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 ◽  
...  

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]

2015 ◽  
Vol 33 (5) ◽  
pp. 394-402 ◽  
Author(s):  
Eric J. Chow ◽  
Yan Chen ◽  
Leontien C. Kremer ◽  
Norman E. Breslow ◽  
Melissa M. Hudson ◽  
...  

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.


2018 ◽  
Vol 36 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Eric J. Chow ◽  
Yan Chen ◽  
Melissa M. Hudson ◽  
Elizabeth A.M. Feijen ◽  
Leontien C. Kremer ◽  
...  

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.


2020 ◽  
Vol 38 (33) ◽  
pp. 3851-3862 ◽  
Author(s):  
Matthew J. Ehrhardt ◽  
Zachary J. Ward ◽  
Qi Liu ◽  
Aeysha Chaudhry ◽  
Anju Nohria ◽  
...  

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.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9556-9556
Author(s):  
B. A. Kurt ◽  
V. G. Nolan ◽  
K. K. Ness ◽  
J. P. Neglia ◽  
J. M. Tersak ◽  
...  

9556 Background: Survivors of childhood cancer have a high burden of chronic health conditions following cancer therapy, but the risk for subsequent hospitalization has not been reported. Methods: Hospitalizations during 1996–2000 among a cohort of 10,367 5-yr survivors of childhood cancer (diagnosed 1970–1986) and 2,540 siblings were ascertained. Age-and gender-stratified standardized incidence ratios (SIRs) for hospitalization were calculated using the sibling cohort and U.S. population from the National Hospital Discharge Survey (NHDS). Associations between demographic, cancer/treatment-related risk factors and non-obstetrical hospitalization among survivors were evaluated in multiple variable logistic regression models. Results: At follow-up, survivors were a mean of 20.9 yrs. from diagnosis (SD: 4.6, range: 13.3–32.2) and mean age of 28.6 yrs. (SD: 7.7, range: 13–51). Overall hospitalization rates among survivors were 1.5 times (95% CI 1.44–1.52) that of siblings and 1.2 times (95% CI 1.16–1.22) that of the U.S. general population. Increased risk of hospitalization was noted irrespective of gender, age at follow-up, or cancer diagnosis, with highest SIRs noted for male (SIR=12.7, 95% CI 9.5–15.8) and female (SIR=72.1, 95% CI 58.8–85.5) survivors aged 45–54. Females (OR=1.2, 95% CI 1.04–1.3) and survivors with a chronic health condition (OR=1.6, 95% CI 1.5–1.8) were more likely to have been hospitalized for non-obstetrical causes after adjusting for age at diagnosis, age at follow-up, cancer diagnosis, household income, insurance, and history of relapse/second malignancy. Among survivors, those with Hodgkin's lymphoma had the highest hospitalization rates for neoplastic, infectious, endocrine, pulmonary and cardiovascular causes. CNS malignancy survivors had the highest hospitalization rates for neurologic, psychological and external (e.g. traumatic) causes. Conclusions: Therapy for childhood and adolescent cancer is associated with a significant increase in subsequent hospitalization rates. Regular medical follow-up and early intervention for chronic health conditions may help to limit severe toxicity that would require hospitalization. No significant financial relationships to disclose.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12073-12073
Author(s):  
Wendy Bottinor ◽  
Cindy Im ◽  
Saro Armenian ◽  
Borah Hong ◽  
Rebecca M. Howell ◽  
...  

12073 Background: The direct impact of a major cardiovascular (CV) event on mortality among childhood cancer survivors is not well described. We hypothesized that mortality following a major CV event would be higher among survivors compared with siblings and that mortality would be influenced by primary cancer treatment. Methods: The CCSS cohort has conducted longitudinal follow-up of 25,658 survivors of childhood cancer and 5,051 siblings. All-cause and CV-cause specific mortality after a first event of heart failure (HF), coronary artery disease (CAD), or stroke occurring at least 5 years after cancer diagnosis, was estimated using the Kaplan-Meier method. The relative hazards (HR) and 95% confidence intervals (CI) between survivors and siblings as well as the influence of demographic (sex, age, race/ethnicity) and cancer treatment factors were estimated via Cox regression. Results: In total, 1780 survivors and 91 siblings experienced a serious CV event. Total deaths included 706 survivors (271 cardiac causes, 381 non-cardiac causes, 54 unknown causes) and 14 siblings. Survivors were a median age of 31.5 years (range 6.5-61.5) and 20.0 years (range 5.0-44.6) since cancer diagnosis at time of CV event. After a CV event, estimated 10- and 20-y all-cause mortality was significantly higher among survivors than siblings (Table). The HR for all-cause mortality was significantly higher among survivors than siblings after HF (HR 5.2, CI 2.1-13.0), CAD (HR 4.2, CI 2.0-9.0), and stroke (HR 4.6, CI 1.5-14.6). HF and stroke-specific mortality were not significantly increased among survivors versus siblings, in contrast to CAD-specific mortality (HR 3.5, CI 1.1-11.0). Among survivors, heart dose from radiotherapy (per 10 Gy) was associated with increased all-cause and cause-specific mortality after HF (HR 1.2, CI 1.0-1.3; HR 1.3, CI 1.0-1.7), all-cause mortality after CAD (HR 1.2, CI 1.0-1.3), and cause-specific mortality after stroke (HR 2.5, CI 1.2-4.9). Brain dose from radiotherapy was associated with increased all-cause mortality (HR 1.1, CI, 1.0-1.2, per 10 Gy) after stroke. Anthracycline dose was not associated with increased overall or cause-specific mortality risk after a CV event. Conclusions: After a CV event, mortality is higher among survivors than siblings. In survivors, mortality is primarily driven by non-cardiac causes. CAD and prior radiotherapy exposure to the heart and brain also influenced mortality.[Table: see text]


2018 ◽  
Vol 25 (8) ◽  
pp. 924-930 ◽  
Author(s):  
Xiruo Ding ◽  
Ziad F Gellad ◽  
Chad Mather ◽  
Pamela Barth ◽  
Eric G Poon ◽  
...  

Abstract Objective As available data increases, so does the opportunity to develop risk scores on more refined patient populations. In this paper we assessed the ability to derive a risk score for a patient no-showing to a clinic visit. Methods Using data from 2 264 235 outpatient appointments we assessed the performance of models built across 14 different specialties and 55 clinics. We used regularized logistic regression models to fit and assess models built on the health system, specialty, and clinic levels. We evaluated fits based on their discrimination and calibration. Results Overall, the results suggest that a relatively robust risk score for patient no-shows could be derived with an average C-statistic of 0.83 across clinic level models and strong calibration. Moreover, the clinic specific models, even with lower training set sizes, often performed better than the more general models. Examination of the individual models showed that risk factors had different degrees of predictability across the different specialties. Implementation of optimal modeling strategies would lead to capturing an additional 4819 no-shows per-year. Conclusion Overall, this work highlights both the opportunity for and the importance of leveraging the available electronic health record data to develop more refined risk models.


2019 ◽  
Vol 37 (25) ◽  
pp. 2217-2225 ◽  
Author(s):  
Jenneke E. van Atteveld ◽  
Saskia M.F. Pluijm ◽  
Kirsten K. Ness ◽  
Melissa M. Hudson ◽  
Wassim Chemaitilly ◽  
...  

PURPOSE To develop and validate prediction models for low and very low bone mineral density (BMD) on the basis of clinical and treatment characteristics that identify adult survivors of childhood cancer who require screening by dual-energy x-ray absorptiometry. PATIENTS AND METHODS White survivors of childhood cancer (n = 2,032; median attained age, 29.3 years [range, 18.1 to 40.9 years]) enrolled in the St Jude Lifetime Cohort (SJLIFE; development) and survivors treated at the Erasmus Medical Center (validation) in the Netherlands (n = 403; median age, 24.2 years [range, 18.0 to 40.9 years]) were evaluated with dual-energy x-ray absorptiometry to determine lumbar spine BMD and total-body BMD. Low and very low BMD were defined as lumbar spine BMD and/or total-body BMD z scores of −1 or lower or −2 or lower, respectively. Multivariable logistic regression was used to build prediction models; performance was assessed using receiver operating characteristic curves. Diagnostic values were calculated at different probabilities. RESULTS Low BMD was present in 51% and 45% of SJLIFE and Dutch participants, respectively, and very low BMD was present in 20% and 10%, respectively. The model for low BMD included male sex (odds ratio [OR], 3.07), height (OR, 0.95), weight (OR, 0.98), attained age (OR, 0.97), current smoking status (OR, 1.48), and cranial irradiation (OR, 2.11). Areas under the curve were 0.72 (95% CI, 0.70 to 0.75) in the SJLIFE cohort and 0.69 (95% CI, 0.64 to 0.75) in the Dutch cohort. The sum of the sensitivity (69.0%) and specificity (64.0%) was maximal at the predicted probability of 50%. The model for very low BMD included male sex (OR, 3.28), height (OR, 0.95), weight (OR, 0.97), attained age (OR, 0.98), cranial irradiation (OR, 2.07), and abdominal irradiation (OR, 1.61), yielding areas under the curve of 0.76 (95% CI, 0.73 to 0.78; SJLIFE cohort) and 0.75 (95% CI, 0.67 to 0.83; Dutch cohort). CONCLUSION Validated prediction models for low and very low BMD, using easily measured patient and treatment characteristics, correctly identified BMD status in most white adult survivors through age 40 years.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J C L Himmelreich ◽  
L Veelers ◽  
W A M Lucassen ◽  
H C P M Van Weert ◽  
R E Harskamp

Abstract Background Atrial fibrillation (AF) presents a considerable burden on our health care systems. Early detection of AF may prevent AF-associated complications, such as stroke and heart failure. Given our aging populations, the number of new AF cases is expected to double over the next decades. As such, there is renewed interest to screen for AF in the community. To optimise screening efforts, risk prediction models may help us identify at-risk patients. Purpose To identify and evaluate the performance of prediction models for AF that may be applicable for screening in community settings. Methods We searched PubMed, Embase, and CINAHL databases for studies that derived and/or validated AF risk models from population-based cohorts. Three investigators independently assessed risk of bias (CHARMS checklist), and performed data extraction and evidence synthesis. The primary expression of associations in meta-analysis was the C-statistic for discrimination between AF and non-AF cases during follow-up, using a random effects model. We calculated 95% prediction intervals (PI) due to high heterogeneity (I2 >30%) in all analyses. Results We identified 23 studies that presented data on 8 risk models derived from 18 cohorts with a total of 1,4 million participants from across the globe. Average age in these cohorts ranged from 43–76 years and follow-up ranged from 3 to 20 years. Two of the 8 risk models had a sufficient number of validation studies to be included in the meta-analysis. The CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology) score had a summary C-statistic of 0.72 (95%-PI: 0.67–0.77; n=7 cohorts, n=53.040 patients). The FHS (Framingham Heart Study) score for AF had a summary C-statistic of 0.71 (95%-PI: 0.59–0.83; n=4 cohorts, n=19.300 patients). Both models include age, height and weight, blood pressure, prevalent heart failure, and antihypertensive medication use as variables. CHARGE-AF additionally includes race, current smoking, and history of diabetes and myocardial infarction. FHS additionally includes sex, PR interval, and significant murmur. Conclusions Currently two risk scores, CHARGE-AF and FHS, have been rigorously tested for predicting atrial fibrillation in general populations. The CHARGE-AF score may present the more promising, user-friendly score for future community screening efforts, as it solely relies on readily available clinical parameters. Acknowledgement/Funding This work was supported by the Netherlands Organisation for Health Research and Development (ZonMw) [80-83910-98-13046]


2015 ◽  
Vol 33 (26) ◽  
pp. 2893-2900 ◽  
Author(s):  
Arin L. Madenci ◽  
Stacey Fisher ◽  
Lisa R. Diller ◽  
Robert E. Goldsby ◽  
Wendy M. Leisenring ◽  
...  

Purpose For adult survivors of childhood cancer, knowledge about the long-term risk of intestinal obstruction from surgery, chemotherapy, and radiotherapy is limited. Methods Intestinal obstruction requiring surgery (IOS) occurring 5 or more years after cancer diagnosis was evaluated in 12,316 5-year survivors in the Childhood Cancer Survivor Study (2,002 with and 10,314 without abdominopelvic tumors) and 4,023 sibling participants. Cumulative incidence of IOS was calculated with second malignant neoplasm, late recurrence, and death as competing risks. Using piecewise exponential models, we assessed the associations of clinical and demographic factors with rate of IOS. Results Late IOS was reported by 165 survivors (median age at IOS, 19 years; range, 5 to 50 years; median time from diagnosis to IOS, 13 years) and 14 siblings. The cumulative incidence of late IOS at 35 years was 5.8% (95% CI, 4.4% to 7.3%) among survivors with abdominopelvic tumors, 1.0% (95% CI, 0.7% to 1.4%) among those without abdominopelvic tumors, and 0.3% (95% CI, 0.1% to 0.5%) among siblings. Among survivors, abdominopelvic tumor (adjusted rate ratio [ARR], 3.6; 95% CI, 1.9 to 6.8; P < .001) and abdominal/pelvic radiotherapy within 5 years of cancer diagnosis (ARR, 2.4; 95% CI, 1.6 to 3.7; P < .001) increased the rate of late IOS, adjusting for diagnosis year; sex; race/ethnicity; age at diagnosis; age during follow-up (as natural cubic spline); cancer type; and chemotherapy, radiotherapy, and surgery within 5 years of cancer diagnosis. Developing late IOS increased subsequent mortality among survivors (ARR, 1.8; 95% CI, 1.1 to 2.9; P = .016), adjusting for the same factors. Conclusion The long-term risk of IOS and its association with subsequent mortality underscore the need to promote awareness of this complication among patients and providers.


2010 ◽  
Vol 28 (4) ◽  
pp. 655-661 ◽  
Author(s):  
Christopher J. Recklitis ◽  
Lisa R. Diller ◽  
Xiaochun Li ◽  
Julie Najita ◽  
Leslie L. Robison ◽  
...  

Purpose To evaluate risk of suicide ideation (SI) after childhood cancer, prevalence of SI in a cohort of adult survivors of pediatric cancers was compared with prevalence in a sibling comparison group. The relationship of SI to cancer treatment and current health was examined, and the hypothesis that poor physical health is significantly associated with suicidality, after adjusting for depression, was specifically tested. Methods Nine thousand one hundred twenty-six adult survivors of childhood cancer and 2,968 siblings enrolled onto the Childhood Cancer Survivor Study completed a survey describing their demographics and medical and psychological functioning, including SI in the prior week. Results Of survivors, 7.8% reported SI compared with 4.6% of controls (odds ratio = 1.79; 95% CI, 1.4 to 2.4). Suicidality was unrelated to age, age at diagnosis, sex, cancer therapy, recurrence, time since diagnosis, or second malignancy. SI was associated with primary CNS cancer diagnosis, depression, and poor health outcomes including chronic conditions, pain, and poor global health rating. A logistic regression analysis showed that poor current physical health was significantly associated with SI even after adjusting for cancer diagnosis and depression. Conclusion Adult survivors of childhood cancers are at increased risk for SI. Risk of SI is related to cancer diagnosis and post-treatment mental and physical health, even many years after completion of therapy. The association of suicidal symptoms with physical health problems is important because these may be treatable conditions for which survivors seek follow-up care and underscores the need for a multidisciplinary approach to survivor care.


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