (n = 11, including 9 hepatocellular carcinoma) and colorectum (n = 16) accounted for 73% of second gastrointestinal malignant neoplasms in this population. The cumulative incidence of second malignant neoplasms at 10 and 20 years from follow-up was 1.0% (95% CI = 0.8-1.2%) and 3.0% (95% CI = 2.3-3.6%), respectively. Conclusions: Childhood cancer survivors in Taiwan experience excess risk of second malignant neoplasms, in particular gastrointestinal cancers, compared with the general population.

103 Background: While survivors of childhood and young adult cancer with a history of radiation therapy (RT) to the chest are known to be at increased risk for lung cancer, whether a CT-based lung cancer screening program is appropriate for this population is unknown. We sought to describe CT findings in a clinic-based population of childhood and young adult cancer survivors. Methods: We performed a detailed review of all diagnostic chest CT scans performed among patients seen in the Adult Long-Term Follow-Up Program at Memorial Sloan Kettering between August 2005 and May 2016. Included survivors were at least 5 years from diagnosis and had a history of RT to the mediastinum, mantle, axilla, lung, thoracic spine, or total body irradiation fields. Results were reviewed by at least two authors (ET, DB, or AK) and discrepancies were resolved by consultation with a pulmonologist (RK). Results: We identified 620 survivors with a history of chest field RT who were at least 5 years from diagnosis. The population was 48% male, with a median age at diagnosis of 17.2 years. Approximately half were survivors of Hodgkin Lymphoma (N=306; 49.5%) and almost one-third had undergone hematopoietic cell transplant (N=188; 31%); other diagnoses included non-Hodgkin Lymphoma and sarcoma. The most frequently cited RT field was mantle (N=219; 36%), followed by total body irradiation (N=142; 24%) and whole lung (N=110;18%). Among 351 survivors with at least one chest CT, 206 (59%) had at least one pulmonary nodule, 174 (50%) had fibrosis, and 132 (38%) had a ground glass opacity. Among those with a pulmonary nodule, the large majority (91% of those with a nodule) were followed expectantly or underwent repeat imaging; these patients were spared biopsy or resection. Among 18 patients who underwent biopsy, wedge resection, fine needle aspiration, or bronchoscopy, 4 were diagnosed with lung adenocarcinoma, 3 with metastatic sarcoma, and one with marginal zone lymphoma (MALT). Conclusions: Benign pulmonary nodules among adults with a history of RT for childhood or young adult cancer are common. Any strategy for lung cancer screening in this population will need to account for a high likelihood of benign findings on chest CT.

110 Background: Approximately one-in-ten adult survivors of childhood cancer are underweight. While the consequences of being overweight or obese have been well-described, outcomes among underweight childhood cancer survivors are unknown. Methods: Underweight was defined as a body mass index (BMI)< 18.5 kg/m2, calculated from self-reported height and weight on either the baseline or the first follow-up questionnaire from the Childhood Cancer Survivor Study (CCSS). National Death Index provided death data and self-reported subsequent malignant neoplasm were validated by pathology report. Chi-square test was used to examine the association between underweight status (< 8.5 kg/m2 vs ≥ 18.5 kg/m2) and baseline demographic characteristics. Marginal models with generalized estimating equations were used to evaluate the associations between BMI and outcomes. Results: Of 9454 survivors (median age 35 years old, range 17-58, with an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline and had at least two years of additional follow-up. 29 of 184 deaths were among underweight survivors. In univariate analysis, underweight status was more common among females (9.1% vs 4.5 %, p=5yr, p=$20,000, p

130 Background: Susceptibility to late-occurring anthracycline-related left ventricular (LV) dysfunction is poorly understood. While higher dose of anthracyclines, radiation therapy, and younger age at exposure are relevant, heterogeneity persists. A recent report suggests that survivors with the rs2229774 retinoic acid receptor γ (RARG) variant represent a high-risk group. We sought to replicate this finding in our population of adult survivors of childhood and young adult cancer. Methods: We collected germline DNA among 455 survivors of childhood and young adult cancer seen in the Memorial Sloan Kettering Long-Term Follow-Up Programs. Participants were 48% male and more that 90% were white, non-Hispanic. Median age at diagnosis was 15 years and median time from diagnosis was 17.8 years. The most common diagnosis was Hodgkin Lymphoma (31%) followed by sarcoma (29%) and leukemia (10%). Initial genetic testing was performed using a low density SNP array (Illumina Exomearray), followed by full gene analysis by LD block testing. LV dysfunction was defined as ventricular ejection fraction less than 55%. Bonferroni-adjusted p values were used to determine significance in a multivariate model. Results: Of 455 participants, 120 did not have a history of anthracycline exposure, 1 was excluded for lack of echo data, and 17 were excluded due to poor genotyping quality control. Out of the remaining 317 participants, 41 had LV dysfunction. On initial testing, survivors with the rs2229774 variant were at lower risk for LV dysfunction (OR 0.14; 95% CI 0.02-0.99; p = 0.02), compared to survivors with other variants. Of note, the allele frequency in those without LV dysfunction was similar to reported studies and public data. In full gene analysis, those with a missense variant in ESPL1 (separase), within LD block but upstream of RARG, were at significantly increased risk of LV dysfunction (OR 5.61; 95% CI 1.48-21.3; p=0.005) compared to those without the ESPL1 variant. Conclusions: Based on these findings, rs2229774 RARG variant does not appear to confer genetic susceptibility to left ventricular dysfunction. ESPL1, a nearby candidate, may be the risk-conferring variant. Replication efforts are ongoing.

87 Background: There are currently over a million survivors of childhood, adolescent, and young adult (CAYA) cancer in the US, many of whom were treated with radiation therapy. Chest radiation with fields including the coronary arteries is a risk factor for cardiovascular disease (CVD). Of note, survivors are often unaware of this increased CVD risk or, if they are aware, do not know how to mitigate the risk. Visual aids and communicating risk in terms of absolute risk reductions are shown to improve patients’ understanding. The Institute of Medicine recommends use of decision aids to optimize patient discussions of benefits and harms of therapies. Our goal is to develop and pilot test a statin therapy risk communication tool for use in high-risk cancer survivors to improve shared decision making and patient knowledge of coronary artery disease risk. Methods: The Statin Risk Communication Tool, modeled after the validated Statin Choice decision aid, presents a pictorial representation of absolute risk of coronary heart disease risk in survivors of CAYA cancer treated with radiation to the chest. The intervention also presents data depicting absolute risk reduction of myocardial infarction with use of statins in similar risk populations (≥7.5% baseline risk). This pilot study compares the statin risk communication tool to usual care. The post-visit assessment uses Likert-like scales to explore patient perceptions of statin use, knowledge questions to assess patient understanding of the risks and benefits of using statins and the validated 16-item Decisional Conflict Scale to measure decisional satisfaction. We will also survey participants three months after introduction of the tool to ascertain statin use and attitudes towards the discussion of statins. Results: The timeline for data collection anticipates analyzable results by August 2017. Conclusions: This risk communication tool will be assessed for acceptability, knowledge enhancement, and decisional conflict. Additionally, we will gather qualitative data regarding usual care. With this information, a future randomized controlled trial across institutions could provide information on how CAYA survivors approach shared decision making with risk communication tools. Clinical trial information: NCT02895880.

108 Background: Previous reports have suggested an increased risk of Type I and Type II diabetes mellitus (DM) in childhood cancer survivors exposed to abdominal radiotherapy (RT). The mechanisms leading to DM in this population, however, remain unknown. We sought to clarify the pathophysiology leading to these derangements by performing dynamic testing of glucose and insulin in survivors previously treated with abdominal RT. Methods: Cross-sectional pilot study of 2-year survivors of childhood cancer treated with abdominal RT at Memorial Sloan Kettering between 1975 – 2009. Eligible participants were < 21 years of age at exposure to abdominal RT; those with a known diagnosis of DM or prior exposure to brain or total body RT were excluded. Survivors underwent formal 2-hour glucose tolerance testing; auto-antibodies (insulin auto-antibodies, islet cell autoantibody, glutamic acid decarboxylase) typically present in patients with Type I DM and hemoglobin A1c levels were assessed. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index. Results: 21 survivors were enrolled (male: 47.6%; median age at RT: 3.3 years; median age at study: 14.4 years [range: 8.3 – 46.9]; median time from abdominal RT: 10.7 years). Primary diagnoses included neuroblastoma (n = 15), rhabdomyosarcoma (n = 3), Wilms (n = 1), Hodgkin lymphoma (n = 1), rhabdoid tumor (n = 1). None of the participants were obese (body mass index [BMI] range: 14.7 – 23.2 kg/m2). Five participants (23.8%, 95% confidence interval: 8% – 47%) had glucose derangements at a median of 8.4 years after RT (one with impaired fasting glucose [fasting glucose ≥ 100 mg/dl) and four with impaired glucose tolerance [2-hour glucose 140-199 mg/dl]). Two additional participants with normal glucose tolerance had impaired insulin sensitivity based on an abnormal Matsuda Index and HOMA-IR. None of the participants had abnormal autoantibodies, insulinopenia, or hemoglobin A1c levels. Conclusions: These findings suggest that nonobese childhood cancer survivors treated with abdominal RT may be at high-risk for subclinical derangements of glucose and insulin. Further study is warranted in larger survivor cohorts. Clinical trial information: NCT02248779.

117 Background: Hepatic adenoma is a rare and poorly understood benign epithelial neoplasm. Because of the potential for spontaneous hemorrhage, rupture, or malignant transformation; hepatic adenoma over 5 cm require resection. In the general population, the prevalence of hepatic adenoma is estimated at 1 in 100,000 and identified predominantly in obese females on oral contraceptives. An increased risk for hepatic adenoma among adult survivors of childhood and young adult cancer has not been previously reported Methods: Cancer diagnosis and treatment, as well as demographic factors, medications, and comorbidities, were collected from the medical chart among patients with pathological confirmation of hepatic adenoma. All cases were patients diagnosed with a non-hepatic cancer before the age of 40 and seen at Memorial Sloan Kettering Cancer Center. Results: Twelve cases of hepatic adenoma were pathologically confirmed; seven patients (58%) had more than one adenoma. Eleven (92%) cases were female. The most common preceding cancer diagnosis was leukemia (N = 4; 33%). Five (42%) had undergone allogeneic hematopoietic cell transplant with total body irradiation (TBI) as part of their preconditioning regimen. Cases were not as a rule obese; median body mass index was 22.2 kg/m2 (range, 17.6-31.0 kg/m2). All eleven females had a history of current or prior hormone therapy with estrogen and progesterone; the single male case was hypogonadal as a result of radiation therapy to the testes during treatment for acute myelogenous leukemia (AML) and was receiving testosterone therapy at the time of chart review. Eight patients (67%) had hypothyroidism and two (17%) were taking anti-epileptic drugs. Only two patients (17%) were monitored radiographically following biopsy; seven patients (58%) underwent hepatic resection and three (25%) underwent embolization. No patient had significant blood loss or has been observed to undergo malignant transformation, although follow-up is ongoing. Conclusions: Adult survivors of childhood and young adult cancer, particularly females with a history of current or prior hormone therapy, may be at increased risk for hepatic adenoma. Further investigation of this potentially morbid condition is warranted.

9552 Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk for obesity, insulin resistance and increased visceral adiposity. A history of cranial radiation therapy (CRT) worsens this risk. In non-cancer populations, adherence to a Mediterranean Diet has been shown to improve metabolic parameters and risk of diabetes mellitus. Whether diet may contribute to insulin resistance and increased adiposity in ALL survivors is not known. Methods: We surveyed 117 adult survivors of childhood ALL using the Harvard Food Frequency Questionnaire. Physical activity energy expenditure (PAEE) was measured with the SenseWear Pro2 Armband. Fasting blood was obtained on all subjects and insulin resistance was estimated using the Homeostasis Model for Insulin Resistance (HOMA-IR). Visceral adiposity was measured by abdominal CT. Adherence to a Mediterranean Diet pattern was calculated using the index developed by Trichopoulou. Subjects were compared using univariate analysis. Results: Subjects were majority female (56%); 25% were minority or Hispanic white. A history of CRT was present in 15 (29%) men and 25 (38%) women. Among all subjects, greater adherence to a Mediterranean diet pattern was associated with improved HOMA-IR (p=0.14), visceral adiposity (p=0.03), subcutaneous adiposity (p=0.005), waist circumference (p=0.02), and body mass index (p=0.03) (all unadjusted analyses). The effect of adherence to a Mediterranean diet on insulin resistance was especially notable in men who did not receive CRT (p=0.06). Higher dairy intake was found to worsen HOMA-IR (p=0.014), but other individual components of the Mediterranean diet, such as low intake of meat and high intake of fruits and vegetables, were not significant. Inclusion of PAEE did not alter our findings, although higher PAEE was associated with lower body mass index. Conclusions: Adherence to a Mediterranean diet pattern, especially low consumption of dairy products, may improve insulin resistance in survivors of childhood ALL. Further study is warranted.

9586 Background: Although most childhood cancer survivors (CCS) report obtaining health care in the community, primary care physicians’ views and knowledge regarding the long-term follow-up (LTFU) care of CCS are largely unknown. Methods: Surveys were mailed to a random sample of 1,907 general internists under age 65 years from the American Medical Association Physician Masterfile in November 2011. A second mailing to non-responders is ongoing. Results: 892 (47%) physicians have responded. Respondents have practiced a median of 10 years (range: 3-20), and see a median of 70 patients/week (range: 40-100). 46% are in solo/group practice, 17% in multi-specialty practice, and 14% in academic practice. In the last five years, 53% have seen at least one CCS, 71% of whom have never received a treatment summary. 85% prefer to care for CCS in consultation with a cancer center based physician. A vignette of a 29-year-old female treated for Hodgkin lymphoma with mantle radiation at age 16 was provided and participants were asked a series of questions regarding monitoring for late effects. The percentage of responses that were concordant with available LTFU Surveillance Guidelines were: breast cancer, 29%; cardiac, 15%; thyroid, 77%; and all three recommendations, only 5%. By logistic regression, greater likelihood of concordance with at least one surveillance recommendation was associated with being female (OR=2.0 95% CI 1.3-3.1), seeing more patients/week (OR=1.4 per SD increase, 95% CI 1.1-1.7) and more years in practice (OR=1.3 per SD increase, 95% CI 1.0-1.6). The two modalities felt to be most useful for independent care of CCS by internists were access to LTFU guidelines and receiving a patient-specific care plan from the cancer center. Conclusions: Although the majority of internists are willing to follow CCS, they appear unfamiliar with the available LTFU guidelines and prefer to care for patients in collaboration with a cancer center based physician.

9509 Background: Childhood ALL survivors have an elevated risk of premature cardiovascular disease. Methods: Maximal oxygen uptake (VO2max) was measured in 118 adult survivors of childhood ALL (med...