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National Cancer Institute

Presentation

Cardiovascular Effects of Radiation Therapy - Ming Hui Chen, MD, MMSc

Cardiovascular disease is a major long-term health risk in cancer survivors who have received cardiac irradiation. Hodgkin’s Disease (HD) serves as a paradigm for studying late cardiac effects of radiation therapy in survivors, due to the high rate of cure and the availability of well-documented, standardized mantle treatment protocols. Studies published, only in the last few years, have highlighted that cardiovascular disease and atherosclerosis are the leading causes of non-cancer mortality for long-term survivors cured of HD. And yet, substantial gaps exist in our understanding of prevalence of subclinical cardiovascular disease in this population. Heidenreich et al published a study demonstrating that asymptomatic valvular dysfunction was common in HD patients. In a cardiac MRI study of 13 asymptomatic HD survivors, without prior cardiac history, treated between 5-10 years ago, we found that over 50% of individuals had a left ventricular ejection fraction (LVEF) below normal, using normative data from the Framingham Heart Study (> 59 EF %). In addition, there were increased atherosclerotic changes of the aorta and increased pericardial thickness in HD survivors as compared with controls. These findings suggest that the decades between XRT and the onset of cardiac events and symptoms represent a potential opportunity for early detection of subclinical cardiac dysfunction, cardiac risk factor management, and even medical or surgical intervention.

Given the growing recognition of increased late cardiac effects, what can be done to limit this toxicity? Initial data in the delivery of XRT to breast cancer patients suggest that small modifications in delivery and methodology can have a significant impact on the degree of cardiac irradiation. Our study in 14 breast cancer patients demonstrated that 93% of the subjects had inclusion of a portion of the heart in the left-breast XRT portal (median: 25.9 cm3, range 4.2-119.1 cm3). During breast cancer treatment, radiation therapy is usually delivered with the patient breathing quietly. We hypothesized that deep inspiration would increase the distance between the left breast and heart, and result in inferior displacement of the heart, which is tethered to the diaphragm, out of the breast XRT portal. In all subjects, inspiratory breathholding decreased irradiated cardiac volume [median change: -18.1 cm3 (-49%), p £ 0.001 vs. baseline]. In 21% of patients, the entire heart could be displaced outside the XRT field with deep inspiration. Age was not correlated with change or percentage change in cardiac volume with respiratory maneuvers. We concluded that deep inspiratory maneuvers significantly decreased irradiated cardiac volume in the left breast radiation field. Such an approach during delivery of radiation therapy allows preservation of radiation dosage to the breast, while reducing cardiac involvement and possible associated cardiovascular toxicity. In the coming years, we are working to apply similar methods to decrease irradiation of vital cardiac structures included in mediastinal XRT portals, improving the health and quality-of-life for not only breast cancer survivors, but also all cancer survivors cured by chest XRT.

Grants that have supported the work:
American Heart Association

References:

  1. Chen, MH et al. Impact of respiratory maneuvers on cardiac volume within left-breast radiation portals. Circulation 1997;96:3269-72.
  2. Chen, MH et al. Respiratory maneuvers decrease irradiated cardiac volume in patients with left-sided breast cancer. Journal of Cardiovascular Magnetic Resonance 2002;4(2):265-71.
  3. Chen MH, et al. Left ventricular systolic dysfunction and impaired aortic compliance in moderate-term survivors of Hodgkin’s mantle radiation: a CMR study.