Rurality, Cardiovascular Risk Factors, and Early Cardiovascular Disease among Childhood, Adolescent, and Young Adult Cancer Survivors.

Background and Aims: Cardiovascular risk factors (CVRFs) later in life potentiate risk for late cardiovascular disease (CVD) from cardiotoxic treatment among survivors. This study evaluated the association of baseline CVRFs and CVD in the early survivorship period. Methods: This analysis included patients ages 0-29 at initial diagnosis and reported in the institutional cancer registry between 2010 and 2017 (n = 1228). Patients who died within five years (n = 168), those not seen in the oncology clinic (n = 312), and those with CVD within one year of diagnosis (n = 17) were excluded. CVRFs (hypertension, diabetes, dyslipidemia, and obesity) within one year of initial diagnosis, were constructed and extracted from the electronic health record based on discrete observations, ICD9/10 codes, and RxNorm codes for antihypertensives. Results: Among survivors (n = 731), 10 incident cases (1.4%) of CVD were observed between one year and five years after the initial diagnosis. Public health insurance (p = 0.04) and late effects risk strata (p = 0.01) were positively associated with CVD. Among survivors with public insurance(n = 495), two additional cases of CVD were identified from claims data with an incidence of 2.4%. Survivors from rural areas had a 4.1 times greater risk of CVD compared with survivors from urban areas (95% CI: 1.1-15.3), despite adjustment for late effects risk strata. Conclusions: Clinically computable phenotypes for CVRFs among survivors through informatics methods were feasible. Although CVRFs were not associated with CVD in the early survivorship period, survivors from rural areas were more likely to develop CVD. Implications for Survivors: Survivors from non-urban areas and those with public insurance may be particularly vulnerable to CVD.

Obesity Predisposes Anthracycline-Treated Survivors of Childhood and Adolescent Cancers to Subclinical Cardiac Dysfunction.

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards models were employed to identify risk factors for abnormal longitudinal strain (> - 16%) following anthracycline treatment. High anthracycline dose (≥ 250 mg/m2 doxorubicin equivalents) and obesity at the time of diagnosis (BMI > 95th percentile-for-age) were both significant predictors of abnormal strain with hazard ratios of 2.79, 95% CI (1.07-7.25), and 3.85, 95% CI (1.42-10.48), respectively. Among pediatric cancer survivors, patients who are obese at the time of diagnosis are at an increased risk of sub-clinical cardiac dysfunction following anthracycline exposure. Future studies should explore the incidence of symptomatic cardiomyopathy 10-15 years post-treatment among patients with early subclinical cardiac dysfunction.

Cardiovascular Risk Factor Disparities in Adult Survivors of Childhood Cancer Compared With the General Population.

Background: It is unknown whether a history of childhood cancer modifies the established disparities in cardiovascular risk factors (CVRFs) observed in the general population. Objectives: We sought to determine if disparities in CVRFs by race/ethnicity are similar among childhood cancer survivors compared with the general population. Methods: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort with a longitudinal follow-up of 24,084 5-year survivors diagnosed between 1970 and 1999. Multivariable piecewise exponential regression estimated incidence rate ratios (IRRs) for hypertension, hyperlipidemia, diabetes, obesity, and ≥2 CVRFs by race/ethnicity. The CCSS sibling cohort and the National Health and Nutrition Examination Survey cohort were used to compare the sociodemographic-adjusted IRRs for same-race/same-ethnicity disparities. Results: Non-Hispanic Black (NHB) (n = 1,092) and Hispanic (n = 1,405) survivors compared with non-Hispanic White (NHW) (n = 13,960) survivors reported a higher cumulative incidence of diabetes (8.4%, 9.7%, and 5.1%, respectively); obesity (47.2%, 48.9%, and 30.2%, respectively); multiple CVRFs (17.7%, 16.6%, and 12.3%, respectively); and, for NHB survivors, hypertension (19.5%, 13.6%, and 14.3%, respectively) by 40 years of age (P < 0.001). Controlling for sociodemographic and treatment factors compared with NHW survivors, IRRs for NHB were increased for hypertension (IRR: 1.4; 95% CI: 1.1-1.8), obesity (IRR: 1.7; 95% CI: 1.4-2.1), and multiple CVRFs (IRR: 1.6; 95% CI: 1.2-2.1). IRRs for Hispanic survivors were increased for diabetes (IRR: 1.8; 95% CI: 1.2-2.6) and obesity (IRR: 1.4; 95% CI: 1.2-1.7). The pattern of IRRs for CVRF differences was similar among CCSS sibling and National Health and Nutrition Examination Survey cohorts. Conclusions: The higher burden of CVRFs among NHB and Hispanic survivors compared with NHW survivors was similar to the general population. The promotion of cardiovascular health equity is critical in this high-risk population.

Informatics tools to implement late cardiovascular risk prediction modeling for population management of high-risk childhood cancer survivors.

BACKGROUND: Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management of childhood cancer survivors at high risk for late heart failure through the implementation of previously validated risk calculators. METHODS: The Oklahoma cohort (n = 365) harnessed data elements from Passport for Care (PFC), and the Duke cohort (n = 274) employed informatics methods to automatically extract chemotherapy exposures from electronic health record (EHR) data for survivors 18 years old and younger at diagnosis. The Childhood Cancer Survivor Study (CCSS) late cardiovascular risk calculator was implemented, and risk groups for heart failure were compared to the Children's Oncology Group (COG) and the International Guidelines Harmonization Group (IGHG) recommendations. Analysis within the Oklahoma cohort assessed disparities in guideline-adherent care. RESULTS: The Oklahoma and Duke cohorts both observed good overall concordance between the CCSS and COG risk groups for late heart failure, with weighted kappa statistics of .70 and .75, respectively. Low-risk groups showed excellent concordance (kappa > .9). Moderate and high-risk groups showed moderate concordance (kappa .44-.60). In the Oklahoma cohort, adolescents at diagnosis were significantly less likely to receive guideline-adherent echocardiogram surveillance compared with survivors younger than 13 years old at diagnosis (odds ratio [OD] 0.22; 95% confidence interval [CI]: 0.10-0.49). CONCLUSIONS: Clinical informatics tools represent a feasible approach to leverage discrete treatment-related data elements from PFC or the EHR to successfully implement previously validated late cardiovascular risk prediction models on a population health level. Concordance of CCSS, COG, and IGHG risk groups using real-world data informs current guidelines and identifies inequities in guideline-adherent care.

Rural, Large Town, and Urban Differences in Optimal Subspecialty Follow-up and Survivorship Care Plan Documentation among Childhood Cancer Survivors.

BACKGROUND: Children with cancer from rural and nonurban areas face unique challenges. Health equity for this population requires attention to geographic disparities in optimal survivorship-focused care. METHODS: The Oklahoma Childhood Cancer Survivor Cohort was based on all patients reported to the institutional cancer registry and ≤ 18 years old at diagnosis between January 1, 2005, and September 24, 2014. Suboptimal follow-up was defined as no completed oncology-related clinic visit five to 7 years after their initial diagnosis (survivors were 7-25 years old at end of the follow-up period). The primary predictor of interest was rurality. RESULTS: Ninety-four (21%) of the 449 eligible survivors received suboptimal follow-up. There were significant differences (P = 0.01) as 36% of survivors from large towns (n = 28/78) compared with 21% (n = 20/95) and 17% (n = 46/276) of survivors from small town/isolated rural and urban areas received suboptimal follow-up, respectively. Forty-five percent of adolescents at diagnosis were not seen in the clinic compared with 17% of non-adolescents (P < 0.01). An adjusted risk ratio of 2.2 (95% confidence interval, 1.5, 3.2) was observed for suboptimal follow-up among survivors from large towns, compared with survivors from urban areas. Seventy-three percent of survivors (n = 271/369) had a documented survivorship care plan with similar trends by rurality. CONCLUSIONS: Survivors from large towns and those who were adolescents at the time of diagnosis were more likely to receive suboptimal follow-up care compared with survivors from urban areas and those diagnosed younger than thirteen. IMPACT: Observed geographic disparities in survivorship care will inform interventions to promote equitable care for survivors from nonurban areas.

Data standards in pediatric oncology: Past, present, and future.

In this commentary, we highlight the central role that data standards play in facilitating data-driven efforts to advance research in pediatric oncology. We discuss the current state of data standards for pediatric oncology and propose five steps to achieve an improved future state with benefits for clinicians, researchers, and patients.

Leveraging Clinical Informatics Tools to Extract Cumulative Anthracycline Exposure, Measure Cardiovascular Outcomes, and Assess Guideline Adherence for Children With Cancer.

PURPOSE: Cardiovascular disease is a significant cause of late morbidity and mortality in survivors of childhood cancer. Clinical informatics tools could enhance provider adherence to echocardiogram guidelines for early detection of late-onset cardiomyopathy. METHODS: Cancer registry data were linked to electronic health record data. Structured query language facilitated the construction of anthracycline-exposed cohorts at a single institution. Primary outcomes included the data quality from automatic anthracycline extraction, sensitivity of International Classification of Disease coding for heart failure, and adherence to echocardiogram guideline recommendations. RESULTS: The final analytic cohort included 385 pediatric oncology patients diagnosed between July 1, 2013, and December 31, 2018, among whom 194 were classified as no anthracycline exposure, 143 had low anthracycline exposure (< 250 mg/m2), and 48 had high anthracycline exposure (≥ 250 mg/m2). Manual review of anthracycline exposure was highly concordant (95%) with the automatic extraction. Among the unexposed group, 15% had an anthracycline administered at an outside institution not captured by standard query language coding. Manual review of echocardiogram parameters and clinic notes yielded a sensitivity of 75%, specificity of 98%, and positive predictive value of 68% for International Classification of Disease coding of heart failure. For patients with anthracycline exposure, 78.5% (n = 62) were adherent to guideline recommendations for echocardiogram surveillance. There were significant association with provider adherence and race and ethnicity (P = .047), and 50% of patients with Spanish as their primary language were adherent compared with 90% of patients with English as their primary language (P = .003). CONCLUSION: Extraction of treatment exposures from the electronic health record through clinical informatics and integration with cancer registry data represents a feasible approach to assess cardiovascular disease outcomes and adherence to guideline recommendations for survivors.

Integration of cancer registry and electronic health record data to construct a childhood cancer survivorship cohort, facilitate risk stratification for late effects, and assess appropriate follow-up care.

BACKGROUND: This retrospective study harnessed an institutional cancer registry to construct a childhood cancer survivorship cohort, integrate electronic health record (EHR) and geospatial data to stratify survivors based on late-effect risk, analyze follow-up care patterns, and determine factors associated with suboptimal follow-up care. PROCEDURE: The survivorship cohort included patients ≤18 years of age reported to the institutional cancer registry between January 1, 1994 and November 30, 2012. International Classification of Diseases for Oncology, third revision (ICD-O-3) coding and treatment exposures facilitated risk stratification of survivors. The EHR was linked to the cancer registry based on medical record number (MRN) to extract clinic visits. RESULTS: Five hundred and ninety pediatric hematology-oncology (PHO) and 275 pediatric neuro-oncology (PNO) survivors were included in the final analytic cohort. Two hundred and eight-two survivors (32.6%) were not seen in any oncology-related subspecialty clinic at Duke 5-7 years after initial diagnosis. Factors associated with follow-up included age (p = .008), diagnosis (p < .001), race/ethnicity (p = .010), late-effect risk strata (p = .001), distance to treatment center (p < .0001), and area deprivation index (ADI) (p = .011). Multivariable logistic modeling attenuated the association for high-risk (OR 1.72; 95% CI 0.805, 3.66) and intermediate-risk (OR 1.23, 95% CI 0.644, 2.36) survivors compared to survivors at low risk of late effects among the PHO cohort. PNO survivors at high risk for late effects were more likely to follow up (adjusted OR 3.66; 95% CI 1.76, 7.61). CONCLUSIONS: Nearly a third of survivors received suboptimal follow-up care. This study provides a reproducible model to integrate cancer registry and EHR data to construct risk-stratified survivorship cohorts to assess follow-up care.

Advances in the Diagnosis and Management of Neonatal Sarcomas.

Neonatal sarcomas comprise a heterogeneous group of rare soft tissue neoplasms that present unique diagnostic and therapeutic challenges. Recent advances in molecular profiling have improved diagnostic capabilities and reveal novel therapeutic targets. Clinical trials demonstrate differences in behavior between sarcoma subtypes that allow for better clinical management. Surgical resection has been replaced with a multimodal approach that includes chemotherapy and radiotherapy. Despite these advances, neonates with sarcoma continue to fare worse than histologically similar sarcomas in older children, likely reflecting differences in tumor biology and the complexities of neonatal medicine. This review focuses on recent advances in managing neonatal sarcomas.

Recent Advances in Dengue: Relevance to Puerto Rico.

Dengue represents an increasingly important public health challenge in Puerto Rico, with recent epidemics in 2007, 2010, and 2012-2013. Although recent advances in dengue vaccine development offer hope for primary prevention, the role of health professionals in the diagnosis and management of dengue patients is paramount. Case definitions for dengue, dengue with warning signs, and severe dengue provide a framework to guide clinical decision-making. Furthermore, the differentiation between dengue and other acute febrile illnesses, such as leptospirosis and chikungunya, is necessary for the appropriate diagnosis and management of cases. An understanding of dengue epidemiology and surveillance in Puerto Rico provides context for clinicians in epidemic and non-epidemic periods. This review aims to improve health professionals' ability to diagnose dengue, and as highlight the relevance of recent advances in dengue prevention and management in Puerto Rico.