What are late effects?

Today, because of advances in treatment, about 80% of children treated for cancer survive 5 years or more. But the treatments that allow these children to live can also cause health problems that may not show up until months or years after treatment. These problems are called late effects. Because childhood cancer survivors are living longer, their long-term health and these late effects have become a focus of care and research.

Just as the treatment of childhood cancer requires a very specialized approach, so does aftercare and watching for late effects. Late effects can involve more than one part of the body (or more than one organ system) and can range from mild to severe.

Careful follow-up after cancer treatment allows doctors to find and treat the late effects as early as possible. This care should focus on the type of cancer the child had, the treatments used, and the risk of late effects from those treatments.

Who is at risk for late effects?

Each child getting cancer treatment is unique. And the treatments used vary from child to child and from one type of cancer to another. Late effects will also vary, and depend mostly on the type of treatment used and the doses given. Other things that have been linked to the risk of a child having late effects are:

• the type of cancer
• where the cancer was in the body
• how old the child was when treated
• the child's overall health before the cancer
• the child's genetic make-up (inherited risk for certain health problems)

What causes late effects?

Most late effects are caused by chemotherapy or radiation. Major surgery may also lead to late effects, but this is less common. Late effects are caused by the damage that cancer treatment causes to healthy cells in the body. Cancer treatments like surgery, radiation therapy, chemotherapy, or bone marrow transplant, kill cells that grow quickly, such as cancer cells. But in a child, healthy cells in the bone, brain, and other organs, are growing fast, too. Treatment can damage these cells and keep them from growing and developing the way they should.

Healthy cells that aren't fed the way they should be, ongoing cell injury, death of healthy cells, and scar tissue formation may all be causes of late effects.

Chemotherapy

Chemotherapy drugs kill cancer cells. But they damage normal cells, too, which can cause short-term and long-term side effects. These side effects depend on the type and dose of drugs, as well as how often and how long they are given.

Chemotherapy drugs attack cells that are quickly growing and dividing. The drugs work because cancer cells grow and divide faster than most normal cells. But some normal cells also divide quickly, such as the cells that make blood cells, those lining the inside of the mouth and stomach, and the hair follicle cells. These dividing cells are the ones most damaged by chemotherapy, which may cause side effects during treatment. These short-term side effects go away over time after treatment is over.

Late effects, on the other hand, may happen many years later. A child's whole body is growing. This means that many different kinds of healthy, normal cells are dividing faster than they would be in an adult. For instance, cells in the bone, brain, and many other organs, are growing and dividing fast, too. Some types of chemotherapy can damage these cells and keep them from growing and developing the way they should.

Radiation

Radiation treatment involves the use of high-energy rays (such as x-rays) to kill cancer cells and shrink tumors. The radiation may come from outside the body (external radiation) or from radioactive materials placed directly in the tumor (internal or implant radiation). Radiation treatment may be used to reduce the size of a cancer before surgery, kill any cancer cells that may be left behind after surgery, or, in some cases it may be the main treatment. As with chemotherapy, radiation therapy can affect normal cells as well as cancer cells.

The actual doses of radiation therapy help predict a person's risk of late effects. Higher doses are often linked to greater risk. The area of the body that is being treated also has a major effect on the type and risk for late effects.

Treatment effects on certain parts of the body

Brain

Chemotherapy given into the spinal column (called intrathecal therapy, or IT chemo) has been linked to learning disabilities in children. These effects usually show up within 2 to 5 years of treatment. They are more common in children who are under age 5 at the time of treatment. The younger the child is at the time of treatment, the greater the risk. Learning disabilities are most common in children who get both IT chemo and radiation to the brain.

The learning problems, often called cognitive impairments, are most often seen as:

• drops of 10 to 20 points in IQ
• lower academic achievement test scores
• problems in memory and attention
• poor hand-eye coordination
• slowed development over time
• behavior problems

Non-verbal skills like math are particularly sensitive to the damaging effects of combined radiation and IT chemo. Doctors will try, whenever possible, not to combine the two. But it is possible for IT chemo, even when given alone, to cause this kind of learning problem.

Other late effects that may show up, depending on the type of treatment used, include things like seizures and headaches.

Eyesight

Cancer treatment can affect vision in a number of ways, and is more likely if the tumor was in or near the eye.

Certain drugs can be toxic to the eye and may lead to problems like blurred vision, double vision, and glaucoma. Many times, these effects go away over time.

Radiation in the area of the eye can sometimes cause cataracts. Radiation treatment to the bones near the eye may also slow bone growth, which can change the shape of the child's face as it grows.

Other late effects on the eye may be:

• dry eye
• eye irritation (feels like something is in the eye)
• discolored sclera (white part of the eye may be a different color)
• damage to the optic nerve and retina
• poor vision
• light sensitivity
• poor night vision
• tumors on the eyelid
• drooping eyelid

Your child's vision will be checked during treatment so that, if possible, the treatment plan can be changed if there are signs of vision loss. After treatment, yearly exams should be done to help find problems. Over time, treatments such as cataract removal or eyeglasses may be needed.

Hearing

Certain chemo drugs and antibiotics may cause high-frequency hearing loss. (This means high-pitched sounds cannot be heard, even though lower-pitched sounds can be.) Radiation given to the brain or ear can lead to hearing loss, too. This risk may be increased in children who are young at the time of treatment. Other late effects may be ringing in the ears, dizziness, and hard, crusty earwax.

The cancer care team will pay attention to your child's hearing during treatment. This may allow for early changes in treatment if hearing loss becomes a concern. After treatment, regular hearing tests will help find any problems. Some children might need hearing aids.

Growth and development

Decreased growth during childhood cancer treatment is a common problem. A certain amount of catch-up growth may occur after treatment, but in some children, short stature (height) is permanent. Chemotherapy may contribute to a slow-down in growth. But when chemo is given alone, without radiation, the change in growth rate is most often short-term. Over time many patients catch up to a normal growth pattern after treatment. But certain chemotherapy drugs, when given in high enough doses, have more lasting effects. And some of the long-term effects of intensive chemotherapy without radiation are still unclear.

Many of the late effects on growth and development are linked to radiation. Radiation has a direct effect on the growth of bones that are in the area that is being treated. 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 hormones of the body (the endocrine system).

The endocrine system is a complex part of the human body that is easily affected by cancer treatment. Endocrine glands release hormones into the bloodstream. Some of the endocrine glands are the pituitary gland, thyroid gland, adrenal glands, the testicles, and the ovaries. Hormones travel through the bloodstream and set in motion many body functions. For example, they control growth, trigger puberty, and control male and female fertility. If this system is disrupted, it can cause problems, such as delayed or early puberty, decreased fertility, or growth problems.

Direct damage to the organs that make hormones, such as the ovary or testicles, can throw the endocrine system off track. Damage to the part of the brain that controls the endocrine system can also disrupt it. (This includes radiation treatments given to the head and/or neck, which may affect this part of the brain.) The changes in hormones that result from this damage can slow the child's growth, and may affect bones, height, and full maturity. Again, very young children are most affected. The slowing of growth is usually seen within 5 years of treatment.

Treatment with growth hormone may reverse some of these damaging effects of radiation treatment. But growth hormone treatment has its own risks. The choice to use growth hormone replacement should be made with your child's doctor, and you should fully discuss its possible side effects.

Thyroid

Thyroid function may be at risk when head and neck radiation or total body irradiation (TBI) is given. Hypothyroidism (not enough thyroid hormone) occurs when the thyroid no longer makes enough thyroid hormone. It is caused by direct damage to the thyroid gland after high doses of radiation. Thyroid hormone replacement can be given, if needed. Signs of hypothyroidism may be extreme tiredness, dry skin, unexplained weight gain, constipation, slowed bone growth, and thinning hair.

Hyperthyroidism, which means too much thyroid hormone, is less likely, but it can happen. Signs of this include nervousness, weight loss, trouble sleeping, diarrhea, and enlarged thyroid gland (goiter).

Yearly thyroid blood tests can help detect these problems. Testing may be needed for more than 10 years after radiation treatment. And, in fact, thyroid problems have been found more than 20 years after treatment.

Muscle and bone

Radiation treatment can have serious effects on the proper growth of bone and muscle in young people. Very young children have a lot of growing to do, and radiation 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. This means children under the age of 6, or children going through a growth spurt at puberty are at great risk for late effects.

Along with stunted bone growth, other late effects related to bone and muscle are:

• unequal growth of body parts (the treated side doesn't grow the same way as the untreated side)
• bone pain
• joint stiffness
• gait changes (changes in the way the child walks)
• weak bones that can break easily (osteoporosis)
• decreased calcium in the bones

Some problems in bone growth can be due to damage to the endocrine system (see the section "Growth and development," above).

Sexual development

Males

Both radiation therapy and chemo can reduce sperm production. Low doses of radiation and some chemotherapy drugs may cause a short-term decrease in sperm production. But high radiation doses and certain chemotherapy drugs lead to permanent reduction of sperm. This affects the patient's ability to father children. It is important to think about this before starting cancer treatment in the older child. Boys who have gone through puberty can bank sperm, so that they can still father children later in life.

While radiation treatment may be necessary, some patients can have the testicles moved out of the radiation field during treatment. And for some, the decrease in sperm count only lasts for a short time. The return to normal sperm production can take place as many as 15 years after treatment. The very young male, who is treated before puberty, is less of a risk.

Other late effects that may affect sexual development are a result of radiation damage to the brain. They include altered testosterone levels, which can lead to failure to complete puberty; accelerated puberty; decreased sexual desire; and impotence (being unable to get and keep an erection).

Females

The ovaries can be affected by both chemotherapy and radiation to the abdomen (belly). The degree of problems mostly depends on the age and stage of puberty at the time of treatment. Girls who have not yet been through puberty are less affected. Protecting the ovaries is a major concern when treating the nearby areas with radiation.

Some chemotherapy drugs may allow for puberty to progress normally after treatment. Still, girls who get these drugs are still at risk for delayed menstruation, early menopause, and reduced fertility.

Radiation treatment to the head can also interfere with the hormones needed for the ovaries to work as they should. This can lead to irregular menstrual periods, changes in the release of eggs, and even early puberty.

The uterus can be affected, too, especially if radiation is given to the abdomen. Late affects include a uterus that is smaller than normal which may not stretch as it should. This can increase the risk of miscarriage, low birth-weight babies, and premature birth. It can also affect how the baby grows in the uterus.

Reproduction

Many survivors of childhood cancer may be concerned about 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 there are risks. Decreased fertility, early menopause, and other treatment-related issues could affect pregnancy outcomes. Some women are encouraged to try and get pregnant early in their childbearing years to improve the chances of success. Problems vary greatly from patient to patient, and knowing one's own risk is key. And genetic counseling may be helpful to best learn about the risk of passing abnormal genes (if the cancer was inherited) onto the survivor's children.

Radiation therapy to the abdomen (belly) or testicles can reduce or eliminate sperm production in males. Abdominal radiation in females interferes with the quality of eggs (ova) and might reduce the ability of the uterus to carry a baby to term. More information about fertility and cancer can be found in Fertility and Cancer: What are My Options? It has more on reproductive options and a section on children with cancer.

Studies continue to look at the risk of congenital anomalies (inborn abnormalities) in the offspring of cancer survivors. While recent studies have not shown a link, treatments given today may use different drugs or doses not yet proven safe to future offspring.

Heart/cardiovascular system

Heart disease can be a serious late effect of cancer treatment. There is a class of drugs called anthracyclines that are used to treat childhood cancers. These drugs have been linked with decreased heart function in childhood cancer survivors. Studies are now being done to see if certain drugs proven to protect the heart in adults during anthracycline chemotherapy may also help children. Other chemo drugs have also been linked, though not as strongly, with the risk of heart problems.

Radiation to the chest area can also pose a risk to the heart. Total dose delivered, type of radiation, and age of the patient at the time of treatment are all linked to this risk.

Careful monitoring is especially important in these patients because often there are no symptoms. It is common to find problems more than 10 years after treatment, and beyond. Only special studies, such as an echocardiogram (an ultrasound of the heart), can show hidden problems. With routine physical exams and testing, heart problems may be found early and treated, if necessary.

Respiratory system

Respiratory (lung or breathing) problems are most common in children who have had radiation to the chest. These children have also been found to have an increased risk for lung cancer, with the risk going up as the child ages.

Other late effects include:

• decreased lung volume (lungs can't hold as much air)
• shortness of breath, which may cause problems with exercise
• chronic (ongoing) dry cough
• lung tissue that becomes scarred, thickened, and coarse (called pulmonary fibrosis)
• pneumonitis (inflamed lung tissue, which can cause trouble breathing)

Certain chemo drugs, such as bleomycin, may lead to these late effects, too. The problems may be worse if both radiation and certain chemo drugs are given. The changes can take place even years after treatment, but for many, problems are seen within the first 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 done on a regular basis in those with a strong risk factor. For some, a pulmonologist (lung and breathing doctor) may be helpful.

Teeth

Radiation therapy in an area that involves the teeth and jaw can lead to late effects, mostly in children who are treated before age 3. But older children may have problems too. Decreased saliva is common. This often leads to dry mouth, which can lead to tooth decay (which causes cavities) and gum disease. When radiation is given to the jaw or teeth of a very young child, tooth development may be delayed. Other late effects may be:

• teeth are small and do not have a normal shape
• missing teeth
• tooth enamel is not normal
• the roots of teeth are shorter than they should be

Regular dental exams are important to find problems early and prevent infection, decay, and tooth loss.

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 given, and genetics. Those survivors who had radiation treatment tend to show a higher risk of second cancers in the areas that were treated. You can get more information on this in Second Cancers Caused by Cancer Treatment, which you can read on our Web site, or you can call us for a copy.

As childhood cancer survivors live longer into adulthood, they are also at higher risk of developing other cancers usually seen in adults, such as prostate, breast, or colon cancer.

As these children grow up and age, things like genetics, diet, activity level, overall health, body weight, exposure to viruses, and environmental exposures all play a part in their cancer risk. It is important to remember and keep detailed records of the cancer treatments that were used during childhood. Sharing this information with all their doctors will help those who had cancer as children to make better screening choices throughout their lives.

Emotional issues

Emotional issues may come up, too, and can affect all levels of maturity. Studies have shown that most cancer survivors function well in daily life and society. But more in-depth studies are needed to determine the real effect that living as a cancer survivor may have. Emotional concerns include things like:

• compromises or losses due to cancer
• living with uncertainty
• developing relationships
• marrying and having a family
• facing discrimination in the workforce

For many survivors, personal growth can be positive. It 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.

Long-term follow-up guidelines

In an effort to increase awareness of late effects and improve follow-up care of childhood cancer survivors throughout their lives, the Children's Oncology Group has developed long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. These guidelines can help you know what to watch for, what type of screening should be done, and how late effects may be treated. You can learn more about the guidelines and download them for free at the CureSearch Web site: www.survivorshipguidelines.org. The guidelines are written for health care professionals, and we urge you to review them with a doctor.

You can also find a list of late effects of childhood cancer treatment to watch for in the "Prevention, Follow-up, and Monitoring" section of the e-medicine article, "Late Effects of Childhood Cancer and Treatment" located online at http://emedicine.medscape.com/article/990815-overview.

Follow-up is key

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

For the rest of the childhood cancer survivor's life, doctors should watch for things like pain, tiredness, and anxiety, as well as other possible signs of late effects. Physical and emotional effects may linger.

It is important to know what kind of treatment your child had and what impact this treatment might have on his life as he grows up. Ask your child's doctor to help you stay aware of what long-term effects might occur based on the treatments your child had. And be sure your adult child knows the details of his childhood cancer so he can share that information with his doctors. If you do not have a copy of this information, contact the doctor who treated the child. If treatment was given at a hospital or clinic, you will need to contact them, too. These records are usually destroyed at some point, and may not be available more than a few years after treatment. There are certain pieces of information that you and your child should have, even into adulthood, including:

• A copy of the pathology report from a biopsy or surgery if there was surgery.

• If there was surgery, a copy of the operative report.

• If there were hospitalizations, a copy of the discharge summaries doctors prepare when patients are discharged from the hospital.

• If there was chemotherapy treatment for the cancer, a list of the final doses of each drug your child received. Certain drugs may have specific long-term side effects. If you can get a list of these from the pediatric oncologist, it might help any new doctors your child has.

• If there was radiation, a final summary of the dose and field.

For all survivors, while late effects may lead to problems, they are the result of life-saving 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

More information from your American Cancer Society

We have selected some related information that may also be helpful to you. These materials may be ordered from our toll-free number, 1-800-227-2345.

• When Your Child's Treatment Ends: A Guide for Families

• Fertility and Cancer: What are my Options?

• Second Cancers Caused by Cancer Treatment

• Cancer Information on the Internet

• Children Diagnosed with Cancer: Dealing with Diagnosis

• Children Diagnosed with Cancer: Financial and Insurance Issues

• Children Diagnosed with Cancer: Understanding the Health Care System (also available in Spanish)

• Children Diagnosed with Cancer: Returning to School

National organizations and Web sites*

Candlelighters™ Childhood Cancer Foundation
Toll-free number: 1-800-366-2223
Web site: www.candlelighters.org
This Web site has sections just for children and teens with cancer and their siblings, as well as for adults. Provides information and parent support groups.

Children's Brain Tumor Foundation
Toll-free number: 1-866-228- HOPE (1-866-228-4673)
Web site: www.cbtf.org
Offers a support line, as well as Web-based and printed information for parents and children with cancer.

CureSearch National Childhood Cancer Foundation
Toll-free number: 1-800-458-6223
Web site: www.curesearch.org (look for "after treatment" section)
Can help you find a Children's Oncology Group in your area. Special information for childhood cancer survivors is available from CureSearch at: www.survivorshipguidelines.org. Information from some of the world's best pediatric cancer specialists is available on their Web site.

National Cancer Institute
Toll-free number: 1-800-4-CANCER
Web site: www.cancer.gov (search for "late effects of childhood cancer")
Provides accurate, up-to-date information about cancer to patients and their families, including clinical trials information for patients.

National Dissemination Center for Children with Disabilities
Toll-free number: 1-800-695-0285 (also for TTY)
Web site: www.nichcy.org
Answers questions about disabilities and provides fact sheets about specific disabilities, state resource sheets, parent guides, information about educational rights, and referrals to parent groups. Spanish materials are also available.

National Coalition for Cancer Survivorship (NCCS)
Toll-free number: 1-877-622-7937: To order the Cancer Survival Toolbox^® or some publications
Toll-free number: 1-888-650-9127
Web site: www.canceradvocacy.org
Provides publications on many topics, including employment and health insurance as it relates to cancer. Materials are also offered in Spanish.

Web sites for teens and children

Beyond the Cure (part of the National Children's Cancer Society for teens)
Web site: www.beyondthecure.org
Online support and education for survivors of childhood cancer and their families.

Fertile Hope
Toll-free number: 1-888-994-4673
Web site: www.fertilehope.org
Provides information on having children in the future to cancer patients whose medical treatments cause the risk of infertility.

Group Loop
Toll-free number: 1-888-793-9355
Web site: www.grouploop.org
An online resource for teens with cancer and their parents -- a way to connect with other teens. Group Loop includes online support groups, chat rooms, educational resources, and more.

I'm too young for this
Web site: http://i2y.org
This is a social networking organization for young adult cancer survivors (ages 15 to 39 years old) and their caregivers that offers support to help improve quality of life for young adults affected by cancer.

SuperSibs!
Toll-free number: 1-866-444-7427
Web site: www.supersibs.org
Supports, honors, and recognizes brothers and sisters of children diagnosed with cancer so they may face the future with strength, courage, and hope.

Teens Living with Cancer
Web site: www.teenslivingwithcancer.org
Teens Living with Cancer is an online-only resource dedicated to teens coping with a cancer diagnosis and treatment. Teens Living with Cancer focuses on teen issues and provides resources to support teens, their families, and friends

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

Other publications*

For adults

Grant Steen and Joseph Mirro (editors). Childhood Cancer: A Handbook from St Jude Children's Research Hospital, .Perseus Publishing, 2000.

Nancy Keene ,Wendy Hobbie, and Kathy Ruccione. Childhood Cancer Survivors: A Practical Guide to Your Future, O'Reilly and Associates, 2000.

Children with Cancer: A Comprehensive Reference Guide for Parents, by Jeanne Munn Bracken and Pruden Pruden. Published by Oxford University Press, 2007.

Nancy Keene, editor. Educating The Child With Cancer: A Guide for Parents and Teachers, Candlelighters Childhood Cancer Foundation, 2003.

Margo Joan Fromer. Surviving Childhood Cancer: A Guide for Families, New Harbinger Publications, 1998.

For children

Nancy Keene, Kathy Ruccione, and Wendy Hobbie Childhood Cancer Survivors: A Practical Guide to Your Future (2nd ed.), Patient Centered Guides, 2006. For older teens.

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

No matter who you are, we can help. Contact us anytime, day or night, for information and support. Call us at 1-800-227-2345 or visit www.cancer.org.

References

Cox CL, Montgomery M, Oeffinger KC, Leisenring W, Zeltzer L, et al. Promoting Physical Activity in Childhood Cancer Survivors. Cancer. 2009 Feb 1;115(3):642-54.

Diller L, Chow EJ, Gurney JG, Hudson MM, Kadin-Lottick NS, et al. Chronic disease in the Childhood Cancer Survivor Study Cohort: A Review of Published Findings. J Clin Oncol. 2009 May 10;27(14):2339-55.

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.

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.

Monteleone PM, Meadows AT. Late Effects of Childhood Cancer and Treatment. Updated May 6, 2009. E-medicine Web site. Accessed at: http://emedicine.medscape.com/article/990815-overview on May 19, 2009.

National Cancer Institute. Late Effects of Treatment for Childhood Cancer (PDQ^®). Accessed May 13, 2009 at www.cancer.gov/cancertopics/pdq/treatment/lateeffects/HealthProfessional.

Robison LL, Green DM, Hudson M, et al. Long-term outcomes of adult survivors of childhood cancer. Cancer. 2005;104(11 Suppl):2557-2564.

Last Medical Review: 06/19/2009
Last Revised: 06/19/2009