Prediction of ischemic heart disease and stroke in survivors of childhood cancer

Eric J. Chow, Yan Chen, Melissa M. Hudson, Elizabeth A.M. Feijen, Leontien C. Kremer, William L. Border, Daniel M. Green, Lillian R. Meacham, Daniel A. Mulrooney, Kirsten K. Ness, Kevin C. Oeffinger, Cécile M. Ronckers, Charles A. Sklar, Marilyn Stovall, Helena J. Van Der Pal, Irma W.E.M. Van Dijk, Flora E. Van Leeuwen, Rita E. Weathers, Leslie L. Robison, Gregory Armstrong & 1 others Yutaka Yasui

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalJournal of Clinical Oncology
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2018

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Myocardial Ischemia
Survivors
Stroke
Neoplasms
Area Under Curve
Siblings
Ageism
Incidence
Cohort Studies
Neck
Radiotherapy
Thorax
Drug Therapy
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chow, E. J., Chen, Y., Hudson, M. M., Feijen, E. A. M., Kremer, L. C., Border, W. L., ... Yasui, Y. (2018). Prediction of ischemic heart disease and stroke in survivors of childhood cancer. Journal of Clinical Oncology, 36(1), 44-52. https://doi.org/10.1200/JCO.2017.74.8673

Prediction of ischemic heart disease and stroke in survivors of childhood cancer. / Chow, Eric J.; Chen, Yan; Hudson, Melissa M.; Feijen, Elizabeth A.M.; Kremer, Leontien C.; Border, William L.; Green, Daniel M.; Meacham, Lillian R.; Mulrooney, Daniel A.; Ness, Kirsten K.; Oeffinger, Kevin C.; Ronckers, Cécile M.; Sklar, Charles A.; Stovall, Marilyn; Van Der Pal, Helena J.; Van Dijk, Irma W.E.M.; Van Leeuwen, Flora E.; Weathers, Rita E.; Robison, Leslie L.; Armstrong, Gregory; Yasui, Yutaka.

In: Journal of Clinical Oncology, Vol. 36, No. 1, 01.01.2018, p. 44-52.

Research output: Contribution to journalArticle

Chow, EJ, Chen, Y, Hudson, MM, Feijen, EAM, Kremer, LC, Border, WL, Green, DM, Meacham, LR, Mulrooney, DA, Ness, KK, Oeffinger, KC, Ronckers, CM, Sklar, CA, Stovall, M, Van Der Pal, HJ, Van Dijk, IWEM, Van Leeuwen, FE, Weathers, RE, Robison, LL, Armstrong, G & Yasui, Y 2018, 'Prediction of ischemic heart disease and stroke in survivors of childhood cancer', Journal of Clinical Oncology, vol. 36, no. 1, pp. 44-52. https://doi.org/10.1200/JCO.2017.74.8673
Chow, Eric J. ; Chen, Yan ; Hudson, Melissa M. ; Feijen, Elizabeth A.M. ; Kremer, Leontien C. ; Border, William L. ; Green, Daniel M. ; Meacham, Lillian R. ; Mulrooney, Daniel A. ; Ness, Kirsten K. ; Oeffinger, Kevin C. ; Ronckers, Cécile M. ; Sklar, Charles A. ; Stovall, Marilyn ; Van Der Pal, Helena J. ; Van Dijk, Irma W.E.M. ; Van Leeuwen, Flora E. ; Weathers, Rita E. ; Robison, Leslie L. ; Armstrong, Gregory ; Yasui, Yutaka. / Prediction of ischemic heart disease and stroke in survivors of childhood cancer. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 1. pp. 44-52.
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abstract = "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.",
author = "Chow, {Eric J.} and Yan Chen and Hudson, {Melissa M.} and Feijen, {Elizabeth A.M.} and Kremer, {Leontien C.} and Border, {William L.} and Green, {Daniel M.} and Meacham, {Lillian R.} and Mulrooney, {Daniel A.} and Ness, {Kirsten K.} and Oeffinger, {Kevin C.} and Ronckers, {C{\'e}cile M.} and Sklar, {Charles A.} and Marilyn Stovall and {Van Der Pal}, {Helena J.} and {Van Dijk}, {Irma W.E.M.} and {Van Leeuwen}, {Flora E.} and Weathers, {Rita E.} and Robison, {Leslie L.} and Gregory Armstrong and Yutaka Yasui",
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T1 - Prediction of ischemic heart disease and stroke in survivors of childhood cancer

AU - Chow, Eric J.

AU - Chen, Yan

AU - Hudson, Melissa M.

AU - Feijen, Elizabeth A.M.

AU - Kremer, Leontien C.

AU - Border, William L.

AU - Green, Daniel M.

AU - Meacham, Lillian R.

AU - Mulrooney, Daniel A.

AU - Ness, Kirsten K.

AU - Oeffinger, Kevin C.

AU - Ronckers, Cécile M.

AU - Sklar, Charles A.

AU - Stovall, Marilyn

AU - Van Der Pal, Helena J.

AU - Van Dijk, Irma W.E.M.

AU - Van Leeuwen, Flora E.

AU - Weathers, Rita E.

AU - Robison, Leslie L.

AU - Armstrong, Gregory

AU - Yasui, Yutaka

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

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