Late Effects of Treatment for Childhood Cancer

Problems with the teeth and jaws are more likely to occur after treatment for certain childhood cancers.

Treatment for these and other childhood cancers may cause late effects of the teeth and jaws:

• head and neck cancers
• Hodgkin lymphoma
• neuroblastoma
• leukemia that spreads to the brain and spinal cord
• nasopharyngeal cancer
• brain tumors
• cancers treated with total-body irradiation (TBI) as part of a stem cell transplant

Radiation to the head and neck and certain types of chemotherapy increase the risk of late effects to the teeth and jaws.

The risk of health problems that affect the teeth and jaws increases after treatment with:

• radiation therapy to the head and neck
• TBI as part of a stem cell transplant
• chemotherapy, especially with higher doses of alkylating agents such as cyclophosphamide
• surgery in the head and neck area

Risk is also increased in survivors who were younger than 5 years at the time of treatment because their permanent teeth had not fully formed.

Late effects that affect the teeth and jaws may cause certain health problems.

Teeth and jaws late effects and related health problems include:

• teeth that are not normal
• tooth decay (including cavities) and gum disease
• salivary glands that do not make enough saliva
• death of the bone cells in the jaw
• changes in the way the face, jaw, or skull form
• a second cancer in the mouth

Possible symptoms of late effects of the teeth and jaws include tooth decay (cavities) and jaw pain.

These and other symptoms may be caused by late effects of the teeth and jaws or by other problems:

• teeth are small or do not have a normal shape
• missing permanent teeth
• permanent teeth come in at a later than normal age
• teeth have less enamel than normal
• more tooth decay (cavities) and gum disease than normal
• dry mouth
• trouble chewing, swallowing, and speaking
• jaw pain
• jaws do not open and close the way they should

The only way to know if these symptoms are caused by late effects of the teeth and jaws is to see a doctor.

Certain tests and procedures are used to diagnose health problems in the mouth and jaws.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Dental exam is an exam of the teeth, mouth, and jaws to check general signs of dental health, including checking for signs of disease, such as cavities or anything that seems unusual. This may also be called a dental check-up.
• Panorex x-ray is an x-ray of all of the teeth and their roots. An x-ray is a type of radiation that can go through the body and make pictures.
• X-ray of the jaws is an x-ray of the jaws. An x-ray is a type of radiation that can go through the body and make pictures.
• CT scan (CAT scan) uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body, such as the head and neck. The pictures are taken from different angles and are used to create 3-D views of tissues and organs. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. Learn more about Computed Tomography (CT) Scans and Cancer.
• Magnetic resonance imaging (MRI) uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the head and neck. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• Biopsy is a procedure in which a sample of tissue is removed from the tumor so that a pathologist can view it under a microscope to check for signs of cancer.

Talk to the doctor about whether tests and procedures are needed to check for signs of teeth and jaw late effects. If tests are needed, find out how often they should be done.

Regular dental care is very important for survivors of childhood cancer.

Doctors suggest that survivors of childhood cancer have a dental check-up and a cleaning and fluoride treatment every 6 months. Children who had radiation therapy to the oral cavity may also see an orthodontist or an otolaryngologist. If lesions are present in the mouth, a biopsy may be needed.

Digestive tract late effects are more likely to occur after treatment for certain childhood cancers.

Treatment for these and other childhood cancers may cause late effects of the digestive tract (esophagus, stomach, small and large intestines, rectum and anus):

• germ cell tumors
• Hodgkin lymphoma
• non-Hodgkin lymphoma
• neuroblastoma
• rhabdomyosarcoma of the bladder or prostate, or near the testicles
• Wilms tumor

Radiation to the bladder, prostate, or testicles and certain types of chemotherapy increase the risk of digestive tract late effects.

The risk of health problems that affect the digestive tract increases after treatment with:

• Radiation therapy to the abdomen or areas near the abdomen, such as the esophagus, bladder, prostate, or testicles, may cause digestive tract problems that begin quickly and last for a short time. In some patients, however, digestive tract problems are delayed and long-lasting. These late effects are caused by radiation therapy that damages the blood vessels. Receiving higher doses of radiation therapy or receiving chemotherapy such as dactinomycin or anthracyclines together with radiation therapy may increase this risk.
• Abdominal surgery or pelvic surgery to remove the bladder.
• Chemotherapy with alkylating agents such as cyclophosphamide, procarbazine, and ifosfamide, or with anthracyclines such as doxorubicin, daunorubicin, idarubicin, and epirubicin.
• Stem cell transplant.

The following may also increase the risk of digestive tract late effects:

• older age at diagnosis or when treatment begins
• treatment with both radiation therapy and chemotherapy
• a history of chronic graft-versus-host disease

Late effects that affect the digestive tract may cause certain health problems.

Digestive tract late effects and related health problems include:

• a narrowing of the esophagus or intestine
• the muscles of the esophagus do not work well
• reflux
• diarrhea, constipation, fecal incontinence, or blocked bowel
• bowel perforation (a hole in the intestine)
• inflammation of the intestines
• death of part of the intestine
• intestine is not able to absorb nutrients from food
• a second cancer

Possible symptoms of digestive tract late effects include abdominal pain and diarrhea.

These and other symptoms may be caused by digestive tract late effects or by other problems:

• trouble swallowing or feeling like food is stuck in the throat
• heartburn
• fever with severe pain in the abdomen and nausea
• pain in the abdomen
• a change in bowel habits (constipation or diarrhea)
• nausea and vomiting
• frequent gas pains, bloating, fullness, or cramps
• reflux

The only way to know if these symptoms are caused by digestive late effects is to see a doctor.

Certain tests and procedures are used to diagnose health problems in the digestive tract.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Digital rectal exam is an exam where the doctor or nurse inserts a lubricated, gloved finger into the rectum to feel for lumps or anything else that seems unusual.
• Blood chemistry studies is a test that uses a blood sample to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual amount of a substance can be a sign of disease.
• Kidney, ureter, and bladder x-ray is a type of radiation that can go through the body and make pictures of the abdomen, kidney, ureter, or bladder to check for signs of disease.
• CT scan (CAT scan) uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create 3-D views of tissues and organs. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. Learn more about Computed Tomography (CT) Scans and Cancer.
• Magnetic resonance imaging (MRI) uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• Barium swallow is a series of x-rays of the throat, esophagus, stomach, and the first part of the small intestine (duodenum). For this procedure, the patient drinks a liquid that contains barium (a silver-white metallic compound). The barium coats the esophagus and stomach which helps them show up more clearly in x-rays. This procedure is also called an upper GI series.

Talk to the doctor about whether tests and procedures are needed to check for signs of digestive tract late effects. If tests are needed, find out how often they should be done.

Liver and bile duct late effects are more likely to occur after treatment for certain childhood cancers.

Treatment for these and other childhood cancers may cause liver or bile duct late effects:

• acute lymphoblastic leukemia (ALL)
• liver cancer
• Wilms tumor
• cancers treated with a stem cell transplant

Certain types of chemotherapy and radiation to the liver or bile ducts increase the risk of late effects.

The risk of liver or bile duct late effects may be increased in childhood cancer survivors treated with:

• surgery to remove part of the liver or a liver transplant
• chemotherapy that includes high-dose cyclophosphamide as part of a stem cell transplant
• chemotherapy such as 6-mercaptopurine, 6-thioguanine, methotrexate, and dactinomycin
• radiation therapy to the liver and bile ducts, with the risk depending on:
  • the dose of radiation and how much of the liver is treated
  • age when treated (the younger the age, the higher the risk)
  • whether there was surgery to remove part of the liver
  • whether chemotherapy, such as doxorubicin or dactinomycin, was given together with radiation therapy
• stem cell transplant

The following may also increase the risk of liver and bile duct late effects:

• hepatitis B or hepatitis C infection
• history of chronic graft-versus-host disease
• liver damage caused by veno-occlusive disease/sinusoidal obstruction syndrome
• tissue and organ damage from the buildup of extra iron after having many blood transfusions

Late effects that affect the liver and bile ducts may cause certain health problems.

Liver and bile duct late effects and related health problems include:

• liver dysfunction
• gallstones
• benign liver lesions
• an overgrowth of connective tissue in the liver (liver fibrosis) or cirrhosis
• fatty liver with insulin resistance (a condition in which the body makes insulin but cannot use it well)

Possible symptoms of liver and bile duct late effects include abdominal pain and jaundice.

These and other symptoms may be caused by liver and bile duct late effects or by other problems:

• weight gain or weight loss
• swelling of the abdomen
• nausea and vomiting
• pain in the abdomen that may occur near the ribs, often on the right side after eating a fatty meal
• yellowing of the skin and whites of the eyes (jaundice)
• light-colored bowel movements
• diarrhea
• dark-colored urine
• a lot of gas
• lack of appetite
• feeling tired or weak

The only way to know if these symptoms are caused by liver and bile duct late effects is to see a doctor.

Sometimes there are no signs or symptoms of liver or bile duct late effects and treatment may not be needed.

Certain tests and procedures are used to diagnose health problems in the liver and bile duct.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Blood chemistry studies use a blood sample to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual amount of a substance can be a sign of disease. For example, there may be a higher level of bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the body if the liver has been damaged.
• Ferritin level uses a blood sample to measure the amount of ferritin. Ferritin is a protein that binds to iron and stores it for use by the body. After a stem cell transplant, a high ferritin level may be a sign of liver disease.
• Complete blood count (CBC) is when a sample of blood is drawn and checked for:
  • the number of red blood cells, white blood cells, and platelets
  • the amount of hemoglobin (the protein that carries oxygen) in the red blood cells
  • the portion of the blood sample made up of red blood cells

  This test is used to check the amount of platelets in the body.

• Prothrombin time (PT) test measures how long it takes for the blood to clot.
• Hepatitis assay uses a blood sample to check for pieces of the hepatitis virus. The blood sample may also be used to measure how much hepatitis virus is in the blood. All patients who had a blood transfusion before 1972 should have a screening test for hepatitis B. Patients who had a blood transfusion before 1993 should have a screening test for hepatitis C.
• Ultrasound exam uses high-energy sound waves (ultrasound) that bounce off internal tissues or organs, such as the gall bladder, and make echoes. The echoes form a picture of body tissues called a sonogram.
• CT scan (CAT scan) uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create 3-D views of tissues and organs. A dye may be injected into a vein or swallowed to help the organs and tissue show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. Learn more about Computed Tomography (CT) Scans and Cancer.
• Magnetic resonance imaging (MRI) uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).

Talk to the doctor about whether tests and procedures are needed to check for signs of liver or bile duct late effects. If tests are needed, find out how often they should be done.

Health habits that promote a healthy liver are important for survivors of childhood cancer.

Childhood cancer survivors with liver late effects should take care to protect their health, including:

• having a healthy weight
• not drinking alcohol
• getting vaccines for hepatitis A and hepatitis B viruses

Radiation therapy increases the risk of pancreatic late effects.

The risk of pancreatic late effects may be increased in childhood cancer survivors after treatment with:

• radiation therapy to the abdomen
• total-body irradiation as part of a stem cell transplant

Late effects that affect the pancreas may cause certain health problems.

Pancreatic late effects and related health problems include:

• Insulin resistance is a condition in which the body does not use insulin the way it should. Insulin is needed to help control the amount of glucose (a type of sugar) in the body. Because the insulin does not work the way it should, glucose and fat levels rise.
• Diabetes mellitus is a disease in which the body does not make enough insulin or does not use it the way it should. When there is not enough insulin, the amount of glucose in the blood increases and the kidneys make a large amount of urine. Survivors also have an increased risk of prediabetes, which can lead to diabetes.

Possible symptoms of pancreatic late effects include frequent urination and being thirsty.

These and other symptoms may be caused by pancreatic late effects or by other problems:

• frequent urination
• feeling very thirsty
• feeling very hungry
• weight loss for no known reason
• feeling very tired
• frequent infections, especially of the skin, gums, or bladder
• blurred vision
• cuts or bruises that are slow to heal
• numbness or tingling in the hands or feet

The only way to know if these symptoms are caused by pancreatic late effects is to see a doctor.

Certain tests and procedures are used to diagnose health problems in the pancreas.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Glycated hemoglobin (A1C) test uses a sample of blood to measure the amount of glucose that is attached to red blood cells. A higher-than-normal amount of glucose attached to red blood cells can be a sign of diabetes mellitus.
• Fasting blood sugar test uses a blood sample to measure the amount of glucose in the blood. This test is done after the patient has had nothing to eat overnight. A higher-than-normal amount of glucose in the blood can be a sign of diabetes mellitus.

Thyroid late effects are more likely to occur after treatment for certain childhood cancers.

Treatment for these and other childhood cancers may cause thyroid late effects:

• acute lymphoblastic leukemia (ALL)
• brain tumors
• head and neck cancers
• Hodgkin lymphoma
• neuroblastoma
• cancers treated with a stem cell transplant

Radiation therapy to the head and neck increases the risk of thyroid late effects.

The risk of thyroid late effects may be increased in childhood cancer survivors after treatment with:

• radiation therapy to the thyroid as part of radiation therapy to the head and neck or to the pituitary gland in the brain
• total-body irradiation or chemotherapy as part of a stem cell transplant
• MIBG (radioactive iodine) therapy for neuroblastoma
• chemotherapy such as alkylating agents, anthracyclines, or bleomycin
• surgery to remove part of the thyroid

The risk also is increased in females, in survivors who were a young age at the time of treatment, in survivors who had a higher radiation dose, and as the time since diagnosis and treatment gets longer. Risk for endocrine problems also depends on the location of the tumor.

Late effects that affect the thyroid may cause certain health problems.

Thyroid late effects and related health problems include:

• Hypothyroidism (not enough thyroid hormone): There is a higher risk of hypothyroidism in survivors treated with head and neck radiation involving the thyroid gland, especially survivors of Hodgkin lymphoma. This is the most common thyroid late effect. It usually occurs 2 to 5 years after treatment ends but may occur more than 25 years after radiation therapy. It is more common in girls than boys. Children, adolescents, and young adults treated with proton beam radiation therapy may have a lower risk of developing hypothyroidism.
• Hyperthyroidism (too much thyroid hormone): The risk of hyperthyroidism increases with higher doses of radiation therapy to the thyroid gland. Hyperthyroidism is less common than hypothyroidism. It usually occurs 5 years after treatment ends, but may occur more than 25 years after radiation therapy.
• Lumps in the thyroid: Higher radiation dose and longer time since diagnosis are linked to an increased risk of developing thyroid lumps. These growths may be benign (not cancerous) or malignant (cancer). It is more common in girls than boys. An enlarged thyroid (goiter) may be caused by lumps in the thyroid.

Symptoms of thyroid late effects depend on whether there is too little or too much thyroid hormone in the body.

These and other symptoms may be caused by thyroid late effects or by other problems:

Rarely, hypothyroidism does not cause any symptoms.

The only way to know if these symptoms are caused by thyroid late effects is to see a doctor.

Certain tests and procedures are used to diagnose health problems in the thyroid.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Blood hormone studies use a blood sample to measure the amounts of certain hormones released into the blood by organs and tissues in the body. An unusual amount of a substance can be a sign of disease in the organ or tissue that makes it. The blood may be checked for abnormal levels of thyroid-stimulating hormone (TSH) or free thyroxine (T4).
• Ultrasound exam uses high-energy sound waves (ultrasound) that bounce off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. This procedure can show the size of the thyroid and whether there are nodules (lumps) on the thyroid.

Talk to the doctor about whether tests and procedures are needed to check for signs of thyroid late effects. If tests are needed, find out how often they should be done.

Neuroendocrine late effects may be caused after treatment for certain childhood cancers.

The neuroendocrine system is the nervous system and the endocrine system working together.

Treatment for these and other childhood cancers may cause neuroendocrine late effects:

• acute lymphoblastic leukemia (ALL)
• brain and spinal cord tumors
• head and neck cancers
• cancers treated with a stem cell transplant

Treatment that affects the hypothalamus or pituitary gland increases the risk of neuroendocrine system late effects.

Childhood cancer survivors have an increased risk for neuroendocrine late effects. These effects are caused by radiation therapy to treat cancer in the brain near the hypothalamus or used as total-body irradiation before a stem cell transplant. The hypothalamus controls the way hormones are made and released into the bloodstream by the pituitary gland. These effects are also caused by surgery in the area of the hypothalamus, pituitary gland, or optic pathways.

Late effects that affect the hypothalamus may cause certain health problems.

Childhood cancer survivors who have neuroendocrine late effects may have abnormal levels of hormones made in the pituitary gland and released into the blood. Neuroendocrine late effects and related health problems include:

• Growth hormone deficiency: Growth hormone helps promote growth and control metabolism. A low level of growth hormone is a common late effect of radiation to the brain in childhood cancer survivors. The higher the radiation dose and the longer the time since treatment, the greater the risk of this late effect. A low level of growth hormone may also occur in childhood ALL and stem cell transplant survivors who received radiation therapy to the brain and spinal cord and/or chemotherapy.

  A low level of growth hormone in childhood results in adult height that is shorter than normal. If the child's bones have not fully developed, low growth hormone levels may be treated with growth hormone replacement therapy beginning one year after the end of treatment.

• Adrenocorticotropin deficiency (ACTH): Adrenocorticotropic hormone controls the making of glucocorticoids. A low level of adrenocorticotropic hormone is an uncommon late effect. It may occur in survivors:
  • of childhood brain tumors, other tumors, or blood cancers
  • with low growth hormone levels or central hypothyroidism
  • who received radiation therapy to the brain
  • who received steroid hormone therapy

  Symptoms of adrenocorticotropin deficiency may not be severe and may not be noticed. Symptoms include:

  • weight loss for no known reason
  • not feeling hungry
  • nausea
  • vomiting
  • abdominal pain
  • low blood pressure
  • feeling tired
  • dizziness
  • muscle or joint pains
  • darkening of the skin
  • pale skin
  • low blood sugar
  • craving salts

  Low levels of adrenocorticotropin may be treated with hydrocortisone therapy.

• Hyperprolactinemia: Prolactin controls the making of breast milk and has many other effects in the body. A high level of the hormone prolactin may occur after a high dose of radiation to the brain or surgery that affects part of the pituitary gland. A high level of prolactin may cause:
  • puberty at a later age than normal
  • flow of breast milk in a woman who is not pregnant or breastfeeding
  • less frequent or no menstrual periods or menstrual periods with a very light flow
  • hot flashes
  • inability to become pregnant
  • inability to have an erection needed for sexual intercourse
  • lower sex drive (in men and women)
  • low bone mineral density (osteopenia)

  Sometimes there are no signs and symptoms. Treatment is rarely needed.

• Thyroid-stimulating hormone (TSH) deficiency: Thyroid-stimulating hormone controls the making of thyroid hormones. A low level of thyroid hormone may occur very slowly over time after radiation therapy to the brain. Thyroid-stimulating hormone deficiency may also be called central hyphothyroidism.

  Sometimes the symptoms of thyroid-stimulating hormone deficiency are not noticed. Low thyroid hormone levels may cause slow growth and delayed puberty, as well as other symptoms. Learn more about the symptoms of hypothyroidism.

  A low level of thyroid hormone may be treated with thyroid hormone replacement therapy.

• Luteinizing hormone or follicle-stimulating hormone imbalance: Luteinizing hormone and follicle-stimulating hormone control reproduction. Abnormal levels of these hormones can cause different health problems. The type of problem depends on the radiation dose and whether hormone levels are higher or lower than normal.

  Childhood cancer survivors who had brain tumors near the hypothalamus or pituitary gland, who were treated with lower doses of radiation to the brain, or who have hydrocephalus may develop central precocious puberty (a condition that causes puberty to start before age 8 in girls and 9 in boys). Central precocious puberty happens when the brain releases luteinizing and follicle-stimulating hormones too soon in the child's development. This condition may be treated with gonadotropin-releasing hormone (GnRH) agonist therapy to delay puberty and help the child's growth.

  Childhood cancer survivors who were treated with higher doses of radiation to the brain may have low levels of luteinizing hormone or follicle-stimulating hormone. This condition may be treated with sex hormone replacement therapy. The dose will depend on the child's age and whether the child has reached puberty.

• Central diabetes insipidus: Central diabetes insipidus may be caused by the absence of or low amounts of all of the hormones made in the front part of the pituitary gland and released into the blood. It may occur in childhood cancer survivors treated with surgery in the area of the hypothalamus or pituitary gland. Symptoms of central diabetes insipidus may include:
  • making large amounts of urine
  • feeling very thirsty
  • fatigue

  Symptoms of central diabetes insipidus in infants may include:

  • vomiting
  • diarrhea
  • irritability
  • slowed growth and development
  • weight loss for no known reason

Certain tests and procedures are used to diagnose health problems in the neuroendocrine system.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Blood chemistry study uses a blood sample to measure the amounts of certain substances, such as glucose, released into the blood by organs and tissues in the body. An unusual amount of a substance can be a sign of disease.
• Blood hormone studies use a blood sample to measure the amounts of certain hormones released into the blood by organs and tissues in the body. An unusual amount of a substance can be a sign of disease in the organ or tissue that makes it. The blood may be checked for abnormal levels of follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, cortisol, or free thyroxine (T4).
• Lipid profile studies use a blood sample to measure the amounts of triglycerides, cholesterol, and low- and high-density lipoprotein cholesterol in the blood.

Talk to the doctor about whether tests and procedures are needed to check for signs of neuroendocrine late effects. If tests are needed, find out how often they should be done.

Metabolic syndrome is more likely to occur after treatment for certain childhood cancers.

Metabolic syndrome is a group of medical conditions that includes having too much fat around the abdomen and at least two of the following:

• high blood pressure
• high levels of triglycerides and low levels of high-density lipoprotein (HDL) cholesterol in the blood
• high levels of glucose (sugar) in the blood

Treatment for these and other childhood cancers may cause metabolic syndrome to occur later in life:

• acute lymphoblastic leukemia (ALL)
• cancers treated with a stem cell transplant
• cancers treated with radiation to the abdomen, such as Wilms tumor or neuroblastoma

Radiation therapy increases the risk of metabolic syndrome.

The risk of metabolic syndrome may be increased in childhood cancer survivors after treatment with:

• radiation therapy to the brain, abdomen, or pelvis
• total-body irradiation (TBI) as part of a stem cell transplant
• chemotherapy, such as alkylating agents
• older age

Certain tests and procedures are used to diagnose metabolic syndrome.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Blood chemistry studies use a blood sample to measure the amounts of certain substances, such as glucose, released into the blood by organs and tissues in the body. An unusual amount of a substance can be a sign of disease.
• Lipid profile studies use a blood sample to measure the amounts of triglycerides, cholesterol, and low- and high-density lipoprotein cholesterol in the blood.

Talk to the doctor about whether tests and procedures are needed to check for signs of metabolic syndrome. If tests are needed, find out how often they should be done.

Metabolic syndrome may cause heart and blood vessel disease and diabetes.

Metabolic syndrome is linked to an increased risk of heart and blood vessel disease and diabetes. Health habits that decrease these risks include:

• having a healthy weight
• eating a heart-healthy diet
• exercising regularly
• not smoking

Being underweight, having excess body weight, or having obesity is a late effect that is more likely to occur after treatment for certain childhood cancers.

Treatment for these and other childhood cancers may cause a change in weight:

• acute lymphoblastic leukemia (ALL)
• brain tumors, especially craniopharyngiomas
• cancers treated with radiation to the brain, including TBI as part of a stem cell transplant

Graft-versus-host disease may also cause a change in weight for patients treated with a stem cell transplant.

Radiation therapy increases the risk of being underweight, having excess body weight, or having obesity.

The risk of being underweight increases after treatment with:

• TBI for females
• radiation therapy to the abdomen for males
• certain types of chemotherapy (alkylating agents and anthracyclines)

The risk of having excess body weight or obesity increases after treatment with:

• radiation therapy to the brain
• surgery that damages the hypothalamus or pituitary gland, such as surgery to remove a craniopharyngioma brain tumor

The following may also increase the risk of obesity:

• having excess body weight at the time of a cancer diagnosis
• being diagnosed with cancer between the ages of 5 and 9
• being female
• having growth hormone deficiency or low levels of the hormone leptin
• lack of physical activity
• taking an antidepressant called paroxetine

Childhood cancer survivors who get enough exercise and have a normal amount of anxiety have a lower risk of obesity.

Certain tests and procedures are used to diagnose a change in weight.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Blood chemistry studies use a blood sample to measure the amounts of certain substances, such as glucose, released into the blood by organs and tissues in the body. An unusual amount of a substance can be a sign of disease.
• Lipid profile studies use a blood sample to measure the amounts of triglycerides, cholesterol, and low- and high-density lipoprotein cholesterol in the blood.

Being underweight, having excess body weight, or having obesity may be measured by weight, body mass index, percent of body fat, or size of the abdomen (belly fat).

Talk to the doctor about whether tests and procedures are needed to check for signs of a change in weight. If tests are needed, find out how often they should be done.

Radiation therapy

Radiation therapy can stop or slow the growth of bone and muscle. The type of bone and joint late effects depends on the part of the body that received radiation therapy. Radiation therapy may cause:

• changes in the way the face or skull form, especially when high-dose radiation with or without chemotherapy is given to children before age 5 years
• short stature (being shorter than normal)
• curving of the spine (scoliosis) or rounding of the spine (kyphosis)
• one arm or leg is shorter than the other arm or leg
• weak or thin bones that can break easily (osteoporosis)
• parts of a bone to die from a lack of blood flow (osteoradionecrosis), especially the jaw
• a benign tumor of the bone (osteochondroma)

Surgery

Amputation or limb-sparing surgery to remove the cancer and prevent it from coming back may cause late effects depending on where the tumor was, age of the patient, and type of surgery. Health problems after amputation or limb-sparing surgery may include:

• having problems with activities of daily living
• not being able to be as active as normal
• chronic pain
• problems with the way prosthetics fit or work
• broken bone
• additional surgeries later in life
• the bone not healing well after surgery
• one arm or leg is shorter than the other

Studies show no difference in quality of life for childhood cancer survivors who had amputation compared to those who had limb-sparing surgery.

Chemotherapy and other drug therapy

Risk may be increased in childhood cancer survivors who received cancer treatment that included methotrexate or corticosteroids or glucocorticoids such as dexamethasone. Drug therapy may cause:

• weak or thin bones that can break easily (osteoporosis)
• one or more parts of a bone to die from a lack of blood flow (osteonecrosis), especially in the hip or knee

Stem cell transplant

A stem cell transplant can affect the bone and joints in different ways:

• Total-body irradiation given as part of a stem cell transplant may affect the body's ability to make growth hormone and cause short stature (being shorter than normal). It may also cause weak or thin bones that can break easily (osteoporosis) and the formation of a benign tumor called osteochondroma.
• Chronic graft-versus-host disease that may occur after a stem cell transplant can cause the muscles around joints to tighten, leading to stiff joints (joint contractures). Chronic graft-versus-host disease may also cause one or more parts of a bone to die from a lack of blood flow (osteonecrosis).

Late effects that affect the testicles may cause certain health problems.

Late effects of the testicles and related health problems include:

• Low sperm count: A zero sperm count or a low sperm count may be temporary or permanent. This depends on the radiation dose and schedule, the area of the body treated, and the age when treated.
• Low testosterone levels: This can lead to underdeveloped testicles, infertility, and sexual problems in adulthood.
• Infertility: The inability to father a child.
• Retrograde ejaculation: Very little or no semen comes out of the penis during orgasm.

After treatment with chemotherapy or radiation, the body's ability to make sperm may come back over time.

Certain tests and procedures are used to diagnose health problems in the testicles.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests:

• Blood hormone studies use a blood sample to measure the amounts of certain hormones released into the blood by organs and tissues in the body. An unusual amount of a substance can be a sign of disease in the organ or tissue that makes it. The blood may be checked for abnormal levels of follicle-stimulating hormone, luteinizing hormone, testosterone.
• Semen analysis (sperm count) measures the amount and quality of semen and sperm to see if there are problems that are causing infertility.

Late effects that affect the ovaries may cause certain health problems.

Ovarian late effects and other health-related problems include:

• early menopause, especially in women who had their ovaries removed or were treated with both an alkylating agent and radiation therapy to the abdomen
• changes in menstrual periods
• infertility (inability to conceive a child)
• puberty does not begin

Hormone replacement therapy can be used to start puberty.

Possible symptoms of ovarian late effects include irregular or absent menstrual periods and hot flashes.

These and other symptoms may be caused by ovarian late effects or by other problems:

• irregular or no menstrual periods
• hot flashes
• drenching night sweats
• trouble sleeping
• mood changes
• lowered sex drive
• vaginal dryness
• sex traits, such as developing arm, pubic, and leg hair or having the breasts enlarge, do not occur at puberty
• weak or thin bones that can break easily (osteoporosis)
• inability to get pregnant

The only way to know if these symptoms are caused by late effects to the ovaries is to see a doctor.

Certain tests and procedures are used to diagnose health problems in the ovaries.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following test.

• Blood hormone studies use a blood sample to measure the amounts of certain hormones released into the blood by organs and tissues in the body. An unusual amount of a substance can be a sign of disease in the organ or tissue that makes it. The blood may be checked for abnormal levels of follicle-stimulating hormone, luteinizing hormone, estradiol, or TSH.

Childhood cancer survivors may have late effects that affect pregnancy.

Late effects on pregnancy include increased risk of:

• high blood pressure
• diabetes during pregnancy
• anemia
• miscarriage or stillbirth
• low birth-weight babies
• early labor and/or delivery
• impaired blood flow to the uterus
• delivery by Cesarean section
• the fetus is not in the right position for birth (for example, the foot or buttock is in position to come out before the head)
• peripartum cardiomyopathy

Long-term survivors of childhood, adolescent, and young adult cancers who have received radiation therapy or certain types of chemotherapy are at risk of a rare type of heart failure during pregnancy called peripartum cardiomyopathy. It may occur during late pregnancy and up to 5 months after giving birth. If cancer treatments have caused damage to the heart, these patients may also be at risk of congestive heart failure during pregnancy. Patients at risk of these conditions should be closely followed for weakness of the heart muscle during pregnancy.

Some studies have not shown an increased risk of late effects on pregnancy.

There are methods that may be used to help childhood cancer survivors have children.

The following methods may be used so that childhood cancer survivors can have children:

• freezing the eggs or sperm before cancer treatment in patients who have reached puberty (egg and sperm banking)
• preventing damage to the ovaries before radiation therapy by moving one or both ovaries and fallopian tubes out of the field of radiation and attaching them to the wall of the abdomen (ovarian transposition)
• removing a small amount of tissue containing sperm from the testicle (testicular sperm extraction)
• fertilizing an egg outside the body by injecting a sperm into it (intracytoplasmic sperm injection)
• in vitro fertilization (IVF), which is a procedure where eggs and sperm are placed together in a container, giving the sperm the chance to enter an egg

Children of childhood cancer survivors are not affected by the parent's previous treatment for cancer.

The children of childhood cancer survivors do not appear to have an increased risk of birth defects, genetic disease, or cancer.

Hearing problems are a late effect that is more likely to occur after treatment for certain childhood cancers.

Treatment for these and other childhood cancers may cause hearing late effects:

• bone cancer
• brain tumors
• germ cell tumors
• head and neck cancers
• liver cancer
• neuroblastoma
• retinoblastoma
• soft tissue sarcoma
• cancers that are treated with a stem cell transplant

Radiation therapy to the brain and certain types of chemotherapy increase the risk of hearing loss.

The risk of hearing loss is increased in childhood cancer survivors after treatment with:

• certain types of chemotherapy, such as cisplatin or high-dose carboplatin
• radiation therapy to the brain

The risk of hearing loss from radiation therapy is greater in children who are diagnosed with cancer before age 5 years, and the risk increases for children of all ages with higher radiation doses. The risk of hearing loss is also greater in childhood cancer survivors who received radiation therapy to the brain and chemotherapy at the same time.

The risk of hearing loss may be lower if children treated with cisplatin were also given a drug called sodium thiosulfate.

Hearing loss is the most common sign of hearing late effects.

These and other symptoms may be caused by hearing late effects or by other problems:

• hearing loss
• ringing in the ears
• feeling dizzy
• too much hardened wax in the ear

The only way to know if these symptoms are caused by hearing late effects is to see a doctor.

Hearing loss may occur during treatment, soon after treatment ends, or several months or years after treatment ends and worsen over time. A young child may have trouble learning, communicating, doing well in school, and interacting with others if they have hearing loss. In adulthood, hearing loss can lead to social isolation, depression, anxiety, and trouble finding stable employment. Talk to a doctor to learn about hearing aids or other ways to cope with hearing loss.

Certain tests and procedures are used to diagnose health problems in the ear and hearing problems.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Otoscopic exam is an exam of the ear. An otoscope is used to look at the ear canal and the eardrum to check for signs of infection or hearing loss. Sometimes the otoscope has a plastic bulb that is squeezed to release a small puff of air into the ear canal. In a healthy ear, the eardrum will move. If there is fluid behind the eardrum, it will not move.
• Hearing test can be done in different ways depending on a person's age. The test is done to check if the person can hear soft and loud sounds and low- and high-pitched sounds. Each ear is checked separately.

Talk to the doctor about whether tests and procedures are needed to check for signs of hearing late effects. If tests are needed, find out how often they should be done.

Eye and vision problems are a late effect that is more likely to occur after treatment for certain childhood cancers.

Treatment for these and other childhood cancers may cause eye and vision late effects:

• acute lymphoblastic leukemia (ALL)
• brain tumors
• head and neck cancers
• retinoblastoma, rhabdomyosarcoma, and other tumors of the eye
• cancers treated with total-body irradiation (TBI) before a stem cell transplant

Radiation therapy to the brain or head increases the risk of eye problems or vision loss.

The risk of eye problems or vision loss may be increased in childhood cancer survivors after treatment with:

• radiation therapy to the brain, eye, or eye socket
• surgery to remove the eye or a tumor near the optic nerve
• certain types of chemotherapy, such as cytarabine and doxorubicin
• TBI, busulfan, and corticosteroids as part of a stem cell transplant

Having a history of chronic graft-versus-host disease after a stem cell transplant can also increase the risk of eye problems and vision loss.

Late effects that affect the eye may cause certain health problems.

Eye late effects and related health problems include:

• having a small eye socket that affects the shape of the child's face as it grows
• loss of vision
• vision problems, such as cataracts or glaucoma
• not being able to make tears
• damage to the optic nerve and retina
• eyelid tumors

Possible signs and symptoms of eye and vision late effects include changes in vision and dry eyes.

These and other symptoms may be caused by eye and vision late effects or by other problems:

• changes in vision, such as:
  • not being able to see objects that are close
  • not being able to see objects that are far away
  • double vision
  • cloudy or blurred vision
  • colors seem faded
  • being sensitive to light or trouble seeing at night
  • seeing a glare or halo around lights at night
• dry eyes that may feel like they are itchy, burning, or swollen, or like there is something in the eye
• eye pain
• eye redness
• having a growth on the eyelid
• drooping of the upper eyelid

The only way to know if these symptoms are caused by eye and vision late effects is to see a doctor.

Certain tests and procedures are used to diagnose health problems in the eye and vision problems.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Eye exam with dilated pupil is when the pupil is dilated (widened) with medicated eye drops to allow the doctor to look through the lens and pupil to the retina. The inside of the eye, including the retina and the optic nerve, is checked using an instrument that makes a narrow beam of light. This is sometimes called a slit-lamp exam. If there is a tumor, the doctor may take pictures over time to keep track of changes in the size of the tumor and how fast it is growing.
• Indirect ophthalmoscopy is an exam of the inside of the back of the eye using a small magnifying lens and a light.

Talk to the doctor about whether tests and procedures are needed to check for signs of eye and vision late effects. If tests are needed, find out how often they should be done.

Kidney problems are a late effect that is more likely to occur after treatment for certain childhood cancers.

Treatment for these and other childhood cancers may cause kidney late effects:

• Wilms tumor
• cancers treated with a stem cell transplant

Certain types of chemotherapy increase the risk of kidney late effects.

The risk of health problems that affect the kidney increases after treatment with:

• chemotherapy including cisplatin, carboplatin, ifosfamide, and methotrexate
• radiation therapy to the abdomen or middle of the back
• surgery to remove part or all of a kidney
• stem cell transplant

The risk of kidney late effects is greater in childhood cancer survivors who were treated with a combination of surgery, chemotherapy, or radiation therapy.

The following may also increase the risk of kidney late effects:

• having cancer in both kidneys
• having a genetic syndrome that increases the risk of kidney problems, such as Denys-Drash syndrome or WAGR syndrome
• being treated with more than one type of treatment

Late effects that affect the kidney may cause certain health problems.

Kidney late effects or related health problems include:

• damage to the parts of the kidney that filter and clean the blood or the parts that remove extra water from the blood
• loss of electrolytes, such as magnesium, calcium, or potassium, from the body
• high blood pressure (hypertension)

Possible symptoms of kidney late effects include problems urinating and swelling of the feet or hands.

These and other symptoms may be caused by kidney late effects or by other problems:

• feeling the need to urinate without being able to do so
• frequent urination (especially at night)
• trouble urinating
• feeling very tired
• swelling of the legs, ankles, feet, face, or hands
• itchy skin
• shortness of breath
• nausea or vomiting
• loss of appetite
• a metal-like taste in the mouth or bad breath
• headache

Sometimes there are no signs or symptoms in the early stages. Signs or symptoms may appear as damage to the kidney continues over time. The only way to know if these symptoms are caused by kidney late effects is to see a doctor.

Certain tests and procedures are used to diagnose health problems in the kidney.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Blood chemistry study uses a blood sample to measure the amounts of certain substances, such as creatinine, released into the blood by organs and tissues in the body. An unusual amount of a substance may be a sign of kidney disease.
• Urinalysis checks the color of urine and its contents, such as sugar, protein, red blood cells, and white blood cells.
• Ultrasound exam uses high-energy sound waves (ultrasound) that bounce off internal tissues or organs, such as the kidney, and make echoes. The echoes form a picture of body tissues called a sonogram.

Talk to the doctor about whether tests and procedures are needed to check for signs of kidney late effects. If tests are needed, find out how often they should be done.

If kidney problems are found, treatment options are available, including kidney transplant.

Health habits that promote healthy kidneys are important for survivors of childhood cancer.

Childhood cancer survivors who had all or part of their kidney removed should talk to their doctor about:

• whether it is safe to play sports that have a high risk of heavy contact or impact such as football or hockey
• bicycle safety and avoiding handlebar injuries
• wearing a seatbelt around the hips, not the waist

Bladder problems are a late effect that is more likely to occur after treatment for certain childhood cancers.

Treatment for these and other childhood cancers may cause bladder late effects:

• retinoblastoma
• cancers treated with a stem cell transplant

Surgery to the pelvic area and certain types of chemotherapy increase the risk of bladder late effects.

The risk of health problems that affect the bladder increases after treatment with:

• surgery to remove part or all of the bladder
• surgery to the pelvis, spine, or brain
• certain types of chemotherapy, such as cyclophosphamide or ifosfamide
• radiation therapy to areas near the bladder, pelvis, or urinary tract
• stem cell transplant

Late effects that affect the bladder may cause certain health problems.

Bladder late effects and related health problems include:

• inflammation of the inside of the bladder wall, which leads to bleeding (hemorrhagic cystitis)
• thickening of the bladder wall
• decreased urine storage
• trouble emptying the bladder
• incontinence
• a blockage in the kidney, ureter, bladder, or urethra
• urinary tract infections that last a long time or keep coming back

Possible symptoms of bladder late effects include changes in urination and swelling of the feet or hands.

These and other symptoms may be caused by bladder late effects or by other problems:

• feeling the need to urinate without being able to do so
• frequent urination (especially at night)
• trouble urinating
• feeling like the bladder does not empty completely after urination
• swelling of the legs, ankles, feet, face, or hands
• little or no bladder control
• blood in the urine

The only way to know if these symptoms are caused by bladder late effects is to see a doctor.

Certain tests and procedures are used to diagnose health problems in the bladder.

In addition to asking the childhood cancer survivor about their personal and family health history and doing a physical exam, the doctor may perform the following tests and procedures:

• Blood chemistry study uses a blood sample to measure the amounts of certain substances, such as magnesium, calcium, and potassium, released into the blood by organs and tissues in the body. An unusual amount of a substance may be a sign of bladder problems.
• Urinalysis checks the color of urine and its contents, such as sugar, protein, red blood cells, and white blood cells.
• Urine culture checks for bacteria, yeast, or other microorganisms in the urine when there are symptoms of infection. Urine cultures can help identify the type of microorganism that is causing an infection. Treatment of the infection depends on the type of microorganism that is causing the infection.
• Ultrasound exam uses high-energy sound waves (ultrasound) that bounce off internal tissues or organs, such as the bladder, and make echoes. The echoes form a picture of body tissues called a sonogram.

Talk to the doctor about whether tests and procedures are needed to check for signs of bladder late effects. If tests are needed, find out how often they should be done.