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Cancer Toxic Side Effects
Ernest H. Rosenbaum, MD

Cardiac Toxicity
Risk Factors for Cardiac Morbidity and Mortality
Renal (Kidney) Toxicity Side Effects
The Need for Long-term Surveillance

Cardiac Toxicity
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Late cardiac toxicity has been seen both in childhood and adolescent cancer survivors, mainly associated with anthracycline and anti-neoplastic agents, including cardiomyopathy and arrhythmias.

Mediastinal radiation also increased the risk for premature atherosclerotic heart disease.1

Cancer therapy cardiac mortality2
Treatment for early-stage breast cancer uses postoperative radiation therapy to destroy small microscopic deposits of residual disease to improve survival and prevent recurrence. This follows surgical removal of gross detectable disease, either with a partial mastectomy or lumpectomy. This is, in general, equal to a full mastectomy - breast conservation with removal of regional lymph nodes as indicated.

Left chest radiation involves possible cardiac toxic damage, which can often be present ten or more years following treatment. The damage can be increased by the use of adjuvant chemotherapy, such as doxorubicin and/or trastuzamab. Newer and improved radiotherapy techniques have helped to reduce toxicity, and using lower doses and limiting extent of chemotherapy have both reduced cardiac toxic side effects (Utilizing Three-DCD based treatment planning to give a more precise radiation therapy target for individual anatomic planning has helped control cardiac dose volume, as well as limit lung damage.)

Few studies have been done on women with existing cardiac disease, who received breast irradiation, and whether there was an increase in additional cardiac toxic events. They usually have been excluded from studies and trials.

Cardiac injury depends on the volume of the heart included in the radiation field, which correlates with an increased likelihood of cardiac injury leading to ischemic heart disease and cardiac mortality. Radiation-induced cardiac injury is a late event, often ten or more years after radiation, and hopefully will be reduced with improved technology.

Fortunately, many patients with cardiac toxicity do not die of a myocardial infarct or coronary artery disease, and with supportive cardiac medical treatment, symptoms can be reduced to help maintain a healthier heart.

Quality of life for breast cancer survivors. Patients need to be informed of their risks, as well as follow-up requirements to improve results. Approximately 3% of patients with left chest radiation had ischemic heart disease, and about 1.7% had acute myocardial infarction or morbidity. In a study by Vallis, et. al., there was a similar incidence of myocardial infarction toxicity from either right- or left-sided breast cancer radiated patients. 3

Risk Factors for Cardiac Morbidity and Mortality
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Heart toxic problems include ischemic heart disease approximately 10%, valvular heart disease approximately 3%, conduction problems approximately 10%, and heart failure about 10%.4

CAD and ischemic heart disease risk factors depend, in part, on preexisting problems, and left-sided radiation therapy is a minor contributor to heart disease versus other risk factors, such as hypercholesterolemia, hypertension, obesity, preexisting cardiac disease, sedentary lifestyle and family history.

Appropriate medical cardiac treatment following assessment and use of cardiac medications, control of diabetes, minimal alcohol, hypertension control, not smoking, hyperlipidemia control and exercise and diet can make a significant difference in reducing cardiac morbidity and mortality.

Controlling hypertension should be one of the major goals, as well as other risk factors, such as diabetes and hyperlipidemia (increased blood lipids/cholesterol). Long-term follow-up is obviously necessary, as events such as a myocardial infarction often occur after ten years or later. Control of other comorbid diseases is important to help extend life expectancy.

This study (Rates of Myocardial Infarction. Coronary Heart Disease and Risk Factors in Patients Treated with Radiation Therapy for Early Breast Cancer) showed that the time from radiation therapy to first cardiac event was 3.7 years, and a ten-year cumulative incidence of myocardial infarction was 1.2%, lower rates than were expected. 5

In conclusion, new technology for radiation therapy and chemotherapy has reduced the risk of cardiac morbidity and mortality, but careful observation following treatment with appropriate cardiac management for risk factors can further reduce the risk of adverse cardiac events. Radiation therapy remains a critical component of breast cancer therapy, and follow-up medical care and precautions are merited.

Renal (Kidney) Toxicity Side Effects
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Patients treated with radiation therapy that included the kidneys, or who received chemotherapy with any of the platinum compounds are at risk for kidney problems and possibly kidney failure. Platinum compounds (cisplatinum and carboplatin) can also result in some hearing loss, especially for high frequency sounds, rather than those in the speech range. Amifostine (Ethyol®) has been effective in reducing platinum kidney toxicity.

Abdominal radiation can cause intestinal adhesions, malabsorption, chronic diarrhea, lactose intolerance, and subsequent discomfort and weight loss.

A full evaluation including chest x-ray, electrocardiogram, echocardiogram, and physical examination are part of the standard assessment for kidney toxicity.

The Need for Long-term Surveillance
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Following the completion of cancer therapy, patients who have received radiation or cardiopulmonary toxic chemotherapy drugs merit long-term follow-up. Left heart ventricular systolic ejection time less than 45%, or a decrease of 5% or more from the resting level, is abnormal and merits careful assessment.

Cardio/pulmonary evaluations include a cardio/pulmonary consultation, EKG, echocardiogram, chest x-ray, CAT scans of the chest, and pulmonary function tests to assess for any pulmonary toxicity. Careful follow-up is recommended.

The treatment plan may require a cardiac and/or pulmonary consultation. Often oxygen combined with a special cardio/pulmonary medication program can be very helpful in reducing cardiac or pulmonary symptoms.

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Adams, MJ, Hardenbergh, PH, Constein, LS, et. al., "Radiation-Associated Cardiovascular Disease", Crit Rev Oncol Hematol, 2003; 45: 55-75.
Bleyer A. Young, "Adult Oncology: The Patient and Their Survival Challenges," CA Cancer J Clin, 2007; 57, 242 -255.
K.A. Vallis, M. Pintile, N. Zhong, et. al., "Assessment of Coronary Heart Disease Morbidity and Mortality after Radiation Therapy for Early Breast Cancer," JCO, 2002; 20: 1036-1042.
SEER database by D. A. Patt, J.S. Godwin, Y.F. Kug, et. al., "Cardiac Morbidity of Adjuvant Radiotherapy for Breast Cancer," JCO, 2005; 23: 7475-7482.
R. Jagsi, K. A. Grifith, T. Koelling, et. al, "Rates of Myocardial Infarction. Coronary Heart Disease and Risk Factors in Patients Treated with Radiation Therapy for Early Breast Cancer," Cancer, 2007; 109: 650-657.

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First appeared August 23, 2009