TY - JOUR
T1 - Therapy-related cardiac risk in childhood cancer survivors
T2 - An analysis of the childhood cancer survivor study
AU - Bates, James E.
AU - Howell, Rebecca M.
AU - Liu, Qi
AU - Yasui, Yutaka
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 T.
AU - Oeffinger, Kevin C.
AU - Constine, Louis S.
N1 - Funding Information:
The Childhood Cancer Survivor Study is supported by National Cancer Institute Grant No. CA55727 and by Cancer Center Support CORE Grant No. CA21765 to St Jude Children’s Research Hospital as well as by the American Lebanese Syrian Associated Charities. Neither the National Cancer Institute nor the American Lebanese Syrian Associated Charities played any role in the design of the study, analysis or interpretation of the data, or decision to submit this manuscript for publication.
Funding Information:
The Childhood Cancer Survivor Study is supported by National Cancer Institute Grant No. CA55727 and by Cancer Center Support CORE Grant No. CA21765 to St Jude Children's Research Hospital as well as by the American Lebanese Syrian Associated Charities. Neither the National Cancer Institute nor the American Lebanese Syrian Associated Charities played any role in the design of the study, analysis or interpretation of the data, or decision to submit this manuscript for publication.
Publisher Copyright:
© 2019 American Society of Clinical Oncology. All rights reserved.
PY - 2019
Y1 - 2019
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.
UR - http://www.scopus.com/inward/record.url?scp=85065307804&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065307804&partnerID=8YFLogxK
U2 - 10.1200/JCO.18.01764
DO - 10.1200/JCO.18.01764
M3 - Article
C2 - 30860946
AN - SCOPUS:85065307804
SN - 0732-183X
VL - 37
SP - 1090
EP - 1101
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 13
ER -