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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.

Background: Although survival has improved dramatically for most adolescents and young adults (AYA; 15–39 years old) with cancer, it remains poor for those presenting with metastatic disease. To better characterize this subset, we conducted a landscape survival comparison with older adults (40–79 years). Methods: Using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, we examined incident cases of poor-prognosis metastatic cancers (5-year survival < 50%) among AYAs (n = 11,518) and older adults (n = 345,681) and compared cause-specific survival by sociodemographic characteristics (race/ethnicity, sex, and socioeconomic status). Adjusted HRs (aHR) for death from metastatic disease [95% confidence intervals (95% CI)] were compared between AYAs and older adults (Pint). Results: AYAs had significantly better survival than older adults for every cancer site except kidney, where it was equivalent (range of aHRs = 0.91; 95% CI, 0.82–1.02 for kidney cancer to aHR = 0.33; 95% CI, 0.26–0.42 for rhabdomyosarcoma). Compared with their older adult counterparts, greater survival disparities existed for AYAs who were non-Hispanic Black with uterine cancer (aHR = 2.20; 95% CI, 1.25–3.86 versus aHR = 1.40; 95% CI, 1.28–1.54; Pint = 0.049) and kidney cancer (aHR = 1.51; 95% CI, 1.15–1.98 versus aHR = 1.10; 95% CI, 1.03–1.17; Pint = 0.04); non-Hispanic Asian/Pacific Islanders with ovarian cancer (aHR = 1.47; 95% CI, 1.12–1.93 versus aHR = 0.89; 95% CI, 0.84–0.95; Pint Conclusions: AYAs diagnosed with these metastatic cancers have better survival than older adults, but outcomes remain dismal. Impact: Overcoming the impact of metastasis in these cancers is necessary for continuing progress in AYA oncology. Sociodemographic disparities affecting AYAs within kidney, uterine, ovarian, and colorectal cancer could indicate plausible effects of biology, environment, and/or access and should be explored.

Adolescent and young adult (AYA) patients with acute leukemia (AL) have inferior outcomes in comparison to younger patients, and are more likely to develop acute and chronic GVHD than younger children following HLA matched sibling donor stem cell transplant (SCT). We compared the incidence of grade II-IV acute GVHD, chronic GVHD, and survival in AYA (age 13-21 years) to younger children (age 2-12 years) who received an unrelated donor SCT for acute leukemia on Children's Oncology Group trials between 2004-2017. One hundred and eighty-eight children and young adults ages 2-21 years underwent URD SCT. Sixty-three percent were aged 2-12 and 37% were age 13-21. Older age was a risk factor for grade II-IV acute GVHD in multivariate analysis with a hazard ratio (HR) of 1.95 [95% confidence interval (CI) 1.23-3.10], but not for chronic GVHD, HR 1.25 [95% CI 0.57-2.71]. Younger patients relapsed more often (34.5 ± 4.4% vs. 22.8 ± 4.0%, p = 0.032), but their Event-Free Survival (42.6 ± 4.7% vs. 51.8 ± 6.1%, p = 0.18) and Overall Survival at 5 years (48.5 ± 4.9% vs. 51.5 ± 6.4%, p = 0.56) were not different than AYA patients. AYA patients who receive an URD SCT for acute leukemia are significantly more likely to develop grade II-IV acute GVHD, though survival is similar.

OBJECTIVE: To (1) characterize change in type of insurance coverage among childhood cancer survivors from diagnosis to survivorship and (2) examine whether insurance change is associated with cancer‐related follow‐up care utilization. DATA SOURCES: Participants in this study were derived from the Project Forward study, a population‐based, observational study of childhood cancer survivors in Los Angeles County that used California Cancer Registry data to identify participants. STUDY DESIGN: Multivariable logistic regression models incorporating survey nonresponse weights estimated the change in the marginal predicted probabilities of insurance change and survivorship care, adjusting for demographic, socioeconomic, and clinical covariates and clustering by treating hospital. DATA COLLECTION/EXTRACTION METHODS: Study participants were diagnosed with cancer who were younger than age 20 years while living in Los Angeles County from 1996 to 2010 and were older than the age 18 years at the time of survey participation, from 2015 to 2017 (N = 1106). PRINCIPAL FINDINGS: Most participants were 18–26 years of age, male, diagnosed before 2004, Hispanic/Latino race/ethnicity, single, without children, highly educated, not employed full time, and lived with their parents at survey. Almost half (N = 529) of participants experienced insurance change from diagnosis to survivorship. Insurance change was associated with insurance coverage at diagnosis, as those who were uninsured were most likely to experience change and gain coverage during survivorship (by 51 percentage points [ppt], standard error [SE] of 0.05). Survivors who experienced any change had decreased probability of reporting a recent cancer‐related follow‐up care visit, a disparity that was magnified for those who lost insurance coverage (−5 ppt, SE 0.02 for those who gained coverage; −15 ppt, SE 0.04 for those who lost coverage). CONCLUSIONS: Insurance coverage change was associated with lower cancer‐related follow‐up care utilization. Indeed, survivors who experienced any insurance coverage change had decreased probability of having a cancer‐related follow‐up care visit, and this was magnified for those who lost their insurance coverage.

Background: Younger adolescents and young adults (AYA) may receive care from either adult or pediatric oncologists. We explored patterns of care in this population and whether survival is associated with provider type. Methods: Utilizing the California Cancer Registry, we examined a cohort of 9,993 AYAs diagnosed with cancer aged 15 to 24 years from 1999 to 2008. Provider type (adult/pediatric) was determined by individual physician identifiers. For provider type, multivariable logistic regression models were adjusted for age, sex, race/ethnicity, socioeconomic status, diagnosis, and stage. For observed survival, Cox proportional hazard models were additionally adjusted for provider type. ORs and HR with 95% confidence intervals (95% CI) were determined. Results: Most patients saw adult providers (87.3% overall; 72.7% aged 15–19 years). Patients with acute leukemia, sarcoma, and central nervous system (CNS) malignancies more often saw pediatric providers [OR (95% CI) adult versus pediatric 0.48 (0.39–0.59), 0.74 (0.60–0.92), 0.76 (0.60–0.96), respectively]; those with germ cell tumors and other cancers, including carcinomas, more often saw adult providers [2.26 (1.72–2.98), 1.79 (1.41–2.27), respectively]. In aggregate and for most cancers individually, there was no survival difference by provider type [overall HR (95% CI) 1.00 (0.86–1.18)]. Higher survival was associated with pediatric providers for CNS malignancies [1.63 (1.12–2.37)] and rhabdomyosarcoma [2.22 (1.03–4.76)], and with adult providers for non-Hodgkin lymphoma [0.61 (0.39–0.96)]. Conclusions: Most AYAs 15 to 24 years old are treated by medical oncologists. In general, survival was not associated with provider type. Impact: Current patterns of care for this population support increased collaboration between medical and pediatric oncology, including joint clinical trials.

Background Survivor‐focused care for adolescent and young adult (AYA) childhood cancer survivors (CCS) often involves their parents. Recognizing the importance of parents in the ongoing care of CCS, our study sought to identify key aspects of a successful transition for CCS from pediatric‐ to adult‐centered care from the parent perspective. Methods We conducted qualitative interviews with 26 parents of CCS who were receiving care in the long‐term follow‐up (LTFU) clinic at a single institution. We used a semi‐structured interview protocol with the parents and conducted a thematic content analysis. Results Using a constant comparison approach, data revealed three primary themes regarding parents’ perspectives toward ensuring a seamless transition from pediatric‐ to adult‐centered follow‐up care: (1) the transition needs to include seamless communication between all involved parties, (2) survivors need to demonstrate sufficient health care self‐efficacy in order to achieve a successful transition, and (3) the survivor‐focused care should include support for survivors’ overall well‐being, including financial and health insurance literacy. Conclusions For parents of AYA CCS, the optimal pediatric to adult care transition model should include mechanisms that facilitate communication between parents, CCS, and survivor‐focused providers while also supporting self‐efficacy and financial literacy as it relates to health insurance., Survivor‐focused care for adolescent and young adult (AYA) childhood cancer survivors (CCS) often involves their parents. To parents, adolescent and young adult (AYA) childhood cancer survivors (CCS), the optimal pediatric to adult care transition model should include mechanisms that facilitate communication between parents, CCS, and survivor‐focused providers while also supporting self‐efficacy and financial literacy as it relates to health insurance.

Leukemia and lymphoma (LL) are the most common cancer diagnoses of childhood with high survival rates, but not without impact on the child's functioning and quality of life. This study aimed to use patient-reported data to describe the symptomatic adverse event (AE) experiences among children with LL diagnoses.Two hundred and fifty seven children and adolescents aged 7-18 years with a first LL diagnosis completed the Pediatric Patient-Reported version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE) and Patient-Reported Outcome Measurement Information System (PROMIS) Pediatric measures before starting a treatment course (T1) and after the treatment (T2).Fatigue was the most severe AE (68.1% at T1; 67% at T2) and caused the most interference over time. Gastrointestinal AEs were also quite common (e.g., nausea 46.3% at T1 and 48.9% at T2; abdominal pain 42.4% at T1; 46.5% at T2). In general, symptoms were present both at T1 and T2 and did not change significantly in severity or interference. The prevalence of AEs varied by LL disease group (e.g., nausea was most common in acute lymphoblastic leukemia (ALL), fatigue was most severe in ALL and Hodgkin Lymphoma (HL), acute myeloid leukemia had the fewest AEs).Despite current supportive care regimens, many children with LL continue to report fatigue, pain, insomnia, and gastrointestinal symptoms as the most frequent or severe symptoms during therapy.

Background Sexual health (SH) is an important concern for adolescents and young adults (AYAs). This study determined current SH communication practices, barriers, and additional resources needed among pediatric oncology clinicians who treat AYAs. Methods A cross‐sectional survey was developed by the Children's Oncology Group (COG) AYA Committee and sent to pediatric oncologists (n = 1,987; 85.9%) and advanced practice providers (APPs, n = 326; 14.1%) at 226 COG institutions. Responses were tabulated and compared using tests of proportion and trend. Results The sample comprised 602 respondents from 168 institutions and was proportionally representative (468 oncologists [77.7%], 76 APPs [12.6%], 58 unidentified [9.6%]; institutional and provider response rates 74.3% and 26.2%, respectively). Almost half of respondents (41.7%) reported no/small role in SH care. Medical topics were discussed most often, including contraception (67.2%), puberty (43.5%), and sexual activity (37.5%). Topics never/rarely discussed included gender identity (64.5%), sexual orientation (53.7%), and sexual function (50.3%). Frequently cited communication barriers included lack of time, low priority, perceived patient discomfort, and the presence of a parent/guardian. Respondents endorsed the need for further education/resources on sexual function (66.1%), gender identity/sexual orientation (59.5%), and body image (46.6%). Preferred education modalities included dissemination of published guidelines (64.7%), skills training modules (62.9%), and webinars (45.3%). By provider type, responses were similar overall but differed for perception of role, barriers identified, and resources desired. Conclusions Many pediatric oncology clinicians play minimal roles in SH care of AYAs and most SH topics are rarely discussed. Provider‐directed education/training interventions have potential for improving SH care of AYA cancer patients., In this cross‐sectional survey, pediatric oncology clinicians recognized the importance of communicating with adolescents and young adults about sexual health (SH) but reported multiple barriers related to lack of content expertise and experience. Participants identified educational resources that would enhance SH communication, including published guidelines, training curricula/modules, and webinars.

Being overweight or obese (OW/OB) during B-cell acute lymphoblastic leukemia (B-ALL) induction is associated with chemoresistance as quantified by minimal residual disease (MRD). We hypothesized that caloric and nutrient restriction from diet/exercise could lessen gains in fat mass (FM) and reduce postinduction MRD. The Improving Diet and Exercise in ALL (IDEAL) trial enrolled patients 10 to 21 years old, newly diagnosed with B-ALL (n = 40), in comparison with a recent historical control (n = 80). Designed to achieve caloric deficits ≥20% during induction, reduce fat intake/glycemic load, and increase activity, IDEAL’s end points were FM gain (primary), MRD ≥0.01%, and adherence/feasibility. Integrated biology explored biomarkers of OW/OB physiology. IDEAL intervention did not significantly reduce median FM change from baseline overall (+5.1% [interquartile range [IQR], 15.8] vs +10.7% [IQR, 16.0]; P = .13), but stratified analysis showed benefit in those OW/OB (+1.5% [IQR, 6.6] vs +9.7% [IQR, 11.1]; P = .02). After accounting for prognostic factors, IDEAL intervention significantly reduced MRD risk (odds ratio, 0.30; 95% confidence interval, 0.09-0.92; P = .02). The trial exceeded its adherence (≥75% of overall diet) and feasibility (≥80% completed visits) thresholds. Integrated biology found the IDEAL intervention increased circulating adiponectin and reduced insulin resistance. The IDEAL intervention was feasible, decreased fat gain in those OW/OB, and reduced MRD. This is the first study in any hematologic malignancy to demonstrate potential benefit from caloric restriction via diet/exercise to augment chemotherapy efficacy and improve disease response. A prospective, randomized trial is warranted for validation. These trials were registered at www.clinicaltrials.gov as #NCT02708108 (IDEAL trial) and #NCT01317940 (historical control).

Background Adolescent and young adult (AYA) patients with cancer are underrepresented on cancer clinical trials (CCTs), and most AYAs are treated in the community setting. Past research has focused on individual academic institutions, but factors impacting enrollment vary across institutions. Therefore, we examined the patterns of barriers and facilitators between high- and low-AYA enrolling community-based clinics to identify targets for intervention. Materials and Methods We conducted 34 semi-structured interviews with stakeholders employed used at National Cancer Institute Community Oncology Research Program (NCORP) affiliate sites (“clinics”). Stakeholders (eg, clinical research associates, patient advocates) were recruited from high- and low-AYA enrolling clinics. We conducted a content analysis and calculated the percentage of stakeholders from each clinic type that reported the barrier or facilitator. A 10% gap between high- and low-enrollers was considered the threshold for differences. Results Both high- and low-enrollers highlighted insufficient resources as a barrier and the presence of a patient eligibility screening process as a facilitator to AYA enrollment. High-enrolling clinics reported physician gatekeeping as a barrier and the improvement of departmental collaboration as a facilitator. Low-enrollers reported AYAs’ uncertainty regarding the CCT process as a barrier and the need for increased physician endorsement of CCTs as a facilitator. Conclusions High-enrolling clinics reported more barriers downstream in the enrollment process, such as physician gatekeeping. In contrast, low-enrolling clinics struggled with the earlier steps in the CCT enrollment process, such as identifying eligible trials. These findings highlight the need for multi-level, tailored interventions rather than a “one-size-fits-all” approach to improve AYA enrollment in the community setting.

Background Despite improvements in survival rates, cancer treatments have significant side effects that affect the quality of life of children and their families. When an ill child cannot self-report symptoms (eg, he or she is too ill), caregiver (parent) reporting becomes critical. This study evaluates the validity and reliability of the caregiver-reported Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE [Caregiver]) measure. Methods A diverse sample of caregivers with children receiving treatment at 9 oncology centers completed the Ped-PRO-CTCAE [Caregiver] measure, the Patient-Reported Outcomes Measurement Information System® (PROMIS® ) Parent Proxy measures, the Lansky Play-Performance Scale (PPS), medication use questions, and Global Impressions of Change (GIC). Construct validity (including convergent, discriminant, and known groups validity and responsiveness over time) and reliability (stability) were examined. Results A majority of the 473 caregivers were female (85%), non-Hispanic White (61%), and married (75%). Symptoms assessed with the Ped-PRO-CTCAE [Caregiver] and PROMIS Parent Proxy measures were strongly correlated (e.g., r for pain = 0.78; r for fatigue = 0.78; and r for depression = 0.83). Most of the Ped-PRO-CTCAE [Caregiver] item mean scores distinguished among PPS function levels and between children who did take medications for symptom control and children who did not. Changes in Ped-PRO-CTCAE [Caregiver] item mean scores were responsive to GIC over time. Test-retest evaluation found moderate to high agreement (57.8%-93.3%) over time. Conclusions This study found strong evidence for the convergent and discriminant validity, known groups validity, responsiveness, and stability of the Ped-PRO-CTCAE [Caregiver] measure in a large and diverse sample of caregivers. The caregiver perspective provides a valuable and unique insight into the experiences of children and adolescents undergoing cancer treatment. Lay summary Despite advances in cancer treatments, children and adolescents continue to suffer from treatment side effects, including pain, nausea, fatigue, and emotional distress, that can adversely affect quality of life for children and their families. Although it is best for children to report how they are feeling, there are times when a child may be too young or too ill to self-report. This study provides critical evidence for a new type of questionnaire that allows the caregiver or parent to report accurately what the child is experiencing. This measure can be used to improve adverse event reporting and child cancer care.

Sexual function is a vital aspect of quality of life among adolescent and young adult (AYA) (ages 15-39 years) cancer survivors. Sexual function encompasses physical, psychosocial, and developmental factors that contribute to sexual health, all of which may be negatively impacted by cancer and treatment. However, limited information is available to inform the care of AYA cancer survivors in this regard. This scoping review, conducted by the Children's Oncology Group AYA Oncology Discipline Committee, summarizes available literature regarding sexual function among AYA cancer survivors, including relevant psychosexual aspects of romantic relationships and body image. Results suggest that, overall, AYA cancer survivors experience a substantial burden of sexual dysfunction. Both physical and psychosocial sequelae influence survivors' sexual health. Interventions to support sexual health and psychosexual adjustment after cancer treatment are needed. Collaborations between the Children's Oncology Group and adult-focused cooperative groups within the National Cancer Institute's National Clinical Trials Network are warranted to advance prospective assessment of sexual dysfunction and test interventions to improve sexual health among AYA cancer survivors.

Background Radiation‐related screening guidelines for survivors of childhood cancer currently use irradiated regions (IR) to determine risk for late effects. However, contemporary radiotherapy techniques utilize volumetric dosimetry (VD) to determine organ‐specific exposures, which could inform need for late effect surveillance. Methods This cross‐sectional cohort study involved patients treated for cancer using computerized tomography‐planned irradiation at Children's Hospital Los Angeles from 2000–2016. Organs at risk were identified using both VD and IR. Under each method, Children's Oncology Group Long‐Term Follow‐Up Guidelines were applied to determine radiation‐related potential late effects and their correlative recommended screening practices. Patients served as their own controls. Mean number of potential late effects per patient and recommended screening practices per patient per decade of follow‐up were compared using paired t‐tests; comparisons were adjusted for diagnosis and gender using random effects, repeated measure linear regression. Results In this cohort (n = 132), median age at end of treatment was 10.6 years (range, 1.4–20.4). Brain tumor was the most common diagnosis (45%) and head/brain the most common irradiated region (61%). Under IR and VD, the mean number of potential late effects flagged was 24.4 and 21.7, respectively (−11.3%, p, In this cross‐sectional cohort study of 132 eligible childhood cancer survivors treated with radiation therapy, we utilized current Children's Oncology Group Long‐term Follow‐Up Guidelines to compare the recommended screening practices triggered by use of conventional radiation fields ("irradiated regions") versus the more precise approach of volumetric dosimetry. This figure shows the number of recommended screening practices per patient per decade of follow‐up, by volumetric dosimetry (VD) compared with irradiated regions (IR). Each scatter plot point represents one patient with the number of recommended screening practices as determined by IR (x‐axis) versus VD (y‐axis); patients below the dotted line had fewer screening practices triggered using VD while those above it had more. Results are shown for all patients (A); by diagnosis (BSTT=bone/soft tissue tumor, LL=leukemia and lymphoma, CNS=central nervous system tumor) (B); by gender (C); and by age at end of therapy (D) Under IR and VD, the mean number of potential late effects flagged was 24.4 and 21.7, respectively (−11.3%, p < 0.001); full concordance between the two methods was 6.1%. We found that under VD, the difference in mean number of recommended screening practices per patient was −7.4% in aggregate but as large as −37.0% for diagnostic imaging and procedures (p < 0.001 for both). Study results show that use of VD rather than IR is feasible and enhances precision of guideline‐based screening for radiation‐related late effects in long‐term childhood cancer survivors.

Purpose: In the Children's Oncology Group (COG), there is precedent for scientific committees designating institutional Responsible Investigators (RIs) to promote clinical trial enrollment and coordinate related research activities. In response to low enrollment of adolescents and young adults (AYAs) on COG clinical trials, the COG AYA RI Network was established. Leveraging this network, we undertook an initiative to identify site-level factors influencing AYA enrollment. Methods: The overarching goal of the AYA RI Network is to increase AYA enrollment onto COG trials. At each site, RIs highlight AYA disparities, facilitate activation of relevant trials, improve recruitment processes, and expand interactions with medical oncologists. Through a series of monthly national webinars and workshops, participating RIs reported local barriers and facilitators enrolling AYAs. A mixed-methods approach was utilized to determine major themes of factors affecting site-level enrollment. Results: For this report, there were 145 participating RIs representing 122 demographically and geographically diverse sites. There were 13 interactive webinars and 3 symposia involving 25 speakers focused on addressing enrollment barriers. Major thematic categories for site-level barriers were (1) Lack of available trials; (2) Poor communication between pediatric and medical oncology; (3) Logistical constraints to accessing trials; and (4) Need for leadership support, sufficient resources and appropriate policies. Conclusion: The COG AYA RI Network has identified multiple site-level barriers impeding AYA clinical trial enrollment and represents a novel model for developing and implementing appropriate solutions through a nationally coordinated strategy.

Background Few adolescents and young adults (AYAs, 15‐39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI‐designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014). Methods Using AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non‐NCICC/non‐CCOP sites from 2004 to 2013 by type of site, study period (2004‐08 vs 2009‐13), and patient demographics. Results Overall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004‐2008 and 2009‐2013 (13.1% vs 8.5%, P, From 2004‐2013, adolescents and young adults (AYA) proportional representation of AYAs on SWOG Cancer Research Network clinical trials decreased significantly across all treatment settings, including community‐based sites. Initiatives are needed to overcome barriers preventing limiting AYA trial enrollment.

Background Patient-reported outcome (PRO) measurements linked to Common Terminology Criteria for Adverse Events (CTCAE) grading may improve symptom adverse event (AE) reporting in pediatric oncology trials. We evaluated construct validity, responsiveness, and test-retest reliability of the Ped-PRO–CTCAE measurement system for children and adolescents undergoing cancer care. Methods A total of 482 children and adolescents (7–18 years, 41.5% not non-Hispanic white) newly diagnosed with cancer and their caregivers participated from nine pediatric oncology hospitals. Surveys were completed at 72 hours preceding treatment initiation (T1) and at follow-up (T2) approximately 7–17 days later for chemotherapy, and 4+ weeks for radiation. Psychometric analyses examined the relationship of Ped-PRO-CTCAE items (assessing 62 symptom AEs) with Patient-Reported Outcomes Measurement Information System, Memorial Symptom Assessment Scale, Lansky Play-Performance Scale, and medication use. A separate test-retest study included 46 children. Results Ped-PRO-CTCAE and Memorial Symptom Assessment Scale were strongly correlated across age groups at T2: 7–12 years (r = 0.62–0.80), 13–15 years (r = 0.44–0.94), and 16–18 years (r = 0.65–0.98); and over time. The Ped-PRO-CTCAE was strongly correlated with Patient-Reported Outcomes Measurement Information System Pediatric measures at T2; for example, pain interference (r = 0.70, 95% confidence interval [CI] = 0.64 to 0.76), fatigue severity (r = 0.63, 95% CI = 0.56 to 0.69), and depression severity (r = 0.76, 95% CI = 0.71 to 0.81). Ped-PRO-CTCAE items differentiated children by Lansky Play-Performance Scale and by medication use. Test-retest agreement ranged from 54.3% to 93.5%. Conclusions This longitudinal study provided evidence for the construct validity and reliability of the core Ped-PRO-CTCAE symptom AE items relative to several established measures. Additional responsiveness data with clinical anchors are recommended. Incorporation of Ped-PRO-CTCAE in trials may lead to a better understanding of the cancer treatment experience.

PURPOSE To examine concordance in symptomatic adverse event (AE) grading using the Common Terminology Criteria for Adverse Events (CTCAE 4.0) for clinicians and its patient-reported outcome (PRO) versions for children (Ped-PRO-CTCAE) and caregivers (Ped-PRO-CTCAE [Caregiver]). METHODS Children age 7-18 years with a first cancer diagnosis, their clinicians, and caregivers completed CTCAE-based measures before starting a treatment course (T1) and after the treatment (T2). Grades (0-3) were assigned by each reporter for 15 core AEs spanning physical and mental health. Mean grades were compared between reporters using two-sample t-tests; agreement was estimated using weighted kappa (κ) statistics. Multivariable mixed regression models were used to evaluate associations of clinical factors with AE reporting concordance. Significance was set at α = .05 (two-sided). RESULTS There were 438 child-clinician-caregiver triads with complete data at either T1 or T2. For children, the mean age was 13 years (standard deviation = 3.4), 53.7% were male, 32.6% non-White, and 56.4% had leukemia/lymphoma. At T1, clinician mean AE grades were significantly lower (ie, better) than children for all AEs and remained significantly lower at T2 except for constipation, nausea, anorexia, neuropathy, and anxiety. Caregiver mean AE grades were similar to children at T1 and significantly higher (ie, worse) at T2 for nausea, vomiting, anorexia, pain, fatigue, anxiety, and depression. Agreement for child-clinician grading was poor-to-fair at T1 (κ range, 0.08-0.34) and T2 (0.11-0.35), and for child-caregiver, was fair-to-good at T1 (0.34-0.65) and T2 (0.24-0.60). No factors were consistently associated with reporter concordance across AEs. CONCLUSION Compared with children, symptomatic AEs were consistently under-reported by clinicians with low agreement and over-reported by caregivers with low-moderate agreement. Direct reporting by children using Ped-PRO-CTCAE or similar measures should be routinely incorporated for toxicity assessment in clinical trials.

Adolescent and young adult (AYA) enrollment in cancer clinical trials (CCT) is suboptimal. Few studies have explored site level barriers and facilitators to AYA enrollment on CCTs and the efficacy of interventions to enhance enrollment. A cross sectional survey was developed by the COG AYA Oncology Discipline Committee Responsible Investigator (RI) Network to identify perceived barriers and facilitators to enrollment, as well as opportunities to improve enrollment. Associations of barriers and facilitators to enrollment with program demographics were assessed. The survey was sent to all AYA RI Network members (n = 143) and quantitative and thematic analyses were conducted. The overall response rate was 42% (n = 60/143). Participants represented diverse institutions based on size, presence or absence of dedicated AYA programs, and proximity and relationship between pediatric and medical oncology practices within the institution. The most frequently cited barriers to enrolling AYAs in CCTs were administrative logistical issues (45%), disparate enrollment practices (42%) and communication issues (27%) between pediatric and medical oncology and perceived limited trial availability (27%). The most frequently reported facilitators to enrollment included having strong communication between pediatric and medical oncology (48%), having a supportive research infrastructure (35%) and the presence of AYA champions (33%). Many barriers and facilitators were similar across institutions and AYA program types. Shared barriers and facilitators to AYA CCT enrollment exist across the landscape of cancer care settings. Interventions aimed at increasing coordination between pediatric and medical oncology clinical trials offices and providers have high potential to improve site-level AYA enrollment.

DNMT3A Overgrowth Syndrome (DOS, also known as Tatton-Brown Rahman Syndrome/TBRS) is one of several overgrowth syndromes with complex phenotypes caused by constitutional mutations in genes encoding epigenetic regulators. The clinical features of DOS are variable but include overgrowth (tall stature and/or obesity) and intellectual disability. DNMT3A is essential for de novo DNA methylation and plays an important role in hematopoiesis. Somatic mutations in DNMT3A are among the most common initiating mutations in normal karyotype acute myeloid leukemia (AML) patients and in elderly people with clonal hematopoiesis. The natural history of DOS has not been fully explored since the first description of this rare condition in 2014. Because of the association of somatic DNMT3A mutations and leukemia development, we assessed information from the ~200 known DOS patients world-wide and were able to document eight with hematologic malignancies. Based on this prevalence, we suggest DOS is a cancer predisposition syndrome, especially for hematologic malignancies. Using recommendations from an expert panel, we suggest DOS patients should be prospectively monitored for hematologic malignancies, which may allow for early intervention and permit its natural history to be better defined.

BackgroundChildhood cancer survivors (CCS) face increased risk of morbidity and are recommended to receive lifelong cancer-related follow-up care. Identifying factors associated with follow-up care can inform efforts to support the long-term health of CCS.MethodsEligible CCS (diagnosed between 1996 and 2010) identified through the Los Angeles County Cancer Surveillance Program responded to a self-report survey that assessed demographic, clinical, health-care engagement, and psychosocial risk and protective factors of recent (prior 2 years) cancer-related follow-up care. Weighted multivariable logistic regression was conducted to identify correlates of care. All statistical tests were 2-sided.ResultsThe overall response rate was 44.9%, with an analytical sample of n = 1106 (54.2% Hispanic; mean [SD] ages at survey, diagnosis, and years since diagnosis were 26.2 [4.9], 11.6 [5.4], and 14.5 [4.4] years, respectively). Fifty-seven percent reported a recent cancer-related visit, with lower rates reported among older survivors. Having insurance, more late effects, receipt of a written treatment summary, discussing long-term care needs with treating physician, knowledge of the need for long-term care, having a regular source of care, and higher health-care self-efficacy were statistically significantly associated with greater odds of recent follow-up care, whereas older age, Hispanic or Other ethnicity (vs non-Hispanic White), and years since diagnosis were associated with lower odds of recent care (all Ps < .05).ConclusionsAge and ethnic disparities are observed in receipt of follow-up care among young adult CCS. Potential intervention targets include comprehensive, ongoing patient education; provision of written treatment summaries; and culturally tailored support to ensure equitable access to and the utilization of care.

Background: Obesity is a known modifiable risk factor associated with adverse outcomes in children with cancer. We sought to determine whether obesity during childhood cancer treatment increases risk for second malignant neoplasms (SMN). Methods: In this case–control study, cases (with SMN) and controls (with a single-primary cancer) were selected from the California Cancer Registry who had primary cancer diagnosed Results: A total of 59 cases and 130 controls were included. Median age at primary cancer diagnosis was 6 years, 64.5% were male, median time from primary cancer to SMN was 7.5 years, and 31.7% were obese or overweight. In matched multivariable analyses, there were elevated but nonsignificant associations between SMN and higher BMI Z-score at diagnosis [OR 1.27 (0.99–1.63)] and higher BMI categories at diagnosis [adjusted OR (aOR) overweight, 1.25 (0.55–2.52); aOR obese, 2.51 (1.00–6.29)]. There was a significantly increased risk for SMN among patients who were obese at both diagnosis and EOT [aOR, 4.44 (1.37–14.34)]. Conclusions: This study suggests that obesity during childhood cancer treatment may be associated with increased risk for SMNs, particularly among those obese throughout therapy. Impact: Additional studies to confirm these findings and to develop interventions have the potential to impact SMN development in children with cancer.

Background Clinicians are the standard source for adverse event (AE) reporting in oncology trials, despite the subjective nature of symptomatic AEs. The authors designed a pediatric patient-reported outcome (PRO) instrument for symptomatic AEs to support the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) (the Pediatric PRO-CTCAE). The current study developed a standardized algorithm that maps all possible Pediatric PRO-CTCAE response patterns to recommended CTCAE grades to improve the accuracy of AE reporting in pediatric oncology trials. Methods Two rounds of surveys were administered to experienced cancer clinicians across 9 pediatric hospitals. In round 1, pediatric oncologists assigned CTCAE grades to all 101 possible Pediatric PRO-CTCAE response patterns. The authors evaluated clinician agreement of CTCAE grades across response patterns and categorized each response pattern as having high or low agreement. In round 2, a survey was sent to a larger clinician group to examine clinician agreement among a select set of Pediatric PRO-CTCAE response patterns, and the authors examined how clinical context influenced grade assignment. Results A total of 10 pediatric oncologists participated in round 1. Of the 101 possible patterns, 89 (88%) had high agreement. The Light weighted kappa was averaged across the 10 oncologists (Light kappa = 0.73; 95% CI, 0.66-0.81). A total of 139 clinicians participated in round 2. High clinician agreement remained for the majority of generic response patterns and the clinical context did not typically change grades but rather improved agreement. Conclusions The current study provides a framework for integrating child self-reported symptom data directly into mandated AE reporting in oncology trials. Translating Pediatric PRO-CTCAE responses into clinically meaningful metrics will guide future cancer care and toxicity grading.

BACKGROUND Survivors of childhood acute lymphoblastic leukemia and lymphoma (ALL/LL) are at risk for cognitive dysfunction, but little is known about its relationship with language proficiency and sociodemographics. PROCEDURE In this cross-sectional cohort study of Latino survivors of childhood ALL/LL, English and Spanish language proficiency and cognitive and academic functioning were measured and their associations determined using paired t-tests, Pearson correlations, and linear regressions. RESULTS Participants (N = 57; 50.9% female) had mean ages (years ± SD) of 4.3 ± 2.6 at diagnosis and 10.6 ± 2.9 at testing (range 6-16); mean time post treatment was 3.7 ± 2.6 years. The majority (73.7%) had low socioeconomic status (SES). Most (78.8%) were dual-language learners in English and Spanish. English proficiency was graded as limited-to-fluent and was significantly higher than Spanish (p

BACKGROUND The Lansky Play-Performance Scale (LPPS) is often used to determine a child's performance status for cancer clinical trial eligibility. Differences between clinician and caregiver LPPS ratings and their associations with child-reported functioning have not been evaluated. METHODS Children aged 7 to 18 years who were receiving cancer treatment and their caregivers were recruited from 9 pediatric cancer centers. Caregivers and clinicians reported LPPS scores, and children completed Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric functioning and symptom measures before treatment (time 1 [T1]) and after treatment (time 2 [T2]). t tests and mixed-linear models were used to assess differences in caregiver and clinician LPPS scores; polyserial correlations quantified associations between PROMIS and LPPS scores. RESULTS Of 482 children, 281 had matched caregiver- and clinician-reported LPPS T1/T2 scores. Caregivers rated children significantly worse on the LPPS than clinicians at both T1 (mean, 73.3 vs 87.4; P < .01) and T2 (mean, 67.9 vs 83.1; P < .01). These differences were not related to a child's age (P = .89), diagnosis (P = .17), or sex (P = .64) or to the time point (P = .45). Small to moderate associations existed between caregiver- and clinician-reported LPPS ratings and child-reported PROMIS scores for mobility (caregiver T1/T2 r = 0.51/0.45; P < .01; clinician T1/T2 r = 0.40/0.35; P < .01), fatigue (caregiver T1/T2 r = -0.46/-0.37; P < .01; clinician T1/T2 r = -0.26/-0.27; P < .01), and pain interference (caregiver T1/T2 r = -0.32/-0.30; P < .01; clinician T1/T2 r = -0.17/-0.31; P < .01). Caregivers and clinicians assigned significantly lower LPPS scores at T2 (caregiver Δ = -5.37; P < .01; clinician Δ = -4.20; P < .01), whereas child-reported PROMIS scores were clinically stable. CONCLUSIONS Significant differences between clinician and caregiver LPPS ratings of child performance were sustained over time; their associations with child reports were predominantly small to moderate. These data suggest that clinician-reported LPPS ratings by themselves are inadequate for determining clinical trial eligibility and should be supplemented by appropriate measures of a child's functional status reflecting the child and caregiver perspectives.

Background Although it is well documented that adolescents and young adults (AYAs) with cancer have low participation in cancer clinical trials (CCTs), the underlying reasons are not well understood. We used the National Cancer Institute Community Oncology Research Program (NCORP) network to identify barriers and facilitators to AYA CCT enrollment, and strategies to improve enrollment at community-based and minority and/or underserved sites. Methods We performed one-on-one semistructured qualitative interviews with stakeholders (NCORP site principle investigators, NCORP administrators, physicians involved in enrollment, lead clinical research associates or clinical research nurses, nurse navigators, regulatory research associates, patient advocates) in the AYA CCT enrollment process. NCORP sites that included high and low AYA–enrolling affiliate sites and were diverse in geography and department representation (eg, pediatrics, medical oncology) were invited to participate. All interviews were recorded and transcribed. Themes related to barriers and facilitators and strategies to improve enrollment were identified. Results We conducted 43 interviews across 10 NCORP sites. Eleven barriers and 13 facilitators to AYA enrollment were identified. Main barriers included perceived limited trial availability and eligibility, physician gatekeeping, lack of provider and research staff time, and financial constraints. Main facilitators and strategies to improve AYA enrollment included having a patient screening process, physician endorsement of trials, an “AYA champion” on site, and strong communication between medical and pediatric oncology. Conclusions Stakeholders identified several opportunities to address barriers contributing to low AYA CCT enrollment at community-based and minority and/or underserved sites. Results of this study will inform development and implementation of targeted interventions to increase AYA CCT enrollment.

Key Points Question In children with acute lymphoblastic leukemia receiving oral mercaptopurine, can an intervention consisting of education and daily text message reminders to prompt directly supervised therapy result in a higher proportion of patients with mercaptopurine adherence 95% or higher, compared with education alone? Findings In this parallel-group, unblinded, randomized clinical trial including 444 children with acute lymphoblastic leukemia, the proportion of patients with mercaptopurine adherence rates 95% or higher did not differ between the intervention and education groups. In exploratory analyses, children aged 12 years and older with baseline adherence less than 90% had higher mean adherence in the intervention group. Meaning This study provides evidence for limiting future trials to older children with acute lymphoblastic leukemia who have low baseline adherence to oral mercaptopurine., This randomized clinical trial examines whether a multicomponent intervention results in a higher proportion of pediatric patients with acute lymphoblastic leukemia maintaining mercaptopurine adherence rates of 95% or higher compared with education alone., Importance Suboptimal adherence to oral mercaptopurine treatment in children with acute lymphoblastic leukemia (ALL) increases the risk of relapse. A frequently expressed barrier to adherence is forgetfulness, which is often overcome by parental vigilance. Objective To determine whether a multicomponent intervention, compared with education alone, will result in a higher proportion of patients with ALL who have mercaptopurine adherence rates 95% or higher, for all study participants and among patients younger than 12 years and vs those aged 12 years and older. Design, Setting, and Participants The adherence intervention trial was an investigator-initiated, multi-institutional, parallel-group, unblinded, randomized clinical trial conducted between July 16, 2012, and August 8, 2018, at 59 Children’s Oncology Group institutions in the US, enrolling patients with ALL diagnosed through age 21 years and receiving mercaptopurine for maintenance. The date of final follow-up was January 2, 2019. Data analysis was performed from February to October 2019. Interventions Patients were randomized 1:1 to education alone or the intervention package, which consisted of education and personalized text message reminders daily to prompt directly supervised therapy. Four weeks of baseline adherence monitoring were followed with a 16-week intervention. Main Outcomes and Measures The primary end point was the proportion of patients with adherence rates 95% or higher over the duration of the intervention for all study participants, and for those younger than 12 years vs those aged 12 years and older. Results There were 444 evaluable patients (median age, 8.1 years; interquartile range, 5.3-14.3 years), including 230 in the intervention group and 214 in the education group. Three hundred two patients (68.0%) were boys, 180 (40.5%) were non-Hispanic White, 170 (38.3%) were Hispanic, 43 (9.7%) were African American, and 51 (11.5%) were Asian or of mixed race/ethnicity. The proportion of patients with adherence rates 95% or higher did not differ between the intervention vs education groups (65% vs 59%; odds ratio, 1.33; 95% CI, 1.0-2.0; P = .08). Exploratory analyses showed that among patients aged 12 years and older, those in the intervention group had higher mean (SE) adherence rates than those in the education group (93.1% [1.1%] vs 90.0% [1.3%]; difference, 3.1%; 95% CI, 0.1%-6.0%; P = .04). In particular, among patients aged 12 years and older with baseline adherence less than 90%, those in the intervention group had higher mean (SE) adherence rates than those in the education group (83.4% [2.5%] vs 74.6% [3.4%]; difference, 8.8%; 95% CI, 2.2%-15.4%; P = .008). No safety concerns were identified. Conclusions and Relevance Although this multicomponent intervention did not result in an increase in the proportion of patients with ALL who had mercaptopurine adherence rates 95% or higher, it did identify a high-risk subpopulation to target for future adherence intervention strategies: adolescents with low baseline adherence. Trial Registration ClinicalTrials.gov Identifier: NCT01503632

OBJECTIVE: The Intensity of Treatment Rating (ITR) Scale condenses treatment and clinical characteristics into a single measure to study treatment effects on downstream health outcomes across cancer types. This rating was originally developed for clinicians to determine from medical charts. However, large studies are often unable to access medical charts for all study participants. We developed and tested a method of estimating treatment intensity (TI) using cancer registry and patient self-reported data. METHODS: We estimated two versions of TI for a cohort of pediatric cancer survivors-one utilized information solely available from cancer registry variables (TI(R)) and the other included registry and self-reported information (TI(S)) from survey participants. In a subset of cases (n=135) for whom the gold standard TI (TI(C)) was known, both TI(R) and TI(S) were compared to TI(C) by calculating percent agreement and weighted Cohen’s kappa, overall and within cancer subtypes. RESULTS: In comparison to TI(C), 71% of TI scores from both methods were in agreement (k = 0.61 TIR / 0.54 TI(S)). Among subgroups, agreement ranged from lowest (46% TI(R)/39% TI(S)) for non-defined tumors (e.g. “Tumor-other”), to highest (94% TI(R)/94% TI(S)) for acute lymphoblastic leukemia (ALL). CONCLUSIONS: We developed a methodology to estimate TI for pediatric cancer research when medical chart review is not possible. High reliability was observed for ALL, the most common pediatric cancer. Additional validation is needed among a larger sample of other cancer subgroups. The ability to estimate TI from cancer registry data would assist with monitoring effects of treatment during survivorship in registry-based epidemiological studies.

Background Cisplatin-induced hearing loss (CIHL) is a common and debilitating toxicity for childhood cancer survivors. Understanding provider perspectives is crucial to developing otoprotection studies that are both informative and feasible. Two international trials (ACCL0431 and SIOPEL6) investigated the drug sodium thiosulfate (STS) as an otoprotectant, but definitive interpretation of the findings of these trials has been challenging. Adoption of STS has therefore been uneven, and provider perspectives on its role are unknown. Procedure The Children's Oncology Group (COG) Cancer Control and Supportive Care Neurotoxicity Subcommittee therefore conducted a survey of providers at COG institutions to determine perspectives on pediatric otoprotection practices and research surrounding three major themes: (1) prevalence of routine use of STS with cisplatin-based regimens, (2) application of audiometry to cisplatin therapy, and (3) preferred modalities for otoprotection research. Results Survey respondents (45%, 44/98 surveyed institutions) were of diverse institutional sizes, practice settings, and geographical locations primarily in the United States and Canada. Overall, respondents considered CIHL an important toxicity and indicated strong enthusiasm for future studies (98%, 40/41). Results indicated that while STS was the current or planned standard of care in a minority of responding institutions (36%, 16/44), most sites were receptive to its inclusion in appropriate study designs. Application of audiometry for ototoxicity monitoring varied widely across sites. For otoprotection research, systemic agents were preferred (68%, 28/41) as compared with intratympanic approaches. Conclusion These results suggest that pediatric otoprotection trials remain of interest to providers; the emphasis of these trials should remain on systemic and not intratympanic therapy.

Objective This study investigated profiles of emotional distress and growth in adolescents and young adults (AYAs) with cancer. Clinical, demographic, and psychosocial factors were examined for their potential to distinguish these profiles and predict health-related quality of life (HRQoL) of AYAs with cancer. Method This was a multicenter, longitudinal study of AYAs diagnosed with cancer at 14-39 years of age. Participants were assessed 3 times over 24 months following a baseline survey administered at diagnosis. Four profiles (resilient, resilient growth, distressed, distressed growth) were derived using published cutoff points on standardized measures of depression, anxiety, posttraumatic stress disorder, and posttraumatic growth. Mixed-effects models were used to examine profile correlates and the extent to which profiles were associated with HRQoL. Results Among 179 participants at Time 1, the proportion of profiles ranged from 18.8% for the resilient profile to 30.4% for the distressed-growth profile. These proportions remained consistent over time. Factors that appeared to distinguish these profiles included work or school status, sex, race, age at diagnosis, treatment status, prognosis, and personality characteristics. When compared to AYAs with resilient-growth profiles, HRQoL was significantly worse for AYAs reporting distressed and distressed-growth profiles, controlling for demographic, clinical, and social characteristics. Conclusion The current study found 4 patterns of psychological adjustment in AYAs with cancer. The resilient-growth profile was associated with better HRQoL, whereas distressed and distressed-growth profiles were associated with worse HRQoL. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

BACKGROUND: For several types of cancer, biological differences and outcome disparities have been documented in adolescents/young adults (AYAs, 15–39 years old) versus children. This study compared clinicopathological features and survival between younger AYAs and children with low-grade glioma (LGG), a common brain tumor among AYAs. METHODS: This was a secondary analysis of Children’s Oncology Group legacy study CCG-9891/POG-9130, which enrolled participants 0–21 years of age with newly-diagnosed LGG treated with surgery alone. For analysis, participants were categorized as children (0–14 years old) or early AYAs (eAYAs, 15–21 years old) and compared on demographics, clinical presentation, tumor characteristics, surgical outcomes, progression-free survival (PFS) and overall survival (OS). RESULTS: Among 468 children and 50 eAYAs, more eAYAs presented with seizures (34.0% vs 19.2%; p=0.015), without other significant differences in clinicopathological features. Five-year PFS rates for children and eAYA were 80.2% (95% Confidence Interval [95%CI], 76.1–83.7) and 83.0% (95%CI, 68.8–91.1), respectively; 5-year OS rates were 97.3% (95%CI, 95.2–98.5) and 95.4% (95%CI, 82.7–98.8), respectively. Multivariable analysis including all participants showed presence of residual tumor to be an independent predictor of PFS (

Ethnic and sex variations in depressive symptoms and quality of life (QOL) among adolescent and young adult (AYA) childhood cancer survivors were explored among a sample of Latino and non-Latino childhood cancer survivors (CCSs) (n = 194) treated at hospitals in Los Angeles County. Latinos scored higher in depressive symptoms and lower in QOL when compared with non-Latinos. Males had higher depressive symptoms. Among Latinos, higher levels of acculturation were associated with depression and a poorer QOL, and we found that more acculturated Latino males were more likely to have meaningful levels of depression than less acculturated males or females. Interventions addressing depressive symptoms may be most needed for Hispanic male CCSs.

Context The National Cancer Institute created the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) to allow direct input on symptomatic adverse events (AEs) from adult patients in oncology trials. Objectives This study sought to determine the youngest age to complete the PRO-CTCAE, evaluated comprehension of PRO-CTCAE among adolescents, tested new items not currently in PRO-CTCAE, and tested a parent-proxy version. Methods From seven pediatric cancer hospitals, 51 adolescents (13–20 years) receiving cancer treatment participated, along with 40 parent proxies. We evaluated 55 AEs from the PRO-CTCAE library (97 questions) and seven new AEs not in PRO-CTCAE that assess symptom frequency, severity, interference, or presence. Questions were distributed across three forms to reduce burden. Cognitive interviews with retrospective probing were completed in age groups of 13–15 and 16–20 year olds. Proxies were interviewed independently. Results In general, the 16–20 year olds and the parent proxies were able to understand and complete the PRO-CTCAE and newly designed AE questions. Five PRO-CTCAE terms (bloating of the abdomen, anxiety, flashing lights in front of your eyes, hot flashes, and bed sores) and the wording of the questions about AE severity were challenging for a few adolescents and proxies. The 13–15 year olds had greater challenges completing the PRO-CTCAE. Conclusion This study extends use of the adult PRO-CTCAE for adolescents as young as 16 years and proposes new questions for seven new symptomatic AEs and a parent-proxy version of PRO-CTCAE. Additional testing of the new questions and alternative language for more challenging PRO-CTCAE items is recommended in adults.

Adolescents with acute lymphoblastic leukemia (ALL) develop osteopenia early in therapy, potentially exacerbated by high rates of concurrent Vitamin D deficiency. We conducted a randomized clinical trial testing a Vitamin D-based intervention to improve Vitamin D status and reduce bone density decline. Poor adherence to home supplementation necessitated a change to directly observed therapy (DOT) with intermittent, high-dose Vitamin D3 randomized versus standard of care (SOC). Compared to SOC, DOT Vitamin D3 successfully increased trough Vitamin 25(OH)D levels (p = .026) with no residual Vitamin D deficiency, 100% adherence to DOT Vitamin D3, and without associated toxicity. However, neither Vitamin D status nor supplementation impacted bone density. Thus, this adherence-optimized intervention is feasible and effective to correct Vitamin D deficiency in adolescents during ALL therapy. Repletion of Vitamin D and calcium alone did not mitigate osteopenia, however, and new, comprehensive approaches are needed to address treatment-associated osteopenia during ALL therapy.

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.

Summary Background Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. Methods ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1–18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m 2 intravenously 6 h after each cisplatin dose or observation. The primary endpoint was incidence of hearing loss 4 weeks after final cisplatin dose. Hearing was measured using standard audiometry and reviewed centrally by audiologists masked to allocation using American Speech-Language-Hearing Association criteria but treatment was not masked for participants or clinicians. Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00716976. Findings Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6–43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3–69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13–0·73; p=0·0036). The most common grade 3–4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 178 participant cycles in the sodium thiosulfate group vs 145 [65%] of 224 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 149 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. Interpretation Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. Funding US National Cancer Institute.

OBJECTIVE: This case-control study compared substance use behaviors between Hispanic adolescent and young adult survivors of childhood cancers (cases) and a community sample of participants without cancer (controls). METHODS: A total of 100 cases (mean age at survey 19.9, SD=2.8), were matched 1-1 by ethnicity, age, and sex to controls (200 participants). Differences in self-reported prior 30-day use of tobacco, alcohol, binge drinking of alcohol, and marijuana were examined using conditional multivariable logistic regression. RESULTS: The odds of tobacco, alcohol, binge drinking, and marijuana use were significantly lower for cases than controls (all p’s

BACKGROUND: Adolescents and young adults (AYA) are underrepresented in cancer clinical trials (CCTs). Limited trial enrollment slows progress in improving survival rates and prevents the collection of valuable biospecimens. A systematic literature review was conducted to assess barriers and facilitators to AYA enrollment onto CCTs and identify opportunities to improve enrollment. METHODS: PubMed Medline, Web of Science, Scopus, and PsychInfo databases were searched to identify studies relevant to AYA CCT enrollment. Eligibility criteria included qualitative and/or quantitative evaluation of barriers and facilitators to AYA enrollment. RESULTS: One-hundred and fifty-five unique manuscripts were identified; 13 manuscripts were included in the final analysis. Barriers to AYA enrollment on CCTs included lack of existing trials applicable to the patient population, limited access to available CCTs, and lack of physician awareness of relevant trials. Facilitators to enrollment included optimization of research infrastructure, improving awareness of available CCTs amongst providers, and enhancing communication about CCTs between providers and patients. CONCLUSIONS: The limited available research reports institution- and patient-level barriers and facilitators to AYA CCT enrollment. Given persistent disparities in AYA enrollment, there is an urgent need to further identify the barriers and facilitators to AYA CCT enrollment to determine actionable areas for intervention.

Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. To develop a clinical practice guideline for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates to update a systematic review of randomised trials for the prevention of cisplatin-induced ototoxicity. The systematic review identified 27 eligible adult and paediatric trials that evaluated amifostine, sodium diethyldithiocarbamate or disulfiram, systemic sodium thiosulfate, intratympanic therapies, and cisplatin infusion duration. Regarding systemic sodium thiosulfate, the panel made a strong recommendation for administration in non-metastatic hepatoblastoma, a weak recommendation for administration in other non-metastatic cancers, and a weak recommendation against its routine use in metastatic cancers. Amifostine, sodium diethyldithiocarbamate, and intratympanic therapy should not be routinely used. Cisplatin infusion duration should not be altered as a means to reduce ototoxicity. Further research to determine the safety of sodium thiosulfate in patients with metastatic cancer is encouraged.

Adolescents and young adults (AYAs, 15–39 years old) are an ideal population to benefit from the ever-expanding number and variety of cancer information and health resources available via the Internet and other digital platforms. However, the ability of individual AYAs to fully utilize such resources depends on their degree of health literacy. Across the trajectory of cancer care, an important role for the oncology clinician is assisting AYAs and caregivers in accessing quality health information consistent with their level of health literacy. Working from the premise that all AYAs with cancer and their caregivers deserve to be empowered with maximal knowledge about their condition, this review provides information to assist oncology clinicians in (1) understanding the variety of contemporary online resources that are currently available, including their strengths and limitations; (2) evaluating the quality of health information; and (3) recommending specific health information resources to their AYA patients.

PURPOSE: There are limited reports describing transition of young adult childhood cancer survivors (CCS) from pediatric to adult-focused survivorship care. The purpose of this study was to characterize current transitional care practices in the United States. PROJECT DESCRIPTION: An online survey was sent to one preselected respondent at 163 Children’s Oncology Group member institutions in the United States. Data were collected about (i) the availability and type of long-term follow-up services for adult CCS and (ii) policies and procedures for transitioning. Logistic regression was used to evaluate factors related to care for CCS. RESULTS: The response rate was 60% (97/163). Eighty-one respondents (84%) represented centers with specialized pediatric-focused CCS programs. Thirty-nine percent (38/97) of programs delivered specialized transitional care for adult CCS. Adult-centered care was delivered in both pediatric (39%, 15/38) and adult oncology clinics (39%, 15/38). The most common perceived transition barriers were lack of available partnering adult providers and adult providers’ lack of knowledge regarding CCS. The larger the program in terms of new diagnoses, the more likely they were to offer formal transitional care (200: odds ratios [OR] 20.0; 95% CI 3.2, 100.0, P = 0.004). CONCLUSIONS: A variety of models are utilized for delivering care to adult CCS. Our results suggest that interventions to establish effective partnerships with adult providers on appropriate care of CCS may facilitate expanded availability of these services.

Summary Background Treatment outcomes among survivors of cancer diagnosed during adolescence and early young adulthood have not been characterised independently of survivors of cancers diagnosed during childhood. We aimed to describe chronic health conditions and all-cause and cause-specific mortality among survivors of early-adolescent and young adult cancer. Methods The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study with longitudinal follow-up of 5-year survivors diagnosed with cancer before the age of 21 years at 27 academic institutions in the USA and Canada between 1970 and 1999. We evaluated outcomes among survivors of early-adolescent and young adult cancer (aged 15–20 years at diagnosis) and survivors diagnosed at age younger than 15 years (matched on primary cancer diagnosis, including leukaemia, lymphoma, CNS tumours, neuroblastoma, Wilms tumour, soft-tissue sarcomas, and bone cancer) by comparing both groups to siblings of the same age. Mortality was ascertained with the National Death Index. Chronic health conditions were classified with the Common Terminology Criteria for Adverse Events. Standardised mortality ratios (SMRs) were estimated with age-specific, sex-specific, and calendar year-specific US rates. Cox proportional hazard models estimated hazard ratios (HRs) for chronic health conditions and 95% CIs. Findings Among 5804 early-adolescent and young adult survivors (median age 42 years, IQR 34–50) the SMR compared to the general population for all-cause mortality was 5·9 (95% CI 5·5–6·2) and among 5804 childhood cancer survivors (median age 34 years; 27–42), it was 6·2 (5·8–6·6). Early-adolescent and young adult survivors had lower SMRs for death from health-related causes (ie, conditions that exclude recurrence or progression of the primary cancer and external causes, but include the late effects of cancer therapy) than did childhood cancer survivors (SMR 4·8 [95% CI 4·4–5·1] vs 6·8 [6·2–7·4]), which was primarily evident more than 20 years after cancer diagnosis. Early-adolescent and young adult cancer survivors and childhood cancer survivors were both at greater risk of developing severe and disabling, life-threatening, or fatal (grade 3–5) health conditions than siblings of the same age (HR 4·2 [95% CI 3·7–4·8] for early adolescent and young adult cancer survivors and 5·6 [4·9–6·3] for childhood cancer survivors), and at increased risk of developing grade 3–5 cardiac (4·3 [3·5–5·4] and 5·6 [4·5–7·1]), endocrine (3·9 [2·9–5·1] and 6·4 [5·1–8·0]), and musculoskeletal conditions (6·5 [3·9–11·1] and 8·0 [4·6–14·0]) when compared with siblings of the same age, although all these risks were lower for early-adolescent and young adult survivors than for childhood cancer survivors. Interpretation Early-adolescent and young adult cancer survivors had higher risks of mortality and severe and life threatening chronic health conditions than the general population. However, early-adolescent and young adult cancer survivors had lower non-recurrent, health-related SMRs and relative risks of developing grade 3–5 chronic health conditions than childhood cancer survivors, by comparison with siblings of the same age, which were most notable more than 20 years after their original cancer. These results highlight the need for long-term screening of both childhood and early-adolescent and young adult cancer survivors. Funding National Cancer Institute and American Lebanese-Syrian Associated Charities.

The identification of preventive interventions that are safe and effective for cisplatin-induced ototoxicity is important, especially in children because hearing loss can impair speech-language acquisition development. Previous randomised trials assessed systemic drugs such as amifostine, sodium diethyldithiocarbamate or disulfiram, and sodium thiosulfate. Amifostine, sodium diethyldithiocarbamate, and disulfiram did not show hearing preservation. Paediatric trials assessing sodium thiosulfate showed efficacy in terms of hearing protection. The SIOPEL 6 trial consisted solely of patients with localised hepatoblastoma and no effects on survival were shown. In the ACCL0431 trial, which included heterogeneous patients, a post-hoc analysis showed significantly worse overall survival among patients who had disseminated disease receiving sodium thiosulfate than among controls, but not among those with localised disease. Intratympanically administered drugs have mainly been assessed in adults and include N-acetylcysteine and dexamethasone. Inconsistent effects of these drugs were identified but these studies were limited by design, small sample size, and statistical approach. Future studies of systemic drugs will need to consider the measurement of disease outcomes through study design and sample size, and ototoxicity endpoints should be harmonised to enhance comparability between trials.

BACKGROUND Low cancer clinical trial (CCT) enrollment may contribute to survival disparities affecting adolescents and young adults (AYAs) (ages 15-39 years). The objective of this study was to evaluate whether differences in CCT availability related to treatment site could explain the low CCT enrollment. METHODS This prospective, observational cohort study was conducted at an academic children's hospital and its affiliated but geographically separated adult cancer hospital within a National Cancer Institute-designated Comprehensive Cancer Center. For consecutive, newly diagnosed AYA patients, it was determined whether an appropriate CCT existed nationally, was available at the treatment site, and was used for enrollment. Proportions of AYAs in these categories were compared between sites using the chi-square test. RESULTS One hundred fifty-two consecutive AYA patients were included from the children's hospital (n = 68; ages 15-20 years) and the adult cancer hospital (n = 84; ages 18-39 years). Although there was no difference in CCT existence for individual AYA patients by site (children's hospital [36 of 68 patients; 52.9%] vs adult cancer hospital [45 of 84 patients; 53.6%]; P = .938), CCT availability was significantly lower at the adult cancer hospital (14 of 84 patients [16.7%] vs 30 of 68 [44.1%] at the children's hospital; P < .001). The proportion of AYAs enrolled was low at both sites (8 of 68 patients [11.8%] vs 6 of 84 patients [7.1%], respectively; P = .327). Fewer existing CCTs were available at the adult cancer hospital (4 of 27 patients [14.8%] vs 8 of 14 patients [57.1%], respectively), and those were directed toward solid tumors and new agents. CONCLUSIONS Efforts to improve low CCT enrollment among AYAs should be differentiated by treatment site. In the adult setting, these efforts should be aimed at improving CCT availability by overcoming site-level barriers to opening existing CCTs.

Although traditional recommendations for mononephric childhood cancer survivors are to avoid contact sports in order to protect the remaining kidney, review of available evidence suggests that the majority of renal loss is caused by accidents not involving sports. An interdisciplinary team performed a review of the English literature published from 1999 to 2012 within the PubMed, Cochrane, Google Scholar, and National Guidelines Clearinghouse databases. The level of evidence and proposed recommendations were graded according to an established rubric and GRADE criteria. Our review found that kidney loss is most commonly caused by nonsports activities such as motor vehicle accidents and falls, implying that restrictions on sports-related activity in mononephric pediatric survivors are not well supported. This favors encouraging ordinary sports and related activities without restriction in mononephric childhood cancer survivors because the known benefits of exercise outweigh the exceedingly low risk of renal loss. Accordingly, activity recommendations for mononephric patients have been revised in the most current version of the Children’s Oncology Group Long-term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers. This has important implications for this and similar populations who may now undertake individual and organized sports without undue regard for their mononephric status.

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.

Adolescents and young adults (AYAs) form a unique group of patients with newly diagnosed acute myeloid leukemia (AML). They differ in terms of disease biology, psychosocial challenges, survival, and in other important respects from children as well as from middle-aged and older adults. AYAs may be treated using pediatric protocols developed in trials composed primarily of younger patients, or using adult protocols developed in trials composed primarily of older patients. After reviewing the distinguishing characteristics of AYAs with AML, we compare and contrast the chemotherapy approaches and argue that neither the pediatric nor adult approaches may be ideally suited for AYAs and the development of AYA-specific approaches merits further consideration. We finish by putting forth ideas for future research to optimize chemotherapy treatment of AYAs with AML.

PURPOSE: Childhood cancer survivors (CCS) report high unmet information needs. This study examined the prevalence of cancer-related information-seeking among CCS, and investigated associations between information-seeking behavior and positive health outcomes such as follow-up care. METHODS: Participants (n=193) were young adult CCS diagnosed with cancer in Los Angeles County, 54% of Hispanic ethnicity, with a mean age of 19.87, in remission, and at least two years from completion of treatment. CCS were asked where they accessed health information related to their cancer with response options categorized into four information domains: hospital resources, social media, other survivors, and family members. Multivariable logistic regression was used to assess variables associated with each information domain, including sociodemographics, post-traumatic growth (i.e., reporting positive changes since cancer diagnosis), health care engagement, level of education, and health insurance status. RESULTS: Hospital resources were the most commonly accessed information domain (65.3%), and CCS of Hispanic ethnicity (vs. non-Hispanic) were more likely to access this source. Seeking information from other cancer survivors was positively associated with follow-up care and post-traumatic growth. Hispanic CCS were marginally less likely to seek information from other survivors and family than non-Hispanics. CONCLUSIONS: While CCS obtain information from a variety of sources, hospital resources are an important site for access, particularly for individuals of Hispanic ethnicity. Information sharing between survivors may promote positive health care engagement; however, Hispanic CCS may be less likely to utilize this resource and may face barriers in information sharing with other cancer survivors.

Poor enrollment of adolescents and young adults (AYAs) (ages 15-39 years) onto cancer clinical trials (CCTs) may contribute to inferior survival gains compared with children. In this study, the authors assessed whether differences in CCT availability would explain lower CCT enrollment for early AYAs (eAYAs) (ages 15-21 years).This prospective, observational cohort study was conducted at a single academic children's hospital. For consecutive patients who were newly diagnosed with cancer over a 13-month period, it was determined whether an appropriate CCT existed nationally or was available locally and whether enrollment on that CCT occurred. The proportions of eAYAs versus children in each category were compared using the chi-square test. The impact of age and other factors on enrollment status was assessed using logistic regression analysis.Among 216 patients, 58 were eAYAs, and 158 were children. There was no difference in the proportion of eAYAs versus children who had an existing CCT (28 of 58 eAYAs [48.3%] vs 85 of 158 children [53.8%]; P = .47) or an available CCT (23 of 58 eAYAs [39.7%] vs 75 of 158 children [47.5%]; P = .31). However, significantly fewer eAYAs were enrolled when a CCT was available (7 of 23 eAYAs [30.4%] vs 50 of 75 children [67.7%]; P = .002). In multivariable analysis, eAYAs were significantly less likely than children to be enrolled in an available CCT (adjusted odds ratio, 0.22; 95% confidence interval, 0.08-0.62).Equal proportions of children and eAYAs had CCTs available, but significantly fewer eAYAs were enrolled. These findings suggest that, for eAYAs, factors other than CCT availability are important enrollment barriers and should be addressed. Cancer 2018;124:983-90. © 2017 American Cancer Society.