Cardiovascular disease as a late complication of radiation therapy may be more common in survivors of Hodgkin’s disease than previously thought, according to an article in the December 3rd issue of the Journal of the American Medical Association.

American investigators reviewed medical records of more than 400 patients with Hodgkin’s disease treated with radiation between 1962 and 1998 at a single university center and compared results with data from 2 national databases for the general population. Conditions found in the survivors included valvular disease, early-onset, severe atherosclerosis and coronary artery disease, and damage to the carotid and subclavian arteries.

Investigators discovered that 88 percent of patients were free of cardiovascular problems 15 years after treatment, and 84 percent were still free of cardiovascular disease at 20 years. "The corollary is that by 15 years, 12 percent of patients had some kind of cardiovascular problem that might or might not be related to the radiation, and by 20 years it was up to 16 percent," Nancy Mendenhall, MD, radiation oncologist and study senior author said. "The incidence of these particular events we studied was higher than what it should have been compared to the national databases. Because of the pattern of problems that we saw and the age at which these patients presented, we felt that many of these were in fact due to the use of radiation."

The findings are likely to prompt physicians to evaluate young-adult survivors for other cardiovascular risk factors such as elevated cholesterol levels, hypertension, smoking or obesity, or positive family history and to monitor them closely for signs of cardiovascular disease, said Mendenhall.

Currently, over 90 percent of the 7,500 Americans diagnosed with Hodgkin’s disease yearly are likely to have long-term survival; newer therapy regimens use lower radiation doses than in the past. However, radiation fields still typically include the carotid or subclavian arteries or both as well as some of the heart itself because of cancer involvement in the lower neck or chest.

"The last 3 decades of the 20th century were focused on trying to use chemotherapy and radiation in different ways to cure as many of these patients as possible," said Mendenhall. "The other side of the coin is that any type of treatment, whether it be chemotherapy or radiation therapy, may cause some damage to normal tissues, and if the damage is minimal it may be many years before it's apparent. So as more and more patients have been cured, we're beginning to see some late effects from moderate doses of radiation therapy that we were not really aware of before. Some of these effects don't show up until about 20 or 25 years after treatment."

"The good news is that in the last 10 to 15 years, by optimally combining chemotherapy and radiation we've been able to reduce our radiation doses substantially, so we don't anticipate seeing nearly as many of these late effects in the patients currently under treatment or those treated in the last decade," Mendenhall added.

Carl J. Pepine, MD, a cardiologist associated with the research team, said that the findings highlight the importance of monitoring patients' cardiovascular health over the long term: "Although these patients are cured of their malignancy, they require very careful surveillance from the cardiovascular risk standpoint over very long periods of time. What's not entirely known is whether they could benefit from extreme preventive therapy. Since we know these patients are going to receive an injury to their blood vessels or heart valves from the radiation, and we know when they will receive it, maybe they should all be treated prophylactically before they get exposed to the radiation. For example, we could lower their low-density lipoprotein cholesterol and even their blood pressure to very low levels."

Peter Mauch, MD, a radiation oncologist who was not part of the current study, said "Many of the effects of treatment are not seen for a decade or more after Hodgkin's disease. Strategies to improve surveillance and prevention of late effects may improve the quality of life and survival of patients. Two other recent studies, one from Stanford University and the other a combined study from Children's Hospital in Boston and the University of Rochester, also document late cardiac effects."