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Review
. 2021 Sep 21;3(3):343-359.
doi: 10.1016/j.jaccao.2021.06.007. eCollection 2021 Sep.

Past, Present, and Future of Radiation-Induced Cardiotoxicity: Refinements in Targeting, Surveillance, and Risk Stratification

Carmen Bergom  1   2   3 , Julie A Bradley  4 , Andrea K Ng  5 , Pamela Samson  1   3 , Clifford Robinson  1   3   6 , Juan Lopez-Mattei  7 , Joshua D Mitchell  2   3   6
Affiliations
Review

Past, Present, and Future of Radiation-Induced Cardiotoxicity: Refinements in Targeting, Surveillance, and Risk Stratification

Carmen Bergom et al. JACC CardioOncol. .

Abstract

Radiation therapy is an important component of cancer therapy for many malignancies. With improvements in cardiac-sparing techniques, radiation-induced cardiac dysfunction has decreased but remains a continued concern. In this review, we provide an overview of the evolution of radiotherapy techniques in thoracic cancers and associated reductions in cardiac risk. We also highlight data demonstrating that in some cases radiation doses to specific cardiac substructures correlate with cardiac toxicities and/or survival beyond mean heart dose alone. Advanced cardiac imaging, cardiovascular risk assessment, and potentially even biomarkers can help guide post-radiotherapy patient care. In addition, treatment of ventricular arrhythmias with the use of ablative radiotherapy may inform knowledge of radiation-induced cardiac dysfunction. Future efforts should explore further personalization of radiotherapy to minimize cardiac dysfunction by coupling knowledge derived from enhanced dosimetry to cardiac substructures, post-radiation regional dysfunction seen on advanced cardiac imaging, and more complete cardiac toxicity data.

Keywords: CAC, coronary artery calcium; CAD, coronary artery disease; CMRI, cardiac magnetic resonance imaging; CT, computed tomography; HL, Hodgkin lymphoma; LAD, left anterior descending artery; LV, left ventricular; MHD, mean heart dose; NSCLC, non–small cell lung cancer; RICD, radiation-induced cardiovascular disease; RT, radiation therapy; SBRT, stereotactic body radiation therapy; breast cancer; cancer survivorship; childhood cancer; esophageal cancer; imaging; lung cancer; lymphoma; radiation physics.

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Conflict of interest statement

This work was supported by the National Institutes of Health (R01HL147884) and National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002345). Dr Bergom has received research funding from the National Institutes of Health, Susan G. Komen Foundation, and Innovation Pathways. Dr Bradley has received an Ion Beam Application travel grant (April 2018) and funding from the Bankhead Coley Foundation and Ocala Royal Dames Foundation. Dr Ng has received funding from ViewRay. Dr Robinson has received research funding from the National Institutes of Health and the American Heart Association. Dr Mitchell has received research funding from Pfizer, Longer Life Foundation, and Children’s Discovery Institute and consultancy for Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Central Illustration
Central Illustration
Heart Regions Associated With Radiation-Induced Cardiovascular Disease and/or Survival First author and year of publication are listed. Highlighted colors indicate cancer type (see Key). Studies demonstrating associations between total heart doses and outcomes are not included. ∗Pericardium, not including the heart. LAD = left anterior descending artery; SVC = superior vena cava.
Figure 1
Figure 1
Evolution of RT in HL (A) Schematic representation of field design, radiation therapy (RT) doses, and radiation techniques for adult Hodgkin lymphoma (HL) as they have evolved over time. (B, C) RT plan comparison of an HL patient treated with involved-site RT to the mediastinum including colorwash dose distribution. Recreated historical mantle field (B), anterior-posterior technique, treated to a dose of 40 Gy, versus involved-site RT using IMRT (C), with deep-inspiration breath hold (note expansion of lungs and elongation of mediastinal structures, displacing lungs and heart away from target volume) with arms down on inclined board (further displacement of heart inferiorly), treated to 30 Gy with a 6-Gy boost to a level 5 node. (D) Dosimetric comparison of plans in B and C. IMRT = intensity-modulated radiation therapy; LAD = left anterior descending artery; LV = left ventricle; PET-CT = positron emission tomography–computed tomography.
Figure 2
Figure 2
Example Breast Plans Using Different RT Techniques and Modalities Example plans using cardiac-sparing techniques and different target volumes are shown. The selection of techniques and modalities is complex, involving availability of the technology, patient anatomy, and target volumes. All plans shown prescribed 50 Gy in 2-Gy fractions, except partial breast RT was prescribed 30 Gy in 5 fractions. 3DCRT = 3-dimensional conformal radiation therapy; DIBH = deep-inspiration breath hold; IMRT = intensity-modulated radiation therapy; MHD = mean heart dose; RT = radiation therapy; VMAT = volumetric-modulated arc therapy.
Figure 3
Figure 3
Comparison of Cardiovascular Imaging Modalities for Assessment of Radiation-Induced Cardiovascular Disease Major strengths and limitations of 4 major cardiovascular imaging modalities are shown. CAD = coronary artery disease; CMR = cardiac magnetic resonance imaging; echo = echocardiography; LVEF = left ventricular ejection fraction; SPECT = single-photon emission computed tomography.
See this image and copyright information in PMC

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