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Nevertheless, every effort should be made to minimize avoidable irradiation of nontarget cardiovascular tissue. Atherosclerotic disease is progressive and life-threatening, and avoidable risk should always be circumvented. Previous research has suggested that coronary artery disease risk is tied to higher total radiation dose (>35-40 Gy), higher radiation dose fractions (>2.0 Gy/day), increased volumes of heart tissue exposed during radiotherapy, younger age at the time of radiotherapy, the presence of other risk factors for vascular disease (eg, obesity and smoking), and time since radiotherapy (likely reflecting the progressive nature of atherosclerotic disease).3
IMPACT ON OTHER CANCERS AND TREATMENTS
In the 1970s and 1980s, mortality from cardiovascular disease may have overshadowed the breast cancer-specific survival benefits of radiation therapy. For patients with non-small cell lung cancer, the current situation is somewhat analogous to that of breast cancer 25 years ago, according to Zagar and Marks. Large-field postoperative radiotherapy in these patients is associated with improved local control and cancer-specific survival rates but lower overall survival rates.6 Smaller conformal radiotherapy fields appear to reduce noncancer mortality rates in these patients.
Evidence-based guidelines for treating radiotherapy- associated cardiovascular disease are not yet established.9 Surgical treatment of radiotherapy-associated cardiovascular disease can be challenging because radiation-associated arterial disease has scar tissue and a higher probability of postsurgical restenosis than non-radiation-associated arterial disease, which highlights the need to use technological advances that minimize irradiation of vascular tissues in the first place. Lifelong antiplatelet therapy and statin therapy are frequently recommended for patients with radiotherapy-associated cardiovascular disease.1 Percutaneous angioplasty and arterial stenting may be feasible treatments; however, restenosis of carotid arteries is more common with radiotherapy-associated stenosis than other carotid artery diseases.1,10 Balloon angioplasty has shown promise in treating radiation-associated carotid, renal, iliac, and femoral artery disease.1,11
Understanding the molecular mechanisms that modulate radiotherapy-associated risks of cardiovascular disease should allow the development of new interventions, but these mechanisms remain poorly understood. Radiotherapy can cause acute elevations in pro-inflammatory cytokines and adhesion proteins in vascular endothelia, but such transient effects cannot alone explain increased long-term risks of cardiovascular disease among radiotherapy patients.12,13 Tissue perfusion imaging studies suggest radiotherapy reduces regional perfusion consistent with microvascular trauma within 6 months of treatment, and that perfusion dysfunction persists for at least 5 years.6 Patient genetics and coronary calcium scores may prove useful for predicting which cancer patients are at high risk of developing coronary artery disease.6,13,14
PREVENTIVE MEASURES
For the time being, increased emphasis should be placed on prevention and postradiotherapy monitoring for coronary or carotid arterial stenosis because treatment of cardiovascular disease can be complicated and less successful in cancer survivors. Primary prevention is crucial for younger patients who face the highest lifetime risk of postradiotherapy cardiovascular disease and depends on appropriate use of contemporary technologies, quality control techniques, and radiotherapy planning tools that minimize avoidable irradiation of the coronary and carotid arteries. Secondary prevention efforts focus on reducing risk among patients whose coronary vasculature is irradiated during therapy.
A reasonable and widely accepted assumption is that secondary prevention of radiation-associated cardiovascular disease is best achieved through amelioration of other risk factors such as tobacco smoking, high-fat diet, and sedentary lifestyle.1 Statin therapy can reduce circulating levels of low-density lipoproteins (LDLs), which contribute to atherosclerotic plaque accumulation and cardiovascular disease. LDL goal of less than 70 mg/dL has been proposed as reasonable for patients with a history of chest radiotherapy and other risk factors for cardiovascular disease; LDL of less than 100 mg/dL is reasonable for patients with an intermediate risk such as patients with a history of radiotherapy and no other cardiovascular risk factors.15
Chest radiotherapy patients should be informed of their increased risk for coronary artery disease, efforts made in their treatment planning to minimize irradiation of the coronary arteries, and behavioral changes they can make to mitigate their risk of cardiovascular disease. Patients should be encouraged to minimize or eliminate dietary trans fats, carbohydrates, processed sugars, and to normalize blood pressure through exercise and cessation of tobacco use. ONA
Bryant Furlow is a medical journalist based in Albuquerque, New Mexico.
REFERENCES
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11. Saka B, Bilge AK, Umman B, et al. Bilateral renal artery stenosis after abdominal radiotherapy for Hodgkin’s diasese. Int J Clin Pract. 2003;57(3):247-248.
12. Halle M, Gabrielsen A, Paulsson-Berne G, et al. Sustained inflammation due to nuclear factor-kappa B activation in irradiated human arteries. J Am Coll Cardiol. 2010;55(12):1227-1236.
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14. Shi W, Zhang Z, Chen MH, et al. Genes within the MHC region have a dramatic influence on radiation-enhanced atherosclerosis in mice. Circ Cardiovasc Genet. 2010;3(5):409-413.
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