Late Effects of Childhood Cancer
Because of significant advances in treatment, 77% of children treated for cancer survive five years or more, an increase of almost 45% since the early 1960's. With childhood cancer survivors living longer, their long-term health has come more into focus in recent years. Researchers have learned that the effects of childhood cancer treatment may affect a survivor's health many years later. This result becomes known as a “late effect.” Just as the treatment of childhood cancer requires a very specialized approach, so does aftercare and monitoring for late effects. Careful follow-up after cancer treatment allows for early identification of and attention to the after-effects of treatment.
What causes late effects?
Late effects are caused by the injury that cancer treatment causes to the healthy cells in the body. They may occur as a result of surgery, radiation therapy, some chemotherapy medications, or bone marrow transplantation. Lack of cell nourishment, chronic cell injury, death of healthy cells, and scar tissue formation may all contribute to late effects.
Who is at risk for late effects?
Each child receiving cancer therapy is unique, with treatment varying from child to child, cancer to cancer. Late effects will also vary, and depend largely on the type of therapy received and the doses of that therapy. The very young child may be at the greatest risk.
Types of late effects
The majority of late effects result from chemotherapy or radiation. Extensive surgery may also lead to late effects, but this is less common. The following offers explanations of chemotherapy and radiation and the late effects that may result after use of these life-saving treatments.
Chemotherapy
Chemotherapy drugs are effective at killing cancer cells but also damage normal cells, which can cause side effects. These side effects depend on the type and dose of drugs, and how often and how long they are given. Drugs used in cancer chemotherapy attack cells that are actively dividing to produce new cells. These drugs are useful because cancer cells reproduce more quickly than do normal cells. However, some normal cells also divide often, such as the cells in the bone marrow, those lining the inside of the mouth and stomach, and the hair follicle cells. These dividing cells are the ones most damaged by chemotherapy and may result in side effects at the time of treatment. Late effects may occur several years later.
Radiation
Radiation therapy involves the use of high-energy rays (such as x-rays) to kill or shrink cancer cells. The radiation may come from outside of the body (external radiation) or from radioactive materials placed directly in the tumor (internal or implant radiation). Radiation therapy may be used to reduce the size of a cancer before surgery, to destroy any remaining cancer cells after surgery, or, in some cases, as the main treatment. As with chemotherapy, radiation therapy can affect normal cells as well as cancerous ones.
How Specific Parts of the Body React
Brain: Chemotherapy delivered into the spinal column (called intrathecal therapy, or IT) has been associated with learning disabilities in children. These effects are more common in children who are under age five at the time of treatment, and usually become apparent within two to five years of treatment. Learning disabilities are most closely associated with children who receive both IT chemotherapy and radiation therapy to the brain.
These deficits, often referred to as cognitive impairments, are typically seen as declines of 10 to 20 points in IQ and in academic achievement scores, as well as specific problems in visual motor skills, memory, and attention. Nonverbal skills like math are particularly vulnerable to the damaging effects of radiation therapy and IT chemotherapy when given together. Doctors will try, whenever possible, to avoid combining the two. However, it is possible for IT chemotherapy, even when given alone, to cause such impairments.
Eyesight and Hearing: Vision may be affected in a number of ways resulting from treatment, particularly if the tumor was on or near the eye. Certain medications can be toxic to the eye and may lead to complications such as blurred vision, double vision, and glaucoma. Many times, these effects are short-lived and are reversible. Radiation in the area of the eye can cause cataracts. Radiation therapy to the bones near the eye may also slow bone growth, possibly leading to facial deformity.
Certain chemotherapy agents and antibiotics may cause high frequency hearing loss. In addition, radiation therapy given to the brain or ear can lead to hearing loss.
Typically, careful evaluation of hearing and vision during treatment may allow for early changes in therapy should vision or hearing loss occur. After therapy, annual examinations will help identify potential problems. Ultimately, treatments such as cataract removal, eyeglasses, or hearing aides may be needed.
Growth and Development: Decreased growth during childhood cancer therapy is a common problem. A certain amount of catch-up growth may occur, but in some instances, short stature (height) is permanent. Chemotherapy may contribute to a slow-down in growth, but when given alone, without radiation, it is usually temporary, and many patients eventually catch up to a normal growth pattern. Certain chemotherapy medications, however, when given in high enough doses, may have more lasting effects. In many cases, the long-term effects of intensive chemotherapy without radiation are unclear.Radiation therapy has a direct effect on the growth of bones that are within the radiation field. Cranial radiation, or radiation to the head, also contributes to growth retardation. Exactly how radiation affects growth is not completely understood. The answer may lie in how it affects the endocrine system.
The endocrine system is a complex part of the human body and is very vulnerable to cancer therapy. Endocrine glands release hormones into the bloodstream. Examples of endocrine glands are the thyroid gland, adrenal glands, and the ovaries. Hormones travel through the bloodstream and set in motion various body functions. Such functions include the stimulation of puberty, male and female fertility, and growth regulation. If this system is disrupted, complications can result, such as delayed or early puberty, decreased fertility, or growth problems. The endocrine system can be disrupted by direct damage to the various organs, such as the ovary or testicles, or to the part of the brain that controls the endocrine system.
Radiation therapy delivered to the head and/ or neck region, may affect this part of the brain. With hormone dysfunction, growth rate may be slow, affecting bones, height, and full maturity. Again, very young children are most affected. Usually, slowing of growth is seen within five years of treatment. Treatment with growth hormone may reverse some of these damaging effects of radiation therapy. Such a choice should be made with your child’s doctor and with careful consideration of the consequences of growth hormone replacement.
Thyroid:Thyroid function may be at risk when head and neck radiation is given. Hypothyroidism occurs when the thyroid no longer produces adequate thyroid hormone. With annual check-ups of thyroid function, thyroid hormone replacement can be given if needed. Hypothyroidism may be indicated by extreme tiredness, dry skin, and thinning hair.
Hyperthyroidism, the overproduction of thyroid hormone, is less likely, but may occur. Annual thyroid evaluations are useful after treatment for up to 10 years or longer to identify such problems.
Sexual Development
Males:Radiation therapy and chemotherapy are both capable of reducing sperm production. Low doses of radiation and certain chemotherapy medications given alone may cause temporary reduction in sperm production. Higher radiation doses and many chemotherapy regimens lead to permanent reduction of sperm. The lack of sperm production affects the patient's ability to father children. This is an important consideration prior to starting cancer treatment in the older child. Sperm banking may be offered so that the patient can still father children through alternative means later in life. While radiation therapy may be necessary, some patients are eligible for testicular manipulation, placing the testicles out of the radiation field during treatment. For some, the decrease in sperm count is reversible. This reversal can take place as many as 15 years after treatment. The very young male, who is treated prior to puberty, is at a reduced risk. For many, it is not clear how their treatment will ultimately affect them as they proceed through puberty.
Other effects that may occur as a result of radiation damage to the brain include altered testosterone levels leading to the failure to complete puberty, or accelerated puberty; decreased sexual desire; and impotence. Careful monitoring and handling of these effects can produce positive outcomes.
Females:Ovarian function can be affected by both abdominal radiation and chemotherapy. The degree of dysfunction is largely influenced by age and stage of puberty at diagnosis. Girls who have not yet been through puberty are less affected. Protecting the ovaries is of primary concern when abdominal radiation is necessary. Some chemotherapy agents may allow for normal pubertal progression and function at the completion of therapy, but women who receive these are still at risk for delayed menses, premature menopause, and reduced fertility.
Cranial radiation therapy can interfere with the hormones necessary for ovarian function. Such alterations can lead to irregular menstrual bleeding, alteration in the release of eggs, and early puberty.
Reproduction:Many survivors of childhood cancer have concerns related to their ability to parent a child, support a pregnancy, and produce healthy offspring. Most survivors of childhood cancer can go on to produce healthy children, though risks do exist. Decreased fertility issues, early menopause, and other treatment related insults could affect pregnancy outcome. Attempting pregnancy may be encouraged during the early childbearing years to improve the likelihood of a successful conception. Individual circumstances vary and being knowledgeable of one's specific risk is key. To best learn about personal risk, genetic counseling may be helpful.
Radiation therapy to the abdomen or testicles can reduce or eliminate sperm production in males. Abdominal radiation in females interferes with the quality of eggs (ovum) and may reduce the ability of the uterus to carry a fetus to term.
Studies continue to monitor the risk of congenital anomalies in the offspring of cancer survivors. While recent studies have shown no significant correlation, treatment protocols may involve different medications or doses not yet proven safe to future offspring.
Heart/Cardiovascular System:A class of drugs used for childhood cancers, known as anthracyclines, have been linked with decreased heart function in childhood cancer survivors. Other medications have also been associated, though not as strongly, with cardiovascular risk. Radiation to the chest area is also considered a risk to the heart. Total dose delivered, type of delivery, and age of the patient at the time of treatment all contribute to one’s risk. Careful cardiac monitoring is especially important in these patients because often there are no symptoms. Only special studies, such as an echocardiogram (an ultrasound of the heart), can identify hidden problems. With routine physical examinations and testing, such a complication may be found early and treated, if necessary.
Studies are now underway to determine if medications proven to protect the heart in adults getting similar chemotherapy may also benefit children.
Respiratory:Respiratory problems, such as decreased lung volume and lung tissue that becomes thickened and coarse (fibrosis), are most common in children who have received radiation therapy to the chest wall. Such therapy is used for patients with Hodgkin’s disease or cancers that have spread to the lung from other primary sites. Other respiratory problems may include pneumonitis, an inflammation of the lung tissue, causing difficulty in breathing, dry cough, and difficulty with exercise.
Certain chemotherapy drugs, such as bleomycin, may also lead to the development of these problems. The problems may be worse if both radiation and specific chemotherapy drugs are given. These changes can occur even years after treatment, but for many, problems are first seen within one to two years.
Treatments are available to help reduce the symptoms of fibrosis and pneumonitis. Careful follow-up with a doctor will help to identify those at risk, and special tests may be required on a regular basis in those with a strong risk factor. For some, a pulmonologist (respiratory specialist) may be helpful.
Muscle and bone:Radiation therapy can have serious adverse effects on the proper growth of bone and muscle in young people. Very young children have much growth ahead of them, and radiation therapy can slow the growth of any given area. Bones, soft tissue, muscle, and blood vessels are very sensitive to radiation during times of rapid growth. Therefore, children under the age of six or children experiencing a pubertal growth spurt are at risk, and there may be unequal growth of body parts. In addition to stunted bone growth, osteoporosis and joint problems can occur.
Teeth:Radiation therapy given to an area that involves the teeth may cause a reduction in salivation, leading to dry mouth and/or cavities. When given to the very young child, tooth development may be delayed. Routine dental examination is important to identify problems early.
Second Cancers:Childhood cancer survivors have a small but increased risk of developing a second type of cancer during their lifetime. This risk is not the same for all survivors. Many factors affect risk, such as the type of original cancer, type of treatments received, and genetics. Those survivors who received radiation therapy tend to show a higher incidence of second cancers in the areas that were irradiated. As childhood cancer survivors live longer into adulthood, they are at higher risk of developing cancers usually seen in adults.
As one ages, lifestyle influences, environmental exposures, and personal choices all play a part in one’s cancer risk. Staying familiar with the cancer treatments that were received during childhood throughout the course of one’s lifetime will help people and their doctors make accurate screening choices.