Nickhill Bhakta

The cost effectiveness of treating paediatric cancer in low-income and middle-income countries: a case-study approach using acute lymphocytic leukaemia in Brazil and Burkitt lymphoma in Malawi

Approximately 90% of children with cancer reside in low-income and middle-income countries (LMIC) where healthcare resources are scarce and allocation decisions difficult. The cost effectiveness of treating childhood cancers in these settings is unknown. The objective of the present work was to determine cost-effectiveness thresholds for common paediatric cancers using acute lymphoblastic leukaemia (ALL) in Brazil and Burkitt lymphoma (BL) in Malawi as examples. Disability-adjusted life years (DALYs) prevented by treatment were compared to the gross domestic product (GDP) per capita of each country to define cost-effectiveness thresholds using WHO-CHOICE (‘CHOosing Interventions that are Cost-Effective’) guidelines. The case examples were selected due to the data available and because ALL and BL both have the potential to yield significant health gains at a low cost per patient treated. The key findings were as follows: the 3:1 cost/DALY prevented to GDP/capita ratio for ALL in Brazil was US

Cumulative burden of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma: an analysis from the St Jude Lifetime Cohort Study

771 225; expenditures below this threshold were cost effective. Costs below US

The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE).

257 075 (1:1 ratio) were considered very cost effective. Analogous thresholds for BL in Malawi were US

Approach for Classification and Severity-grading of Long-term and Late-onset Health Events among Childhood Cancer Survivors in the St. Jude Lifetime Cohort

42 729 and US

Late outcomes of adult survivors of childhood non-Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study

14 243. Actual costs were far less. In Brazil, US

Blood Pressure Status in Adult Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study

16 700 was spent to treat each patient while in Malawi total drug costs were less than US

Chronic disease burden and frailty in survivors of childhood HSCT: a report from the St. Jude Lifetime Cohort Study

50 per child. In summary, treatment of certain paediatric cancers in LMIC is very cost effective. Future research should evaluate actual treatment and infrastructure expenditures to help guide policymakers.

The global burden of childhood cancer: Knowing what we do not know: Frazier et al.

Background The magnitude of cardiovascular morbidity among survivors of pediatric, adolescent, and young adult Hodgkin lymphoma is not known. Using medically ascertained data, we applied the cumulative burden metric to compare chronic cardiovascular health conditions among Hodgkin survivors and general population controls. Methods Among 670 survivors treated at St. Jude Children’s Research Hospital, who survived ≥10 years and became 18 years old, 348 were clinically assessed in the St. Jude Lifetime Cohort Study (SJLIFE). Age-sex-frequency-matched SJLIFE community-controls (n=272) were used for comparison. All SJLIFE participants underwent evaluation for 22 chronic cardiovascular health conditions. Direct assessments, combined with retrospective clinical reviews, were used to assign severity to conditions using a modified Common Terminology Criteria of Adverse Events (CTCAE) grading schema. Occurrences and CTCAE-grades of the conditions for 322 eligible non-SJLIFE participants were accounted for by multiple imputation. The mean cumulative count (treating death as a competing risk) was used to estimate cumulative burden. Findings At 50 years of age, the cumulative incidence of survivors experiencing at least one grade 3-5 cardiovascular condition was 45.5%. The survivor cohort experienced, on average, 430·6 (95% confidence interval, 380·7-480·6) grade 1-5 and 100·8 (77·3-124·3) grade 3-5 cardiovascular conditions per 100 survivors. At age 50, the grade 1-5 and 3-5 cumulative burdens of community-controls were appreciably lower at 227·4/100 (192·7-267·5) and 17·0/100 (8·4-27·5), respectively. Myocardial infarction and structural heart defects were the major contributors to the excess grade 3-5 cumulative burden among survivors. Higher cardiac radiation dose (≥35 Gy) was associated with an increased grade 3-5 cardiovascular burden. Interpretation The true impact of cardiovascular morbidity among pediatric Hodgkin lymphoma survivors is reflected in the cumulative burden. 50-year-old Hodgkin survivors will experience over two times the number of chronic cardiovascular health conditions compared community-controls and, on average, have one severe/life-threatening/fatal cardiovascular condition. The cumulative burden metric provides a more comprehensive approach to evaluating overall morbidity and will assist clinical researchers when designing future trials and refining general practice screening guidelines.

Absence of Basal Cell Carcinoma in Irradiated Childhood Cancer Survivors of Black Race: A Report from the St. Jude Lifetime Cohort Study.

Background Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity among survivors, however, has not been described. Methods Among 5,522 patients treated for childhood cancer at St. Jude Children’s Research Hospital who survived ≥10 years and were ≥18 years old, 3,010 underwent prospective clinical assessment and retrospective medical validation of health records as part of the St. Jude Lifetime Cohort Study. Age- and sex-frequency-matched community-controls (n=272) were used for comparison. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs among the 2512 survivors not clinically evaluated. Mean cumulative count and marked-point-process regression were used for descriptive and inferential cumulative burden analyses, respectively. Findings The cumulative incidence of any grade CHC at age 50 was 99·9%; 96·0% (95·3%–96·8%) for severe/disabling, life-threatening or fatal CHCs. By age 50, a survivor experienced, on average, 17·1 (16·2–18·0) CHCs including 4·7 (4·6–4·9) graded as severe/disabling, life-threatening or fatal. The cumulative burden among survivors was nearly 2-fold greater than matched community-controls (p<0·001). Second neoplasms, spinal disorders and pulmonary disease were major contributors to the excess total cumulative burden. Significant heterogeneity in CHCs among survivors with differing primary cancer diagnoses was observed. Multivariable analyses demonstrated that age at diagnosis, treatment era and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs. Interpretation The burden of surviving childhood cancer is substantial and highly variable. The total cumulative burden experienced by survivors of pediatric cancer, in conjunction with detailed characterization of long-term CHCs, provide data to better inform future clinical guidelines, research investigations and health services planning for this vulnerable, medically-complex population.

Determinants and Consequences of Financial Hardship Among Adult Survivors of Childhood Cancer: A Report From the St. Jude Lifetime Cohort Study

Characterization of toxicity associated with cancer and its treatment is essential to quantify risk, inform optimization of therapeutic approaches for newly diagnosed patients, and guide health surveillance recommendations for long-term survivors. The NCI Common Terminology Criteria for Adverse Events (CTCAE) provides a common rubric for grading severity of adverse outcomes in cancer patients that is widely used in clinical trials. The CTCAE has also been used to assess late cancer treatment-related morbidity but is not fully representative of the spectrum of events experienced by pediatric and aging adult survivors of childhood cancer. Also, CTCAE characterization does not routinely integrate detailed patient-reported and medical outcomes data available from clinically assessed cohorts. To address these deficiencies, we standardized the severity grading of long-term and late-onset health events applicable to childhood cancer survivors across their lifespan by modifying the existing CTCAE v4.03 criteria and aligning grading rubrics from other sources for chronic conditions not included or optimally addressed in the CTCAE v4.03. This article describes the methods of late toxicity assessment used in the St. Jude Lifetime Cohort Study, a clinically assessed cohort in which data from multiple diagnostic modalities and patient-reported outcomes are ascertained. Cancer Epidemiol Biomarkers Prev; 26(5); 666–74. ©2016 AACR.