Therapy-related cardiac risk in childhood cancer survivors

An analysis of the childhood cancer survivor study

James E. Bates, Rebecca M. Howell, Qi Liu, Yutaka Yasui, Daniel A. Mulrooney, Sughosh Dhakal, Susan A. Smith, Wendy M. Leisenring, Daniel J. Indelicato, Todd M. Gibson, Gregory Armstrong, Kevin C. Oeffinger, Louis S. Constine

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

PURPOSE The impacts of radiotherapy dose and exposed cardiac volume, select chemotherapeutic agents, and age at exposure on risk for late-onset cardiac disease in survivors of childhood cancer remain unresolved. PATIENTS AND METHODS We determined the rates of severe to fatal cardiac disease in 24,214 5-year survivors in the Childhood Cancer Survivor Study diagnosed between 1970 and 1999 at a median age of 7.0 years (range, 0 to 20.9 years), with a median attained age of 27.5 years (range, 5.6 to 58.9 years). Using piecewise exponential models, we evaluated the association between cardiac disease rates and demographic and treatment characteristics. RESULTS The cumulative incidence of cardiac disease 30 years from diagnosis was 4.8% (95% CI, 4.3 to 5.2). Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥ 50% of heart) were associated with an increased rate of cardiac disease (relative rate, 1.6; 95% CI, 1.1 to 2.3) compared with survivors without cardiac radiotherapy exposure. Similarly, high doses (≥ 20 Gy) to small cardiac volumes (0.1% to 29.9%) were associated with an elevated rate (relative rate, 2.4; 95% CI, 1.4 to 4.2). A dose-response relationship was observed between anthracycline chemotherapy and heart failure with younger children (age ≤ 13 years) at the greatest risk for heart failure after comparable dosing. CONCLUSION These observations support advances in radiation field design and delivery technology to reduce cardiac dose/volume and should guide future treatment protocols. They also inform clinical practice guidelines for post-therapy surveillance and risk-reducing strategies.

Original languageEnglish (US)
Pages (from-to)1090-1101
Number of pages12
JournalJournal of Clinical Oncology
Volume37
Issue number13
DOIs
StatePublished - Jan 1 2019

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Cardiac Volume
Survivors
Heart Diseases
Radiotherapy
Neoplasms
Heart Failure
Therapeutics
Anthracyclines
Clinical Protocols
Practice Guidelines
Demography
Radiation
Technology
Drug Therapy
Incidence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Bates, J. E., Howell, R. M., Liu, Q., Yasui, Y., Mulrooney, D. A., Dhakal, S., ... Constine, L. S. (2019). Therapy-related cardiac risk in childhood cancer survivors: An analysis of the childhood cancer survivor study. Journal of Clinical Oncology, 37(13), 1090-1101. https://doi.org/10.1200/JCO.18.01764

Therapy-related cardiac risk in childhood cancer survivors : An analysis of the childhood cancer survivor study. / Bates, James E.; Howell, Rebecca M.; Liu, Qi; Yasui, Yutaka; Mulrooney, Daniel A.; Dhakal, Sughosh; Smith, Susan A.; Leisenring, Wendy M.; Indelicato, Daniel J.; Gibson, Todd M.; Armstrong, Gregory; Oeffinger, Kevin C.; Constine, Louis S.

In: Journal of Clinical Oncology, Vol. 37, No. 13, 01.01.2019, p. 1090-1101.

Research output: Contribution to journalArticle

Bates, JE, Howell, RM, Liu, Q, Yasui, Y, Mulrooney, DA, Dhakal, S, Smith, SA, Leisenring, WM, Indelicato, DJ, Gibson, TM, Armstrong, G, Oeffinger, KC & Constine, LS 2019, 'Therapy-related cardiac risk in childhood cancer survivors: An analysis of the childhood cancer survivor study', Journal of Clinical Oncology, vol. 37, no. 13, pp. 1090-1101. https://doi.org/10.1200/JCO.18.01764
Bates, James E. ; Howell, Rebecca M. ; Liu, Qi ; Yasui, Yutaka ; Mulrooney, Daniel A. ; Dhakal, Sughosh ; Smith, Susan A. ; Leisenring, Wendy M. ; Indelicato, Daniel J. ; Gibson, Todd M. ; Armstrong, Gregory ; Oeffinger, Kevin C. ; Constine, Louis S. / Therapy-related cardiac risk in childhood cancer survivors : An analysis of the childhood cancer survivor study. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 13. pp. 1090-1101.
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abstract = "PURPOSE The impacts of radiotherapy dose and exposed cardiac volume, select chemotherapeutic agents, and age at exposure on risk for late-onset cardiac disease in survivors of childhood cancer remain unresolved. PATIENTS AND METHODS We determined the rates of severe to fatal cardiac disease in 24,214 5-year survivors in the Childhood Cancer Survivor Study diagnosed between 1970 and 1999 at a median age of 7.0 years (range, 0 to 20.9 years), with a median attained age of 27.5 years (range, 5.6 to 58.9 years). Using piecewise exponential models, we evaluated the association between cardiac disease rates and demographic and treatment characteristics. RESULTS The cumulative incidence of cardiac disease 30 years from diagnosis was 4.8{\%} (95{\%} CI, 4.3 to 5.2). Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥ 50{\%} of heart) were associated with an increased rate of cardiac disease (relative rate, 1.6; 95{\%} CI, 1.1 to 2.3) compared with survivors without cardiac radiotherapy exposure. Similarly, high doses (≥ 20 Gy) to small cardiac volumes (0.1{\%} to 29.9{\%}) were associated with an elevated rate (relative rate, 2.4; 95{\%} CI, 1.4 to 4.2). A dose-response relationship was observed between anthracycline chemotherapy and heart failure with younger children (age ≤ 13 years) at the greatest risk for heart failure after comparable dosing. CONCLUSION These observations support advances in radiation field design and delivery technology to reduce cardiac dose/volume and should guide future treatment protocols. They also inform clinical practice guidelines for post-therapy surveillance and risk-reducing strategies.",
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AU - Mulrooney, Daniel A.

AU - Dhakal, Sughosh

AU - Smith, Susan A.

AU - Leisenring, Wendy M.

AU - Indelicato, Daniel J.

AU - Gibson, Todd M.

AU - Armstrong, Gregory

AU - Oeffinger, Kevin C.

AU - Constine, Louis S.

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N2 - PURPOSE The impacts of radiotherapy dose and exposed cardiac volume, select chemotherapeutic agents, and age at exposure on risk for late-onset cardiac disease in survivors of childhood cancer remain unresolved. PATIENTS AND METHODS We determined the rates of severe to fatal cardiac disease in 24,214 5-year survivors in the Childhood Cancer Survivor Study diagnosed between 1970 and 1999 at a median age of 7.0 years (range, 0 to 20.9 years), with a median attained age of 27.5 years (range, 5.6 to 58.9 years). Using piecewise exponential models, we evaluated the association between cardiac disease rates and demographic and treatment characteristics. RESULTS The cumulative incidence of cardiac disease 30 years from diagnosis was 4.8% (95% CI, 4.3 to 5.2). Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥ 50% of heart) were associated with an increased rate of cardiac disease (relative rate, 1.6; 95% CI, 1.1 to 2.3) compared with survivors without cardiac radiotherapy exposure. Similarly, high doses (≥ 20 Gy) to small cardiac volumes (0.1% to 29.9%) were associated with an elevated rate (relative rate, 2.4; 95% CI, 1.4 to 4.2). A dose-response relationship was observed between anthracycline chemotherapy and heart failure with younger children (age ≤ 13 years) at the greatest risk for heart failure after comparable dosing. CONCLUSION These observations support advances in radiation field design and delivery technology to reduce cardiac dose/volume and should guide future treatment protocols. They also inform clinical practice guidelines for post-therapy surveillance and risk-reducing strategies.

AB - PURPOSE The impacts of radiotherapy dose and exposed cardiac volume, select chemotherapeutic agents, and age at exposure on risk for late-onset cardiac disease in survivors of childhood cancer remain unresolved. PATIENTS AND METHODS We determined the rates of severe to fatal cardiac disease in 24,214 5-year survivors in the Childhood Cancer Survivor Study diagnosed between 1970 and 1999 at a median age of 7.0 years (range, 0 to 20.9 years), with a median attained age of 27.5 years (range, 5.6 to 58.9 years). Using piecewise exponential models, we evaluated the association between cardiac disease rates and demographic and treatment characteristics. RESULTS The cumulative incidence of cardiac disease 30 years from diagnosis was 4.8% (95% CI, 4.3 to 5.2). Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥ 50% of heart) were associated with an increased rate of cardiac disease (relative rate, 1.6; 95% CI, 1.1 to 2.3) compared with survivors without cardiac radiotherapy exposure. Similarly, high doses (≥ 20 Gy) to small cardiac volumes (0.1% to 29.9%) were associated with an elevated rate (relative rate, 2.4; 95% CI, 1.4 to 4.2). A dose-response relationship was observed between anthracycline chemotherapy and heart failure with younger children (age ≤ 13 years) at the greatest risk for heart failure after comparable dosing. CONCLUSION These observations support advances in radiation field design and delivery technology to reduce cardiac dose/volume and should guide future treatment protocols. They also inform clinical practice guidelines for post-therapy surveillance and risk-reducing strategies.

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