Radiation-Induced Heart Disease: Vigilance Is Still Required

Abstract

Radiation therapy (RT) plays an important role in the multimodality management of patients with breast cancer. Trials conducted in the 1970s established that survival is equivalent after either breast conservation (local excision and RT) or mastectomy. Studies performed in the 1980s showed that the addition of RT to lumpectomy significantly reduces the risk of local recurrence and, in a meta-analysis, enhanced survival as well. Finally, trials conducted in the 1980s also demonstrated that RT after mastectomy dramatically decreases locoregional recurrence and significantly improves overall survival in patients with involved axillary nodes or large primary tumors. This silver cloud unfortunately has a black lining. In the late 1980s, data emerged that older radiotherapy (RT) techniques used in the treatment of breast cancer, particularly after mastectomy, resulted in increased rates of both cardiac morbidity and mortality. In a meta-analysis involving 19,582 women with breast cancer enrolled onto 40 randomized trials begun before 1990, the Early Breast Cancer Trialists Collaborative Group found that RT reduced the annual mortality from breast cancer by 13% but increased the annual mortality rate from other causes by 21% and that this increase was due primarily to an excess number of deaths from vascular causes (death rate ratio, 1.3 [SE 0.09]). In a similar meta-analysis, Cuzick et al reviewed individual patient-level data from 7,941 women enrolled onto 10 randomized trials of mastectomy, with or without RT, initiated before 1975 and found that the standardized mortality ratio was significantly higher for patients treated with RT compared with controls (1.11 v 0.69; P .001). Critical factors in the genesis of radiation-induced heart disease are the volume of heart exposed and the radiation dose deposited in that volume. Older methods of delivering postmastectomy RT resulted in relatively large volumes of heart being incidentally exposed to moderate to high doses of radiation. The main culprit was thought to be the use of anterior photons to treat the ipsilateral internal mammary nodes, often as part of a larger L-shaped socalled hockey-stick field that also covered the supraclavicular and sometimes the axillary nodes. Once the adverse effects of RT on the heart were recognized, techniques evolved to irradiate the chest wall and regional nodes while reducing exposure of the heart. The hockey-stick method was abandoned by most radiation oncologists in favor of methods that included the internal mammary nodes (IMNs) within the same tangential RT fields used to irradiate the chest wall (so-called deep or partially wide tangents) or treated the IMNs mostly or entirely with superficially penetrating electrons, rather than deeply penetrating photons. Given the controversy about the necessity of treating the IMNs and the possible increased cardiac risk that came from electively doing so, other radiation oncologists elected to abandon IMN treatment altogether. The safety of irradiating the chest wall was also improved by the development of treatment planning based on computed tomography that enabled better visualization of the heart, leading to the selection of RT fields that minimized cardiac exposure. These heart-sparing RT methods for irradiating the chest wall (with or without the regional nodes), were also applied to the treatment of patients with an intact breast, which rapidly gained in popularity following the publication of the randomized trials comparing mastectomy with breast conservation. For patients with an intact breast, but uninvolved axillary lymph nodes, tangential fields that minimized cardiac exposure were used to treat only the breast itself. Have these modern methods of delivering adjuvant RT following mastectomy or lumpectomy eliminated the risk of cardiac injury? In this issue of the Journal of Clinical Oncology, Patt et al from the M.D. Anderson Cancer Center (Houston, TX) attempt to answer this question. Using data from the Surveillance, Epidemiology, and End Results JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 30 OCTOBER 2