Cardiovascular Manifestations From Therapeutic Radiation: A Multidisciplinary Expert Consensus Statement From the International Cardio-Oncology Society

Abstract

Radiation therapy is a cornerstone of cancer therapy, with >50% of patients undergoing therapeutic radiation. As a result of widespread use and improved survival, there is increasing focus on the potential long-term effects of ionizing radiation, especially cardiovascular toxicity. Radiation therapy can lead to atherosclerosis of the vasculature as well as valvular, myocardial, and pericardial dysfunction. We present a consensus statement from the International Cardio-Oncology Society based on general principles of radiotherapy delivery and cardiovascular risk assessment and risk mitigation in this population. Anatomical-based recommendations for cardiovascular management and follow-up are provided, and a priority is given to the early detection of atherosclerotic vascular disease on imaging to help guide preventive therapy. Unique management considerations in radiation-induced cardiovascular disease are also discussed. Recommendations are based on the most current literature and represent a unanimous consensus by the multidisciplinary expert panel.

Keywords: CABG, coronary artery bypass graft; CAC, coronary artery calcium; CAD, coronary artery disease; CI, confidence interval; CT, computed tomography; CTCA, computed tomography coronary angiography; CV, cardiovascular; DIBH, deep inspiratory breath hold; HF, heart failure; HL, Hodgkin lymphoma; HNC, head and neck cancer; HR, hazard ratio; LIMA, left internal mammary artery; MRI, magnetic resonance imaging; NT-proBNP, N-terminal pro–B-type natriuretic peptide; OR, odds ratio; PAD, peripheral arterial disease; RT, radiation therapy; SAVR, surgical aortic valve replacement; SVC, superior vena cava; TAVR, transcatheter aortic valve replacement; TTE, transthoracic echocardiogram; aHR, adjusted hazard ratio; cancer; cardiovascular disease; imaging; prevention; radiation therapy; screening.

Graphical abstract

Central Illustration

Therapeutic Radiation: Potential Cardiovascular Effects and Practical Screening Tools The figure highlights the potential cardiovascular sequelae as well as physical examination findings and diagnostic tests that can aid in evaluation. BP = blood pressure; CAC = coronary artery calcium; CTA = computed tomography angiography; CT = computed tomography; MRA = magnetic resonance angiography; MRI = magnetic resonance imaging; TSH = thyroid-stimulating hormone; US = ultrasound.

Figure 1

Summary of Screening Guidelines Summary of recommended monitoring intervals and evaluation procedures based on anatomical exposure of radiation therapy. CT = computed tomography; CV = cardiovascular; ECG = electrocardiogram; TTE = transthoracic echocardiogram; US = ultrasound.

Figure 2

Coronary Artery Calcium on CT Imaging for Cancer Staging A 68-year-old man was diagnosed with prostate cancer on biopsy and underwent computed tomography (CT) imaging for cancer staging. Severe coronary calcifications are noted extending from the left main coronary artery to the left anterior descending artery. He subsequently presented with unstable angina ∼1 year later and underwent bypass surgery.

Figure 3

Evolution of Cancer Radiation Techniques and Impact on Cardiac Dose Advances in radiation techniques over the last 30 years have significantly decreased the mean heart dose during radiation therapy, especially in breast cancer (top) and lymphoma (bottom). In breast cancer, modern computed tomography (CT) planning and techniques such as deep inspiratory breath hold can help reduce the mean heart dose to <1 Gy. With the changes in systemic therapy and radiation treatment delivery techniques in lymphoma, modern radiation oncology practice has also evolved to reduce the size of historical mantle radiotherapy fields in a risk-adapted fashion to “involved site” or “involved nodal” fields, minimizing dose to surrounding organs while maintaining disease control. (A) Mantle radiotherapy. (B) Involved field radiotherapy. (C) Involved site radiotherapy. 2D = 2-dimensional; 3D = 3-dimensional; 3DCRT = 3-dimensional conformal radiation therapy; IMRT = intensity-modulated radiation therapy; RT = radiation therap; VMAT = volumetric modulated arc therapy.

Figure 4

RT Plan for Carcinoma of the Left Tonsil Coronal and axial views of the radiation therapy (RT) plan used to treat a human papillomavirus–positive carcinoma of the left tonsil metastatic to the left neck lymph nodes (blue shaded region) in a 44-year-old woman. Isodose lines, in Gray (Gy), represent the dose distribution similar to topographical lines on a map. This patient was prescribed 70 Gy in 35 treatments to gross tumor (red line), with an intermediate-dose region of 63 Gy (green line) and a low-dose region of 56 Gy to the at-risk lymphatics (magenta line). One can appreciate the high radiation exposure to the carotid vessels, including the carotid bulb (red arrow).

Figure 5

Cases of Radiation-Induced Cardiovascular Disease (A) Severe coronary artery disease on coronary computed tomography angiography. A 57-year-old woman underwent adjuvant chemotherapy and radiation therapy for left-sided breast cancer 14 years ago with normal coronary arteries on cardiac catheterization 7 years ago. She developed electrocardiography changes on ribociclib but was asymptomatic. A computed tomography angiogram showed >70% proximal left anterior descending artery (LAD) disease, and she was started on preventive therapy. A few months later, she began having angina and underwent percutaneous coronary intervention. (B) Iliac vein stenosis 1 year after pelvic radiation. A 70-year-old with prostate cancer developed iliac vein stenosis requiring stenting 1 year after radiation therapy. He notably also had baseline atherosclerotic disease manifesting as an abdominal aortic aneurysm and aorto-iliac calcifications before his radiation therapy.