Search

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.

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

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

Many survivors of childhood acute lymphoblastic leukemia (ALL) develop neurocognitive deficits that compromise academic functioning, especially in the presence of sociodemographic risk factors. The extent to which these risk factors coexist for Latino ALL survivors is not well described, but with shifts in U.S. demographics and improved survival in ALL, culturally competent interventions are needed. The Achieving Best Cognitive Successes after Cancer service was designed and implemented by a team representing nursing, medicine, psychology, and social work. Service components include neurocognitve assessment and individualized intervention for treatment-related risks and improving academic success for school-aged ALL survivors. Interventions are child-focused and parent-directed, recognizing that parents are major sources of support and advocates for their children within school systems. The service was designed to be culturally appropriate for the predominantly Latino patient population at our center, based on (1) linguistic competency of children and parents; (2) multicultural and ecological considerations for urban, low socioeconomic status, and migrant populations; (3) literacy barriers; and (4) contextual factors. This report describes methodological considerations and practice implications relevant to the design and implementation of similar culturally competent services for Latino pediatric cancer survivors.

BACKGROUND To evaluate tumor responses, event-free survival (EFS), overall survival (OS), and toxicity of chemotherapy, children with neurofibromatosis type 1 (NF1) and progressive low-grade glioma were enrolled into the Children's Oncology Group (COG) A9952 protocol and treated with carboplatin and vincristine (CV). METHODS Non-NF1 patients were randomized to CV or thioguanine, procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and vincristine in COG A9952. NF1 patients were assigned to CV only. NF1 patients and non-NF1 patients who were treated with CV were compared with respect to baseline characteristics, toxicity, tumor responses, EFS, and OS. RESULTS A total of 127 eligible patients with NF1 were nonrandomly assigned to CV: 42 NF1 patients (33%) had events, and 6 (4.7%) died. The 5-year EFS rate was 69% ± 4% for the CV-NF1 group and 39% ± 4% for the CV–non-NF1 group (P

Each year, 70,000 adolescents and young adults (AYAs) between ages 15 and 39 years in the United States are diagnosed with cancer. In 2006, a National Cancer Institute (NCI) Progress Review Group (PRG) examined the state of science associated with cancer among AYAs. To assess the impact of the PRG and examine the current state of AYA oncology research, the NCI, with support from the LIVESTRONG Foundation, sponsored a workshop entitled "Next Steps in Adolescent and Young Adult Oncology" on September 16 and 17, 2013, in Bethesda, Maryland. This report summarizes the findings from the workshop, opportunities to leverage existing data, and suggestions for future research priorities. Multidisciplinary teams that include basic scientists, epidemiologists, trialists, biostatisticians, clinicians, behavioral scientists, and health services researchers will be essential for future advances for AYAs with cancer.

By 2020, there will be more than 500,000 childhood cancer survivors (CCS) in the United States. CCS experience disparities in economic, social, and health‐related quality of life outcomes, and these disparities are magnified for CCS who are uninsured. Access to long‐term follow‐up (LTFU) care for surveillance, preventive care, and treatment of late effects for survivors are vital to improve long‐term outcomes. Inadequate insurance coverage, high out‐of‐pocket costs, and lack of perceived need for care have been shown to affect access to LTFU care among CCS. The objectives of this study were to (1) assess insurance instability longitudinally and describe patient factors that correlate with instability and (2) examine whether insurance instability and financial or patient factors influence access to LTFU care. Project Forward was a population‐based, observational study of CCS in Los Angeles County using California Cancer Registry (CCR) data to identify participants who completed a survey. Change in insurance coverage was assessed at diagnosis using CCR data and at survey and its impact on LTFU care. Those who experienced any change in insurance coverage (“insurance instability”) were set equal to one. Multivariable logistic regression models incorporating survey nonresponse weights were used to estimate the change in the marginal predicted probabilities of insurance instability and LTFU care, adjusted for demographic, socioeconomic, and clinical covariates and clustered by treating hospital. Study participants were diagnosed with cancer between the ages of 0 and 19 while living in Los Angeles County between 1996 and 2010 and were older than 21 at the time of survey, from 2015 to 2017 (N = 1106). Almost half (48%; N = 529) of participants experienced insurance instability from diagnosis to survivorship, while 577 did not. After adjusting for demographic, socioeconomic, and clinical covariates, the multivariable model predicting insurance instability indicated that being uninsured at diagnosis or at survey increased the probability of instability by 37% (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.

Background Adolescent and young adult (AYA) acute leukemia patients have inferior outcomes in comparison to their younger counterparts, related to higher risk disease and increased toxicity (Hochberg J, et al., BJH, 2013). AYA recipient age (≥13 years) vs children (ages 2-12 years) has been associated with increased acute and chronic graft versus host disease (GVHD) in matched sibling donor SCT (Qayed M, et al., BBMT, 2017). Objective To determine the association between recipient age (age ≥13 years vs age 2-12 years) and risk of acute grade II-IV and chronic GVHD following MUD SCT in acute leukemia recipients. Methods We reviewed all pediatric and young adult recipients receiving a MUD SCT enrolled on Children's Oncology Group clinical trials ASCT0431, AAML03P1, AAML0531, AAML1031 from 2004-present. Variables assessed included age at transplant, sex, race, performance score, leukemia type (ALL vs AML), remission (CR1 vs CR2), stem cell source, donor/recipient ABO, CMV, and sex matching, GVHD prophylaxis, year of transplant, time from diagnosis to transplant. Overall survival (OS), event-free survival (EFS), acute and chronic GVHD were assessed with Kaplan-Meier curves, cumulative incidence curves, and multivariable Cox proportional hazard models. Results Four-hundred eighty-six children and young adults underwent transplant on these trials, including 205 patients undergoing MUD SCT. For the MUD population, 8% were under age 2 years, 58% were age 2-12, and 34% were age 13-29. Seventy-one percent of patients had AML in CR1; 8% had ALL in CR1; 21% had ALL in CR2. Stem cell source included bone marrow (48%), peripheral blood stem cells (14%), and cord blood (38%). Complete HLA match in 60%, 1 allele HLA mismatch in 27%, 2+ HLA mismatches in 13%. Five-year OS and EFS rates (± standard error) for MUD were 48.4±3.8% and 44.6±3.6%, respectively. In multivariable analysis, older recipient age was associated with a significant increase in grade II-IV acute GVHD, hazard ratio or HR (95% CI) =2.03(1.28, 3.22) for age ≥13 vs age 2-12, p=0.004 (see Figure 1). HLA mismatches (≥2) were associated with grade II-IV acute GVHD, HR=2.35(1.30, 4.24) for ≥2 HLA mismatches vs matched, p=0.039 (see Figure 2). Older recipient age was not associated with chronic GVHD (p=0.83). However, significant association was found between chronic GVHD vs leukemia type and remission status (p=0.007; see Figure 3), with ALL in CR2 having more chronic GVHD than did AML in CR1 (HR=3.54(1.56, 8.03)). Acute GVHD, as expected, was a risk factor for the development of chronic GVHD (HR=2.18(1.03, 4.60), p=0.040). Conclusion Older recipient age (ages ≥13 years vs ages 2-12 years) was associated with significantly increased risk of grade II-IV acute GVHD in patients with acute leukemia following MUD SCT. Further evaluations of differential toxicity of AYA vs younger pediatric patients undergoing MUD SCT are underway.

BACKGROUND. Cisplatin-induced hearing loss (CIHL) develops in majority of children receiving cisplatin chemotherapy. Recently two phase-3 clinical trials demonstrated effectiveness of sodium thiosulfate (STS) in preventing CIHL. This study quantifies the potential economic impact of STS on cisplatin-treated children with hepatoblastoma (HB) in US. METHODS. We used an incidence-based approach to model CIHL cost for standard risk HB patients 19 yrs. Input data included: 1) estimates of incidence and survival, and age distribution of HB in US; 2) incidence of CIHL and effectiveness of STS; 3) lifelong health care and education cost and lost productivity (up to 65 yrs). Market cost of STS is unknown and not included but expected to be a small part of lifelong cost. When estimating the total and reduced costs, costs of CIHL were calculated by age and degree of CIHL severity (none, mild, severe), and the uncertainty in the input estimates were incorporated through Monte Carlo simulation. RESULTS. For a child diagnosed with HB at 1yr old and developed severe CIHL, the estimated lifelong cost is $825K ($347K health care and education cost; $478K lost productivity). Given an incidence of 0.13 cases per 100,000 in US, the annual cost of CIHL is estimated to be $16.7 million (95% CI 15.5–17.8). Assuming that all new HB patients receive STS and CIHL is reduced from 70% to 30%, the annual reduced cost in the US would be $1.81million (95% CI 1.29–2.34) after 5 years, $3.60million (95% CI 2.87–4.37) and $6.96million (95% CI 5.98–8.03), respectively, after 10 and 20 years. CONCLUSION. STS treatment could potentially lead to significant reduction in CIHL-related cost to society. Further analyses will evaluate the economic impact of STS on all childhood solid tumors, and include STS cost. Such economic impact will help inform the future clinical role of STS.

For young adults with acute lymphoblastic leukemia, pediatric-based regimens are likely to provide the following when compared to hyper-CVAD regimens: better disease control, less hospitalization time, diminished acute toxicities, decreased financial cost, more quality-adjusted life years, and fewer adverse late effects, such as infertility, myelodysplasia, and second malignant neoplasms. There are also reasons to expect less cardiac and cognitive dysfunction after pediatric regimens. The improved quality and quantity of life associated with pediatric regimens renders them preferable to hyper-CVAD regimens for the treatment of Philadelphia-negative B-precursor or T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma in young adults.

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.

Background Intensified therapy with platinum-based regimens for pediatric brain tumors has dramatically increased the number of pediatric brain tumor survivors (PBTS) but frequently causes permanent sensorineural hearing loss (SNHL). Although neurocognitive decline in PBTS is known to be associated with radiation therapy (RT), SNHL represents a potential additional contributor whose long-term impact has yet to be fully determined. Methods The neurocognitive impact of significant SNHL (Chang scale ≥ 2b) in PBTS was assessed through a retrospective cohort study of audiograms and neurocognitive testing. Scores for neurocognitive domains and subtest task performance were analyzed to identify specific strengths and weakness for PBTS with SNHL. Results In a cohort of PBTS (n = 58) treated with platinum therapy, significant SNHL was identified in more than half (55%, n = 32/58), of which the majority required hearing aids (72%, 23/32). RT exposure was approximately evenly divided between those with and without SNHL. PBTS were 6.7 ± 0.6 and 11.3 ± 0.7 years old at diagnosis and neurocognitive testing, respectively. In multivariate analyses adjusted for RT dose, SNHL was independently associated with deficits in intelligence, executive function, and verbal reasoning skills. Subtests revealed PBTS with SNHL to have poor learning efficiency but intact memory and information acquisition. Conclusions SNHL in PBTS increases the risk for severe therapy-related intellectual and neurocognitive deficits. Additional prospective investigation in malignant brain tumors is necessary to validate these findings through integration of audiology and neurocognitive assessments and to identify appropriate strategies for neurocognitive screening and rehabilitation specific to PBTS with and without SNHL.

BACKGROUND Poor accrual to cancer clinical trials may contribute to the lower improvement in survival observed for adolescents and young adults (AYAs) (those aged 15-39 years) with cancer. This has been difficult to quantify without reliable mechanisms to link incident cases with study enrollments. Using unique resources available at their National Cancer Institute-designated comprehensive cancer center, the authors compared the percentage of AYAs, children, and older adults enrolled onto cancer clinical trials and determined predictors of enrollment. METHODS Patients diagnosed with cancer from January 2008 through December 2012 at 1 pediatric and 2 adult University of Southern California hospitals were identified through the California Cancer Registry and individually linked to institutional trial enrollment databases. The availability of clinical trials was assessed. RESULTS Across the center, the enrollment percentage for AYAs (6%) was equal to that of older adults (6%), but was less than that for children (22%) (P

An 11-year-old boy with Down syndrome and acute lymphoblastic leukemia developed hepatic dysfunction after only 10 months of treatment. MRI revealed severe iron deposition in the liver, pancreas, and heart. In stark contrast to what is seen in hemoglobinopathies, pancreatic and cardiac iron overload occurred with relatively low transfusion exposure and in a very short time period in this patient. Although extensive experience managing iron overload in hemoglobinopathies informs our approach in other diseases, it is clear that factors not present in hemoglobinopathies may be operative in patients with malignancy undergoing intense chemotherapy that lead to high levels of free iron and rapid loading of the heart and endocrine organs.

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.

Background Epidemiologic studies find sex-based differences in incidence, survival, and long-term outcomes for children with cancer. The purpose of this study was to determine whether male and female patients differ with regard to acute treatment-related toxicities. Procedures We reviewed data collected on the Children's cancer group (CCG) high-risk acute lymphoblastic leukemia (ALL-HR) study (CCG-1961), and compared male and female patients' toxicity incidence and related variables in the first four phases of treatment. Similar analyses were performed with standard-risk ALL (ALL-SR) patients enrolled in CCG-1991. Results Among ALL-HR patients, females had significantly more hospital days, delays in therapy, grade 3 or 4 toxicities (e.g., gastrointestinal, liver), and supportive care interventions (e.g., transfusions, intravenous antibiotics) than males. Females were significantly more likely to have died of treatment-related causes than males (Hazard ratio = 2.8, 95%CI = 1.5–5.3, P = 0.002). Five months after beginning the treatment, the cumulative incidence of treatment-related deaths was 2.6% for females and 1.2% for males. Similar disparities were found among ALL-SR patients, with females experiencing significantly more hospital days and treatment-related toxicities than males. Conclusions This study complements cancer survivorship studies that also report an increase in treatment-related late effects among females. Risk profiles appear to be different for male and female patients, with females having greater risk of developing both acute and long-term treatment-related toxicities. The underlying biological mechanisms for these sex differences are poorly understood and warrant further study in order to determine how sex-based outcome disparities can be addressed in future clinical trials and practice. Pediatr Blood Cancer 2015;9999:1–10. © 2015 Wiley Periodicals, Inc.

While the use of targeted therapies, particularly radiosurgery, has broadened therapeutic options for CNS metastases, patients respond minimally and prognosis remains poor. The inability of many systemic chemotherapeutic agents to penetrate the blood-brain barrier (BBB) has limited their use and allowed brain metastases to become a burgeoning clinical challenge. Adequate preclinical models that appropriately mimic the metastatic process, the BBB, and blood-tumor barriers (BTB) are needed to better evaluate therapies that have the ability to enhance delivery through or penetrate into these barriers and to understand the mechanisms of resistance to therapy. The heterogeneity among and within different solid tumors and subtypes of solid tumors further adds to the difficulties in determining the most appropriate treatment approaches and methods of laboratory and clinical studies. This review article discusses therapies focused on prevention and treatment of CNS metastases, particularly regarding the BBB, and the challenges and opportunities these therapies present.

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.

Previous work in pediatric oncology has found that clinicians and parents tend to under-report the frequency and severity of treatment-related symptoms compared to child self-report. As such, there is a need to identify high-quality self-report instruments to be used in pediatric oncology research studies. This study's objective was to conduct a systematic literature review of existing English language instruments used to measure self-reported symptoms in children and adolescents undergoing cancer treatment.A comprehensive literature search was conducted in MEDLINE/PubMed, EMBASE, CINAHL, and PsycINFO to identify relevant articles published through November 10, 2016. Using pre-specified inclusion/exclusion criteria, six trained reviewers carefully screened abstracts and full-text articles for eligibility.There were 7738 non-duplicate articles identified in the literature search. Forty articles met our eligibility criteria, and within these articles, there were 38 self-report English symptom instruments. Most studies evaluated only cross-sectional psychometric properties, such as reliability or validity. Ten studies assessed an instrument's responsiveness or ability to detect changes in symptoms over time. Eight instruments met our criteria for use in future longitudinal pediatric oncology studies.This systematic review aids pediatric oncology researchers in identifying and selecting appropriate symptom measures with strong psychometric evidence for their studies. Enhancing the child's voice in pediatric oncology research studies allows us to better understand the impact of cancer and its treatment on the lives of children.

BACKGROUND: Cancer-related sexual dysfunction has been reported among adolescents and young adults (AYAs); however, its prevalence over time has not been examined. This longitudinal study investigated sexual dysfunction in AYAs over the course of 2 years after the initial diagnosis. METHODS: Young adult patients (18–39 years old) completed the Medical Outcomes Study Sexual Functioning Scale within the first 4 months of their diagnosis (n = 123) and again 6 (n = 107) and 24 months later (n = 95). An ordered multinomial response model analyzed changes in the probability of reporting sexual dysfunction over time and the independent effects of demographic, clinical, and psychosocial variables. RESULTS: More than half of the participants reported sexual functioning to be problematic at each assessment. The probability of reporting sexual dysfunction increased over time (P < .01) and was greater for cancer patients who were female (P < .001), older (P < .01), married or in a committed relationship (P < .001), treated with chemotherapy (P < .05), and reporting comorbid psychological distress (P < .001) and lower social support (P < .05). For women, being in a relationship increased the likelihood of reporting sexual problems over time; for men, the likelihood of reporting sexual problems increased regardless of their relationship status. CONCLUSIONS: A substantial proportion of young adults report ongoing problems with sexual functioning in the first 2 years after their cancer diagnosis. These findings justify the need to evaluate and monitor sexual functioning throughout a continuum of care.

Background Adverse event (AE) reporting in oncology trials is required, but current practice does not directly integrate the child's voice. The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being developed to assess symptomatic AEs via child/adolescent self-report or proxy-report. This qualitative study evaluates the child's/adolescent's understanding and ability to provide valid responses to the PRO-CTCAE to inform questionnaire refinements and confirm content validity. Procedure From seven pediatric research hospitals, children/adolescents ages 7–15 years who were diagnosed with cancer and receiving treatment were eligible, along with their parent-proxies. The Pediatric PRO-CTCAE includes 130 questions that assess 62 symptomatic AEs capturing symptom frequency, severity, interference, or presence. Cognitive interviews with retrospective probing were completed with children in the age groups of 7–8, 9–12, and 13–15 years. The children/adolescents and proxies were interviewed independently. Results Two rounds of interviews involved 81 children and adolescents and 74 parent-proxies. Fifteen of the 62 AE terms were revised after Round 1, including refinements to the questions assessing symptom severity. Most participants rated the PRO-CTCAE AE items as “very easy” or “somewhat easy” and were able to read, understand, and provide valid responses to questions. A few AE items assessing rare events were challenging to understand. Conclusions The Pediatric and Proxy PRO-CTCAE performed well among children and adolescents and their proxies, supporting its content validity. Data from PRO-CTCAE may improve symptomatic AE reporting in clinical trials and enhance the quality of care that children receive.

Obesity is associated with poorer event-free survival (EFS) in pediatric acute lymphoblastic leukemia (ALL). Persistent minimal residual disease (MRD) in the bone marrow as measured by multidimensional flow cytometry (MDF) is a key early prognostic indicator and is strongly associated with EFS. We therefore hypothesized that obesity during induction would be associated with positive end-of-induction MRD (≥0.01%). We analyzed MDF of end-induction bone marrow samples from a historical cohort of 198 children newly diagnosed with B-precursor ALL (BP-ALL) and treated with Children's Oncology Group induction regimens. We assessed the influence of body mass index on risk for positive end-induction MRD in the bone marrow. In our cohort of BP-ALL, 30 children (15.2%) were overweight and 41 (20.7%) were obese at diagnosis. Independent of established predictors of treatment response, obesity during induction was associated with significantly greater risk for persistent MRD (odds ratio, 2.57; 95% confidence interval, 1.19 to 5.54; P = .016). Obesity and overweight were associated with poorer EFS irrespective of end-induction MRD (P = .012). Obese children with newly diagnosed BP-ALL are at increased risk for positive end-induction MRD and poorer EFS.

BACKGROUND Follow-up care is critical for childhood cancer survivors (CCS), who are at high risk for comorbidities and late effects of cancer treatments. Understanding the factors associated with maintaining follow-up care is needed, especially for Hispanic CCS, who have been under-represented in previous studies. METHODS Risk factors and protective factors for receiving cancer-related follow-up care were examined among 193 Los Angeles County CCS diagnosed between 2000 and 2007 (54% Hispanic; mean ± standard deviation age, 19.9 ± 2.8 years; age at diagnosis, 12.1 ± 3.0 years; time since diagnosis, 7.8 ± 2.0 years). Self-report surveys were used to assess follow-up care, insurance status, demographics, clinical factors, and psychosocial risk (eg, depression) and protective (eg, self-efficacy [SE]) factors. Multivariable logistic regression was used to identify factors associated with the previous receipt of cancer-related follow-up care (in prior 2 years) and the intent to seek future cancer-related follow-up care. RESULTS Seventy-three percent of CCS reported a cancer follow-up visit in the previous 2 years, which was positively associated (P

Background: Childhood cancer survivors (CCS) receiving packed red blood cell (PRBC) transfusions may have increased risk for vital organ iron deposition causing serious late effects. Methods: This cross-sectional cohort study of a CCS cohort quantified organ iron content by magnetic resonance imaging. Iron status by serum markers and hemochromatosis gene mutation status were assessed. Results: Seventy-five patients who had received a range (0–392 mL/kg) of cumulative PRBC transfusion volumes were enrolled (median age 14 years, range 8–25.6 years at evaluation). Median follow-up time was 4.4 years, and median time since last transfusion was 4.9 years. Cancer diagnoses included acute lymphoblastic or myelogenous leukemia (ALL/AML; n = 33) and solid tumors (n = 42). Liver and pancreatic iron concentrations were elevated in 36 of 73 (49.3%) and 19 of 72 (26.4%) subjects, respectively. Cardiac iron concentration was not increased in this cohort. In multivariate analysis, cumulative PRBC volume (P < 0.0001) and older age at diagnosis (P < 0.0001) predicted elevated liver iron concentration. Conclusions: Iron overload (IO) may occur in children and adolescents/young adults treated for cancer and is associated with cumulative PRBC transfusion volume and age at diagnosis. Impact: These findings have implications for development of monitoring and management guidelines for cancer patients and survivors at risk for IO, exploration of the additive risk of liver/pancreatic damage from chemotherapeutic exposures, and health education to minimize further liver/pancreatic damage from exposures such as excessive alcohol intake and hepatotoxic medications. Cancer Epidemiol Biomarkers Prev; 23(9); 1913–9. ©2014 AACR.

BACKGROUND Thyroid cancer is one of the 5 most common malignancies in adolescent and young adult (AYA) patients (ages 15-39 years) and may develop de novo or in patients previously treated for cancer. This study compared the tumor characteristics, treatment, and overall survival (OS) of secondary malignant neoplasm (SMN) versus primary thyroid cancer in AYA patients. METHODS All cases of AYA thyroid cancer contained in the 1998 to 2010 American College of Surgeons National Cancer Database were divided into 2 cohorts according to primary or secondary occurrence. Comparisons using appropriate statistical methods were performed. RESULTS Of 41,062 cases, 1349 (3.3%) had experienced a prior malignancy. Compared with cases of primary thyroid cancer, SMNs were more likely multifocal (odds ratio [OR] = 1.173, 95% confidence interval [CI] = 1.049-1.313) microcarcinomas 4 cm in size (OR = 0.610, 95% CI = 0.493-0.758). There was a 6.63-fold (95% CI = 4.97-8.86, P

Background Abnormalities in pulmonary function tests (PFT) and clinical symptoms have been reported in up to one third of patients with Hodgkin lymphoma (HL) treated with irradiation. The purpose of this study is to describe the prevalence of pulmonary complications in HL patients treated using contemporary protocols. Procedures Eligible patients at Children's Hospital Los Angeles from 1999 to 2009 were identified from the radiation oncology database. Clinical features, radiographic findings, PFT, and radiation details were retrospectively ascertained. Results The median age at diagnosis of 65 patients with HL was 13.6 years and the median follow-up was 3.7 years. The median prescribed radiation dose was 21 Gy. The prevalence of clinical symptoms was low: chronic cough (3%), dyspnea (9.2%), and supplemental oxygen requirement (1.5%). Radiological interstitial lung changes were observed in 31% of the patients. PFT results following irradiation were available in 38 patients. Forced expiratory volume in 1 second (FEV1) and forced expiratory flow 25–75% (FEF25–75%) were decreased in 13% and 11% of patients respectively. Residual volume (RV) was elevated in 21%. Total Lung capacity (TLC) was decreased in 8%. Age at irradiation (P = 0.004), maximum lung dose (P = 0.03), and volume of lung receiving >25 Gy were associated with development of adverse pulmonary outcomes on univariate analysis. On multivariate analysis, older age was associated with worse outcomes. Conclusion In survivors of pediatric HL, involved field irradiation was accompanied by a low prevalence of pulmonary symptoms but substantial subclinical dysfunction. Older age at irradiation was associated with worse pulmonary outcomes. Pediatr Blood Cancer 2014;61:1277–1281. © 2014 Wiley Periodicals, Inc.

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.

The financial impact of cancer treatment among adolescents and young adults (AYAs, 15-39 years) is deep and long lasting. Compared with other age groups, because of their life stage, AYAs are particularly vulnerable to the adverse economic effects of cancer treatment, also known as financial toxicity. Clinical manifestations of cancer-related financial toxicity include interrupted work and income loss, accumulated debt, treatment nonadherence, avoidance of medical care, and social isolation. Effective clinical interventions should include efforts to increase financial self-efficacy as well as direct support. Measures that are valid, reliable, multidimensional, and age-appropriate are needed to study and address financial toxicity in the AYA population.

Background Anthracycline agents are used for treatment of acute myeloid leukemia (AML) but may cause late-onset cardiomyopathy. Current frontline therapy for AML in North America, as reflected in the approach of the Children's Oncology Group (COG) and other pediatric consortia, is adapted from the anthracyline-intensive Medical Research Council (MRC) regimen. The purpose of this study was to describe early post-treatment cardiac function as a potential indicator of acute and long-term risk associated with this approach. Procedure A multi-center retrospective cohort analysis was conducted of AML survivors diagnosed from 2004 to 2009 and treated with MRC-based regimens. Change in left ventricular shortening fraction (LVSF) on echocardiogram was determined from baseline to latest post-treatment/pre-relapse value; associations with potential predictors were examined. Results This cohort of pediatric survivors (n = 52) was assessed at a median interval of 13 months from end of treatment. Mean cumulative anthracycline dose was 339 ± 14 mg/m2. Mean baseline and post-treatment LVSF were 39.3 ± 0.8% and 35.4 ± 0.9%, respectively; mean percent change for individuals was −8.4 ± 2.8% (P

By several measures, adolescents and young adults (AYAs, age 15–39 years) represent the population segment at greatest risk for economic calamity. In particular, AYAs with cancer face numerous financial challenges that pose barriers to their receipt of appropriate and timely medical care. The health-related financial issues examined in this chapter include employment, health insurance, out-of-pocket expenses, and selected health-related quality-of-life issues that may influence them (e.g., education and marital status). For purposes of this discussion, the AYA population is divided into two groups, the younger adolescent (less than 18 years old) and the older adolescent and young adult (18–39 years old). Younger adolescents are nearly always financially dependent on their parents or guardians, making their financial issues essentially equivalent to those of younger children. These are mostly associated with active therapy and result in increased family financial burden, especially out-of-pocket expenses, which are estimated to represent one third of after-tax income. In contrast, older AYAs tend to be or aspire to become financially independent. Their issues relate to preserving income, paying for care, and providing for dependents. For some, the priority is completing higher education or career preparation, while for others it is launching, maintaining, or returning to work. For cancer survivors, these challenges do not necessarily abate, as clinically significant late effects require medical management, pose excess financial burdens, and diminish functional status. Although the landmark Affordable Care Act of 2010 has partially improved the situation in the USA, many AYAs remain vulnerable through remaining discontinuities, incompleteness, and sheer complexity of coverage. Further, many financial challenges are universally overrepresented among AYAs, regardless of payer system. A proactive, socio-ecological, multidisciplinary approach involving physicians, nurses, oncology social workers, and other professionals is likely to be most effective for assisting individual patients and developing systemic solutions.

A large proportion of survivors of cancer diagnosed when they were AYAs experience some adverse effects on their health, some that do not become apparent for years or even decades after the exposure to the anticancer therapies. The developing and maturing organ systems of AYAs have different sensitivities to radiation therapy, chemotherapy, and surgery than do those of younger or older cancer patients. Virtually all organ systems can be affected, depending upon the therapeutic exposure, leading to a wide array of late effects, including second cancers, cardiovascular and pulmonary disease, cognitive dysfunction, and musculoskeletal problems. Some initially subclinical effects may exacerbate common diseases associated with aging, such as cardiovascular, skeletal, and endocrine disorders, and contribute to poor quality of life and premature death. Sociodemographic factors, details of treatment, and health behaviors also influence the magnitude of impairment in specific health status domains. Through risk-based care and education about the health risks conferred by the cancer experience, clinicians caring for long-term survivors play a critical role in the prevention, diagnosis, and rehabilitation of cancer-related complications and adjustment to chronic health conditions predisposed or exacerbated by cancer. Consequently, health professionals caring for AYA cancer survivors may influence their future health positively by correcting knowledge deficits, addressing factors that enhance an individual survivor’s vulnerability to health problems, and providing personalized health counseling that promotes the practice of health-promoting behaviors. This chapter describes the healthcare of survivors of cancer diagnosed during the AYA years, including risk-based screening and surveillance for late effects, transition of AYA healthcare, and models of AYA survivorship care. The promotion of healthy lifestyle habits is discussed, emphasizing the impact of such habits on the expression of late effects.

© 2016 by American Society of Clinical Oncology. QUESTION ASKED: Given the importance of cancer clinical trials and the fact that most adolescents and young adults (AYAs) are treated in the community setting, did historical Community Clinical Oncology Program (CCOP) sites enroll a higher proportion of AYAs to Children's Oncology Group (COG) studies than non-CCOP sites? SUMMARY ANSWER: Over the 10-year period studied, CCOP sites enrolled a significantly lower proportion of AYAs onto COG studies than non-CCOP sites. Further, while proportional enrollment of AYAs declined over time at both CCOP and non-CCOP sites, the decline was greater at CCOP sites. METHODS: This was a retrospective cross-sectional analysis of clinical trial enrollment onto COGtrials utilizing the National Cancer Institute (NCI) Division of Cancer Prevention database. For the period 2004 through 2013, the proportional enrollment of AYAs (number of AYAenrollments divided by total enrollments) onto relevantCOGstudies was compared between CCOP and non-CCOP sites and potential changes over time were evaluated. All sites were COG member institutions. MAIN RESULT(S): During the study period, a total of 9,821 and 81,164 patients were enrolled onto COG trials at CCOP and non-CCOP sites, respectively. In aggregate, a significantly lower proportion of AYAs was enrolled onto applicable COG studies at CCOP than at non-CCOP sites (24.1% [1,606/6,672] v 28.2% [16,357/58,059], P,.001). During the intervals 2004 through 2008 and 2009 through 2013, the proportional enrollment of AYAs at CCOP sites and non-CCOP sites declined significantly (from 26.7% [844/3,156] to 21.7% [762/3,516], P,.001 and from 29.1% [8,189/28,115] to 27.3% [8,168/29,944], P,.001, respectively). Between those intervals, proportional enrollment of AYAs at CCOP sites declined for acute lymphoblastic leukemia studies (33.9% [108/319] v 23.6% [144/611], P =.001) but not for other cancers (Fig). BIAS, CONFOUNDING FACTOR(S), DRAWBACKS: A major strength of this study is the use of proportional rather than absolute AYA enrollment because this is less dependent on the changing availability of trials for AYA patients. Limitations of this study include being (1) restricted to enrollments onto COG and not adult cooperative group trials; and (2) unable to account for the observed differences between CCOP and non-CCOP sites and within site categories over time. REAL-LIFE IMPLICATIONS: This study suggests that despite many CCOPs being located in the community where AYAs tend to be treated, having a commitment to serving disparity populations, and having a clinical research infrastructure involving both medical and pediatric oncologists, these characteristics alone are not enough to result in higher AYA enrollment than in traditional treatment settings. However, the NCI Community Oncology Research Program (NCORP), which replaced the CCOP in 2014, is well-positioned to leverage these advantages through development and study of targeted interventions aimed at increasing AYA clinical trial accrual. Within NCORP sites, pediatric and medical oncologists should collaborate more actively in the recruitment and management of AYAs on clinical trials to improve care and outcomes.

Obesity as defined by body mass index percentile (BMI%) is strongly associated with relapse and poorer survival in childhood ALL. Whether BMI% accurately reflects body fat percentage (BF%) in this population is unknown. We conducted a prospective study assessing body composition during frontline ALL therapy. Dual-energy X-ray absorptiometry measured BF% and lean muscle mass (LMM) at diagnosis, end of Induction, and end of Delayed Intensification. Sarcopenic obesity (gain in BF% with loss of LMM) was surprisingly common during ALL treatment, resulting in poor correlation between changes in BMI% (expressed as Z-score) and BF% overall (r = -0.05) and within patients (r = -0.09). BMI Z-score and BF% changed in opposite directions in >50% of interval assessments. While BMI% at diagnosis is a suitable predictor of obesity/BF% for epidemiological studies, change in BMI% (as expressed as Z-score) does not reflect body composition. Studies evaluating obesity in leukemia should consider using direct measures of body composition.

Background Packed red blood cell (PRBC) transfusion is a mainstay in childhood cancer treatment, but has potential for inducing iron overload. The purpose of this study was to determine whether treatment intensity is predictive of projected iron burden resulting from PRBC transfusions among survivors of several forms of childhood cancer. Procedure This retrospective cohort study involved patients treated at Children's Hospital Los Angeles (CHLA) between June 1, 2004 and December 31, 2009. Clinical/demographic data were abstracted from medical records. Treatment Intensity Level was determined for each patient using a published scale. Adjusted cumulative PRBC transfusion volume for each patient (ml/kg) was used to compute the adjusted total iron burden (mg/kg) based upon the average hematocrit of the product. Results Median age of the cohort (n = 214) was 7.9 years (range 0.2–20.2). One hundred and fourteen (53.3%) were male and 129 (60.3%) were Hispanic/Latino. Diagnoses included acute leukemia and six solid tumors, management of which represents a range of cancer treatment intensities. The number of transfusions, transfusion volumes, and projected iron burden were significantly increased and exceeded upper limits of normal among patients with higher treatment intensity. Multivariate analysis found younger age and lower hemoglobin at diagnosis to be associated with greater iron burden after adjusting for treatment intensity. Conclusion Greater treatment intensity is associated with need for more PRBC transfusions, and thus increased risk of iron overload among childhood cancer survivors. Iron overload may represent another clinically significant late effect following childhood cancer treatment. Pediatr Blood Cancer 2012;59:697–702. © 2011 Wiley Periodicals, Inc.

While intensification of therapy has improved event-free survival (EFS) and survival in newly diagnosed children with acute lymphoblastic leukemia (ALL), postrelapse outcomes remain poor. It might be expected that patients relapsing after inferior initial therapy would have a higher retrieval rate than after superior therapy. In the Children's Oncology Group Study CCG-1961, significantly superior EFS and survival were achieved with an augmented (stronger) versus standard intensity regimen of postinduction intensification (PII) for children with newly diagnosed high-risk ALL and rapid day 7 marrow response (EFS/survival 81.2%/88.7% vs 71.7%/83.4%, respectively). This provided an opportunity to evaluate postrelapse survival (PRS) in 272 relapsed patients who had received randomly allocated initial treatment with augmented or standard intensity PII. As expected, PRS was worse for early versus late relapse, marrow versus extramedullary site, adolescent versus younger age and T versus B lineage. However, no difference in 3-year PRS was detected for having received augmented versus standard intensity PII (36.4% ± 5.7% vs 39.2% ± 4.1%; log rank P = .72). Similar findings were noted within subanalyses by timing and site of relapse, age, and immunophenotype. These findings provide insight into mechanisms of relapse in ALL, and are consistent with emergence of a resistant subclone that has acquired spontaneous mutations largely independent of initial therapy. This study is registered at www.clinicaltrials.gov as NCT00002812.

INTRODUCTION: Obesity is associated with increased treatment-related toxicity during therapy for acute lymphoblastic leukemia (ALL). During induction, hepatotoxicity due to L-asparaginase results in significant morbidity and chemotherapy delays/modifications. While hepatotoxicity is more common in older adolescent and young adult (AYA) patients, it cannot be predicted with high accuracy. Obesity defined by the surrogate marker of body mass index (BMI) has been shown to be a risk factor for hepatotoxicity; however, BMI does not accurately reflect body adiposity during ALL therapy due to concurrent muscle loss and adiposity gain. Because excess adiposity is generally believed to be responsible for most of the comorbidities of obesity, we hypothesized that body fat measured by direct assessment would be a better predictor of asparaginase-induced hepatotoxicity, and that non-obese patients with increased adiposity might be identified as an at-risk population which would not otherwise be recognized. METHODS: We conducted an interim analysis of a prospective trial for an obesity intervention in pre-adolescent and AYA patients ≥10 years old newly diagnosed with B-ALL (NCT02708108). Whole-body dual-energy x-ray absorptiometry (DXA) performed at diagnosis and end of induction (EOI) directly quantified adiposity as total body fat percentage (TBF%) and fat mass (FM). Overweight or obesity (OW/OB) was defined using CDC-norms as a BMI percentile (BMI%) ≥85%. All patients were treated with Children's Oncology Group ALL regimens using a four-drug induction inclusive of glucocorticoids, daunorubicin, vincristine, and pegylated L-asparaginase. Obese and/or patients ≥15 years were considered at-risk for hepatotoxicity and thus eligible to receive exogenous supplementation with levocarnitine for hepatoprotection per provider discretion. The primary endpoint for the analysis was CTCAE Grade 3+ hepatotoxicity. Stepwise multivariable logistic regression models were constructed for the primary endpoint inclusive of TBF% and FM at diagnosis, change in FM during induction, and demographic candidate predictors. All tests were two-sided and significance was set at p RESULTS: We analyzed a cohort of 25 subjects enrolled on trial with DXA results at diagnosis. The cohort was divided equally by age ≥15 years (48%) and sex (44% female). The majority were of Hispanic ethnicity (64%) consistent with institutional demographics. Over half the cohort was OW/OB at diagnosis with mean TBF% of 39.5±1.3% and FM 31.7±2.5kg. In this AYA population, Grade 3+ hepatotoxicity occurred in 10/25 (40%) overall; all episodes included transaminitis (10/10) ± concurrent hyperbilirubinemia (2/10). Two of these patients met criteria for CTCAE Grade 4 hepatotoxicity (2/25, 8%); both were older, obese, with TBF% >40% at diagnosis. After accounting for age, radiographic measures of adiposity at diagnosis were not significant predictors of hepatotoxicity on multivariable analyses (FM at diagnosis p=0.299; TBF% at diagnosis p=0.599). Similarly, gain or loss of FM was not significantly associated with hepatotoxicity after adjusting for age or starting BMI category (p=0.818). Successful loss of fat due to the intervention occurred in 7/13 (54%) of OW/OB patients (mean loss -3.9±8.9kg) but was similarly not associated with decreased risk of hepatotoxicity (p=0.734). Only age ≥15 years was significantly associated with risk for Grade 3 hepatotoxicity across all models. Levocarnitine supplementation was prescribed by the primary providers to five of six eligible at-risk patients; no reported adverse events occurred. No severe, CTCAE Grade 4 hepatotoxicity occurred in the four patients adherent to levocarnitine supplementation. CONCLUSION: Contrary to our hypothesis, neither directly measured adiposity at diagnosis nor changes in adiposity during ALL induction predicted hepatotoxicity for this AYA cohort. Older AYA patients were at significant risk for hepatotoxicity irrespective of level of adiposity. However, the potential impact of extreme obesity on hepatotoxicity requires further investigation. Validation of these results is necessary in a larger cohort; should they be confirmed, future trials targeting hepatotoxicity reduction from ALL induction should focus on age-related differences in drug metabolism and effects. Disclosures No relevant conflicts of interest to declare.

OBJECTIVES/SPECIFIC AIMS: Low cancer clinical trial (CCTs) enrollment may contribute to the poor survival improvement for adolescents and young adults (AYAs, aged 15–39 years) with cancer. Treatment site is thought to exacerbate this problem. This study evaluated whether differences in CCT availability explain lower CCT enrollment depending on treatment site for AYAs. METHODS/STUDY POPULATION: This prospective, observational cohort study was conducted at an academic children’s hospital and an adult cancer hospital, 2 affiliated sites within a NCI-designated Comprehensive Cancer Center over 13 months. In consecutive AYA patients newly diagnosed with cancer at both site, it was determined whether an appropriate CCT existed nationally, was available locally, and if enrollment occurred. The proportions of AYAs in these categories were compared by site using the χ2 test. RESULTS/ANTICIPATED RESULTS: Among 152 consecutive AYA patients, 68 and 84 were treated at the children’s hospital and adult cancer hospital, respectively. AYAs treated at the children’s hospital had similar CCT existence nationally compared with AYAs treated at the adult hospital [36/68 (52.9%) vs. 45/84 (53.6%), p=0.938]. However, a significantly higher percentage of children’s hospital treated AYAs than adult hospital treated AYAs had an available CCT [30/68 (44.1%) vs. 14/84 (16.7%), pp=0.327]. DISCUSSION/SIGNIFICANCE OF IMPACT: Significantly fewer AYAs treated at the adult hospital had a CCT available, but national existence was similar at both sites. This suggests that institutional barriers to opening CCT have more importance at adult centers.

Importance The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39 years) in the United States is increasing at a greater rate than in younger or older persons. Their optimal treatment has been increasingly debated as pediatric regimens have become more widely used in the age group. This review compares the basic features of pediatric and adult chemotherapy regimens for ALL and LBL, recognizes and describes the challenges of the pediatric regimen, and suggests strategies to facilitate its adoption for AYAs with ALL and LBL. Observations All but 2 of 25 published comparisons of outcomes with pediatric and adult regimens for ALL and LBL in AYAs and 1 meta-analysis favor the pediatric regimen. After more than a half-century of clinical trials of the pediatric regimens, including at least 160 phase 3 trials in the United States, the pediatric regimens have become far more complex than most adult regimens. Asparaginase, a critical component of the pediatric regimens, is more difficult to administer to AYAs (and older patients) but nonetheless has a favorable benefit to toxicity ratio for AYAs. A dramatic reduction in outcome of ALL and LBL during the AYA years (the “survival cliff”) is coincident with similar reductions in proportions of AYAs referred to academic centers and enrolled on clinical trials (the “accrual cliff” and “referral cliff”). Conclusions and Relevance The accumulating data increasingly support treating AYAs with ALL and LBL with a pediatric-inspired regimen or an approved institutional or national clinical trial tailored for this patient group. A need to develop clinical trials specifically for AYAs and to encourage their participation is paramount, with a goal to improve both the quantity and quality of survival.