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Background Medulloblastoma is a rare diagnosis among adolescents and young adults (AYA). Though prognostic factors and treatment are well characterized among children with medulloblastoma, equivalent data for AYA are sparse. We conducted a systematic review to identify predictors of survival among AYA with medulloblastoma. Methods We searched for primary studies of AYA (age 15–39 at diagnosis) with medulloblastoma in high-income countries within OVID MEDLINE, EMBASE, and EBM Reviews-Cochrane library databases from inception to August 2020. Patient demographics, primary outcomes, and univariate and multivariable data on all prognostic factors were collected from included studies. Prognosticators were characterized as patient, disease, or treatment-related. Results We identified 18 articles. 5-year overall survival ranged between 40% and 89%, while disease-free survival ranged from 49% to 89%. Study quality was low as assessed by the Quality in Prognostic factor Studies tool. Though meta-analyses were not possible due heterogeneity, narrative summaries suggested that lower disease burden, superior postoperative functional status, and higher doses and larger fields of radiation were associated with improved survival. Reported chemotherapy regimens were heterogeneous in timing, agents, and relationship with radiation, precluding meaningful comparisons. Only one study included molecular subgroups for analysis, with the majority (76.5%) of tumors classified as Sonic Hedgehog (SHH). Conclusions Prognostication and treatment of AYA medulloblastoma is limited by a dearth of primary evidence and lack of specificity for patients aged 15–39. Dedicated prospective trials to delineate the benefit of various chemotherapy and radiation regimens are required in this population to identify prognosticators and ideal treatment regimens.

Pediatric hemorrhagic stroke (HS) accounts for a large proportion of childhood strokes, 1 of the top 10 causes of pediatric deaths. Morbidity and mortality lead to significant socio-economic and psychosocial burdens. To understand published data on recognizing and managing children with HS, we conducted a systematic review of the literature presented here. We searched PubMed, Embase, CINAHL and the Cochrane Library databases limited to English language and included 174 studies, most conducted in the USA (52%). Terminology used interchangeably for HS included intraparenchymal/intracranial hemorrhage, spontaneous ICH, and cerebrovascular accident (CVA). Key assessments informing prognosis and management included clinical scoring (Glasgow coma scale), and neuroimaging. HS etiologies reported were systemic coagulopathy (genetic, acquired pathologic, or iatrogenic), or focal cerebrovascular lesions (brain arteriovenous malformations, cavernous malformations, aneurysms, or tumor vascularity). Several scales were used to measure outcome: Glasgow outcome score (GOS), Kings outcome score for head injury (KOSCHI), modified Rankin scale (mRS) and pediatric stroke outcome measure (PSOM). Most studies described treatments of at-risk lesions. Few studies described neurocritical care management including raised ICP, seizures, vasospasm, or blood pressure. Predictors of poor outcome included ethnicity, comorbidity, location of bleed, and hematomagt;2% of total brain volume. Motor and cognitive outcomes followed independent patterns. Few studies reported on cognitive outcomes, rehabilitation, and transition of care models. Interdisciplinary approach to managing HS is urgently needed, informed by larger cohort studies targeting key clinical question (eg development of a field-guide for the clinician managing patients with HS that is reproducible internationally).

Background Prognostic factors in adolescent and young adult (AYA) glioma are not well understood. Though clinical and molecular differences between pediatric and adult glioma have been characterized, their application to AYA populations is less clear. There is a major need to develop more robust evidence-based practices for managing AYA glioma patients. Methods A systematic review using PRISMA methodology was conducted using multiple databases with the objective of identifying demographic, clinical, molecular and treatment factors influencing AYA glioma outcomes. Results 40 Studies met inclusion criteria. Overall survival was highly variable across studies depending on glioma grade, anatomic compartment and cohort characteristics. Thirty-five studies suffered from high risk of bias in at least one domain. Several studies included older adults within their cohorts; few captured purely AYA groups. Despite study heterogeneity, identified favorable prognosticators included younger age, higher functional status at diagnosis, low-grade pathology, oligodendroglioma histology and increased extent of surgical resection. Though isocitrate dehydrogenase (IDH) mutant status was associated with favorable prognosis, validity of this finding within AYA was compromised though may studies including older adults. The prognostic influence of chemotherapy and radiotherapy on overall survival varied across studies with conflicting evidence. Conclusion Existing literature is heterogenous, at high risk of bias, and rarely focused solely on AYA patients. Many included studies did not reflect updated pathological and molecular AYA glioma classification. The optimal role of chemotherapy, radiotherapy, and targeted agents cannot be determined from existing literature and should be the focus of future studies.

Many survivors of childhood cancer are at high risk of late effects of their cancer therapy, including cardiac toxicity and subsequent malignant neoplasms (SMN). Current North American guidelines recommend periodic surveillance for these late effects. We conducted a systematic review of the literature to estimate rates of adherence to recommended surveillance and summarize studies evaluating interventions intended to increase adherence. We searched MEDLINE, Embase, Web of Science, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) for articles published between January 2000 and September 2018 that reported adherence to surveillance for cardiac toxicity and SMN (breast and colorectal cancer) and interventions implemented to improve completion of recommended testing. Risk of bias was assessed using relevant Cochrane checklists. Due to heterogeneity and overlapping study populations, we used narrative synthesis to summarize the findings. This review was registered in PROSPERO: CRD42018098878. Thirteen studies met our inclusion criteria for assessing adherence to surveillance, while five assessed interventions to improve rates of surveillance. No studies met criteria for low risk of bias. Completion of recommended surveillance was lowest for colorectal cancer screening (11.5–30.0%) followed by cardiomyopathy (22.3–48.1%) and breast cancer (37.0–56.5%). Factors such as patient-provider communication, engagement with the health care system, and receipt of information were consistently reported to be associated with higher rates of surveillance. Of five randomized controlled trials aimed at improving surveillance, only two significantly increase completion of recommended testing—one for echocardiography and one for mammography. Both involved telephone outreach to encourage and facilitate these tests. The majority of childhood cancer survivors at high risk of cardiac toxicity or SMN do not receive evidence-based surveillance. There is paucity of rigorous studies evaluating interventions to increase surveillance in this population. Robust trials are needed to assess whether tailored interventions, designed based on unique characteristics and needs of each survivor population, could improve adherence.

BACKGROUND Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with substantial health care utilization and burden on families. Little is known about health care utilization during specific treatment phases. PROCEDURES We identified children with ALL diagnosed during 2002-2012 in Ontario, Canada and treated according to Children's Oncology Group (COG) protocols. Disease and treatment data were chart abstracted. Population-based health care databases identified all outpatient visits, emergency department (ED) visits, and hospitalizations. In addition to comparing standard and intensified versions of treatment phases, we compared patients receiving different steroids (dexamethasone vs. prednisone) and different versions of interim maintenance (IM) (Capizzi vs. high-dose methotrexate [HD-MTX]). RESULTS Six hundred thirty-seven children met inclusion criteria. During intensified consolidation, 76.2% of patients were hospitalized at least once, compared to only 32.3% of patients receiving standard consolidation (p

Although different treatment protocols for childhood acute lymphoblastic leukaemia (ALL) all achieve high cure rates, their health care utilisation and costs have not been rigorously compared.Disease, treatment, and outcome data were chart abstracted for all children with ALL in Ontario, Canada, diagnosed 2002-2012. Linkage to population-based databases identified health care utilisation. Utilisation-associated costs were determined through validated algorithms. Chemotherapy-associated costs were calculated separately. Health care utilisation and costs were compared between patients receiving Children's Oncology Group (COG) versus Dana-Farber Cancer Institute (DFCI)-based treatment.Of 802 patients, 146 (18.2%) were treated on DFCI-based protocols. COG patients experienced significantly higher rates of emergency department (ED) visits (adjusted rate ratio [aRR]: 1.3, 95% confidence interval [CI]: 1.1-1.5; p = 0·01), whereas outpatient visit rates were 60% higher among DFCI patients (aRR: 1.6, 95% CI: 1.5-1.7, p 0.0001). In adjusted analyses, DFCI-associated cost intensity was 70% higher (aRR: 1.7, 95% CI: 1.5-1.9; p 0.0001), mainly attributable to outpatient visit costs. Total chemotherapy costs were higher among COG-treated patients ($39,400 ± $1100 versus $33,400 ± $2800; p = 0.02). Among PEG-ASNase-treated patients, total chemotherapy costs were highest among DFCI patients (median $54,200 ± $7400; p = 0.003 versus COG patients).COG and DFCI treatments were associated with higher ED visit rates and higher outpatient visit rates, respectively. Overall utilisation-associated costs were increased in DFCI-treated patients. Administration of some intravenous chemotherapy at home and decreases in PEG-ASNase cost would decrease health care utilisation and costs for all patients and mitigate differences between COG and DFCI protocols.C

BACKGROUND: Though cooperative trial groups use different treatment protocols for newly diagnosed childhood acute lymphoblastic leukemia (ALL), all achieve high cure rates. The healthcare utilization and costs associated with different treatment strategies have not been rigorously compared. Minimizing utilization and costs may increase quality of life and decrease health system burden. We compared Children's Oncology Group (COG) and Dana-Farber Cancer Institute (DFCI)-based treatment. METHODS: We identified all children diagnosed with ALL in pediatric cancer centers in Ontario, Canada between 2002 and 2012 through the Pediatric Oncology Group of Ontario Networked Information System (POGONIS), a provincial pediatric cancer registry. Detailed data on demographics, disease risk factors (e.g. cytogenetics, minimal residual disease), treatment (e.g. treatment protocol, start and end date of each therapy phase) and events (relapse/progression, death, second cancer) were captured via chart abstraction. Treatment protocols were categorized as either based on COG or DFCI trials. Linkage to population-based health services databases identified all outpatient and emergency department (ED) visits, hospitalizations, and physician billings. Healthcare utilization-associated costs were determined through validated costing algorithms. Chemotherapy-associated costs were calculated separately using local prices. All administered doses of asparaginase (ASNase), including E. Coli, PEG-ASNase, and Erwinia ASNase were recorded. Event-free survival (EFS), overall survival (OS), healthcare utilization rates, and costs were compared between COG and DFCI-treated patients while adjusting for demographics and disease-factors using appropriate regression models. Healthcare-associated costs, ASNase costs, and total chemotherapy costs (2018 Canadian dollars) were compared. RESULTS: The study cohort included 802 patients, 146 (18.2%) of whom were treated on DFCI-based protocols. Median follow-up did not differ between between COG and DFCI patients; nor did EFS or OS. When adjusted for all demographic and disease-related variables, COG patients experienced significantly higher rates of ED visits [rate ratio (RR) 1.3, 95% confidence interval (95CI) 1.1-1.5; p=0.01]. Neither hospitalization rates nor rates of inpatient days differed between the two groups of patients. However, rates of outpatient visits were 60% higher among DFCI patients (RR 1.6, 95CI 1.5-1.7; p The median healthcare-associated cost in the first 5 years following initial diagnosis was $193,700 among COG patients [interquartile range (IQR) 149,200-272,700] compared to $288,000 among DFCI patients (IQR 233,300-407,300; p The median ASNase-related cost was similar between COG and DFCI patients [$21,100, IQR 14,800-35,400 vs. $19,900, IQR 15,600-39,900; p=0.91]. The median total chemotherapy cost was higher among COG patients ($29,100, IQR 20,300-50,300 vs. $22,400, IQR 17,300-42,600; p CONCLUSIONS: Though COG and DFCI protocols are associated with equivalent EFS and OS, patterns of healthcare utilization differ with the former associated with a 30% increase in the rate of ED visits and the latter associated with a 60% increase in the rate of outpatient visits. Overall, healthcare utilization-associated costs were increased in DFCI-treated patients. Though ASNase costs historically did not differ, the shift to PEG-ASNase is associated with higher ASNase and total chemotherapy costs on DFCI protocols. Decreases in PEG-ASNase cost and the ability to administer intravenous or intramuscular chemotherapy at home would decrease overall healthcare utilization and costs, and mitigate differences between COG and DFCI protocols. These results can inform efforts to decrease burden on both families and health systems. Disclosures No relevant conflicts of interest to declare.

Although a cancer diagnosis during the adolescent and young adult (AYA) years is a traumatic event, and psychiatric disorders generally manifest during the AYA period, the impact of a cancer diagnosis on long-term mental health outcomes in this population is not well characterized. We conducted a systematic review and meta-analysis to determine if survivors of AYA cancers are more likely to develop psychiatric disorders. A systematic literature search of five databases, MEDLINE, CINAHL, Web of Science, EMBASE, and PsycINFO, was conducted from their inception to November 2018. The outcome measures were psychiatric disorders as per the Diagnostic Statistical Manual criteria, or psychiatric medication use. Study eligibility, appraisal, and data abstraction were independently conducted by two reviewers. Of 7934 total studies, four met eligibility criteria for the systematic review, three of which were included in the meta-analysis. Compared to cancer-free controls, survivors were at an elevated risk of mood disorders (odds ratio [OR] 1.36; 95% CI 1.19-1.55) and anxiety disorders (OR 1.16; 95% CI 1.05-1.28), but not substance-related disorders, (OR 0.88; 95% CI 0.63-1.22). The most commonly identified risk factors were the female sex and older age at diagnosis. We found higher odds of anxiety and mood disorders in AYA-onset cancer survivors. However, few AYA-specific studies currently exist that analyze psychiatric disorders using consistent and standardized methods. Additional studies confirming these findings are warranted.

IntroductionA major barrier to improving childhood cancer survival is the perception that paediatric oncology services are too costly for low-income and middle-income country (LMIC) health systems. We conducted a systematic review to synthesise existing evidence on the costs and cost-effectiveness of treating childhood cancers in LMICs.MethodsWe searched multiple databases from their inception to March 2019. All studies reporting costs or cost-effectiveness of treating any childhood cancer in an LMIC were included. We appraised included articles using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Where possible, we extracted or calculated the cost per disability-adjusted life year (DALY) averted using reported survival and country-specific life expectancy. Cost/DALY averted was compared with per capita gross domestic product (GDP) as per WHO-Choosing Interventions that are Cost-Effective guidelines to determine cost-effectiveness.ResultsOf 2802 studies identified, 30 met inclusion criteria. Studies represented 22 countries and nine different malignancies. The most commonly studied cancers were acute lymphoblastic leukaemia (n=10), Burkitt lymphoma (n=4) and Wilms tumour (n=3). The median CHEERS checklist score was 18 of 24. Many studies omitted key cost inputs. Notably, only 11 studies included healthcare worker salaries. Cost/DALY averted was extracted or calculated for 12 studies and ranged from US$22 to US$4475, although the lower-end costs were primarily from studies that omitted key cost components. In all 12, cost/DALY averted through treatment was substantially less than country per capita GDP, and therefore considered very cost-effective.ConclusionMany included studies did not account for key cost inputs, thus underestimating true treatment costs. Costs/DALY averted were nonetheless substantially lower than per capita GDP, suggesting that even if all relevant inputs are included, LMIC childhood cancer treatment is consistently very cost-effective. While additional rigorous economic evaluations are required, our results can inform the development of LMIC national childhood cancer strategies.

Background For parents, a diagnosis of cancer in their child is a traumatic experience. However, there is conflicting evidence about the risk of developing mental illness among parents following diagnosis. Our objective was to conduct a meta-analysis to determine the prevalence of mental illness in parents of children with cancer. Methods Four databases were searched to identify articles describing the prevalence of anxiety, depression, or posttraumatic stress disorder (PTSD) in parents of pediatric cancer patients. Two reviewers independently screened and extracted data. Subgroup analyses by gender and phase of cancer experience were selected a priori. Studies were reviewed in accordance with PRISMA guidelines. Results Of 11 394 articles identified, 58 met inclusion criteria. Reported prevalence was highly heterogeneous, ranging from 5% to 65% for anxiety (pooled prevalence 21% [95% CI, 13%-35%]), 7% to 91% for depression (pooled prevalence 28% [95% CI, 23%-35%]), and 4% to 75% for PTSD (pooled prevalence 26% [95% CI, 22%-32%]). Prevalence was consistently higher than noncancer parental controls. Heterogeneity was not explained by parental gender or child's cancer phase and was instead likely due to significant methodological differences in measurement tools and defined thresholds. Conclusions Parents of children with cancer have a higher prevalence of anxiety, depression, and PTSD compared with population controls. Yet, the reported prevalence of mental illness was highly variable, hampering any conclusive findings on absolute prevalence. To better understand the risk of long-term mental illness in this population and target interventions, future studies must adhere to standardized reporting and methods.

7031 Background: Outcomes in pediatric acute lymphoblastic leukemia (ALL) have shown remarkable improvements in large part due to sequential clinical trials. Concerns however persist around whether access to clinical trials is equitable. It is also unclear whether patient outcomes are improved simply by enrolling on a clinical trial. Our objective was to therefore determine which patient and disease-related factors are associated with enrollment, and whether enrollment was associated with clinical outcomes among children and adolescents with ALL in a single-payer health system in Ontario, Canada. Methods: We included all Ontario patients diagnosed with ALL between 0-18 years of age from 2002-2012 treated at a pediatric center, identified through a provincial pediatric cancer registry. Clinical trial availability was determined by whether each patient’s primary institution had an open frontline trial for which the patient was eligible at the time of their diagnosis, considering individual disease characteristics such as lineage, central nervous system (CNS) status and risk group. Demographic, disease, trial enrolment, and outcome data were obtained through chart abstraction. Logistic regression models determined factors associated with trial enrolment, while Cox proportional hazard models determined factors associated with event-free and overall survival (EFS, OS). Results: Of 858 patients, 693 (81%) were eligible for an open clinical trial at their time of diagnosis. 476 (69%) enrolled on a trial. In adjusted analyses, age > 15 years (odds ratio 0.4 vs. age 5-9, 95th confidence interval (95CI) 0.2-0.8; p = 0.01) and CNS3 disease (OR 0.38 vs. CNS1, 95CI 0.17-0.83; p = 0.01) were significantly associated with decreased likelihood of enrolment, while sex and neighborhood income quintile were not associated with enrolment. Adjusted for disease and demographic factors, clinical trial enrolment was not significantly associated with either EFS (hazard ratio (HR) 1.1, 95CI 0.7-1.7; p = 0.83) or OS (HR 1.3, 95CI 0.7-2.5; p = 0.44). Conclusions: The majority of patients with ALL eligible for available clinical trials at their time of diagnosis were enrolled. While no disparities in enrolment by income status were noted, adolescents were substantially less likely to participate in trials even within pediatric centers. Studies of mechanisms underlying this disparity are warranted in order to design and implement effective interventions targeting increased enrolment rates in this patient population. Our results however also suggest that clinical trial enrolment on its own is not associated with improved outcomes in the context of a single payer health system.