scholarly journals Individual Prediction of Heart Failure Among Childhood Cancer Survivors

2015 ◽  
Vol 33 (5) ◽  
pp. 394-402 ◽  
Author(s):  
Eric J. Chow ◽  
Yan Chen ◽  
Leontien C. Kremer ◽  
Norman E. Breslow ◽  
Melissa M. Hudson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Childhood Cancer ◽  
Cancer Diagnosis ◽  
Prediction Models ◽  
Wilms Tumor ◽  
Area Under The Curve ◽  
Risk Groups ◽  
Childhood Cancer Survivors ◽  
Risk Scores ◽  
Individual Risk

Purpose To create clinically useful models that incorporate readily available demographic and cancer treatment characteristics to predict individual risk of heart failure among 5-year survivors of childhood cancer. Patients and Methods Survivors in the Childhood Cancer Survivor Study (CCSS) free of significant cardiovascular disease 5 years after cancer diagnosis (n = 13,060) were observed through age 40 years for the development of heart failure (ie, requiring medications or heart transplantation or leading to death). Siblings (n = 4,023) established the baseline population risk. An additional 3,421 survivors from Emma Children's Hospital (Amsterdam, the Netherlands), the National Wilms Tumor Study, and the St Jude Lifetime Cohort Study were used to validate the CCSS prediction models. Results Heart failure occurred in 285 CCSS participants. Risk scores based on selected exposures (sex, age at cancer diagnosis, and anthracycline and chest radiotherapy doses) achieved an area under the curve of 0.74 and concordance statistic of 0.76 at or through age 40 years. Validation cohort estimates ranged from 0.68 to 0.82. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups, corresponding to cumulative incidences of heart failure at age 40 years of 0.5% (95% CI, 0.2% to 0.8%), 2.4% (95% CI, 1.8% to 3.0%), and 11.7% (95% CI, 8.8% to 14.5%), respectively. In comparison, siblings had a cumulative incidence of 0.3% (95% CI, 0.1% to 0.5%). Conclusion Using information available to clinicians soon after completion of childhood cancer therapy, individual risk for subsequent heart failure can be predicted with reasonable accuracy and discrimination. These validated models provide a framework on which to base future screening strategies and interventions.

Development and validation of a prediction model for kidney failure in long-term survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10047-10047
Author(s):  
Natalie Lucy Wu ◽  
Yan Chen ◽  
Bryan V. Dieffenbach ◽  
Nan Li ◽  
Matthew J. Ehrhardt ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Cancer Diagnosis ◽  
Kidney Failure ◽  
Prediction Models ◽  
Wilms Tumor ◽  
Risk Groups ◽  
Risk Scores ◽  
Individual Risk ◽  
C Statistic ◽  
Survivors Of Childhood Cancer

10047 Background: Kidney failure (need for dialysis or kidney transplantation, or death due to kidney disease) is a rare but serious late effect for survivors of childhood cancer. We aimed to develop a model using demographic and treatment characteristics to predict individual risk of kidney failure among five-year survivors of childhood cancer. Methods: CCSS survivors without kidney failure at five years after cancer diagnosis (n = 25,483) were assessed for subsequent kidney failure by age 40. Outcomes were self-reported and corroborated by the Organ Procurement and Transplantation Network and the National Death Index. A sibling cohort (n = 5045) served as a comparator. Piecewise exponential models with backward selection estimated the relationships between potential predictors and kidney failure and were converted to integer risk scores. Additional results from the St. Jude Lifetime Cohort Study (SJLIFE, n = 2490) and the National Wilms Tumor Study (NWTS, n = 6760) validated the models. Results: Among CCSS survivors, 204 developed late kidney failure. We developed a model with sex, race/ethnicity, age at cancer diagnosis, nephrectomy, exposure to specific chemotherapy, any abdominal radiation, presence of genitourinary anomalies, and early-onset hypertension (Table). Risk scores achieved an area under the curve (AUC) and concordance (C) statistic of 0.65 and 0.68 for kidney failure by age 40. Validation cohort AUC and C statistics were 0.83/0.86 for SJLIFE (8 cases) and 0.61/0.63 for NWTS (91 cases). An alternative model with specific chemotherapy doses and kidney-specific radiation dosimetry had similar AUC and C statistic (0.67/0.70). Integer risk scores were collapsed to form statistically distinct low (score <3; 87 cases of 17,326), moderate (score 3-5; 63 cases of 4667), and high (score 6+; 18 cases of 401) risk groups. These groups corresponded to cumulative incidences in CCSS of kidney failure by age 40 of 0.6% (95% CI 0.4-0.7%), 2.3% (95% CI 1.6-3.2%), and 9.4% (95% CI 4.4-16.7%), compared with 0.2% (95% CI 0.1-0.5%) among siblings. Conclusions: Using readily available information, we were able to identify low, moderate, and high risk groups for developing kidney failure following treatment for childhood cancer. These prediction models may help guide screening and interventional strategies for higher risk survivors.[Table: see text]

scholarly journals Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer

2018 ◽  
Vol 36 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Eric J. Chow ◽  
Yan Chen ◽  
Melissa M. Hudson ◽  
Elizabeth A.M. Feijen ◽  
Leontien C. Kremer ◽  
...  
Keyword(s):  
Heart Disease ◽  
High Risk ◽  
Ischemic Heart Disease ◽  
Childhood Cancer ◽  
Area Under The Curve ◽  
Risk Groups ◽  
Ischemic Heart ◽  
Risk Scores ◽  
Individual Risk ◽  
Survivors Of Childhood Cancer

Purpose We aimed to predict individual risk of ischemic heart disease and stroke in 5-year survivors of childhood cancer. Patients and Methods Participants in the Childhood Cancer Survivor Study (CCSS; n = 13,060) were observed through age 50 years for the development of ischemic heart disease and stroke. Siblings (n = 4,023) established the baseline population risk. Piecewise exponential models with backward selection estimated the relationships between potential predictors and each outcome. The St Jude Lifetime Cohort Study (n = 1,842) and the Emma Children’s Hospital cohort (n = 1,362) were used to validate the CCSS models. Results Ischemic heart disease and stroke occurred in 265 and 295 CCSS participants, respectively. Risk scores based on a standard prediction model that included sex, chemotherapy, and radiotherapy (cranial, neck, and chest) exposures achieved an area under the curve and concordance statistic of 0.70 and 0.70 for ischemic heart disease and 0.63 and 0.66 for stroke, respectively. Validation cohort area under the curve and concordance statistics ranged from 0.66 to 0.67 for ischemic heart disease and 0.68 to 0.72 for stroke. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups. The cumulative incidences at age 50 years among CCSS low-risk groups were < 5%, compared with approximately 20% for high-risk groups ( P < .001); cumulative incidence was only 1% for siblings ( P < .001 v low-risk survivors). Conclusion Information available to clinicians soon after completion of childhood cancer therapy can predict individual risk for subsequent ischemic heart disease and stroke with reasonable accuracy and discrimination through age 50 years. These models provide a framework on which to base future screening strategies and interventions.

scholarly journals Traditional Cardiovascular Risk Factors and Individual Prediction of Cardiovascular Events in Childhood Cancer Survivors

2019 ◽  
Vol 112 (3) ◽  
pp. 256-265 ◽  
Author(s):  
Yan Chen ◽  
Eric J Chow ◽  
Kevin C Oeffinger ◽  
William L Border ◽  
Wendy M Leisenring ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Cardiovascular Risk ◽  
Childhood Cancer ◽  
Cardiovascular Risk Factors ◽  
Operating Characteristic ◽  
Prediction Models ◽  
Characteristic Curve ◽  
Childhood Cancer Survivors ◽  
Operating Characteristic Curve

Abstract Background Childhood cancer survivors have an increased risk of heart failure, ischemic heart disease, and stroke. They may benefit from prediction models that account for cardiotoxic cancer treatment exposures combined with information on traditional cardiovascular risk factors such as hypertension, dyslipidemia, and diabetes. Methods Childhood Cancer Survivor Study participants (n = 22 643) were followed through age 50 years for incident heart failure, ischemic heart disease, and stroke. Siblings (n = 5056) served as a comparator. Participants were assessed longitudinally for hypertension, dyslipidemia, and diabetes based on self-reported prescription medication use. Half the cohort was used for discovery; the remainder for replication. Models for each outcome were created for survivors ages 20, 25, 30, and 35 years at the time of prediction (n = 12 models). Results For discovery, risk scores based on demographic, cancer treatment, hypertension, dyslipidemia, and diabetes information achieved areas under the receiver operating characteristic curve and concordance statistics 0.70 or greater in 9 and 10 of the 12 models, respectively. For replication, achieved areas under the receiver operating characteristic curve and concordance statistics 0.70 or greater were observed in 7 and 9 of the models, respectively. Across outcomes, the most influential exposures were anthracycline chemotherapy, radiotherapy, diabetes, and hypertension. Survivors were then assigned to statistically distinct risk groups corresponding to cumulative incidences at age 50 years of each target outcome of less than 3% (moderate-risk) or approximately 10% or greater (high-risk). Cumulative incidence of all outcomes was 1% or less among siblings. Conclusions Traditional cardiovascular risk factors remain important for predicting risk of cardiovascular disease among adult-age survivors of childhood cancer. These prediction models provide a framework on which to base future surveillance strategies and interventions.

Predicting and Preventing Anthracycline-Related Cardiotoxicity

2018 ◽  
pp. 3-12 ◽  
Author(s):  
Saro Armenian ◽  
Smita Bhatia
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Prediction Models ◽  
Lymphoblastic Leukemia ◽  
Childhood Cancer Survivors ◽  
Chemotherapeutic Agents ◽  
Increased Risk ◽  
Risk Reducing

Anthracyclines (doxorubicin, daunorubicin, epirubicin, and idarubicin) are among the most potent chemotherapeutic agents and have truly revolutionized the management of childhood cancer. They form the backbone of chemotherapy regimens used to treat childhood acute lymphoblastic leukemia, acute myeloid leukemia, Hodgkin lymphoma, Ewing sarcoma, osteosarcoma, and neuroblastoma. More than 50% of children with cancer are treated with anthracyclines. The clinical utility of anthracyclines is compromised by dose-dependent cardiotoxicity, manifesting initially as asymptomatic cardiac dysfunction and evolving irreversibly to congestive heart failure. Childhood cancer survivors are at a five- to 15-fold increased risk for congestive heart failure compared with the general population. Once diagnosed with congestive heart failure, the 5-year survival rate is less than 50%. Prediction models have been developed for childhood cancer survivors (i.e., after exposure to anthracyclines) to identify those at increased risk for cardiotoxicity. Studies are currently under way to test risk-reducing strategies. There remains a critical need to identify patients with childhood cancer at diagnosis (i.e., prior to anthracycline exposure) such that noncardiotoxic therapies can be contemplated.

Cost-effectiveness of screening guidelines to prevent heart failure in childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10052-10052
Author(s):  
Matthew J. Ehrhardt ◽  
Zachary J. Ward ◽  
Qi Liu ◽  
Aeysha Chaudhry ◽  
Anju Nohria ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cost Effectiveness ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Risk Group ◽  
Cost Effective ◽  
Risk Groups ◽  
Childhood Cancer Survivors ◽  
Low Risk ◽  
Screening Guidelines

10052 Background: Childhood cancer survivors treated with anthracyclines or chest radiation therapy (RT) are at risk for left ventricular dysfunction (LVD) and subsequent heart failure (HF). The International Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms for LVD, but evidence supporting its frequency and cost-effectiveness is limited. Methods: Using data from the CCSS, we developed a microsimulation model of the clinical course of LVD and HF to estimate long-term health and economic outcomes associated with screening for IGHG-defined risk groups (low [anthracycline 1-99 mg/m2 and/or RT < 15 Gy], moderate [100 to < 250 mg/m2 or 15 to < 35 Gy], high [≥ 250 mg/m2 or ≥ 35 Gy or (≥ 100 mg/m2 and ≥ 15 Gy)]). We compared 1, 2, and 5-year interval-based screening to no screening. Screening performance and pharmacological treatment effectiveness were based on published studies. Costs and quality of life weights were based on US averages and published studies. Outcomes included lifetime HF risk, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs < $100,000/QALY gained were considered cost-effective. Results: Among the IGHG risk groups, the lifetime HF risk in the absence of screening was 37% (high), 25% (moderate) and 17% (low). Screening every 2 or 5 years was cost-effective for the high-risk group, and every 5 years for the moderate-risk group. In contrast, routine screening may not be cost-effective for the low risk group, representing ~40% of those for whom screening is currently recommended. Conclusions: Our findings can inform screening guidelines and suggest that LVD/HF surveillance for low-risk survivors warrants careful consideration. [Table: see text]

scholarly journals External assessment of the EUROMACS right-sided heart failure risk score

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hirak Shah ◽  
Thomas Murray ◽  
Jessica Schultz ◽  
Ranjit John ◽  
Cindy M. Martin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Risk Score ◽  
Pressure Ratio ◽  
Area Under The Curve ◽  
Left Ventricular ◽  
Right Atrial ◽  
Risk Scores ◽  
External Assessment ◽  
Failure Risk

AbstractThe EUROMACS Right-Sided Heart Failure Risk Score was developed to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) placement. The predictive ability of the EUROMACS score has not been tested in other cohorts. We performed a single center analysis of a continuous-flow (CF) LVAD cohort (n = 254) where we calculated EUROMACS risk scores and assessed for right ventricular heart failure after LVAD implantation. Thirty-nine percent of patients (100/254) had post-operative RVF, of which 9% (23/254) required prolonged inotropic support and 5% (12/254) required RVAD placement. For patients who developed RVF after LVAD implantation, there was a 45% increase in the hazards of death on LVAD support (HR 1.45, 95% CI 0.98–2.2, p = 0.066). Two variables in the EUROMACS score (Hemoglobin and Right Atrial Pressure to Pulmonary Capillary Wedge Pressure ratio) were not predictive of RVF in our cohort. Overall, the EUROMACS score had poor external discrimination in our cohort with area under the curve of 58% (95% CI 52–66%). Further work is necessary to enhance our ability to predict RVF after LVAD implantation.

Abstract P341: Juvenile Exposure To Doxorubicin Differentially Alters The Cardiac Response To Angiotensin II And Isoproterenol In Adult Mice

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Marianne K Grant ◽  
Beshay N Zordoky
Keyword(s):  
Heart Failure ◽  
Risk Factor ◽  
Angiotensin Ii ◽  
Cardiac Function ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Childhood Cancer Survivors ◽  
Cardiac Response

Hypertension is the most significant risk factor for heart failure in doxorubicin (DOX)-treated childhood cancer survivors. We previously developed a two-hit mouse model of juvenile DOX-induced latent cardiotoxicity that is exacerbated by adult-onset angiotensin II (ANGII)-induced hypertension. Nevertheless, it is still not known how juvenile exposure to DOX would predispose the heart to other cardiovascular pathologic stimuli that do not cause hypertension. The objective of this work was to compare the effects of ANGII to those of isoproterenol (ISO) in adult C57BL6/N mice pre-exposed to DOX as juveniles. Five-week-old male mice were administered a low dose of DOX (4 mg/kg/week) or saline for 3 weeks and then allowed to recover for 5 weeks. Thereafter, mice were either infused with ANGII (1.4 mg/kg/day) or injected with ISO (10 mg/kg/day) for 14 days. Juvenile exposure to DOX abrogated the hypertrophic response to both ANGII and ISO, while it failed to correct ANGII- and ISO-induced upregulation in the hypertrophic markers ANP and BNP. ANGII, but not ISO, worsened cardiac function in DOX-exposed mice as measured by echocardiography. Cardiac fibrosis was also exacerbated by ANGII, but not ISO, in DOX-exposed mice as evident by Masson’s trichrome staining and upregulation of the inflammatory and fibrotic markers, Cox-2, Col1a1, Col3a1 , and galectin-3 . In conclusion, the current work demonstrates that ANGII causes more severe deterioration in cardiac function and adverse cardiac remodeling in DOX-exposed mice when compared to ISO. The comparison between DOX/ANGII and DOX/ISO models is critical to understanding why hypertension is the most significant risk factor for heart failure in DOX-treated childhood cancer survivors and thereby devising effective therapeutic strategies against this significant clinical problem.

Palliative care of cancer survivors

2015 ◽  
pp. 661-670
Author(s):  
Mary S. McCabe ◽  
Stacie Corcoran
Keyword(s):  
Quality Of Life ◽  
Palliative Care ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cancer Diagnosis ◽  
Childhood Cancer Survivors ◽  
The Family ◽  
Heavy Burden ◽  
Optimal Quality

Being told you are cancer-free does not mean you are free of the consequences of the disease. Seventy-six percent of cancer survivors are over age 60 years and have coexisting medical conditions that complicate posttreatment recovery to maximum health. Childhood cancer survivors also carry a heavy burden of medical and psychological problems resulting from their experience with cancer. Cancer diagnosis and treatment affects the family as well as the patient. Improvements are needed in the coordination of care for cancer survivors to assure optimal quality of life.

The Impact of Cancer on Early Childhood Development: A Linked Data Study

2020 ◽  
Author(s):  
Julia N Morris ◽  
David Roder ◽  
Deborah Turnbull ◽  
Hugh Hunkin
Keyword(s):  
Physical Health ◽  
Childhood Cancer ◽  
Cancer Diagnosis ◽  
Protective Factor ◽  
Developmental Outcomes ◽  
Population Data ◽  
Childhood Cancer Survivors ◽  
General Knowledge ◽  
Health And Wellbeing ◽  
The Impact

Abstract Objective  This study used retrospective linked population data to investigate the impact of early childhood cancer on developmental outcomes. Methods  Children aged &lt;9 years with a recorded malignant neoplasm were identified in the South Australian Cancer Registry. They were then linked to developmental data recorded in the Australian Early Development Census (AEDC) for the 2009, 2012, and 2015 data collection periods; and assigned five matched controls from the same AEDC year. Results  Between 2000 and 2015, 43 children had a malignant cancer diagnosis and also participated in the AEDC. Compared to controls, childhood cancer survivors exhibited greater developmental vulnerability in their physical health and wellbeing. Between survivors and controls, no significant developmental differences were observed in social, emotional, language and cognitive, and communication and general knowledge domains. Rural or remote location had a significant positive effect on developmental outcomes for childhood cancer survivors relative to controls, suggesting this was a protective factor in terms of physical health and wellbeing, social competence, communication, and general knowledge. Among all children, socioeconomic advantage was linked to better developmental outcomes on all domains except physical health and wellbeing. Conclusion  Following an early cancer diagnosis, children may require targeted care to support their physical health and wellbeing. Geographic variation in developmental outcomes indicates remoteness was a protective factor and requires further investigation. This study highlights the feasibility of using administrative whole-population data to investigate cancer outcomes.

scholarly journals Cost-Effectiveness of the International Late Effects of Childhood Cancer Guideline Harmonization Group Screening Guidelines to Prevent Heart Failure in Survivors of Childhood Cancer

2020 ◽  
Vol 38 (33) ◽  
pp. 3851-3862 ◽  
Author(s):  
Matthew J. Ehrhardt ◽  
Zachary J. Ward ◽  
Qi Liu ◽  
Aeysha Chaudhry ◽  
Anju Nohria ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cost Effectiveness ◽  
High Risk ◽  
Childhood Cancer ◽  
Late Effects ◽  
Cost Effective ◽  
Risk Groups ◽  
Low Risk ◽  
Moderate Risk ◽  
Survivors Of Childhood Cancer

PURPOSE Survivors of childhood cancer treated with anthracyclines and/or chest-directed radiation are at increased risk for heart failure (HF). The International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms, but evidence supporting its frequency and cost-effectiveness is limited. PATIENTS AND METHODS Using the Childhood Cancer Survivor Study and St Jude Lifetime Cohort, we developed a microsimulation model of the clinical course of HF. We estimated long-term health outcomes and economic impact of screening according to IGHG-defined risk groups (low [doxorubicin-equivalent anthracycline dose of 1-99 mg/m2 and/or radiotherapy < 15 Gy], moderate [100 to < 250 mg/m2 or 15 to < 35 Gy], or high [≥ 250 mg/m2 or ≥ 35 Gy or both ≥ 100 mg/m2 and ≥ 15 Gy]). We compared 1-, 2-, 5-, and 10-year interval-based screening with no screening. Screening performance and treatment effectiveness were estimated based on published studies. Costs and quality-of-life weights were based on national averages and published reports. Outcomes included lifetime HF risk, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs < $100,000 per QALY gained were considered cost-effective. RESULTS Among the IGHG risk groups, cumulative lifetime risks of HF without screening were 36.7% (high risk), 24.7% (moderate risk), and 16.9% (low risk). Routine screening reduced this risk by 4% to 11%, depending on frequency. Screening every 2, 5, and 10 years was cost-effective for high-risk survivors, and every 5 and 10 years for moderate-risk survivors. In contrast, ICERs were > $175,000 per QALY gained for all strategies for low-risk survivors, representing approximately 40% of those for whom screening is currently recommended. CONCLUSION Our findings suggest that refinement of recommended screening strategies for IGHG high- and low-risk survivors is needed, including careful reconsideration of discontinuing asymptomatic left ventricular dysfunction and HF screening in low-risk survivors.

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