Acute and Late Toxicities of Radiation Therapy

Radiation pneumonitis. In a retrospective analysis of 1,624 women treated with conservative surgery and adjuvant breast radiation at a single institution, the overall incidence of symptomatic radiation pneumonitis was 1.0% at a median follow-up of 77 months.[33] The incidence of pneumonitis increased to 3.0% with the use of a supraclavicular radiation field and to 8.8% when concurrent chemotherapy was administered. The incidence was only 1.3% in patients who received sequential chemotherapy.[33][Level of evidence C1]

Cardiac events. Controversy existed as to whether adjuvant radiation therapy to the left chest wall or breast, with or without inclusion of the regional lymphatics, was associated with increased cardiac mortality. In women treated with radiation therapy before 1980, an increased cardiac death rate was noted after 10 to 15 years, compared with women with nonradiated or right-side-only radiated breast cancer.[24,34-36] This was probably caused by the radiation received by the left myocardium.Modern radiation therapy techniques introduced in the 1990s minimized deep radiation to the underlying myocardium when left-sided chest wall or left-breast radiation was used. Cardiac mortality decreased accordingly.[37,38]An analysis of the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (SEER) data from 1973 to 1989 that reviewed deaths caused by ischemic heart disease in women who received breast or chest wall radiation showed that since 1980, no increased death rate resulting from ischemic heart disease in women who received left chest wall or breast radiation was found.[39,40][Level of evidence C1]A population-based case-control study evaluated major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2,168 women who underwent radiation therapy for breast cancer. The study found the overall average mean dose to the whole heart was 4.9 Gy (range, 0.03–27.72). The rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per Gy (95% CI, 2.9%–14.5%; P < .001), with no apparent threshold.[41]

Arm lymphedema. Lymphedema remains a major quality-of-life concern for breast cancer patients. Single-modality treatment of the axilla (surgery or radiation) is associated with a low incidence of arm edema. In patients who receive axillary dissection, adjuvant radiation therapy increases the risk of arm edema. Edema occurs in 2% to 10% of patients who receive axillary dissection alone compared with 13% to 18% of patients who receive axillary dissection and adjuvant radiation therapy.[42-44] For more information, see Lymphedema.

Brachial plexopathy. Radiation injury to the brachial plexus after adjuvant nodal radiation therapy is a rare clinical entity for breast cancer patients. In a single-institution study using current radiation techniques, 449 breast cancer patients treated with postoperative radiation therapy to the breast and regional lymphatics were monitored for 5.5 years to assess the rate of brachial plexus injury.[45] The diagnosis of such injury was made clinically with computed tomography to distinguish radiation injury from tumor recurrence. When 54 Gy in 30 fractions was delivered to the regional nodes, the incidence of symptomatic brachial plexus injury was 1.0%, compared with 5.9% when increased fraction sizes (45 Gy in 15 fractions) were used.

Contralateral breast cancer. One report suggested an increase in contralateral breast cancer for women younger than 45 years who received chest wall radiation therapy after mastectomy.[46] No increased risk of contralateral breast cancer occurred in women aged 45 years and older who received radiation therapy.[47] Techniques to minimize the radiation dose to the contralateral breast are used to keep the absolute risk as low as possible.[48]

Risk of second malignancy. The rate of second malignancy after adjuvant radiation therapy is very low. Sarcomas in the treated field are rare, with a long-term risk of 0.2% at 10 years.[49] In nonsmokers, the risk of lung cancer as a result of radiation exposure during treatment is minimal when current dosimetry techniques are used. Smokers, however, may have a small increased risk of lung cancer in the ipsilateral lung.[50]