UF Researchers Find Some Hodgkin’s Patients Develop Heart Problems Years After Radiation Treatment

Published: December 2 2003

Category:Research

GAINESVILLE, Fla. — Patients who successfully weather the powerful treatments used to send Hodgkin’s lymphoma soundly into remission are often considered cured of their cancer. But a new study shows that years later they may develop serious heart problems because of the radiation therapy they receive, University of Florida researchers report in this week’s issue of the Journal of the American Medical Association.

“They’re cured from their malignancy but they’re not out of the woods from the standpoint of their blood vessels and their heart,” said study co-author Dr. Carl J. Pepine, chief of cardiovascular medicine at UF’s College of Medicine and the current president of the American College of Cardiology.

UF scientists scoured the medical records of more than 400 Hodgkin’s patients treated with radiation between 1962 and 1998 at Shands at UF medical center and found a substantial number developed serious cardiovascular complications. Many developed malfunctioning valves that became rigid and leaky, experienced the onset or worsening of atherosclerosis leading to coronary artery disease, or suffered damage to the carotid and subclavian arteries in the neck.

The findings are likely to prompt physicians to continue to track Hodgkin’s survivors closely not only for the development of these problems but also the presence of other risk factors associated with heart disease, such as elevated cholesterol levels, high blood pressure, family history, smoking or obesity, said the study’s senior author Dr. Nancy Mendenhall, chairwoman of the department of radiation oncology at UF’s College of Medicine.

The treatment of Hodgkin’s lymphoma – a disease of the lymphatic system, which helps the body fight disease and infection – is one of medicine’s phenomenal success stories. As late as the 1950s, it was considered incurable. Today, thanks to radiation therapy and chemotherapy, over 90 percent of the 7,500 Americans who will develop it this year are likely to survive long term, and newer therapies are relying on lower doses of radiation than the past. Hodgkin’s patients typically receive radiation to the carotid and/or subclavian arteries as well as some of the heart, because 90 percent of the time the cancer involves the lower neck or chest, where the heart and these arteries are found.

“The last three 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, who also is affiliated with the UF Shands Cancer Center. “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.”

UF researchers compared the incidence and severity of heart problems and of associated risk factors found in their patients with two national databases that record disease rates in the general population. They discovered that 88 percent of patients were free of cardiovascular problems 15 years after treatment, and 84 percent 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,” Mendenhall 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 complications are likely related to the dose of radiation patients received, Mendenhall said.

“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,” she said.

Pepine said the findings highlight the importance of carefully monitoring patients’ cardiovascular health 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,” Pepine said. “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 LDL cholesterol and even their blood pressure to very low levels.”

Hodgkin’s patients treated at UF are closely monitored for the rest of their lives and are counseled about good health habits, said Mendenhall, who is involved in designing Hodgkin’s lymphoma trials for the Children’s Oncology Group.

“We also are continually trying to find new methods of treatment that will produce a better quality of life with less late toxicity but equal cure rates,” she said. “Attempts to eliminate radiation have often resulted in higher Hodgkin’s disease recurrences. We’ve been able to lower the radiation dose with the use of chemotherapy, however, and we’re hopeful that judicious use of combined therapies will produce the best disease control rates with the lowest complication rates in the future.”

The UF study and other related research is extremely important for developing guidelines for the follow-up of patients cured of Hodgkin’s disease and other malignancies, said Dr. Peter Mauch, a professor of radiation oncology at Harvard Medical School.

“Many of the effects of treatment are not seen for a decade or more after Hodgkin’s disease,” he said. “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. In addition, The Rockefeller Foundation sponsored an international workshop in July on late effects of treatment after Hodgkin’s disease, and the European Organization for the Research and Treatment of Cancer is beginning to look at treatment complications in (long-term survivors).”

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  • Melanie Fridl Ross

Category:Research