Radiation and the heart: systematic review of dosimetry and cardiac endpoints

ABSTRACT

Introduction: Recent trials in radiotherapy have associated heart dose and survival, inadequately explained by the existing literature for radiation-related late cardiac effects.  Authors aimed to review the recent literature on cardiac dosimetry and survival/cardiac endpoints.

Areas covered: Systematic review of the literature in the past 10 years (2008–2017) was performed to identify manuscripts reporting both cardiac dosimetry and survival/cardiac endpoints.  Authors identified 64 manuscripts for inclusion, covering pediatrics, breast cancer, lung cancer, gastrointestinal diseases (primarily esophageal cancer), and adult lymphoma.

Expert commentary: In the first years after radiotherapy, high doses (>40 Gy) to small volumes of the heart are associated with decreased survival from an unknown cause.  In the long-term, mean heart dose is associated with a small increased absolute risk of cardiac death.  For coronary disease, relative risk increases roughly 10% per Gy mean heart dose, augmented by age and cardiac risk factors.  For valvular disease and heart failure, doses >15 Gy substantially increase risk, augmented by anthracyclines.  Arrhythmias after radiotherapy are poorly described but may account for the association between upper heart dose and survival.  Symptomatic pericardial effusion typically occurs with doses >40 Gy.  Close follow-up and mitigation of cardiovascular risk factors are necessary after thoracic radiotherapy.

KEYWORDS:

• Radiotherapy
• cardiotoxicity
• radiation Injuries
• adverse effects
• radiotherapy dosage
• dose-response relationship
• radiation

Key issues

• Traditionally, late cardiac events after radiotherapy have been associated with a timeframe of years to decades. However, high dose (≥40 Gy) to small volumes of the heart appears to be associated with decreased overall survival in the first years after radiotherapy due to an unknown cause. The magnitude of survival change may be approximately 10–25%. Dose to left ventricle and upper heart substructures (heart base) may play a role.

• Increasing mean heart dose correlates with late cardiac toxicity and a small absolute increase in cardiac death many years later.

• As mean heart dose increases, cancer survivors experience approximately 10% relative increase in coronary artery disease per Gy of mean heart dose. This translates into one to two additional deaths per 1000 patients treated at 10 years. Persistent smoking, age at treatment, and cardiovascular risk factors increase the risk.

• For pediatric cancer survivors, valvular heart disease is associated with doses > 15 Gy and especially > 30 Gy, augmented by anthracycline use.

• Over 10% of lung cancer patients experience documented arrhythmia after radiotherapy, and high dose (≥60 Gy) to the right atrium is predictive.

• Pericardial effusion increases with doses > 30 Gy, with higher doses (>40 Gy) associated with symptomatic pericardial effusion.

• Patients receiving high mean heart doses or high doses to a portion of the heart may benefit from long-term follow-up with a cardio-oncology clinic. Cardiovascular risk factors, especially smoking, should be minimized.

• With a better understanding of radiation-related cardiac toxicity, the associated risk factors, and the dose thresholds for toxicity of the heart and heart substructures, modern radiotherapy techniques (e.g. proton therapy) may be able to minimize cardiac toxicity while maximizing tumor control.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Supplementary material

Supplemental data can be accessed here.

Additional information

Funding

This paper was not funded.