What are late effects?

Because of significant advances in treatment, 77% of children treated for cancer survive 5 years or more, an increase of almost 45% since the early 1960s. 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 that child’s health later in life. 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 recognition 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 medicines, or bone marrow transplant.

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. The treatment varies from child to child and from one type of cancer to another. 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

Most late effects result from chemotherapy or radiation. Extensive surgery may also lead to late effects, but this is less common. The following offers some information on 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 they 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.

The actual doses given of chemotherapy and/or radiation therapy help predict one’s risk of certain late effects. Higher doses may be linked to greater risk.

How Specific Parts of the Body React

Brain: Chemotherapy delivered into the spinal column (called intrathecal therapy, or IT) has been linked to learning disabilities in children. These effects are more common in children who are under age 5 at the time of treatment, and usually show up within 2 to 5 years of treatment. Learning disabilities are most common in 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. Non-verbal skills like math are particularly sensitive to the damaging effects of combined radiation and IT chemotherapy. 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 medicines can be toxic to the eye and may lead to problems such as blurred vision, double vision, and glaucoma. Many times, these effects go away after a short time.

Radiation in the area of the eye can sometimes 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 which high-pitched sounds cannot be heard, even though lower-pitched sounds can be.) 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 exams will help identify potential problems. Ultimately, treatments such as cataract removal, eyeglasses, or hearing aids 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 after treatment, 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. 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. Some of the long-term effects of intensive chemotherapy without radiation are still 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 slower growth. Exactly how radiation affects growth is not completely understood. The answer may lie in how it affects the endocrine system and its hormones.

The endocrine system is a complex part of the human body and is easily affected by 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. For example, they regulate growth, stimulate puberty, and control male and female fertility. 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. When the endocrine system is disrupted, 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 5 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 possible effects of replacing growth hormone.

Thyroid: Thyroid function may be at risk when head and neck radiation is given. Hypothyroidism (low thyroid) occurs when the thyroid no longer produces enough 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, which results in too much thyroid hormone, is less likely, but may occur. Yearly thyroid checkups can help detect these problems. They may be needed for more than 10 years after treatment.

Sexual Development

Males: Radiation therapy and chemotherapy are both capable of reducing sperm production. Low doses of radiation or certain chemotherapy medications 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 concern to consider before 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 can have the testicles moved 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 less of a 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, which can lead to failure to complete puberty, accelerated puberty, decreased sexual desire, and impotence. Careful monitoring and handling of these effects can produce better outcomes.

Females: Ovarian function can be affected by both chemotherapy and radiation to the abdomen. The degree of dysfunction largely depends on the age and stage of puberty at diagnosis. Girls who have not yet been through puberty are less affected. Protecting the ovaries is a major concern when abdominal radiation is necessary. Some chemotherapy drugs may allow for puberty to progress normally after treatment, but girls who receive these are still at risk for delayed menses, premature menopause, and reduced fertility.

Radiation treatment to the head can interfere with the hormones needed for ovarian function. Such alterations can lead to irregular menstrual bleeding, changes 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 problems could affect pregnancy outcome. Some women are encouraged to try and get pregnant during the early childbearing years to improve the chances 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 (ova) and may reduce the ability of the uterus to carry a fetus to term.

Studies continue to monitor the risk of congenital anomalies (inborn abnormalities) in the offspring of cancer survivors. While recent studies have shown no significant link, treatment protocols may involve different medicines 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 linked, though not as strongly, with the risk of heart problems. 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 this risk. Careful 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 exams and testing, such complications may be found early and treated, if necessary.

Studies are now underway to determine if medications proven to protect the heart in adults during similar chemotherapy may also help children.

Respiratory: Respiratory (breathing) 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. Such therapy is used for patients with Hodgkin disease or cancers that have spread to the lung from other primary sites. Other lung problems may include pneumonitis, an inflammation of the lung tissue which can cause trouble breathing, dry cough, and problems with exercise.

Certain chemotherapy drugs, such as bleomycin, may also lead to these problems. The problems may be worse if both radiation and certain chemotherapy drugs are given. These changes can occur even years after treatment, but for many, problems are first seen within 1 to 2 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 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 6 or children undergoing a growth spurt at puberty are at risk, and there may be unequal growth of body parts. In addition to stunted bone growth, osteoporosis (weakened bones) and joint problems can occur.

Teeth: Radiation therapy given to an area that involves the teeth may cause a reduced salivation, leading to dry mouth and/or cavities. When given to the very young child, tooth development may be delayed. Routine dental exams are important to identify problems early.

Second cancers: Childhood cancer survivors have a small but increased risk of developing a second cancer during their lifetime. This risk is not the same for all survivors. Many factors affect risk, such as the type of the first cancer, type of treatments received, and genetics. Those survivors who received radiation therapy tend to show a higher risk 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 these children grow up and age, lifestyle influences, environmental exposures, and personal choices all play a part in their cancer risk. It is important to remember and keep permanent, detailed records of the cancer treatments that were received during childhood. Sharing this information with their doctors will help those who had cancer as children to make better screening choices throughout their lives.

Summary

For several years after treatment of childhood cancer, regular follow-up exams will be very important. The doctors will watch for signs of recurrent disease, as well as for short-term and long-term effects of treatment. These effects vary with each patient and with each type of treatment.

Physical and emotional effects may linger. It is important to be aware of the treatment your child received and what impact this treatment might ultimately have on his life as he grows up. Ask your child’s doctor to help you stay aware of what may happen with long-term effects based on specific treatments received.

Emotional issues may arise that can affect all levels of maturity. Studies have shown that most survivors function well in daily life and society. However, more in-depth studies are needed to determine the real effect that living as a cancer survivor may have. Emotional concerns include compromises or losses due to cancer, living with uncertainty, developing relationships, marrying and having a family, facing discrimination in the workforce, etc. For many survivors, personal growth is positive and allows for clearer setting of priorities and helps establish strong self-values. With strong support from family, other survivors, mental health professionals, and others, many people who have survived cancer can thrive in spite of the challenges they’ve had to face.

For all survivors, while late effects may offer significant problems, they are the result of lifesaving treatment. Researchers will continue to search for ways to reduce long-term effects. Meanwhile, the gift of life may involve coping with the late effects of treatment.

Additional Resources

National Organizations and Web Sites*

Candlelighters Childhood Cancer Foundation
Telephone: 1-800-366-2223
Internet Address: www.candlelighters.org

National Cancer Institute
Telephone: 1-800-4-CANCER
Internet Address: www.cancer.gov (search for “late effects of childhood cancer”)

CureSearch, a combined effort of National Childhood Cancer Foundation and Children’s Oncology Group
Telephone: 1-800-458-6223 (for information or to find a Children’s Oncology Group in your area)
Internet Address: www.curesearch.org (look for “after treatment” section)

National Dissemination Center for Children with Disabilities (NICHCY)
Telephone: 1-800-695-0285
Internet Address: http://www.nichcy.org

*Inclusion on this list does not imply endorsement by the American Cancer Society.

The American Cancer Society is happy to address almost any cancer-related topic. If you have any more questions, please call us at 1-800-ACS-2345 at any time, 24 hours a day.

References

Hobbie W, Ruccione K, Harvey J, Moore IM. Care of Survivors. In Baggott CR, Kelly KP, Fochtman D, Foley GV (Eds), Nursing Care of Children and Adolescents with Cancer, 3rd Ed. 2002. WB Saunders; Philadelphia: 426-465.

Dreyer ZE, Blatt J, Bleyer A. Late Effects of Childhood Cancer. In Pizzo PA, Poplack DG (Eds), Principles and Practice of Pediatric Oncology, 4th Ed. 2002. Lippincott, Williams, & Wilkins:1431-1462.

Robison, Green, Hudson, et al. Long-Term Outcomes of Adult Survivors of Childhood Cancer. In Cancer-Survivorship: Resilience Across the Lifespan. Supplement to Cancer. American Cancer Society. Oct 24, 2005; 2557-2664.

Revised: 02/16/2006