Timothy Zagar, MD, assistant professor of radiation oncology, and Lawrence Marks, MD, professor and chair of radiation oncology, co-authored an editorial in the December 27, 2011 issue of the Journal of Clinical Oncology.
Their editorial, titled, “Breast Cancer Radiotherapy and Coronary Artery Stenosis: Location, Location, Location,” is an accompanying communication to a research article titled, “Distribution of Coronary Artery Stenosis After Radiation for Breast Cancer” by Nilsson et al.
Marks and Zagar observe that radiation therapy plays an integral role in the treatment of breast cancer. They cite a meta-analysis of nearly 42,000 women treated within randomized clinical trials demonstrating that radiation therapy improves both local control and overall survival in patients who have had either a mastectomy or lumpectomy. They also point out that with older radiation techniques, there is a risk of radiation-associated clinical cardiac events with most events not becoming clinically evident until greater than 10-15 years after radiation therapy.
The Nilsson study reports on distribution of coronary artery stenosis among patients irradiated for breast cancer and provides an assessment of correlation between radiotherapy and location of stenosis. Patients with left-sided breast cancer had a statistically significant increased rate of stenosis in coronary artery branches on the left anterior surface of the heart when compared with those with right-sided breast cancer, while those with right-sided breast cancer had a slightly higher rate of stenosis in the proximal right coronary artery. Marks and Zagar note that these findings are logical given the location and orientation of typical radiation fields used to treat patients with left- vs. right-sided breast cancer.
Marks and Zagar cite several study shortcomings that might limit interpretation of the data due to biases with respect to which patients were sent for angiograms, based on their previous radiation therapy exposure, for example.
Marks and Zagar state that the Nilsson study results “lend additional support to the mounting evidence that radiation therapy can cause coronary artery disease or that there seems to be an association between the location of the radiation therapy beam and the location of the excess coronary events.” They express hope that altering the radiation therapy dose distribution will alter the risks. Further, they note that the risks of coronary artery disease following radiation therapy are far less with more modern techniques that markedly reduce the degree of cardiac exposure. In addition, the magnitude of the risk of radiation therapy-associated cardiac disease is far less than the anti-cancer benefits afforded by radiation therapy. Nevertheless, they suggest that radiation oncologists exploit available treatment planning and delivery tools, such as the judicious use of three-dimensional planning and breath-hold techniques to reduce doses to cardiovascular structures.
They point out that the issue is not limited to breast cancer patients. There is an increased risk of heart disease in patients who receive radiation therapy for lymphoma involving the mediastinum and perhaps for those who receive radiation therapy for lung cancer. They hypothesize that altering the radiation therapy fields and techniques in these patients might reduce the risks of such toxicities and further improve the therapeutic ratio in these patients.
Given the long natural history of radiation therapy-associated coronary artery disease, investigators who have conducted prospective clinical studies to address this issue have looked to biochemical findings or imaging to evaluate possible markers of cardiac injury, although to date, none have proven useful in routine clinical practice.
Single photon emission computed tomography (SPECT) cardiac imaging has been used to assess early post-radiation therapy subclinical cardiac injury in patients treated for left-sided breast cancer. In a prospective study conducted by Marks and colleagues of more than 130 patients treated with radiation therapy, new cardiac SPECT abnormalities were noted in close to 50 percent of the patients, but these abnormalities have not been linked to any clinical events, thus their clinical relevance is unclear.
In considering the cardiac risks associated with radiation therapy, Zagar and Marks cite the importance of: the location of the radiation dose, the location of the at-risk cardiac structures, and the location of where researchers look for injury. For example, they cite that angiograms assess for coronary lesions, SPECT scans assess for myocardial microvascular injury, and echocardiograms assess for pericardial and valvular abnormalities. “Therefore,” they say, “fairly comprehensive evaluations may be needed to understand the full spectrum of cardiac effects and their potential interactions.”
They recommend that radiation oncologists use the increasing array of techniques to manipulate the RT dose to additionally improve the therapeutic value of RT for patients who receive this treatment for breast cancer and other thoracic diseases.