A Prospective Study of Early Radiation Associated Cardiac Toxicity Following Neoadjuvant Chemoradiation for Distal Esophageal Cancer

Burke, Aidan M.; Yeh, Celine; Kim, Sunnie S. Y.; Bergquist, Peter; Krishnan, Pranay; Barac, Ana; Srichai, Monvadi B.; Unger, Keith

doi:10.3389/fonc.2020.01169

Cited by 12 publications

(15 citation statements)

References 33 publications

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“…2021 ) and sweetened beverages that have been linked to CVD ( Kim et al. 2020 ), radiation therapy that could give rise to a great number of myocardial pathologies ranging from fibrosis to ischemic disease ( Burke et al. 2020 ), and the well-known endocarditis induced by Streptococcal infections ( Chamat-Hedemand et al.…”

Section: Discussionmentioning

confidence: 99%

Key Characteristics of Cardiovascular Toxicants

Lind¹,

Araujo

Barchowsky

et al. 2021

Environ Health Perspect

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Background: The concept of chemical agents having properties that confer potential hazard called key characteristics (KCs) was first developed to identify carcinogenic hazards. Identification of KCs of cardiovascular (CV) toxicants could facilitate the systematic assessment of CV hazards and understanding of assay and data gaps associated with current approaches. Objectives: We sought to develop a consensus-based synthesis of scientific evidence on the KCs of chemical and nonchemical agents known to cause CV toxicity along with methods to measure them. Methods: An expert working group was convened to discuss mechanisms associated with CV toxicity. Results: The group identified 12 KCs of CV toxicants, defined as exogenous agents that adversely interfere with function of the CV system. The KCs were organized into those primarily affecting cardiac tissue (numbers 1–4 below), the vascular system (5–7), or both (8–12), as follows: 1) impairs regulation of cardiac excitability, 2) impairs cardiac contractility and relaxation, 3) induces cardiomyocyte injury and death, 4) induces proliferation of valve stroma, 5) impacts endothelial and vascular function, 6) alters hemostasis, 7) causes dyslipidemia, 8) impairs mitochondrial function, 9) modifies autonomic nervous system activity, 10) induces oxidative stress, 11) causes inflammation, and 12) alters hormone signaling. Discussion: These 12 KCs can be used to help identify pharmaceuticals and environmental pollutants as CV toxicants, as well as to better understand the mechanistic underpinnings of their toxicity. For example, evidence exists that fine particulate matter [PM in aerodynamic diameter ( )] air pollution, arsenic, anthracycline drugs, and other exogenous chemicals possess one or more of the described KCs. In conclusion, the KCs could be used to identify potential CV toxicants and to define a set of test methods to evaluate CV toxicity in a more comprehensive and standardized manner than current approaches. https://doi.org/10.1289/EHP9321

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Section: Discussionmentioning

confidence: 99%

Key Characteristics of Cardiovascular Toxicants

Lind¹,

Araujo

Barchowsky

et al. 2021

Environ Health Perspect

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“…Patients exposed to radiation with more than 280 mL of V5000 cGy had a 16.8 times more likely chance of developing these cardiac events than those who received a smaller volume ( 192 ). In a prospective study of patients with non-metastatic esophageal cancer, the authors showed that 30% of the patients developed myocardial fibrosis and/or reversible ischemia as early as 3 months following neoadjuvant chemoradiation ( 193 ). Furthermore, several large-scale studies have demonstrated similar findings that chemoradiotherapy increases the risk of cardiotoxicity in lymphoma ( 194 , 195 ) and esophageal cancer treatment ( 196 ) as compared to radiotherapy alone.…”

Section: Synergistic Cardiotoxicities With Chemoradiation or Radioimm...mentioning

confidence: 99%

Preclinical models of radiation-induced cardiac toxicity: Potential mechanisms and biomarkers

Dreyfuss

Velalopoulou²,

Avgousti³

et al. 2022

Front. Oncol.

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Radiation therapy (RT) is an important modality in cancer treatment with >50% of cancer patients undergoing RT for curative or palliative intent. In patients with breast, lung, and esophageal cancer, as well as mediastinal malignancies, incidental RT dose to heart or vascular structures has been linked to the development of Radiation-Induced Heart Disease (RIHD) which manifests as ischemic heart disease, cardiomyopathy, cardiac dysfunction, and heart failure. Despite the remarkable progress in the delivery of radiotherapy treatment, off-target cardiac toxicities are unavoidable. One of the best-studied pathological consequences of incidental exposure of the heart to RT is collagen deposition and fibrosis, leading to the development of radiation-induced myocardial fibrosis (RIMF). However, the pathogenesis of RIMF is still largely unknown. Moreover, there are no available clinical approaches to reverse RIMF once it occurs and it continues to impair the quality of life of long-term cancer survivors. Hence, there is an increasing need for more clinically relevant preclinical models to elucidate the molecular and cellular mechanisms involved in the development of RIMF. This review offers an insight into the existing preclinical models to study RIHD and the suggested mechanisms of RIMF, as well as available multi-modality treatments and outcomes. Moreover, we summarize the valuable detection methods of RIHD/RIMF, and the clinical use of sensitive radiographic and circulating biomarkers.

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“…Although MRiPT is still in its infancy, research is currently underway to develop prototype systems for clinical use ( 49 ). In addition to MR-guided daily plan adaptation and PTV margin reduction with consequently better sparing of OARs, MRI may also provide a way to detect subclinical cardiac toxicity after CRT by visualizing areas of myocardial fibrosis and changes in ejection fraction ( 50 ).…”

Section: Rational For Mr-guided Radiotherapy In Esophageal Cancermentioning

confidence: 99%

Review of MR-Guided Radiotherapy for Esophageal Cancer

et al. 2021

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In this review, we outline the potential benefits and the future role of MRI and MR-guided radiotherapy (MRgRT) in the management of esophageal cancer. Although not currently used in most clinical practice settings, MRI is a useful non-invasive imaging modality that provides excellent soft tissue contrast and the ability to visualize cancer physiology. Chemoradiation therapy with or without surgery is essential for the management of locally advanced esophageal cancer. MRI can help stage esophageal cancer, delineate the gross tumor volume (GTV), and assess the response to chemoradiotherapy. Integrated MRgRT systems can help overcome the challenge of esophageal motion due to respiratory motion by using real-time imaging and tumor tracking with respiratory gating. With daily on-table MRI, shifts in tumor position and tumor regression can be taken into account for online-adaptation. The combination of accurate GTV visualization, respiratory gating, and online adaptive planning, allows for tighter treatment volumes and improved sparing of the surrounding normal organs. This could lead to a reduction in radiotherapy induced cardiac toxicity, pneumonitis and post-operative complications. Tumor physiology as seen on diffusion weighted imaging or dynamic contrast enhancement can help individualize treatments based on the response to chemoradiotherapy. Patients with a complete response on MRI can be considered for organ preservation while patients with no response can be offered an earlier resection. In patients with a partial response to chemoradiotherapy, areas of residual cancer can be targeted for dose escalation. The tighter and more accurate targeting enabled with MRgRT may enable hypofractionated treatment schedules.

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A Prospective Study of Early Radiation Associated Cardiac Toxicity Following Neoadjuvant Chemoradiation for Distal Esophageal Cancer

Cited by 12 publications

References 33 publications

Key Characteristics of Cardiovascular Toxicants

Key Characteristics of Cardiovascular Toxicants

Preclinical models of radiation-induced cardiac toxicity: Potential mechanisms and biomarkers

Review of MR-Guided Radiotherapy for Esophageal Cancer

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