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		Hodgkin's Lymphoma - Improved Ways of Reducing Toxicity Ernest H. Rosenbaum, MD

1. Safer radiotherapy programs have a more regulated dose and radiation field size, and also the fields of treatment better encompass the disease.

2. To reduce the risk of breast cancer, improved axillary and more localized breast protection radiation fields (reduced field size, using careful computerized tomography - Cat Scan-based planning) reduces the mediastinal volume, especially after chemotherapy. Reduced breast, heart and lung exposure are also a goal.

3. Programs using chemotherapy alone without radiation have been advocated and are under study.

4. Reduction of chemotherapy programs using newer drug innovations are being studied, especially alkylating agent-based combinations and anthracycline-based combination (ABVD). Second tumors, primarily lung cancer, could be dose-related.

The ABVD program (Adriamycin, Bleomycin, Vinblastine, and Procarbazine and the newer Stanford V program {Adriamycin, Vinblastine, Prednisone, Vincristine, Bleomycin, and Etoposide}) allows a shorter chemotherapy course of twelve weeks, which helps maintain fertility, and decreases the incidence of secondary leukemia. Bulky Hodgkin's sites were often treated with local radiation therapy.

5. CAT scan imaging has helped in staging and assessment for improved treatments.

6. Screening programs: A long-term follow up - greater than twenty to thirty years - is necessary.

Careful breast cancer follow up for women is vital with physical examination, mammography, and MRI as indicated. Patient education on self-examination and healthy lifestyles is helpful and recommended.

Smokers require careful evaluations for potential lung cancer, especially if they received alkylating agents. Do not smoke!

Early menopause secondary to chemotherapy along with radiation-induced breast cancer are problems. Using hormonal replacement therapy to reduce menopausal side effects or replacement therapy is discouraged in women at potential risk for breast cancer post-radiation therapy. There was an increase in synchronous or matachronous breast cancer, and some women have had prophylactic mastectomies.

The risk of coronary heart disease in those who've had mediastinal radiation merits attention to help reduce the risk of myocardial ischemia and heart damage. Cardiac stents and coronary bypass for symptomatic patients post-radiation therapy (mean dose 43 Gy) merit a stress electrocardiogram, radionuclide profusion imaging, and sometimes coronary angiography as indicated. Coronary stenosis was noted in 50-55% of patients, often requiring bypass surgery.

An increase in ischemic heart disease has been noted, and a heart risk reduction program is merited, including tests such as C-reactive protein and homocysteine tests. Healthy lifestyles, smoking cessation, control of hypertension and hypercholesterolemia may help reduce the risk of coronary heart disease in Hodgkin's lymphoma patients.

A study of 1,474, five-year survivors in the Netherlands showed a three- to five-times increased incidence of coronary vascular disease versus the general population. It is believed that 80% of the problem was related to therapy. In a Stanford report, 2,498 patients showed a 16% risk of death from coronary CVD (coronary vascular disease). Thus, the consequences of radiation therapy, including the heart structures, and anthracycline chemotherapy can cause irreversible and fatal cardiac damage. Altering lifestyle may help reduce the risk of heart damage, as well as with early recognition and treatment, survival and quality of life can be improved. Myocardial biopsies showed damage to cardiac myocytes (cells) with cell hypertrophy and interstitial fibrosis noted in children treated with Adriamycin. Late cardiac failure can be a consequence. Fatal congestive heart failure is another potential problem. Electrocardiographic changes, left ventricular dysfunction, decreased exercise capability, and heart failure may develop. Cardiomyopathy (enlarged heart), left heart ventricular function, contractibility decreases, and increased coronary artery disease are other risks. Pericarditis (inflammation of the sac lining outside the heart) is less common with current radiation therapy techniques. About 20% of those who have pericarditis develop a chronic condition that may require an operation - pericardiectomy -, opening up the constricting fibrotic sac surrounding the heart.

Cardiac valve abnormalities have been noted with either restriction/stenosis or insufficiency of the heart valves. This can affect both the aortic and mitral valves (with narrowing stenosis), and in one report by Adams, 42% of patients had at least one significant valve abnormality. Symptoms of aortic stenosis and mitral valve regurgitation with cardiac dysfunction have been reported.

Secondary to radiation fibrosis, there can be abnormalities in the electrical conduction pathway, leading to life-threatening arrhythmias post therapy. These are not common.

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