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PURPOSE For survivors of childhood cancer treated with doxorubicin, dexrazoxane is cardioprotective for at least 5 years. However, longer-term data are lacking. METHODS Within the Children's Oncology Group and the Dana Farber Cancer Institute's Childhood Acute Lymphoblastic Leukemia Consortium, we evaluated four randomized trials of children with acute lymphoblastic leukemia or Hodgkin lymphoma, who received doxorubicin with or without dexrazoxane, and a nonrandomized trial of patients with osteosarcoma who all received doxorubicin with dexrazoxane. Cumulative doxorubicin doses ranged from 100 to 600 mg/m2 across these five trials, and dexrazoxane was administered uniformly (10:1 mg/m2 ratio) as an intravenous bolus before doxorubicin. Cardiac function was prospectively assessed in survivors from these trials, plus a matched group of survivors of osteosarcoma treated with doxorubicin without dexrazoxane. Two-dimensional echocardiograms and blood biomarkers were analyzed centrally in blinded fashion. Multivariate analyses adjusted for demographic characteristics, cumulative doxorubicin dose, and chest radiotherapy determined the differences and associations by dexrazoxane status. RESULTS From 49 participating institutions, 195 participants were assessed at 18.1 ± 2.7 years since cancer diagnosis (51% dexrazoxane-exposed; cumulative doxorubicin dose 297 ± 91 mg/m2). Dexrazoxane administration was associated with superior left ventricular fractional shortening (absolute difference, +1.4% [95% CI, 0.3 to 2.5]) and ejection fraction (absolute difference, +1.6% [95% CI, 0.0 to 3.2]), and lower myocardial stress per B-type natriuretic peptide (–6.7 pg/mL [95% CI, –10.6 to –2.8]). Dexrazoxane was associated with a reduced risk of having lower left ventricular function (fractional shortening < 30% or ejection fraction < 50%; odds ratio, 0.24 [95% CI, 0.07 to 0.81]). This protective association was primarily seen in those treated with cumulative doxorubicin doses ≥ 250 mg/m2. CONCLUSION Among young adult-aged survivors of childhood cancer, dexrazoxane was associated with a cardioprotective effect nearly 20 years after initial anthracycline exposure.

PURPOSE: Fertility discussions are an integral part of comprehensive care for pediatric, adolescent, and young adult patients newly diagnosed with cancer and are supported by national guidelines. Current institutional practices are poorly understood. METHODS: A cross-sectional survey was distributed to 220 Children's Oncology Group member institutions regarding fertility discussion practices. Descriptive statistics were calculated for all variables. The association between specific practices and selected outcomes on the basis of sex was examined via multivariable logistic regression. RESULTS: One hundred forty-four programs (65.5%) returned surveys. Of these, 65 (45.1%) reported routine discussions of fertility with all female patients and 55 (38.5%) all male patients ( P = .25). Ninety-two (63.8%) reported no specific criteria for offering females fertility preservation (FP), compared with 40 (27.7%) for males ( P < .001). Program characteristics associated with fertility discussions included reproductive endocrinology and infertility on site (females odds ratio [OR], 2.1; 95% CI, 1.0 to 4.3), discussion documentation mandate (females OR, 2.3; 95% CI, 1.0 to 5.5; males OR, 3.5; 95% CI, 1.4 to 8.7), and cumulative institution-based FP infrastructure (which included [1] routine practice of documentation, [2] template for documentation, [3] mandate for documentation, and [4] availability of FP navigation; females OR, 1.6; 95% CI, 1.1 to 2.3; males OR, 2.3; 95% CI, 1.6 to 3.4). Utilization of practices unsupported by guidelines included offering sperm banking after treatment initiation (39/135 programs; 28.9%), gonadotropin-releasing hormone analogs for ovarian suppression/FP (75/144 programs; 52.1%), ovarian tissue cryopreservation at diagnosis for patients with leukemia (19/64 programs; 29.7%), and testicular tissue cryopreservation (23/138 programs; 16.7%) not part of a clinical trial. CONCLUSION: Despite recommended guidelines, fertility discussions with patients/families before treatment initiation are not routine at Children's Oncology Group institutions. Standard criteria to determine which options should be offered to patients are more common for males than females.

PURPOSE: Young adult childhood cancer survivors (YACCSs) are often impacted by cancer-related cognitive impairment (CRCI) and psychological distress. Using the Project Forward Cohort, we evaluated the relationship between CRCI and substance use behaviors. METHODS: YACCSs were surveyed between 2015 and 2018 (N = 1,106, female = 50.8%, Hispanic = 51.5%, median age = 25.5 years). Associations between CRCI and substance use (tobacco, binge drinking, marijuana, prescription drug misuse, and e-cigarette/vaporizer) were examined in multivariate logistic or log-binomial regressions, adjusting for child at diagnosis (0-14 years), years since diagnosis, sex, race/ethnicity, cancer type, and treatment intensity. Mediation analysis was performed to determine opportunities for interventions. RESULTS: CRCI was reported by 144 (13.0%) survivors. The highest prevalence was observed in CNS cancers (25.4%) and leukemia (13.3%) survivors. After covariate adjustment, CRCI was associated with 2.26 times the odds of prior 30-day vaping (95% CI, 1.24 to 4.11; P = .007). Mediators with significant indirect effects in the CRCI-vaping relationship include depressive symptoms (Center for Epidemiological Studies Depression Scale) and having two or more cancer-related late effects ( P < .05). CONCLUSION: CRCI among YACCSs was associated with reports of vaping. Oncologists should screen for vaping behavior if CRCI is apparent. Increasing access to long-term follow-up clinics, addressing physical and mental health issues, and monitoring and educating on vaping and other substance use behaviors is recommended to improve the long-term health of YACCSs.

Adolescents and young adults (AYAs; age 15-39 years) with cancer are under-represented in cancer clinical trials because of patient, provider, and institutional barriers. Health care technology is increasingly available to and highly used among AYAs and has the potential to improve cancer care delivery. The COVID-19 pandemic forced institutions to rapidly adopt novel approaches for enrollment and monitoring of patients on cancer clinical trials, many of which have the potential for improving AYA trial participation overall. This consensus statement from the Children's Oncology Group AYA Oncology Discipline Committee reviews opportunities to use technology to optimize AYA trial enrollment and study conduct, as well as considerations for widespread implementation of these practices. The use of remote patient eligibility screening, electronic informed consent, virtual tumor boards, remote study visits, and remote patient monitoring are recommended to increase AYA access to trials and decrease the burden of participation. Widespread adoption of these strategies will require new policies focusing on reimbursement for telehealth, license portability, facile communication between electronic health record systems and advanced safeguards to maintain patient privacy and security. Studies are needed to determine optimal approaches to further incorporate technology at every stage of the clinical trial process, from enrollment through study completion.

PURPOSE: Fertility preservation (FP) services are part of comprehensive care for those newly diagnosed with cancer. The capacity to offer these services to children and adolescents with cancer is unknown. METHODS: A cross-sectional survey was sent to 220 Children's Oncology Group member institutions regarding institutional characteristics, structure and organization of FP services, and barriers to FP. Standard descriptive statistics were computed for all variables. The association between site-specific factors and selected outcomes was examined using multivariable logistic regression. RESULTS: One hundred forty-four programs (65.5%) returned surveys. Fifty-three (36.8%) reported a designated FP individual or team. Sperm banking was offered at 135 (97.8%) institutions, and testicular tissue cryopreservation at 37 (27.0%). Oocyte and embryo cryopreservation were offered at 91 (67.9%) and 62 (46.6%) institutions, respectively; ovarian tissue cryopreservation was offered at 64 (47.8%) institutions. The presence of dedicated FP personnel was independently associated with the ability to offer oocyte or embryo cryopreservation (odds ratio [OR], 4.7; 95% CI, 1.7 to 13.5), ovarian tissue cryopreservation (OR, 2.7; 95% CI, 1.2 to 6.0), and testicular tissue cryopreservation (OR, 3.3; 95% CI, 1.4 to 97.8). Only 26 (18.1%) participating institutions offered all current nonexperimental FP interventions. Barriers included cost (70.9%), inadequate knowledge or training (60.7%), difficulty characterizing fertility risk (50.4%), inadequate staffing (45.5%), and logistics with reproductive specialties (38%-39%). CONCLUSION: This study provides the most comprehensive view of the current landscape of FP infrastructure for children and adolescents with cancer and demonstrates that existing infrastructure is inadequate to offer comprehensive services to patients. We discuss modifiable factors to improve patient access to FP.

88 Background: From 1995-2016, rates of colorectal cancer (CRC) have increased among young adults (YA) under 50 years by 2% annually, despite overall rates of CRC among adults over age 65 decreasing. Unfortunately, this population is disproportionately affected by diagnosis at later stage of disease due to systematic and healthcare factors. Such late diagnoses are associated with higher symptom burden among survivors; however, symptom burden among YA early-onset CRC (EOCRC) survivors is poorly understood. The present study aims to characterize symptom burden among YA EOCRC survivors. Methods: A cross sectional survey was administered online in collaboration with a national organization for YA CRC survivors. Respondents (18-49 years) were EOCRC survivors who were 6-36 months from diagnosis/relapse. Survivors endorsed symptoms they experienced among 23 common CRC late effects. Responses were stratified by symptom duration (6-18 versus 19-36 months) to examine differences in endorsement rates among respondents. Results: Respondents (n=235) were colon (n=86) and rectal (n=149) cancer survivors, primarily male 63%, diagnosed at 32.4 years (SD=6.65), with an average of 5.1 (SD=2.57) symptoms. Overall, the most highly reported symptoms were fatigue, perceived change in appearance after treatment, and nail color changes. Comparisons of 6-18 and 19-36 months-from-diagnosis groups revealed similar symptom endorsement rates, with those 19-36 months from diagnosis endorsing constipation/diarrhea, anal bleeding, and incisional discomfort at higher rates than those 6-18 months from diagnosis. The 6-18 and 19-36 months-from-diagnosis groups carried similar symptom burdens of 4.9 (SD=2.57) and 5.1 (SD=2.58), respectively. Conclusions: YA EOCRC survivors endorse numerous symptoms that may interfere with their daily living and quality of life. Similarities in endorsement between 6-18 month and 19-36-month groups suggest symptoms may become chronic and persist beyond cancer treatment. Fortunately, many symptoms can be mitigated or prevented with proper medical and/or psychosocial intervention, patient education, and resource availability. Providers can leverage these findings in their evaluation of YA EOCRC patients during treatment and follow-up care to ensure the delivery of optimal symptom management. [Table: see text]

11026 Background: There are limited data on the extent of adolescent and young adult (AYA) education in pediatric and medical oncology fellowship programs. The purpose of this study was to assess the prevalence and content of AYA-focused training during pediatric and medical oncology fellowship and identify knowledge gaps for targeted educational curricular development. Methods: An anonymous, web-based survey for educators and trainees was developed, piloted and optimized by a study team comprising pediatric and adult oncologists. The survey contained questions on respondent demographics, AYA curriculum, provider comfort in managing specific AYA care domains, and priorities for future AYA educational content. In October 2021, email invitations containing the survey link were sent to program directors (PDs) and associate program directors (APDs) at 251 hematology/oncology fellowship programs (with 119 pediatric and 178 adult PDs/APDs) identified through the American Medical Association’s Fellowship and Residency Electronic Interactive Database Access. PDs were asked to participate and also distribute the survey to current fellows. The survey remained open for 3 months. Fisher’s exact test was used to assess for associations between discrete variables including amount of current education vs level of importance and demographic groups. Results: Respondents represented 69 programs (27%). There were 130 respondents who completed curriculum and demographic questions and 112 who completed detailed topic questions. Respondents comprised 51 PDs/APDs (32 pediatric and 19 adult) and 58 fellows (33 pediatric and 25 adult). 85% of PDs (44/51) do not have a formal AYA curriculum. Of these, 80% (35/44) offer some topic-specific lectures, while 20% (9/44) provide little/no education in any topics. For nearly all topics, at least 45% of respondents reported little/no education. Although onco-fertility and survivorship are the most frequently taught topics, 36% and 42% of respondents, respectively, reported little/no education in these areas. Substance abuse is least commonly taught. Both PDs and fellows believe that AYA topics are more important for inclusion in future curricula despite how infrequently they are currently taught (very/extremely important for inclusion vs moderate/great deal of current amount of education, p = 0.0001 for all topics). Overall, respondents indicated the most important topics for inclusion in fellowship curriculum were onco-fertility (82%), survivorship (78%), and communication (77%). Conclusions: These data highlight the large gap in hematology/oncology fellowship education in AYA topics and a paucity of formal educational curricula. Efforts are needed to provide both medical and pediatric oncology fellows with the knowledge and skills required to provide optimal care for AYAs.

71 Background: The information needs of young adult (YA) cancer survivors have been described, however, the specific needs of YA colorectal cancer (CRC) survivors are not well-documented. Characterizing the distinct unmet needs of YA CRC survivors is important given their unique cancer experience which may include an ostomy, chronic bowel symptoms, and functional deficits. The purpose of this study was to examine CRC survivors’ unmet needs across general, clinical, and psychosocial domains. Methods: An online, cross-sectional survey was administered via Facebook in collaboration with a national YA CRC patient advocacy organization. Respondents (diagnosed 18-39) endorsed areas in which they required more information on aspects of their lives that may have been affected by their cancer experience. Needs were stratified by life stage (emerging [18-29 years] and young [30-39] adulthood). Results: Respondents (n=189) were colon (40.2%) and rectal (59.8%) cancer survivors with a mean current age of 32.2 years (SD=4.6) and a mean age of 30.2 years (SD=4.3) at diagnosis. Most endorsed items per domain included: nutrition and diet (52.1%), complementary and alternative treatments (45.4%), and talking about your cancer experience with family, friends, and co-workers (36.1%). Survivors in emerging adulthood (n=80), compared with those in young adulthood (n=109), endorsed notably greater needs in: staying physically fit (57.5% versus 38.5%), complementary and alternative treatments (57.5% versus 36.7%), and advice/help about dating and intimate relationships (18.8% versus 6.4%). Conclusions: Overall, half of respondents endorsed a desire for information on nutrition and diet, staying physically fit, and complementary and alternative treatments. Differing endorsement rates by age group indicate the importance of tailored approaches. Optimal counseling, resources, and referrals specific to life stage can mitigate the unmet needs of YA CRC survivors to improve health outcomes and quality of life.[Table: see text]

34 Background: Survivors of colorectal cancer (CRC) are at risk for late effects of therapy and recurrence of cancer. With recurrence rates ranging between 30-40% (Siegal et al., 2020), consistent, survivor-focused follow-up care is needed for early detection of late effects and recurrence (Jeffery et al., 2019). CRC-related care delivery has been significantly disrupted by the SARS-CoV-2 pandemic, with decreases of 40% in CRC services in the United States between April 2020 and 2019 (Jammu, 2020). Consequentially, survivors may be left with fewer options for care, potentially causing increases in emergency room (ER) utilization. Methods: This cross-sectional study examined the patterns of ER utilization during the SARS-CoV-2 pandemic among young adult CRC survivors and assessed the relationship between self-reported care satisfaction and ER use. Eligible participants were diagnosed with colon or rectal cancer between 18-39 years, between 6-36 months from diagnosis/relapse, English speaking, and based in the United States. Questions on care satisfaction were Consumer Assessment of Healthcare Providers and Systems (CAHPS) questions. A multivariable logistic regression was conducted to assess the association between patient satisfaction and ER utilization, adjusting for factors related to the pandemic. Covariates for this analysis were chosen based on a significance of p < 0.1 at the univariate level, as well as general clinical significance. Results: The overall sample was N = 196, mean age (SD) was 32.1 years (4.5), and 116 survivors (59%) were male. Tumor location was colon or rectal in 42% and 57%, respectively, and the majority (56%) were diagnosed with stage 2 disease; 42.6% reported relapsed disease, and 20% had an ostomy. The majority of survivors (72.5%) had between 1-4 visits to an emergency room in the last 12 months and were categorized as normal users. Approximately 24.7% of the sample had greater than 4 visits to the ER in the last 12 months and were categorized as super-utilizers (Johnson et al., 2015). Colorectal cancer survivors that reported a delay in their follow-up cancer care as a result of the pandemic were two times (OR: 2.05, 95% CI 0.99, 4.24) more likely to be super-utilizers of the ER. Higher self-reported satisfaction with overall care was associated with a 13.7% (OR: 0.86, 95%CI: -0.68, 1.09) lower likelihood of being a super-utilizer. Conclusions: This study found strong associations between delays in care, self-reported care satisfaction, and being a super-utilizer of the ER during the pandemic among young adult CRC survivors off treatment. Increasing patient satisfaction and minimizing care interruptions amongst this vulnerable population may aid in mitigating over-utilization in the ER during an ongoing pandemic.

138 Background: Childhood cancer survivors (CCS) are often impacted by cancer-related cognitive impairment (CRCI), requiring long-term follow-up care. It is unknown whether survivors reporting CRCI are at higher likelihood to suffer from adverse lifestyle behaviors such as smoking and vaping. Using the Project Forward cohort, we analyzed the prevalence of CRCI and its association with substance abuse. Methods: The Project Forward study surveyed adolescent and young adult CCS between 2015 to 2018 to evaluate the quality of cancer follow-up care. Associations between self-reported CRCI and adverse lifestyle behaviors were examined in multivariable logistic regressions, adjusting for covariates: cancer type, treatment intensity, race/ethnicity, gender, and age at diagnosis. Stratified analysis by recency of latest cancer follow-up care was performed to examine its impact on the risk of substance abuse among CRCI patients. Results: The cohort comprised 1,106 CCS, with median ages of 25.5 years (IQR: 22, 29) at survey completion and 13 years (IQR: 7, 16) at diagnosis, with over half (n = 570, 51.5%) were being Hispanic. A total of 144 (13%) patients self-reported CRCI, with the highest prevalence observed among brain cancer (25.4%) and leukemia (13.3%) survivors. Cancer-related follow-ups were more frequently observed among survivors reporting CRCI, comparing to non-CRCI survivors (66.7% vs 56.9%, p = 0.030). After adjusting for confounders, survivors reporting CRCI were at higher odds to vape with e-cigarettes than those without CRCI (OR = 2.24, 95% CI = 1.24–4.09, p = 0.008). Among those who did not engage any recent cancer follow-up care (n = 455), CRCI was associated with 2.9 times the odds of vaping with e-cigarettes (OR = 2.9, 95% CI = 1.07–7.88, p = 0.037). No association was observed between CRCI and the use of cigarettes, alcohol, or marijuana. Conclusions: Vaping is more prevalent among CCS reporting CRCI, especially those who are less likely to attend follow-up care. Our data suggests the importance of encouraging long-term follow-ups to monitor adverse lifestyle behaviors in CCS experiencing cognitive symptoms and provide timely interventions.

3518 Background: Clinical guidelines indicate that oncologists should discuss potential treatment-induced infertility with patients with reproductive potential. Due to tumor location and use of multimodal therapies, young adults with colorectal cancer (CRC) are at heightened risk for treatment-related infertility. Methods: An online, cross-sectional survey was administered in collaboration with a national patient advocacy organization for young adult CRC survivors (currently under age 50). Survivors were asked to indicate if a doctor had ever talked to them about potential problems with their ability to have children after treatment and if they banked eggs/embryos (females) or sperm (males) prior to their cancer therapy. Those who reported that they did not preserve fertility were asked to indicate why ( not sure; I chose not to; I did not know this was an option; I wanted to, but could not afford it; and I wanted to, but my treatment would not allow it). Results: A total of 234 colon (N=86) or rectal (N=148) cancer survivors were included in the study (male [61.9%] and White [77.9%; table]). Most respondents were diagnosed with stage 2 cancer (55.8% colon, 61.6% rectal). Over half of male and female survivors reported that their doctor did not talk to them about problems with their ability to have children after treatment, and 75% did not bank eggs/embryos or sperm prior to their cancer therapy. Of those, over 20% endorsed ‘I wanted to, but could not afford it’ and over 20% endorsed ‘I did not know this was an option’. Conclusions: Most CRC survivors in this study reported never having a fertility discussion with their provider, suggesting that survivors are not receiving, or cannot recall, comprehensive and guideline-concordant cancer care. In addition, one-fifth were not aware of preservation options, suggesting potential healthcare and/or provider-level barriers to appropriate fertility counseling. Fertility preservation cost is another barrier to the appropriate delivery of care. Providers must ensure that patients receive timely fertility discussions covering options to preserve fertility to mitigate this late effect of cancer treatment to ensure optimal quality of life for CRC patients with reproductive potential.[Table: see text]

12066 Background: Late effects screening guidelines for survivors of childhood cancer treated with radiation therapy currently use irradiated regions (IR) rather than volumetric dosimetry (VD), which more precisely identifies organs-at-risk (OAR). We recently showed that VD reduced mean number of recommended screening diagnostic imaging studies and procedures by 37.0% per patient (p1 Here we have incorporated chemotherapy and refined volumetric dosimetry dose thresholds. Methods: This was a cross-sectional cohort study of patients (n=132) treated for cancer using computerized tomography-planned irradiation at Children’s Hospital Los Angeles from 2000-2016. For each patient, both VD and IR methods were used to determine radiation exposure to the cochlea, heart, lung, breast, and colon. Dose thresholds for VD were based on those supplied in the Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines. Relevant chemotherapy exposures were recorded. Under each method, COG Long-Term Follow-Up Guidelines were applied to determine potential chemotherapy- and radiation-related late effects and their correlative screening practices (complete audiologic evaluation, pure tone audiometry, mammogram, breast MRI, echocardiogram, pulmonary functions test, and/or colonoscopy). Identified OAR were compared using Exact McNemar’s test. Total numbers of screening practices were computed using VD and IR and compared. Results: Median age at end of treatment was 10.6 years (range 1.4-20.4). The most frequent cancer type was brain tumor (45%), followed by bone and soft tissue tumor (39%) and leukemia/lymphoma (16%). Head/brain was the most commonly irradiated region (61%), followed by abdomen (22%). Anthracyclines were received by 25% of patients at < 250 mg/m2 and by 16% at ≥ 250 mg/m2. With use of VD, fewer patients were flagged for screening for each organ of interest: cochlea (-21.3%, p

Purpose Optimal assessment methods and criteria for reporting hearing outcomes in children who receive treatment with cisplatin are uncertain. The objectives of our study were to compare different ototoxicity classification systems, to evaluate the feasibility of including otoacoustic emissions and extended high frequency audiometry, and to evaluate a central review mechanism for audiologic results for cisplatin-treated children in the cooperative group setting. Patients and Methods Eligible participants were 1 to 30 years, with planned cisplatin-containing treatment. Hearing evaluations were conducted at baseline, before each cisplatin cycle, and at the end of therapy. Audiologic results were assessed and graded by the testing audiologist and by two central review audiologists using the American Speech-Language-Hearing Association Ototoxicity Criteria (ASHA), Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE), and Brock Ototoxicity Grades (Brock). One central reviewer also used the International Society of Pediatric Oncology Ototoxicity Scale (SIOP). Results At the end of treatment, the prevalence of any degree of ototoxicity ranged from 40% to 56%, and severe ototoxicity ranged from 7% to 22%. Compared with CTCAE, SIOP detected significantly more ototoxicity ( P = .004), whereas Brock criteria detected significantly fewer patients with any or severe ototoxicity ( P < .001 for both). SIOP detected ototoxicity earlier than did the other scales. Agreement between the central reviewers and the institutional audiologist was almost perfect for ASHA and Brock, whereas the poorest agreement occurred with CTCAE. Conclusion The SIOP scale may be superior to ASHA, Brock, and CTCAE scales for classifying ototoxicity in pediatric patients who were treated with cisplatin. Future studies should evaluate inter-rater reliability of the SIOP scale.

34 Background: Incidence of colorectal cancer (CRC) in patients under 50 years of age is rising. Quality of life in survivorship is not well-described in this population. We compared health-related quality of life (HRQoL) in CRC survivors ≤ 50 years old who were 6-18 months or 19-36 months from initial diagnosis or relapse. Methods: A cross-sectional online survey was administered in collaboration with a national organization for young CRC survivors. The Functional Assessment of Cancer Therapy (FACT-C) was used to measure HRQoL, which assesses HRQoL globally, including a CRC specific scale, and emotional, physical, social, and functional well-being domains. T-tests were conducted to compare HRQoL between survivors who were 6-18 months versus 19-36 months from diagnosis/relapse. Results: This sample (n=308) had a mean age of 33.76 SD±6.68; 201 (65.3%) were male; tumor location was colon or rectal in 41.7% and 58.3%, respectively. The majority (55.23%) were diagnosed with stage 2 disease; 98.0% were non-metastatic. 42.2% experienced relapse; 25% had an ostomy. Most survivors were 6-18 months (N=189; 61.4%) from diagnosis/relapse, and key demographics and disease characteristics did not significantly differ between those who were shorter versus longer time from diagnosis/relapse. The mean global HRQoL score was 67.3 out of a possible score of 136. Across domains, scores were low, with social well-being the highest (15.15/28) and emotional well-being the lowest (11.44/24). Social well-being was significantly higher among survivors who were 6-18 months from diagnosis/relapse compared to those 19-36 months (15.98 for 6-18 months vs. 13.83 for 19-36; p

e19050 Background: Cancer clinical trials (CCTs) contribute to improving patient survival and quality of life; however, adolescents and young adults (AYAs, 15-39 years old), are underrepresented in CCTs, especially in the community setting. We aimed to identify barriers and facilitators to AYA CCT enrollment in the NCORP. Methods: We conducted 43 one-on-one semi-structured qualitative interviews with key stakeholders involved in the enrollment of AYAs across a diverse group of NCORP primary (n = 5) and affiliate (n = 10) sites. Interviews were conducted remotely by 3 trained interviewers using the Zoom platform. Stakeholders were recruited from high and low AYA enrolling sites (AYA/total site enrollments > 10% and < 3%, respectively). Stakeholders were overall NCORP Site PIs (n = 5), lead NCORP administrators (n = 4), clinical research associates (n = 11), medical and pediatric oncologists involved in the enrollment of AYAs (n = 7), regulatory research associates (n = 5), nurse navigators (n = 6), and patient advocates (n = 5). Interviews were audiotaped and transcribed. Thematic analysis was conducted to identify themes and relate them back to our primary research questions regarding barriers and facilitators to AYA CCT enrollment. Results: Stakeholder views on enrollment barriers centered on 5 main themes: (1) lack of site-level prioritization or discussion of AYA enrollment; (2) limited number of clinical trials for AYAs available nationally, with few trials opened locally; (3) insufficient resources and research staff; (4) concerns about the cost effectiveness of opening AYA trials due to low numbers of eligible patients; and (5) patient misconceptions about CCTs. Stakeholder views on enrollment facilitators centered on 3 main themes: (1) presence of an AYA program focused on increasing enrollment; (2) having a designated site AYA “champion”; and (3) having site leadership identify AYA enrollment as a priority. Stakeholders agreed that incentivizing AYA enrollments via increased reimbursement and/or study credits could potentially lead to increased enrollment. Conclusions: In addition to identifying multiple shared barriers to AYA CCT enrollment, our study also identified possible interventions for enrollment improvement, including designation of AYA “champions”, increased reimbursement for AYA enrollments, and improving AYA’s understanding of CCTs. Further studies are needed to assess the impact of interventions aimed at increasing AYA enrollment across the NCORP.

10513 Background: Dexrazoxane (DRZ) has cardioprotective effects among doxorubicin (DOX) treated childhood cancer survivors up to 5 years after therapy. However, longer-term data are lacking. Methods: P9404, P9425, P9426, and DFCI 95-01 were randomized trials of acute lymphoblastic leukemia and Hodgkin lymphoma, where patients were randomly assigned to DOX±DRZ. P9754 enrolled osteosarcoma patients who all received DOX+DRZ. In all studies, DRZ was given as an intravenous bolus before DOX (10:1mg ratio). DOX doses ranged from 100-600 mg/m2 across these 5 trials. A subset of COG institutions prospectively assessed cardiac function in long-term survivors from these trials, plus a matched group of osteosarcoma survivors treated with DOX alone. Echocardiograms (left ventricular [LV] Biplane ejection fraction [EF], shortening fraction [SF]) and blood biomarkers (b-type natriuretic peptides [BNP], N-terminal [NT] proBNP) were all analyzed centrally, with DRZ status masked. Lower LV function was defined as EF2) 17.6±2.4y since cancer diagnosis, DRZ+ participants were slightly younger (27.8 vs 29.6y, p=0.02), but baseline characteristics otherwise did not differ significantly by DRZ status. DRZ status was associated with higher FS (34.7±3.6% vs 33.4±4.3%, p=0.04) and EF (63.4±5.4% vs 61.4±5.5%, p=0.01), and lower BNP (median 10.4 pg/mL [IQR 6.0-18.0] vs 13.0 [IQR 6.0-28.2], p=0.03) and NT-proBNP (median 30.8 pg/mL [IQR 18.9-58.2] vs 47.1 [IQR 23.0-83.1], p2 (vs 2). Results from multivariate models were similar: DRZ was associated with higher SF (1.4% [95% CI 0.2, 2.6]) and EF (2.7% [95% CI 0.8, 4.6]), and reduced BNP (-4.0 pg/mL [95% CI -7.6, -0.4]) and NT-proBNP (-20.7 pg/mL [95% CI -33.5, -7.9]). Overall, DRZ was associated with a reduced risk of having lower LV function (odds ratio 0.27 [95% CI 0.08-0.96]). Conclusions: After >17y, childhood cancer survivors treated with DOX+DRZ had better LV systolic function and less myocardial wall stress compared with those treated with DOX alone. DRZ may preferentially benefit females and those treated with greater DOX doses.

Purpose Given concerns that dexrazoxane may reduce treatment efficacy, induce second cancers, and thus compromise overall survival among children, we examined long-term overall and cause-specific mortality and disease relapse rates from three randomized clinical trials. Patients and Methods Children's Oncology Group trials P9404 (T-cell acute lymphoblastic leukemia/lymphoma; n = 537), P9425 (intermediate/high-risk Hodgkin lymphoma; n = 216), and P9426 (low-risk Hodgkin lymphoma; n = 255) were conducted between 1996 and 2001. Each trial randomly assigned patients to doxorubicin with or without dexrazoxane. The dexrazoxane:doxorubicin dose ratio was 10:1, and the cumulative protocol-specified doxorubicin dose was 100 to 360 mg/m2. Dexrazoxane was given as an intravenous bolus before each doxorubicin dose. Data from all three trials were linked with the National Death Index to determine overall and cause-specific mortality by dexrazoxane status. Results Among 1,008 patients (507 received dexrazoxane) with a median follow-up of 12.6 years (range, 0 to 15.5 years), 132 died (67 received dexrazoxane). Overall mortality did not vary by dexrazoxane status (12.8% with dexrazoxane at 10 years v 12.2% without; hazard ratio [HR], 1.03; 95% CI, 0.73 to 1.45). Findings were similar when each trial was examined separately. Dexrazoxane also was not significantly associated with differential causes of death. The original cancer caused 76.5% of all deaths (HR, 0.90; 95% CI, 0.61 to 1.32) followed by second cancers (13.6% of deaths; HR, 1.24; 95% CI, 0.49 to 3.15). Specifically, dexrazoxane was not associated with deaths from acute myeloid leukemia/myelodysplasia or cardiovascular events. Conclusion Among pediatric patients with leukemia or lymphoma, after extended follow-up, dexrazoxane use did not seem to compromise long-term survival.

10007 Background: We previously reported that > 40% of children with ALL are non-adherent to 6MP, and > 52% of ALL relapses are attributable to 6MP non-adherence. The most common barrier is forgetting to take 6MP; the most common facilitator is parental vigilance. These observations informed a randomized trial to enhance 6MP adherence (COG-ACCL1033, #NCT01503632; 89 COG sites). Results are described here. Methods: The Intervention Package (IP) consisted of: i) Education; ii) 6MP schedules; iii) daily personalized text message reminders from physician to patient and caregiver, to prompt iv) directly supervised therapy (DST), with text back response by patient/caregiver. Baseline adherence was measured for 4 wks, followed by intervention for 16 wks to examine the impact of IP vs. Edu (education) on 6MP adherence (measured electronically by MEMs Cap) in all patients, ≥12yo, < 12yo. Longitudinal binomial logistic regression using generalized estimating equations was used. Missing data were handled by multiple imputation. Results: 444 patients were randomly assigned to IP (n = 230) or Edu (n = 214). Baseline characteristics (age at study: 8.6y vs 7.5y; males: 67% vs 69%; non-Hispanic whites: 40% vs 42%) and adherence rates (92% vs 94%) were comparable (except paternal education: 49% vs 38%, p = 0.04). No study arm*time interaction was found; thus, the 16-week overall mean fitted adherence rates were compared between IP and Edu, adjusting for baseline adherence, time on study, parental education. All patients: Adherence rates were marginally higher on IP (94% vs 92.5%, p = 0.09). On IP, for times with a record of text response, adherence rates were higher (94%) when compared with times with no response (89%), p = 0.002. < 12yo: Adherence rates were comparable (IP: 94.4% vs Edu: 93.7%, p = 0.5). ≥12yo: Adherence rates were significantly higher on IP (93.1% vs 90.0%, p = 0.037). ≥12yo with baseline adherence < 90%: IP had the highest impact for this subgroup (83.4% vs 74.6%, p = 0.008). Conclusions: A 16-week comprehensive intervention resulted in higher 6MP adherence rates in children with ALL who were 12y or older at study. IP was most impactful in adolescents with baseline non-adherence. Clinical trial information: #NCT01503632.

11567 Background: Preserved fertility after cancer is a priority for female survivors and their families. Embryo/oocyte cryopreservation are standard of care (SOC) for post-pubertal females. Experimental ovarian tissue cryopreservation (OTC) is the only current option for pre-pubertal girls. We surveyed COG sites about their FP infrastructure and practices. Methods: A REDcap survey was emailed to one individual previously identified as knowledgeable about FP or the Principal Investigator at each COG site. Site specific factors associated with outcomes were determined using logistic regression. All study procedures were IRB-approved. Results: Responses were received from 144 of 220 sites (65%). Discussions about fertility at diagnosis were reported as routinely held with all females “at risk” of infertility, all post pubertal females, and all females at 113 (78%), 94 (65%), and 65 (45%) of sites respectively. Embryo/oocyte cryopreservation was offered at 95 (70%) institutions and independently associated with large (>120 new patients/year) sites (OR 6.0 95%CI 1.6-22.8) and presence of a FP navigator/team (OR 4.7 95%CI 1.7-13.5). OTC was offered at 64 (48%) sites: 34 (25%) by referral to another institution, 18 (13%) under an IRB protocol, and 12 (9%) as a clinical service. OTC accessibility was associated with large sites (OR 3.2 95% CI 1.1-8.9) and a FP navigator/team (OR 3.2 95%CI 1.4-7.0). A total of 102/133 (77%) sites use gonadotropin releasing hormone analogues (GnRHa) for any indication; 90 (68%) for menstrual suppression, 75 (56%) with the goal of ovarian suppression for fertility preservation, and 27 (20%) for contraception. Conclusions: Variation in FP services exists across COG. Discussion of infertility risk is not universal. The availability of OTC at treating institutions is limited. The presence of an FP navigator/team is a modifiable factor associated with greater likelihood of accessing SOC and experimental options. Despite conflicting evidence and lack of endorsement from professional societies, GnRHa’s are commonly used for FP. These survey results suggest FP services remain inadequate but highlight opportunities for improvement and areas of needed research.

e18016 Background: The COG has previously developed a successful model in which institutional RIs are identified to champion site-level research activities and trial enrollment. In response to low participation of AYAs in COG clinical trials, the COG AYA RI Network was developed. Methods: In January 2018, the COG AYA Committee solicited nominations of AYA RIs by site Principal Investigators. The AYA RI role is focused on the following site-level activities: 1. Working with the local IRB to prioritize AYA relevant studies; 2. Developing systems for screening AYAs for enrollment; 3. Serving as a liaison with medical oncology; 4. Educating staff on disparities in AYA outcomes. Increased site-level interaction with adult NCTN groups is a goal of this initiative. Results: The network was launched in February 2018. Subsequently, 144 RIs (physicians, research staff, psychologists, administrators) from 118 demographically and geographically diverse sites have joined the initiative. To date, there have been 9 interactive webinars, with 18 presenters from diverse institutions, each attended by 60-90 RIs. Two symposia on addressing barriers to enrollment were held at COG meetings. Shared site-level barriers and facilitators to enrollment have been identified. The most common recommendations for improving AYA accrual are: 1. Increase the number and diversity of AYA trials; 2. Increase collaboration between pediatric and medical oncology; 3. Increase support and resources from institutional leadership; and 4. Overcome logistical constraints to accruing AYAs to COG trials. Recently, the COG AYA RI Network joined with the SWOG AYA Committee to identify site-level dyads involving an AYA RI representing each group. Conclusions: To our knowledge, the COG AYA RI network is a novel model for enhancing AYA-focused cooperative group research at the site level, including enrollment on clinical trials. Next steps include conducting a formal survey to gather site-level data and establishing metrics to assess impact of this initiative, as well as continuing to work closely with SWOG to improve cross-group trial enrollment of AYAs.

Purpose Patients 16 to 21 years of age with acute lymphoblastic leukemia (ALL) have an inferior outcome compared with younger children, leading some medical oncologists to advocate allogeneic stem-cell transplantation in first remission for these patients. We examined outcome for young adults with ALL enrolled onto the Children's Cancer Group (CCG) 1961 study between 1996 and 2002. Patients and Methods CCG 1961 entered patients with ALL 1 to 21 years of age with initial WBC count ≥ 50,000/μL and/or age ≥ 10 years. Randomly assigned therapies evaluated the impact of postinduction treatment intensification on outcome. We examined outcome and prognostic factors for 262 young adults with ALL. Results Five-year event-free and overall survival rates for young adult patients are 71.5% (SE, 3.6%) and 77.5% (SE, 3.3%), respectively. Rapid responder patients (< 25% bone marrow blasts on day 7) randomly assigned to augmented therapy had 5-year event-free survival of 81.8% (SE, 7%), as compared with 66.8% (SE, 6.7%) for patients receiving standard therapy (P = .07). One versus two interim maintenance and delayed intensification courses had no significant impact on event-free survival. WBC count more than 50,000/μL was an adverse prognostic factor. Conclusion Young adult patients with ALL showing a rapid response to induction chemotherapy benefit from early intensive postinduction therapy but do not benefit from a second interim maintenance and delayed intensification phase. Given the excellent outcome with this chemotherapy, there seems to be no role for the routine use of allogeneic stem-cell transplantation in first remission for young adults with ALL.

e21043 Background: Melanoma is the third most common cancer among adolescents and young adults (AYAs; aged 15-39). Disease characteristics have not been well-described in this age group, particularly among diverse populations. We describe clinical features of AYAs diagnosed with melanoma at a large public hospital serving an ethnically diverse population. Methods: We reviewed medical chart data from patients diagnosed with melanoma between 2001-2016 at Los Angeles County + USC Medical Center. We describe clinical characteristics of AYA patients and compare to non-AYAs (aged ≥40) using Fisher’s exact test. A p-value < 0.05 was considered statistically significant. Results: Of the 273 melanoma patients identified, 47 (17.3%) were AYAs (mean age 32.3; SD±4.45; lower age range 18). The majority of patients were Hispanic (AYA, 53.2%; non-AYA, 51.1%), followed by non-Hispanic whites (AYA, 38.3%; non-AYA, 38.7%). A greater proportion of AYA patients were female (59.6%) compared to non-AYAs (38.2%) (p < 0.01). No AYA patients reported prior skin cancer compared to 19.9% of non-AYAs; 8.5% of AYAs reported family history of melanoma compared to 6.3% of non-AYAs. For all patients, superficial spreading melanoma was the most common histological subtype (AYA, 21.3%; non-AYA, 20.9%). Nodular melanoma was the second most common subtype in AYAs (17.02%) in contrast to acral lentiginous melanoma among non-AYAs (20.9%). Median Breslow depth was 3.0 mm for AYAs and 2.55 mm among non-AYAs. A slightly higher percentage of AYAs were diagnosed with regional disease (31.9%) than non-AYAs (24.4%), and a greater proportion of non-AYAs presented with distant metastases (AYA, 6.4%; non-AYA, 18.7%). The most common site of diagnosis were the extremities for all patients (AYA, 45.0%; non-AYA, 29.3%). Conclusions: We found similar clinical characteristics between AYA and non-AYA melanoma patients. However, we found a statistically significant difference for gender. The increased incidence of melanoma in female AYAs may be driven by biological factors such as sex hormones or genotype, or tanning behaviors. Further research is warranted to identify predictive and prognostic factors of melanoma among diverse AYAs, particularly females.

197 Background: Because childhood cancer survivors (CCS) report a high number of unmet cancer-related information needs, knowing where CCS access information may provide insights into appropriate delivery systems to address information deficits. Active seeking of health information among CCS is associated with positive health behaviors, including adherence to follow-up care. This study examined patterns of cancer-related health information seeking as an indicator of health care engagement. Methods: Participants (N = 193) were young adult CCS diagnosed with any cancer type in Los Angeles County, 54% Hispanic, with a mean age of 19.87, and at least two years from treatment. CCS were asked where they accessed health information related to their cancer with 8 response options which were categorized into four information domains: hospital resources, social media, other survivors, and family members. Multivariable logistic regression was used to assess correlates of each information domain, including sociodemographic information, post-traumatic growth, and health care engagement, controlling for age, ethnicity, sex, education, and health insurance status. Results: Hospital resources were the most frequently endorsed information domain (65.3%), and Hispanic CCS (vs. non-Hispanic) were more likely to access this source. Online sources were more likely accessed by female CCS. Seeking information from other cancer survivors was associated with follow-up care and post-traumatic growth after cancer. Hispanic CCS were less likely to seek information from other survivors and their family than non-Hispanics. Conclusions: While CCS obtain information from a variety of sources, hospital resources were the most commonly accessed, particularly for Hispanics. Information sharing between survivors may promote positive health care engagement; however, Hispanics may be less likely to pursue this resource. Future work should address barriers Hispanic CCS face in information sharing with other cancer survivors. [Table: see text]

10058 Background: Lack of participation in clinical trials has been proposed as a key explanation for the survival deficit of AYAO patients. We compared the proportion of newly diagnosed AYAO patie...

10017 Background: Cisplatin frequently causes irreversible hearing loss in children treated for cancer. STS is a thiol reducing agent shown in preclinical studies to protect hearing but not the tum...

10024 Background: DRZ use as a cardioprotectant in pediatric oncology has been limited by concerns regarding its efficacy and possible induction of second cancers, both of which may compromise over...

10020 Background: Anthracyclines are associated with left ventricular (LV) dysfunction in CCS with inevitable progression to congestive heart failure (CHF). Use of ejection fraction (EF) to identify LV dysfunction precludes intervention, because EF decline is a late event in the progression to CHF. Further, better understanding of pathogenesis at the cellular level could facilitate development of targeted interventions. Methods: Study design: Cross-sectional; Biomarkers: Echocardiographic (echo), and blood biomarkers in asymptomatic individuals exposed to anthracyclines ≥300mg/m2 (high-risk [HR]: n=100) compared with: i) CCS exposed to 2 (low-risk [LR]: n=50): and ii) matched healthy controls (Con: n=50). Pathogenesis: Metabolomic analyses (351 plasma metabolites; 64 pathways). Results: Time from dx to study was comparable for HR (12.0y) vs. LR (13.2y, p=0.8). All CCS had EF≥50%. Echo: HR had lower LV chamber thickness-dimension (T-D) ratio (Z-score: -0.62) compared with LR (-0.03) and Con (-0.02; P2, LR: 58 g/cm2, Con: 55 g/cm2, p2 SD ESWS) had reduced plasma carnitine levels (relative ratio [RR]: 0.88, p

9506 Background: In the CCG 2961 trial for newly diagnosed AML, adolescent and young adult patients (aged 16-21 years, AYA) had inferior survival relative to younger patients. To more broadly defin...

e20009 Background: Vitamin D regulates several metabolic and hormonal pathways, which may be important in both the biology of acute lymphoblastic leukemia (ALL) and the pathogenesis of therapy-rela...

9515 Background: Drug dosing is based on a gender-independent estimate of body surface area. In childhood acute lymphoblastic leukemia (ALL), females have a consistently better event-free survival ...