Childhood Cancer

The human body has three types of blood vessels: arteries, veins, and capillaries. Arteries are large vessels that carry blood away from the heart. They branch into smaller arteries and then into arterioles. Arterioles eventually split into capillaries, which are vessels so small that blood cells have to flow through single file. The thin walls of the capillaries allow exchange of gases (i.e., oxygen and carbon dioxide), nutrients, and waste products. Capillaries merge into venules, which in turn merge into veins. Veins return blood to the heart.

The arteries that carry oxygen to the heart muscle itself are called coronary arteries.

Organ damage

The interiors of healthy blood vessels are usually smooth, but radiation can roughen them inside. These rough spots provide sites for fatty deposits (plaques) to develop in coronary arteries and other arteries and veins. Calcium deposits can harden the plaques, resulting in atherosclerosis (hardening of the arteries). When this happens in the coronary arteries in the heart, it is called coronary artery disease.

Survivors of Hodgkin lymphoma have been studied extensively due to the risk of vascular injury in the field of radiation (e.g., carotid arteries in the neck). An inflammatory process that damages the endothelial lining of the blood vessels is suspected. In these studies, survivors of Hodgkin lymphoma who did not have neck irradiation also had increased premature carotid artery disease and the reason is not yet understood. 2 , 3

Atherosclerosis can cause three problems. First, the fatty deposits narrow the blood vessels, reducing flow of blood. Second, layers of plaque decrease the strength and elasticity of the arteries. Third, plaques roughen the lining of the vessel, allowing platelets to form clots at the rough spots. If a clot breaks free, it can block blood flow in narrow arteries, reducing or stopping the supply of oxygen to that area. When oxygen is slowed to areas of the heart, angina (chest pain) results. If the clot blocks a coronary artery completely, it causes a heart attack.

The tendency to develop atherosclerosis is related not only to treatment for childhood cancer, but also to family history, weight, and lifestyle choices such as diet, exercise, and smoking.

  • Smoking vastly increases the risk of heart disease. The nicotine in cigarettes increases the heart rate and accelerates plaque formation that narrows arteries. It also damages the lungs, reducing their efficiency. Consequently, the heart must pump faster to deliver adequate oxygen to the cells of the body.

  • A diet high in saturated fat (e.g., red meat, dairy foods, and eggs) can lead to high levels of cholesterol. This can increase the chance of developing fatty deposits in the arteries, making a heart attack or stroke more likely.

  • Exercise helps maintain a healthy weight, increases lung capacity, and strengthens body muscles, including the heart. A note of caution is that if you received anthracyclines or radiation to the heart, you should consult your follow-up healthcare provider prior to starting an exercise program.

  • High blood pressure (over 140/90 mm Hg) is a risk factor for heart disease and promotes atherosclerosis.

A healthcare provider who specializes in treating survivors of childhood cancer cautions:

A significant problem that we are just beginning to understand is the effect of cranial radiation and chemotherapy in promoting premature coronary artery disease. Leukemia (ALL) survivors, especially those treated with cranial radiation, have an increased incidence of obesity and are more likely to be physically inactive. Obesity and physical inactivity at a young age are significant risk factors for the development of high blood pressure, diabetes, and dyslipidemia (high LDL cholesterol, low HDL cholesterol, high triglycerides) and these aid in the development of premature coronary artery disease. Because of this, it is essential that survivors exercise, eat a prudent diet, and get regular follow-up.

To slow the atherosclerotic process and help keep blood pressure low, you should:

  • Eat a diet low in saturated fats, cholesterol, salt, and processed foods.

  • Eat whole grains, fruits, and vegetables.

  • Eat foods high in fiber.

  • Exercise regularly (30 minutes every day).

  • Keep body fat low.

  • Limit alcohol intake (including beer).

Your physician may prescribe medications to lower your blood pressure.

Medical problems such as hypothyroidism, high blood pressure, high cholesterol, and diabetes can increase your risk of developing atherosclerosis.

Another problem that can occur after cancer treatment is development of thick and ropy blood vessels caused by chemotherapy damage. Currently, most children and adolescents get chemotherapy through implanted catheters. In earlier years, however, all medications were given through peripheral IVs (using a needle in an arm or hand vein). If the vein burst, the drugs leaked into the surrounding tissue, causing damage and scarring. Sometimes the scar tissue from such damage forms on the inner walls of the blood vessels, leaving them hard and inelastic.

I was diagnosed with neuroblastoma when I was 5 months old in 1966. Back then they didn’t have central lines so I had 3½ years of intravenous (IV) sticks. My veins got very hard so they placed IVs in my head, feet, and hands—pretty much everywhere they could find an open vein. My veins are still hard now, and I don’t think anyone could ever get a needle into my left arm. The veins in that arm are like a solid rope. My right arm has softened up. Other than that, I have no side effects from all those years of treatment.

Raynaud’s phenomenon can also develop in long-term survivors with vascular disease. This is when the fingers and toes become white or bluish due to spasms of the arteries leading to the hands. It is usually precipitated by cold or emotion, and affected individuals often have a genetic predisposition for developing Raynaud’s. This may also occur in survivors treated with bleomycin. The condition is usually chronic, but it may improve slowly over several years in some survivors.

Signs and symptoms

Risk of coronary artery disease and heart attack is lower for patients who had lower doses of radiation (less than 4000 cGy) using modern techniques and higher for patients treated with high doses of radiation and no heart shielding. Signs and symptoms of coronary artery disease are as follows:

  • Chest pain (or pressure-like sensation)

  • Chest, neck, or jaw pain upon exertion

  • Indigestion upon exertion

  • Shortness of breath upon exertion

Symptoms of inadequate oxygen to the heart and heart attack are as follows:

  • Crushing chest pain

  • Pain or numbness down the left arm

  • Shortness of breath

  • Sweating

  • Nausea

  • Feelings of impending doom

Many of these signs and symptoms can be caused by other illnesses or conditions; however, it is prudent to get an evaluation if any of these symptoms are present.

Screening and detection

Screening and detection for coronary artery disease includes some of the tests described above for the heart. A stress test is also needed. Routine cholesterol screening for those at risk for coronary artery disease is also essential.

Medical management

Medical management should involve frequent surveillance for symptoms in at-risk survivors. A variety of medications and lifestyle modifications are used to treat coronary artery disease. Advanced coronary artery disease is sometimes treated with a coronary artery bypass graft (open heart surgery) or balloon dilation angioplasty.