The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study.

BACKGROUND: The effect of the increasing lifetime burden of non-major cardiovascular conditions on risk for a subsequent major adverse cardiovascular event among survivors of childhood cancer has not been assessed. We aimed to characterise the prevalence of major adverse cardiovascular events and their association with the cumulative burden of non-major adverse cardiovascular events in childhood cancer survivors. METHODS: This is a longitudinal cohort study with participant data obtained from an ongoing cohort study at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE). Prospective clinical follow-up was of 5-year survivors of childhood cancer who were diagnosed when aged younger than 25 years from 1962 to 2012. Age-frequency, sex-frequency, and race-frequency matched community-control participants completed a similar one-time clinical assessment. 22 cardiovascular events were graded using a St Jude Children's Research Hospital-modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Cumulative incidence and burden of the primary outcome of major adverse cardiovascular events (cardiomyopathy, myocardial infarction, stroke, and other cardiovascular-related mortality) were estimated. Rate ratios (RR) of the association of major adverse cardiovascular events with 22 non-major adverse cardiovascular events were estimated using multivariable piecewise-exponential regression adjusting for attained age, age at diagnosis, sex, race and ethnicity, treatment era, diagnosis of diabetes, and exposure to cardiotoxic cancer therapies. The St Jude Lifetime Cohort study is registered with ClinicalTrials.gov, NCT00760656, and is ongoing. FINDINGS: 9602 5-year survivors of childhood cancer, and 737 community controls were included in the longitudinal follow-up (from Sept 13, 2007, to Dec 17, 2021). The median follow-up was 20·3 years (IQR 12·0-31·4) from the date of primary cancer diagnosis (4311 [44.9%] were females). By the age of 50 years (analysis stopped at age 50 years due to the low number of participants older than that age), the cumulative incidence of major adverse cardiovascular events among survivors was 17·7% (95% CI 15·9-19·5) compared with 0·9% (0·0-2·1) in the community controls. The cumulative burden of major adverse cardiovascular events in survivors was 0·26 (95% CI 0·23-0·29) events per survivor compared with 0·009 (0·000-0·021) events per community control participant. Increasing cumulative burden of grade 1-4 non-major adverse cardiovascular events was associated with an increased future risk of major adverse cardiovascular events (one condition: RR 4·3, 95% CI 3·1-6·0; p<0·0001; two conditions: 6·6, 4·6-9·5; p<0·0001; and three conditions: 7·7, 5·1-11·4; p<0·0001). Increased risk for major adverse cardiovascular events was observed with specific subclinical conditions (eg, grade 1 arrhythmias [RR 1·5, 95% CI 1·2-2·0; p=0·0017]), grade 2 left ventricular systolic dysfunction (2·2, 1·6-3·1; p<0·0001), grade 2 valvular disorders (2·2, 1·2-4·0; p=0·013), but not grade 1 hypercholesterolaemia, grade 1-2 hypertriglyceridaemia, or grade 1-2 vascular stenosis. INTERPRETATION: Among an ageing cohort of survivors of childhood cancer, the accumulation of non-major adverse cardiovascular events, including subclinical conditions, increased the risk of major adverse cardiovascular events and should be the focus of interventions for early detection and prevention of major adverse cardiovascular events. FUNDING: The US National Cancer Institute and the American Lebanese Syrian Associated Charities.

Addressing the gap in health economics data to support national cancer control plans in low- and middle-income countries: The Childhood Cancers Budgeting Rapidly to Incorporate Disadvantaged Groups for Equity (CC-BRIDGE) tool.

BACKGROUND: National cancer control plans (NCCPs) are complex public health programs that incorporate evidence-based cancer control strategies to improve health outcomes for all individuals in a country. Given the scope of NCCPs, small and vulnerable populations, such as patients with childhood cancer, are often missed. To support planning efforts, a rapid, modifiable tool was developed that estimates a context-specific national budget to fund pediatric cancer programs, provides 5-year scale-up scenarios, and calculates annual cost-effectiveness. METHODS: The tool was codeveloped by teams of policymakers, clinicians, and public health advocates in Zimbabwe, Zambia, and Uganda. The 11 costing categories included real-world data, modeled data, and data from the literature. A base-case and three 5-year scale-up scenarios were created using modifiable inputs. The cost-effectiveness of the disability-adjusted life years averted was calculated. Results were compared with each country's projected gross domestic product per capita for 2022 through 2026. RESULTS: The number of patients/total budget for year 1 was 250/$1,109,366 for Zimbabwe, 280/$1,207,555 for Zambia, and 1000/$2,277,397 for Uganda. In year 5, these values were assumed to increase to 398/$5,545,445, 446/$4,926,150, and 1594/$9,059,331, respectively. Base-case cost per disability-adjusted life year averted/ratio to gross domestic product per capita for year 1, assuming 20% survival, was: $807/0.5 for Zimbabwe, $785/0.7 for Zambia, and $420/0.5 for Uganda. CONCLUSIONS: This costing tool provided a framework to forecast a budget for childhood-specific cancer services. By leveraging minimal primary data collection with existing secondary data, local teams obtained rapid results, ensuring that childhood cancer budgeting is not neglected once in every 5 to 6 years of planning processes.

Local evidence in sub-Saharan Africa; the CANCaRe Africa experience-Lessons learned and shared thoughts about the way forward.

Collaborative research generating local evidence is key to closing the research and survival gap between sub-Saharan Africa and high-income countries. Lessons learned by CANCaRe Africa, the Collaborative African Network for Childhood Cancer Care and Research while pioneering such research are being discussed together with recommendations for the future.

Financial hardship in families of children or adolescents with cancer: a systematic literature review.

Financial hardship in childhood cancer contributes to poor health outcomes and global disparities in survival, but the extent of the financial burden on families is not yet fully understood. We systematically reviewed financial hardship prevalence and individual components characterising financial hardship across six domains (medical, non-medical, and indirect costs, financial strategies, psychosocial responses, and behavioural responses) and compared characteristics across country income levels using an established theory of human needs. We included 123 studies with data spanning 47 countries. Extensive heterogeneity in study methodologies and measures resulted in incomparable prevalence estimates and limited analysis. Components characterising financial hardship spanned the six domains and showed variation across country income contexts, yet a synthesis of existing literature cannot establish whether these are true differences in characterisation or burden. Our findings emphasise a crucial need to implement a data-driven methodological framework with validated measures to inform effective policies and interventions to address financial hardship in childhood cancer.

Dietary supplement use among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Adult survivors of childhood cancer have poor adherence to nutrition guidelines and inadequate intake of dietary vitamins D and E, potassium, fiber, magnesium, and calcium. The contribution of vitamin and mineral supplement use to total nutrient intake in this population is unclear. METHODS: We examined the prevalence and dose of nutrient intake among 2570 adult survivors of childhood cancer participating in the St. Jude Lifetime Cohort Study, and the association of dietary supplement use with treatment exposures, symptom burden, and quality of life. RESULTS: Nearly 40% of the adult survivors of cancer survivors reported regular use of dietary supplements. Although cancer survivors who used dietary supplements were less likely to have inadequate intake of several nutrients, they were also more likely to have excessive intake (total nutrient intake ≥ tolerable upper intake levels) of folate (15.4% vs. 1.3%), vitamin A (12.2% vs. 0.2%), iron (27.8% vs. 1.2%), zinc (18.6% vs. 1%), and calcium (5.1% vs. 0.9%) compared with survivors who did not use dietary supplements (all p < 0.05). Treatment exposures, symptom burden, and physical functioning were not associated with supplement use, whereas emotional well-being and vitality were positively associated with supplement use among childhood cancer survivors. CONCLUSIONS: Supplement use is associated with both inadequate and excessive intake of specific nutrients, but positively impacts aspects of quality of life among childhood cancer survivors.

The cost-effectiveness of gene therapy for severe hemophilia B: a microsimulation study from the United States perspective.

Adeno-associated virus (AAV)-mediated gene therapy is a novel treatment promising to reduce morbidity associated with hemophilia. Although multiple clinical trials continue to evaluate efficacy and safety, limited cost-effectiveness data have been published. This study compared the potential cost-effectiveness of AAV-mediated factor IX (FIX)-Padua gene therapy for patients with severe hemophilia B in the United States vs on-demand FIX replacement and primary FIX prophylaxis, using either standard or extended half-life FIX products. A microsimulation Markov model was constructed, and transition probabilities between health states and utilities were informed by using published data. Costs were aggregated by using a microcosting approach. A time horizon from 18 years old until death, from the perspective of a third-party payer in the United States, was conducted. Gene therapy was more cost-effective than both alternatives considering a $150 000/quality-adjusted life-year threshold. The price for gene therapy was assumed to be $2 000 000 in the base case scenario; however, one of the 1-way sensitivity analyses was conducted by using observed manufacturing, administration, and 5-year follow-up costs of $87 198 for AAV-mediated gene therapy vector as derived from the manufacturing facility and clinical practice at St Jude Children's Research Hospital. One-way sensitivity analyses revealed 10 of 102 scenarios in which gene therapy was not cost-effective compared with alternative treatments. Notably, gene therapy remained cost-effective in a hypothetical scenario in which we estimated that the discounted factor concentrate price was 20% of the wholesale acquisition cost in the United States. Probabilistic sensitivity analysis estimated gene therapy to be cost-effective at 92% of simulations considering a $150 000/quality-adjusted life-year threshold. In conclusion, based on detailed simulation inputs and assumptions, gene therapy was more cost-effective than on-demand treatment and prophylaxis for patients with severe hemophilia B.

Implementation of a formalized evaluation and planning tool to improve pediatric oncology outcomes in Kenya.

BACKGROUND: Survival from pediatric cancers in low middle-income countries is often very low compared to that of high-income countries due to multifactorial etiologies, including late presentation, delayed diagnosis, difficulty with accessing healthcare, drug unavailability, and treatment abandonment. The St. Jude Pediatric Oncology Facility Integrated Local Evaluation Tool (PrOFILE) was developed to map and evaluate childhood cancer healthcare delivery in individual institutions and entire countries, identifying the strengths and weaknesses, as well as opportunities for advancement of care. PROCEDURE: Using the PrOFILE self-assessment tool, selected Kenyan pediatric oncology facilities entered data into 12 modules: national context, facility and local context, finances and resources, personnel, service capacity, service integration, diagnostics, chemotherapy, supportive care, surgery, radiation therapy, and patients and outcomes. These modules are grouped into five specific components, including Context, Workforce, Diagnostics, Therapy, and Patients and Outcomes. The St. Jude PrOFILE team analyzed the data and organized the first hybrid workshop, containing both in-person and virtual components. RESULTS: Multidisciplinary stakeholders prioritized recommendations for improving care and developed smart objectives to accomplish identified goals over the following 2 years. Strengths and weaknesses of conducting a hybrid global workshop were identified. CONCLUSIONS: We demonstrated successful use of the PrOFILE tool to conduct a hybrid workshop and identify strategies to improve pediatric oncology care in Kenya. The voluntarily structured work groups will methodically aim to achieve outcome-oriented goals moving forward.

Outcomes of SARS-CoV-2 infection in 126 children and adolescents with central nervous system tumors.

BACKGROUND: The Global Registry of COVID-19 in Childhood Cancer (GRCCC) seeks to describe the natural history of SARS-CoV-2 in children with cancer across the world. Here, we report the disease course and management of coronavirus disease 2019 (COVID-19) infection in the subset of children and adolescents with central nervous system (CNS) tumors who were included in the GRCCC until February 2021, the first data freeze. PROCEDURE: The GRCCC is a deidentified web-based registry of patients less than 19 years of age with cancer or recipients of a hematopoietic stem cell transplant and laboratory-confirmed SARS-CoV-2 infection. Demographic data, cancer diagnosis, cancer-directed therapy, and clinical characteristics of SARS-CoV-2 infection were collected. Outcomes were collected at 30 and 60 days post infection. RESULTS: The GRCCC included 1500 cases from 45 countries, including 126 children with CNS tumors (8.4%). Sixty percent of the cases were from middle-income countries, while no cases were reported from low-income countries. Low-grade gliomas, high-grade gliomas, and CNS embryonal tumors were the most common CNS cancer diagnoses (67%, 84/126). Follow-up at 30 days was available for 107 (85%) patients. Based on the composite measure of severity, 53.3% (57/107) of reported SARS-CoV-2 infections were asymptomatic, 39.3% (42/107) were mild/moderate, and 6.5% (7/107) were severe or critical. One patient died from SARS-CoV-2 infection. There was a significant association between infection severity and absolute neutrophil count less than 500 (p = .04). Of 107 patients with follow-up available, 40 patients (37.4%) were not receiving cancer-directed therapy. Thirty-four patients (50.7%) had a modification to their treatment due to withholding of chemotherapy or delays in radiotherapy or surgery. CONCLUSION: In this cohort of patients with CNS tumors and COVID-19, the frequency of severe infection appears to be low, although severe disease and death do occur. We found that greater severity was seen in patients with severe neutropenia, although treatment modifications were not associated with infection severity or cytopenias. Additional analyses are needed to further describe this unique group of patients.

Processes and perceptions of chemotherapy supply chain in Ethiopia: A mixed-method study.

BACKGROUND: The impact and downstream effects of the chemotherapy supply chain in Ethiopia are not well understood. The purpose of this study was to identify perceived gaps in supply chain and characterize their impact on patient care. METHODS: A concurrent mixed-method study was conducted at a large academic cancer center in Ethiopia. In-depth interviews (IDIs) and surveys were completed in collaboration with external stakeholders with knowledge about chemotherapy supply chain in Ethiopia. Thematic coding was used for qualitative analysis of IDI and descriptive statistics were used to summarize quantitative survey data. RESULTS: Six stakeholders participated in the IDIs and seven completed surveys. IDIs revealed that most chemotherapeutic agents are purchased by the Ethiopian Pharmaceutical Supply Agency (EPSA) and are distributed to cancer treatment centers. A free-market purchasing option also exists, but for chemotherapy obtained outside of government-subsidized channels, the potential for substandard or falsified chemotherapy was a concern. Participants expressed confidence that the correct treatment was administered to patients, but viewpoints on reliability and consistency of medication supply were variable. Quantitative data from the survey showed that participants were not confident that medications are prepared safely and correctly. Improper storage and manipulation of high-risk medications remain a significant risk to staff. CONCLUSIONS: This study provides insight from a healthcare staff perspective on how gaps in the chemotherapy supply chain process impact patient care in a low-income country. Inventory management, disruptions in supply chain, and product integrity were perceived as the largest gaps in the current chemotherapy supply chain structure.

Childhood Neurotoxicity and Brain Resilience to Adverse Events during Adulthood.

OBJECTIVE: This study used childhood cancer survivors as a novel model to study whether children who experience central nervous system (CNS) injury are at higher risk for neurocognitive impairment associated with subsequent late onset chronic health conditions (CHCs). METHODS: Adult survivors of childhood cancer (n = 2,859, ≥10 years from diagnosis, ≥18 years old) completed a comprehensive neurocognitive battery and clinical examination. Neurocognitive impairment was defined as age-adjusted z score < 10th percentile. Participants impaired on ≥3 tests had global impairment. CHCs were graded using the Common Terminology Criteria for Adverse Events v4.3 (grade 1, mild; 2, moderate; 3, severe/disabling; 4, life-threatening) and were combined into a severity/burden score by frequency and grade (none/low, medium, high, and very high). A total of 1,598 survivors received CNS-directed therapy including cranial radiation, intrathecal methotrexate, or neurosurgery. Logistic regression estimated the odds of neurocognitive impairment associated with severity/burden score and grade 2 to 4 conditions, stratified by CNS treatment. RESULTS: CNS-treated survivors performed worse than non-CNS-treated survivors on all neurocognitive tests and were more likely to have global neurocognitive impairment (46.9% vs 35.3%, p < 0.001). After adjusting for demographic and treatment factors, there was a dose-response association between severity/burden score and global neurocognitive impairment, but only among CNS-treated survivors (high odds ratio [OR] = 2.24, 95% confidence interval [CI] = 1.42-3.53; very high OR = 4.07, 95% CI = 2.30-7.17). Cardiovascular and pulmonary conditions were associated with processing speed, executive function, and memory impairments in CNS-treated but not non-CNS-treated survivors who were impacted by neurologic conditions. INTERPRETATION: Reduced cognitive/brain reserve associated with CNS-directed therapy during childhood may make survivors vulnerable to adverse cognitive effects of cardiopulmonary conditions during adulthood. ANN NEUROL 2021;89:534-545.

Patient-reported outcomes in survivors of childhood hematologic malignancies with hematopoietic stem cell transplant.

Patient-reported outcomes among survivors of pediatric hematopoietic stem cell transplant (HSCT) are understudied. We compared symptom prevalence, health-related quality of life (HRQOL), and risk factors in adult survivors of childhood hematologic malignancies treated with HSCT to those treated with conventional therapy and noncancer controls. Survivors of childhood hematologic malignancies (HSCT N = 112 [70% allogeneic, 30% autologous]; conventionally treated N = 1106) and noncancer controls (N = 242) from the St. Jude Lifetime Cohort Study completed surveys assessing 10 symptom domains and SF-36 HRQOL summary scores. Chronic health conditions (CHCs) were validated by clinical assessment. Multivariable logistic regression reveals that compared with noncancer controls, HSCT survivors endorsed a significantly higher symptom prevalence in sensation (OR = 4.7, 95% confidence interval [CI], 2.6-8.4), motor/movement (OR = 4.3, 95% CI, 1.6-11.0), pulmonary (OR = 4.6, 95% CI, 1.8-11.8), and memory domains (OR = 4.8, 95% CI, 2.5-9.2), and poorer physical HRQOL (OR = 6.9, 95% CI, 2.8-17.0). HSCT and conventionally treated survivors had a similar prevalence of all symptom domains and HRQOL (all P > .05); however, HSCT survivors had a significantly higher cumulative prevalence for specific symptoms: double vision (P = .04), very dry eyes (P < .0001), and trouble seeing when wearing glasses (P < .0001). Occurrence of organ-specific CHCs, instead of transplant receipt, was significantly associated with a higher prevalence of all symptom domains (all P < .05) in adult survivors of childhood cancer, except for pain and anxiety domains. This study found that patient-reported outcomes were equally impaired between HSCT and conventionally treated survivors, but poorer in both groups compared with noncancer controls. Poor patient-reported outcomes in all survivors of childhood hematologic malignancies correlated with the presence of CHCs, whether treated with conventional therapy or HSCT.

Cost analysis of acute care resource utilization among individuals with sickle cell disease in a middle-income country.

BACKGROUND: The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC). We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea in a specialized hematology center in Brazil. METHODS: The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. The reasons for acute hospital visits were grouped as: 1) vaso-occlusive (VOC) pain, 2) infection, 3) anemia exacerbation, and 4) chronic organ damage complications. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period. RESULTS: In total, 1144 patients, median age 17 years (range 0-70), 903 (78.9%) with HbSS/HbSß0-thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions. Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2176.40/visit). Compared with other genotypes, individuals with HbSS/HbSß0-thalassemia were admitted more often (79% versus 21%, p < 0.0001), and their admission costs were higher ($1677.18 versus $1224.47/visit, p = 0.0001). Antibiotics and analgesics accounted for 43% and 42% of the total ED costs, respectively, while housing accounted for 46% of the total admission costs. Costs of ED visits not resulting in admissions were lower among HbSS/HbSß0-thalassemia individuals with hydroxyurea MPR ≥65% compared with visits by patients with MPR <65% ($98.16/visit versus $182.46/visit, p = 0.0007). No difference in admission costs were observed relative to hydroxyurea use. DISCUSSION: In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Hydroxyurea may reduce ED costs among individuals with HbSS/HbSß0-thalassemia but is dependent on adherence level.

Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study.

BACKGROUND: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. METHODS: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. FINDINGS: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8-8·8]; p<0·0001) and upper-middle-income (1·6 [1·2-2·2]; p=0·0024) country status; age 15-18 years (1·6 [1·1-2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8-3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3-2·4]; p=0·0001), and intensive treatment (1·8 [1·3-2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3-0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3-0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3-2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1-2·3]; p=0·020). INTERPRETATION: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. FUNDING: American Lebanese Syrian Associated Charities and the National Cancer Institute.

Cumulative burden of chronic health conditions among adolescent and young adult survivors of childhood cancer: Identification of vulnerable groups at key medical transitions.

The cumulative burden of chronic health conditions as childhood cancer survivors transition to adult health care and insurance systems is unknown. We estimated the cumulative burden (N = 4612 survivors, 625 controls) in the St. Jude Lifetime Cohort. At 18 and 26 years old, survivors experienced (per 100 individuals) an average of 22.3 (95% confidence interval [CI]: 17.2-27.4) and 40.3 (95% CI: 34.8-45.8) disabling conditions versus 3.5 (95% CI: 2.0-5.0) and 5.7 (95% CI: 3.7-7.7) in controls, and 128.7 (95% CI: 119.5-137.8) and 240.5 (95% CI: 229.9-251.0) lower severity conditions versus 12.4 (95% CI: 8.9-16.0) and 51.3 (95% CI: 43.1-59.4) in controls. Survivors experience a high cumulative burden at key health care transition ages, underscoring the need to optimize access to care.

The Global COVID-19 Observatory and Resource Center for Childhood Cancer: A response for the pediatric oncology community by SIOP and St. Jude Global.

The COVID-19 pandemic quickly led to an abundance of publications and recommendations, despite a paucity of information on how COVID-19 affects children with cancer. This created a dire need for a trusted resource with curated information and a space for the pediatric oncology community to share experiences. The Global COVID-19 Observatory and Resource Center for Childhood Cancer was developed, launched, and maintained by the International Society of Pediatric Oncology and St. Jude Children's Research Hospital. The three components (Resource Library, Global Registry, and Collaboration Space) complement each other, establishing a mechanism to generate and transfer knowledge rapidly throughout the community.

Development of paediatric non-stage prognosticator guidelines for population-based cancer registries and updates to the 2014 Toronto Paediatric Cancer Stage Guidelines.

Population-based cancer registries (PBCRs) generate measures of cancer incidence and survival that are essential for cancer surveillance, research, and cancer control strategies. In 2014, the Toronto Paediatric Cancer Stage Guidelines were developed to standardise how PBCRs collect data on the stage at diagnosis for childhood cancer cases. These guidelines have been implemented in multiple jurisdictions worldwide to facilitate international comparative studies of incidence and outcome. Robust stratification by risk also requires data on key non-stage prognosticators (NSPs). Key experts and stakeholders used a modified Delphi approach to establish principles guiding paediatric cancer NSP data collection. With the use of these principles, recommendations were made on which NSPs should be collected for the major malignancies in children. The 2014 Toronto Stage Guidelines were also reviewed and updated where necessary. Wide adoption of the resultant Paediatric NSP Guidelines and updated Toronto Stage Guidelines will enhance the harmonisation and use of childhood cancer data provided by PBCRs.

Sustainable care for children with cancer: a Lancet Oncology Commission.

We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020-50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.

Clinically ascertained health outcomes, quality of life, and social attainment among adult survivors of neuroblastoma: A report from the St. Jude Lifetime Cohort.

BACKGROUND: The objective of this study was to characterize chronic disease, health-related quality of life (HRQOL), emotional distress, and social attainment among long-term survivors of neuroblastoma. METHODS: Chronic health conditions among 136 ≥10-year neuroblastoma survivors (median age, 31.9 years; range, 20.2-54.6 years) and 272 community controls (median age, 34.7 years; range, 18.3-59.6 years) were graded with a modified version of the Common Terminology Criteria for Adverse Events (version 4.03). HRQOL and emotional distress were assessed with the Medical Outcomes Study 36-Item Short Form Health Survey and the Brief Symptom Inventory-18. Log-binomial regression and logistic regression were used to compare the prevalence of chronic conditions and the frequency of reduced HRQOL, distress, and social attainment between survivors and controls. The cumulative burden approach was used to estimate multimorbidity. RESULTS: By the age of 35 years, survivors had experienced, on average, 8.5 grade 1 to 5 conditions (95% confidence interval [CI], 7.6-9.3), which was higher than the average for controls (3.3; 95% CI, 2.9-3.7). Compared with controls, survivors had a higher prevalence of any pulmonary (P = .003), auditory (P < .001), gastrointestinal (P < .001), neurological (P = .003), or renal condition (P < .001); were more likely to report poor physical HRQOL (P = .01) and symptoms of anxiety (P = .01) and somatization (P = .01); and were less likely to live independently (P = .01) or marry (P = .01). In analyses limited to survivors, those with 1 or more grade 3 to 5 conditions were more likely to report reduced general health (odds ratio [OR], 6.6; 95% CI, 1.6-26.9), greater bodily pain (OR, 4.2; 95% CI, 1.0-17.0), and unemployment (OR, 3.2; 95% CI, 1.2-8.5). CONCLUSIONS: Because of the high burden of chronic diseases and the associations of these morbidities with reduced HRQOL and social attainment, screening and interventions that provide opportunities to optimize health are important among neuroblastoma survivors.

The management of Hodgkin lymphoma in adolescents and young adults: burden of disease or burden of choice?

Adolescents and young adults (AYAs) comprise the largest age group affected by Hodgkin lymphoma (HL). Despite excellent overall survival of AYA patients with HL due to advances in treatment regimens, therapy-associated late effects continue to be a concern in HL survivors, especially for younger patients who have decades of life remaining. Since the first clinical trial for HL with chemotherapy in 1964, subsequent protocols have attempted to reduce chemotherapy-induced toxicities and yet maintain high overall survival rates. Today, new analytic methods applied to data from survivorship cohorts, such as the recently described cumulative burden of disease metric, can be used to inform changes for future protocols. Although pediatric and adult trial consortia have followed this process, the AYA population, an age cohort split between pediatric and adult health care services, faces many barriers to care and is the least likely to be enrolled in clinical trials. AYA patients with HL theoretically have a choice to be treated in pediatric or adult protocols when presented with these options. Recent efforts by the National Clinical Trials Network, the Children's Oncology Group, and others have been made to ensure that the burden of choice for the AYA population is not greater than the burden of disease.

Global childhood cancer survival estimates and priority-setting: a simulation-based analysis.

BACKGROUND: Accurate childhood cancer survival estimates are crucial for policy makers and clinicians for priority-setting and planning decisions. However, observed survival estimates are lacking for many countries, and when available, wide variation in outcomes is reported. Understanding the barriers to optimising survival can help improve childhood cancer outcomes. We aimed to provide estimates of global childhood cancer survival, accounting for the impact of multiple factors that affect cancer outcomes in children. METHODS: We developed a microsimulation model to simulate childhood cancer survival for 200 countries and territories worldwide, accounting for clinical and epidemiologic factors, including country-specific treatment variables, such as availability of chemotherapy, radiation, and surgery. To ensure model results were consistent with reported survival data, we calibrated the model to estimates from the CONCORD-2 and CONCORD-3 studies using an Approximate Bayesian Computation approach. We estimated 5-year net survival for diagnosed cases of childhood cancer in each country and territory and estimated potential survival gains of seven policy interventions focused on improving treatment availability and delivery (ie, increasing the availability of chemotherapy, radiation, general surgery, neurosurgery, or ophthalmic surgery, reducing treatment abandonment, and improving the quality of care to the mean of high-income countries) implemented in isolation or as packages. FINDINGS: Our model estimated that, for diagnosed cases, global 5-year net childhood cancer survival is currently 37·4% (95% uncertainty interval 34·7-39·8), with large variation by region, ranging from 8·1% (4·4-13·7) in eastern Africa to 83·0% (81·6-84·4) in North America. Among the seven policy interventions modelled, each individually provided small gains, increasing global 5-year net survival to between 38·4% (35·8-40·9) and 44·6% (41·7-47·4). 5-year net survival increased more substantially when policy interventions were bundled into packages that improved service delivery (5-year net survival 50·2% [47·3-53·0]) or that expanded treatment access (54·1% [50·1-58·5]). A comprehensive systems approach consisting of all policy interventions yielded superadditive gains with a global 5-year net survival of 53·6% (51·5-55·6) at 50% scale-up and 80·8% (79·5-82·1) at full implementation. INTERPRETATION: Childhood cancer survival varies widely by region, with especially poor survival in Africa. Although expanding access to treatment (chemotherapy, radiation, and surgery) and addressing financial toxicity are essential, investments that improve the quality of care, at both the health-system and facility level, are needed to improve childhood cancer outcomes globally. FUNDING: Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard TH Chan School of Public Health, Harvard Medical School, National Cancer Institute, SickKids, St Jude Children's Research Hospital, Union for International Cancer Control, Children with Cancer UK Davidson and O'Gorman Fellowship.