Sutton, UK - A new study attempts to quantify the risk for fatal MI after treatment for Hodgkin's disease and suggests the risk remains high for at least 25 years after therapy [1]. Reporting in the February 2007 issue of the Journal of the National Cancer Institute, researchers say the increased risk is related to supradiaphragmatic radiotherapy and may also be linked to anthracycline and vincristine treatment.

"The effects of treatment for Hodgkin's lymphoma appear to be lifelong, and cancer survivors should be monitored for late cardiac abnormalities throughout their lives," Dr John Boice (Vanderbilt University School of Medicine, Nashville, TN) writes in an accompanying editorial [2]. "The goal of keeping these patients alive has been achieved; the next challenge is to continue to reduce the toxicity of curative treatments and to make long-term survival as disease free as possible, breaking as few hearts as possible along the way."

CVD is the second-highest cause of death—after second cancers—in long-term survivors of Hodgkin's disease, and of these CV deaths, MI is the most common cause. But researchers, led by Dr Anthony Swerdlow (Institute of Cancer Research, Sutton, UK), point out that there is limited information on the effects of specific chemotherapy regimens on their risk for death from MI.

To assess MI mortality risk associated with specific drug treatment regimens and radiation, the group studied a cohort of more than 7000 patients treated for Hodgkin's disease in Britain. They compared their MI risk with that in the general population of England and Wales.

A total of 166 deaths from MI occurred in the cohort—significantly more than expected (standardized mortality ratio [SMR] 2.5; 95% CI 2.1-2.9)—with an absolute excess risk of 125.8 per 100 000 person-years. SMRs decreased sharply with older age at first treatment, but absolute excess risks for death from MI increased with older age up to age 65 years at first treatment.

MI risk was particularly high for patients treated with the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (SMR 9.5; 95% CI 3.5-20.6). Risk at 20 or more years after first treatment was very high for patients who had received supradiaphragmatic radiotherapy and vincristine without anthracyclines (SMR 14.8; 95% CI 4.8-34.5).

"We were not able to adjust the standardized mortality ratios for other risk factors associated with MI (nor were authors of other large cohort studies of Hodgkin's disease patients)," Swerdlow and his team point out. "But we believe that there is no obvious reason why these factors should vary substantially between Hodgkin's disease patients and the general population."

In his editorial, Boice notes that one difficulty with the present analysis is the fact that so many patients received both radiotherapy and different combinations of chemotherapy that it is difficult to tease out the contribution of a single agent. For example, he writes, "the risk of death from MI was evaluated over five broad treatment modalities for six radiotherapy subgroups, seven chemotherapy regimens, and 13 individual chemotherapy agents or combinations of agents."

The researchers plan to conduct a nested case-control study to further quantify risks in terms of amount of chemotherapy administered and amount of radiation dose to the heart.

Boice concludes, "Long-term studies that follow lymphoma survivors for many years, such as the one conducted by Swerdlow et al, are needed to help better understand the processes and factors that worsen heart function—especially now that patients in remission are living to older ages, when cardiac disease is common."