BREAST RT AND CARDIOTOXICITY

Evidence has long been accumulating that radiotherapy involving the heart can result in premature ischemic heart disease, but interest peaked last spring when a case control study published in The New England Journal of Medicine¹ found an increased risk for cardiac-related deaths in breast cancer patients who received radiotherapy.

Radiation oncologists speaking at the 2013 Breast Cancer Symposium in San Francisco, including Jay R. Harris, MD, Professor of Radiation Oncology at Harvard Medical School and Chief of Radiation Oncology at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, examined the results, put them into contemporary perspective, and provided a more reassuring view of radiotherapy for breast cancer in today’s practice.

Study Limitations

The NEJM study was a population-based case control study involving 2,168 Scandinavian women treated between 1958 and 2001. It found that rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (Gy) (P < .001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per Gy was similar in women with and without cardiac risk factors at the time of radiotherapy. The overall average of the mean doses to the whole heart was 4.9 Gy.

“It is important to note the major limitations of the study, mainly, it is a case control study and this does not provide the highest level of evidence. Also, there were limitations in design,” said Dr. Harris.

The investigators developed virtual simulations of radiotherapy dose based on computed tomography scanning of patients with “typical anatomy,” which they used to construct an idealized radiation field; with this they estimated the doses to the heart and the left anterior descending artery.

David E. Wazer, MD, Radiation Oncologist-in-Chief and Professor and Chairman of Radiology at Tufts Medical Center, Boston, agreed with Dr. Harris’ concerns. “Radiation oncologists looked at this study critically, because the patients were treated in a different era. They were subject to two-dimensional treatment planning, which we in the United States have not done for at least 15 years,” he said. “Even more unsettling was that the heart dose was estimated based on extrapolating from a ‘typical patient,’ whatever that is. And what was surprising to a lot of us was that the mean heart dose was so much higher than in our experience.”

Absolute Increase in Risk Is Minor

Dr. Harris emphasized that despite the proportional relationship between radiotherapy dose and heart disease, the absolute increase was small. For a 50-year-old women without cardiac risk factors, the lifetime increased risk was 0.5% after 0.5 Gy, 0.2% after 1 Gy, and just 0.5% after 3 Gy delivered to the heart. Today, for most node-negative women having breast-conserving therapy, the mean heart dose is only about 1 Gy, although though higher doses (still only about 2 Gy) are more common for women with left-sided postmastectomy radiotherapy, according to Dr. Harris.

Dr. Harris further emphasized that current mean heart doses result in a mortality risk that is minor, compared to the survival benefit from radiation. In the latest Oxford Overview, radiotherapy after mastectomy and axillary dissection provided an 11.4% absolute gain in 10-year recurrence-free survival and a 9.4% gain in 15-year breast cancer mortality in patients with one to three positive nodes.²

“The survival benefit seen for radiotherapy in these trials includes the deleterious effects on the heart seen with doses as high as 10 Gy,” he noted. “This means that using current techniques that spare the heart, radiotherapy will provide even greater benefit.”

Dr. Harris concluded, “While the NEJM article has major limitations, it is a very important publication for radiation oncologists. Radiation oncologists should operate on the principle that there is no totally safe radiation dose to the heart, and we should keep the heart dose as low as possible.”

A number of maneuvers, such as using cardiac blocks, prone techniques and deep inspiration breath holds, make radiation delivery much safer now.  “In virtually all our patients we have eliminated direct cardiac radiation,” he pointed out. ■