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Cancer Supportive and Survivorship Care Programs Improving Quality of Life Logo

Enhancing Cancer Survivorship Care Through a Comprehensive Program
Ernest H. Rosenbaum, MD

Late Cardiorespiratory Effects in Survivors

Symptoms and Signs of Cardiac and Pulmonary Disease
Cardiopulmonary Surveillance
Cancer Survivor Follow-up

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The recent Institute of Medicine (IOM) report recommends comprehensive programs covering the psychosocial and physical sequelae of cancer treatments, their short- and long-term side effects, functional impairment, and disabling symptoms, as well as health promotion for disease prevention. This requires education of patients as well as the medical profession, including primary health care physicians, internists, nurses and cancer specialists.
1. Often, early information about cancer treatments is provided, but frequently, the stress following a cancer diagnosis can negate the provided information.

2. It is necessary to provide wellness information, treatment programs, and cover essentials such as necessary changes in diet, exercise, the availability of support groups, and resources that may be of help to the patient and family.

3. The creation of a treatment summary care plan should cover future examinations for prevention needs, weight control to avoid gaining weight or obesity, control of fatigue, as well as reviewing side effects of therapy, both short- and long-term.

4. Medical prevention plans for osteoporosis, psychological distress and depression, lymphedema and chronic pain are very valuable for health promotion.

5. A screening program is necessary for the possibility of a cancer recurrence, development of a new cancer, and for observation of early and late side effects that can sometimes be permanent and disabling.

6. Resources should be made available for return to work problems, community programs for supportive care, and resources that promote better health.

Some of the common early and late side effects include cardiac and pulmonary toxicities. These differ from the side effects of drug and radiation therapy twenty and thirty years ago due to the availability of new drugs, new programs, and the development of cardiac, pulmonary and kidney protective drug programs to reduce organ impairment. There may be a need for medical supportive care including oxygen at home, medications, as well as possible hospice care.

Late Cardiorespiratory Effects in Survivors
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Many patients who've had Hodgkin's disease, non-Hodgkin's lymphoma, breast and testicular cancers and have received chemotherapy and radiotherapy experience late side effects with cardiorespiratory toxicity. These late side effects may show up as much as twenty or twenty-five years post initial therapy.

Anthracycline-based chemotherapy with or without mediastinal radiation can not only cause secondary cancers but also cardiovascular ventricular function deficits, as well as possible pulmonary fibrosis, pneumonia, hypersensitivity toxicities, myocardial infarctions, coronary artery disease, valvular complications, as well as Reynaud's disease post cancer therapy.

Sometimes, the cardiopulmonary effects occur early within the first year following chemotherapy or radiation therapy. Changes are seen in the left ventricular ejection fraction and on EKG with a chance of progression to irreversible congestive heart failure. The three most toxic cardiac side effects are seen with Adriamycin, daunorubicin (Cerubinidine), or epirubicin (Ellence). There is direct cardiac damage to heart cells with loss of myocardial (heart) fibrils, as well as destruction of heart tissue. This can also be seen with high dose Cytoxan, 5-FU, Taxol, Ifex, and Herceptin. Radiation effects are seen months or years post treatment. Pericarditis (inflammation of the sac around the heart) is the most common effect from radiation therapy. Thickening of the coronary artery walls can lead to coronary vascular disease.

Symptoms and Signs of Cardiac and Pulmonary Disease
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Cardiac Signs and Symptoms
1. Chest pain
2. Dyspnea - shortness of breath
3. Fast heart rate - tachycardia
4. Non-productive cough
5. Arrhythmia - gallop rhythms
6. Congestive heart failure: moist lungs (rales), leg edema, and enlarged heart (cardiomegaly)
7. Fatigue

Pulmonary Signs and Symptoms
1. Non-productive cough
2. Shortness of breath
3. Low-grade fever
4. Fast heart rate - tachycardia
5. Wheezing
6. Fatigue
7. Rapid breathing - tachypenia
8. Chest pain
9. Decreased oxygen saturation - cyanosis

Additional Risk Factors for Cardiopulmonary Disease
1. Older age
2. History of heart disease or lung disease
3. Smokers
4. Kidney insufficiency
5. High blood pressure - hypertension

Pulmonary toxic drugs include bleomycin greater than 450 mg/m2, mitomycin-C, BiCNU, Busulfan, high-dose Cytoxan greater than 1000 mg/m2, methotrexate, CytosarU greater than 1000 mg/m2, Gemzar, Taxotere, Matulane, and thoracic radiation.

Pulmonary side effects from chemotherapy involve the endothelial cells with an inflammatory reaction, resulting in drug-induced pneumonitis. There are extensive changes in the pulmonary tissue with obliteration of alveoli and dilatation of air spaces.

Prevention of Cardiopulmonary Side Effects
1. Control of the radiation fields using CAT scan technology and limited field size to shield the heart and lung tissue as much as possible.
2. The use of cardioprotectants, such as dexrazoxane (Zinecard), and liposomal anthracyclines, such as Doxil, can reduce cardiorespiratory toxicities.

Cardiopulmonary Surveillance
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Evaluation of cardiac function with EKG, echocardiogram, and radionuclide cardiography, assessing the ejection fraction, which if less than 45% or a decrease of 5% or more from prior resting value is abnormal. Follow-up evaluations are most important when comparing old and new echocardiograms or radionuclide angiographies three months, six months, and a year after treatment to assess late toxicities. Long-term follow up with yearly scans and echocardiograms are essential.

Pulmonary function monitoring includes chest x-rays, CT scans, and pulmonary function tests to assess any late pulmonary toxicity and lung damage.

Long-term management includes assessment of physical functions, such as aids to daily living and debility assessment as part of the cardiopulmonary follow up.

Signs and symptoms for surveillance are:
1. Shortness of breath - dyspnea
2. Chest pain and heaviness
3. A non-productive cough
4. A fast heartbeat - tachycardia
5. Leg swelling - edema
6. Fatigue
7. A low-grade fever

These factors are part of the questions in the history that are complemented by chest x-ray, electrocardiogram, and/or echocardiogram.

Patient education is vital, as they must be advised of signs and symptoms to look for and report if they occur.

The question is whether monitoring for cardiopulmonary toxicities will help prevent illness? New and more intensive therapies, such as dose-dense chemotherapy, have thus far not had long-term follow-up for late toxicities.

Cancer Survivor Follow-up
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Cancer survivors need to be followed either in specialty clinics with oncologists and specialized cancer nurses or by their primary care physicians and internists who are guided by the specialized oncologic follow-up clinics with guidelines for follow up of various types of cancer.

1. The need for the tools to provide consistent quality care using evidence-based medical practice guidelines is essential.
2. There is a need for health insurance coverage to defray the costs of physician or clinic follow up, as well as the necessary tests for the assessment of early and late side effects post therapy.
3. There is also a need to provide services for psychosocial care to promote better health.
4. Patients and families who have a genetic mutation, such as the BRCA mutations, benefit from additional survivorship care and recommendations, as they have a predisposition to cancer, second cancers, and recurrent cancers.
5. Preventive strategies should be employed, including vaccinations, cervix and colon cancer screening, blood lipid testing, bone density testing, and breast cancer screening.
6. Use of a Navigator Program to help guide patients through the maze of follow up testing and recommendations to achieve a better health survivorship.
7. Advice for patients on insurance, disability, and work-related problems through social services and other resources.
8. By providing a cancer plan summary, the patient and family can be more knowledgeable about the care received and future follow-up guidelines that need to be followed.
9. To reduce anxiety and apprehension, patients need to be informed as early as possible about test results and be counseled with as positive an attitude as possible about future needs and treatments.
Of note is that long-term Hodgkin's disease survivors have adverse sequelae, and second primary cancers have become the leading cause of death.
Hoppe, R. T., "Hodgkin's Disease: Complications of Therapy and Excess Mortality, "Amm Oncol, 1997; 8:S 115-118 and Tores, G. M., Schonfeld, S., Chen, J., et. al., "Long-Term Cause-Specific Mortality Among 41,146 One-Year Survivors of Hodgkin's Lymphoma, "J Clin Oncol, 2005; 23: 562S.)
Lois B. Tarvis, M.D., in a presentation at ASCO 2006 entitled, "Cancer Survivorship: Understanding the Risk," stated, "For a woman treated at age 25 with a mantle dose of at least 40 Gy without alkylating agents, the estimated cumulative absolute risk of breast cancer by age 35, 45, and 55 years was 1.4%, 11.1%, and 29%, respectively." It was felt that there were many factors also affecting these figures including lifestyle factors of tobacco use, alcohol, diet, as well as the length and completeness of follow-up. (Reference: Travis, L.B., "Controversies, Therapy-Associated Solid Tumors," Acta Oncol, 2002; 41: 323-333.

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