Childhood cancers are malignant diseases that affect children under the age of 18 years.
Cancer in children (pediatric cancers) differs from cancer in adults in several important ways. The most important difference is that children have generally better prognoses than do adults. Two-thirds of children with cancer are cured of the disease. Still, despite enormous progress in the treatment of childhood cancer since the 1960s, it is the second-most common cause of death in children older than one year, with accidents being the first.
One difference between pediatric and adult cancer is found in the cells in which the cancers originate. Many adult cancers begin in specific organs, such as a lung, the breast, or the colon. Childhood cancer, except for leukemias and brain tumors, often arise in connective tissues such as bone and muscle.
Childhood cancer is often more aggressive than adult cancers. It grows faster and is frequently metastatic (has moved to other parts of the body or to the major organs) by the time of diagnosis. Thus, surgery alone is less likely to cure a child. Nevertheless, the cancers children develop tend to be more responsive to chemotherapy and radiation than those of adults.
The median age for children at the time of a cancer diagnosis is six years; for adults it is 67 years. Most children with cancer are otherwise healthy; many adults have conditions, such as heart disease, that make their treatment and recovery more difficult. Another important difference is that screening tests are available for some adult cancers, such as mammograms for breast cancer and Pap smears for cervical cancer. There are no useful screening tests for childhood cancers. Not infrequently, the diagnosis is made at a routine pediatric visit.
An extremely important factor in the improved prognosis of children with cancer has been the enrollment of the majority of children with cancer in research trials. Although only 2% of all cancers diagnosed in the United States occur in children, more than 70 percent of those children are enrolled in formal research protocols. By contrast, although adults have 98% of all cancers diagnosed in the United States, only 3% enroll in trials. Research protocols permit rapid collection of data on the effectiveness of treatment; they recognize adverse effects quickly, and foster valuable communication and collaboration among pediatric oncologists throughout the country
About 8, 700 cases of cancer are diagnosed in children under the age of 15 years in the United States each year. Another 2, 000-3, 000 are diagnosed in teenagers over 15 years of age, but these are often recorded with adult diagnoses. The number of cases of childhood cancer has remained steady for a number of years. Researchers estimate that 1 of every 333 children will be diagnosed with cancer before the age of 20 years.
Leukemia accounts for 31% of the cancers in children, with about three-quarters of those being acute lymphoblastic leukemia and the other one-fourth mostly acute myelocytic leukemia. Central nervous system (CNS) cancers, commonly lumped together as brain tumors, are the next largest group, constituting another 17%. Lymphoma, both Hodgkin's and non-Hodgkin's, accounts for 15 percent of childhood cancers. The rest of the diagnoses are divided among what are referred to as solid tumors, such as neuroblastoma, retinoblastoma, Wilms' tumor, rhabdomyosarcoma, and bone cancers.
These statistics are similar in other parts of the developed world. In Africa, the most common form of childhood cancer is Burkitt's lymphoma, which is associated with the Epstein-Barr viral infection.
The survival rate for children with cancer is approaching 80% in the United States.
The causes of most childhood cancers are unknown, but some associations are recognized. The risk of childhood leukemia is increased in children with Down syndrome, in boys, in whites, and in those of higher socioeconomic status. Exposure to radiation in utero increases the risk as well. Central nervous system cancers are also more common in boys, in whites, and in those who have received radiation treatments for other cancers.
A number of inherited and developmental conditions are associated with an increased risk of childhood cancer. These include neurofibromatosis, Bloom's syndrome, ataxia-telangiectasia, and tuberous sclerosis. A family history of Hodgkin's disease increases its likelihood, and a family history of retinoblastoma in both eyes confers a 50% chance of an offspring carrying the gene. Ninety percent of children carrying the gene will develop the disease.
Few situations test a family or a marriage like a diagnosis of cancer in a child. One day, parents have a healthy child with unlimited potential and a bright future; the next day, they have a child with a possibly fatal disease.
With a diagnosis of cancer in a child, parents must begin to negotiate complicated medical, social, family, and financial issues. Because children are generally best treated in centers that have pediatric oncologists, and because such centers can be far from a family's home, whole families can be uprooted, parents forced to spend weeks apart, and siblings left home with other relatives for long stretches of time.
Guilt can consume parents. They often assume they are responsible for their child's illness, they feel guilty if finances or insurance coverage issues force both to remain employed during their child's illness, and they worry that they are neglecting their other children.
One of the most difficult aspects of dealing with a diagnosis of cancer in a child is deciding what to tell that child and when. For infants and toddlers, this is not a concern, but older children need to know that they are ill, that they need these painful and unpleasant treatments, and—importantly—that they are not being punished for some misdeed, which is a common fear.
More than 80% of children with cancer miss at least some school during their treatments. Some children must miss school for prolonged periods. Federal law requires all states to provide education to handicapped children, and children with cancer are considered handicapped under the law. An individual education plan must be developed and an education provided, even for those who are homebound due to illness. Hospital social workers can be good resources for parents to explore their children's rights under their state's laws.
Completion of treatment
One of the surprisingly difficult aspects of cancer treatment comes when the treatment itself is completed. Parents, and certainly older children, can find the loss of the routine of regular treatment and the comfort of knowing that something active is being done to keep the cancer at bay can be quite frightening. Some parents and children become excessively focused on minor symptoms,
Though the survival rates for children with cancer continue to improve, the tragic truth is that some children will die of their disease. For parents, the day they learn that no further treatment is available is even harder than the day they learned their child's diagnosis. No decision is more difficult than stopping futile treatment and turning to care that is palliative (aimed solely at making the child comfortable).
Hospice care can be a valuable part of the end-of-life treatment for a child with cancer. Though not all inpatient hospice facilities accept children, they do provide home hospice care. Most families find that bringing their terminally ill child home, letting the child die in familiar surroundings with their loved ones at their side, offers them the only comfort to be had in a time of great sadness.
Grief for the death of a parent or spouse can last for months or even years, but most adults eventually come to accept those losses. Grief for the death of a child is life long. One of the hardest tasks for a parent in mourning can be offering the necessary support and love to their other surviving children. Some parents who lose a child to cancer can find some solace from support groups. Such groups are available through hospitals, hospices, churches, counseling, and cancer organizations. Other parents prefer solitude and time to face their loss.
The treatment of childhood cancer depends on the specific disease, what tissues are affected, and how extensively it has spread at the time of diagnosis.
Acute lymphocytic leukemia and acute myelocytic leukemia
Acute lymphocytic leukemia (ALL) is the most common form of cancer in children, occurring about three times as often as acute myelocytic leukemia (AML). Leukemia of either type causes symptoms such as fevers, pallor, fatigue, bleeding or bruising, swollen glands, and bone pain—which can manifest itself as a limp or refusal to walk.
The diagnosis is made based on blood tests and bone marrow studies. The treatment is similar for both types. ALL has a very good prognosis, with a cure rate of about 80%; AML has a poorer prognosis, with different studies citing cure rates of 35-55%.
Treatment for ALL requires prolonged chemotherapy, consisting of remission induction, consolidation or intensification therapy, and maintenance. An essential component of the successful treatment of ALL is prophylactic (preventative) treatment to the CNS, a common site of relapse. In the past, children received radiation to the CNS, but this carried a risk of later brain tumors and significant neurologic and psychiatric deficits. Only the highest-risk children now receive CNS radiation; the rest receive intrathecal chemotherapy, which means that the medications are introduced directly into the spinal fluid during spinal taps.
Similar strategies are used in children with AML, but since far more of these patients relapse, bone marrow transplantation becomes an important option.
Non-Hodgkin's lymphoma constitutes about 60% of the lymphomas in children, and 10% of all childhood cancers. It is a cancer of the lymphatic system, which includes the spleen and lymph nodes. It is more common in boys than in girls, and other risks for the development of non-Hodgkin's lymphomas include conditions that depress the immune system, such as AIDS or immune suppressive treatment after organ or bone marrow transplant. Many such cases are Burkitt's lymphomas, and are associated with the presence of Epstein-Barr virus. These often manifest as masses in the jaw.
Non-Hodgkin's lymphoma has survival rates of 60-90%, depending upon the stage at which it is diagnosed. Lymphoma might be found at a routine examination, with nothing but swollen lymph nodes or an enlarged spleen as early signs. Some children do experience fevers or drenching night sweats, while others complain of persistent itching. Like adults, some teenagers will experience unexplained abdominal pain with alcohol ingestion, but might never report this symptom to parents for fear of consequences for underage drinking.
Non-Hodgkin's lymphoma is treated with chemotherapy, with radiation generally reserved for emergency treatment of bulky tumors that threaten other organs.
Hodgkin's disease is rare in young children but becomes more common in the teen years. Early Hodgkin's disease is one of the most curable of all cancers, with a cure rate as high as 95%. Early disease is often treated with chemotherapy alone, while more advanced disease is often treated with both chemotherapy and radiation.
Central nervous system cancers
CNS tumors account for about 17% of all childhood cancers. Several major categories of brain cancers are found in children.
This is the most common brain tumor found in children. Its symptoms can appear as headaches, nausea and vomiting, and it can also cause gait disturbances and damage to the cranial nerves (those nerves that control such functions as eye movement and facial muscle control). Medulloblastoma is treated by surgical removal of the tumor and postoperative radiation. Chemotherapy appears to improve survival rates in those children with the most advanced disease at the time of diagnosis.
These arise most often in the brainstem, at the base of the brain. Those that arise in the segment of the brain known as the pons have the poorest prognosis. Many gliomas produce gait abnormalities and cranial nerve problems such as double vision, and swallowing and speech disorders. Their location makes them difficult to reach surgically, so the primary treatment is radiation therapy. Most trials of chemotherapy have not shown benefit, but newer agents are being explored.
High-grade malignant gliomas include astrocytomas and glioblastomas. They are treated by surgical removal when possible, radiation therapy, and sometimes chemotherapy.
These cancers arise in the cells that line spaces within the brain—known as the ventricles— or the spinal column. In addition to nausea, vomiting, and headache, an ependymoma can cause head tilting and hearing loss. Treatment consists of surgery to remove the tumor followed by radiation. Chemotherapy does have benefit in children under three years of age but has less value in older children.
, which accounts for about 8% of all childhood cancers, is far more common in infants than in older children. It originates in the sympathetic nervous system, a complicated system involving nerves and the adrenal glands, which produce hormones such as epinephrine and norepinephrine (also called adrenaline and noradrenaline). Most neuroblastomas arise in the adrenal glands, and are noticed as a mass in the abdomen. However, they can arise anywhere in the sympathetic nervous system, appearing as masses in the neck, the chest, or the pelvis.
Symptoms are usually related to whatever organs are compressed by the growing tumors. Thus, abdominal masses produce discomfort, vomiting or loss of appetite.
Neuroblastomas are staged based on the age at diagnosis, location of the tumor, and degree of spread. Children considered at low or intermediate risk have the best prognoses, with up to 90% achieving long-term survival. Those at the highest risk have traditionally had a poor prognosis, with only about 15% surviving. The use of more intensive chemotherapy had improved the survival rate to 30% 1995.
Treatment consists of surgery to remove as much tumor as possible, chemotherapy, and often radiation therapy.
Wilms' tumor, or nephroblastoma, is a cancer that arises in the kidney. It accounts for 5% of all cancers in children. Signs and symptoms of Wilms' tumors include abdominal masses, abdominal pain or swelling, high blood pressure, and blood in the urine—either visible or in microscopic examination. Treatment consists of removal of the kidney along with the tumor. Many children also receive radiation or chemotherapy, depending upon the extent of the original disease and the specific cell types involved. Wilms' tumors diagnosed at the very earliest stages have extremely favorable prognoses, with as high as a 98% cure rate.
Soft tissue sarcomas are broadly divided into rhabdomyosarcoma and nonrhabdomyosarcoma soft tissue sarcomas. These are cancers of connective tissue. Rhabdomyosarcomas constitute about half of these types of cases. It is the fourth most common solid tumor in children, after brain tumors, neuroblastoma, and Wilms' tumor. It begins most commonly in sites in the head and neck, but can also arise in the urinary tract and the extremities. Symptoms can vary depending on the site of origin but, most often, rhabdomyosarcoma develops as a painless mass.
The nonrhabdomyosarcomas arise in a variety of different cell types. Among those cell types are the cells of the linings of peripheral nerves, the linings of joints, and other fibrous tissue. The most common sites of origin are the limbs, the trunk, the abdomen, and the pelvis.
The prognosis of both types of sarcomas varies with the extent of spread at the time of diagnosis and the type of cell from which the cancer arose. About 90% of children with early stage sarcomas can be cured, while only 20% of those with the most advanced disease at the time of diagnosis can be cured. Treatment consists of surgery and chemotherapy.
This is a form of bone cancer. In the past, all such cancers were treated with amputation. Now, limb salvage surgery can be performed in a number of cases. Chemotherapy and surgery combined have improved the prognosis for this disease to a 60% long-term survival rate.
Ewing's sarcoma is a rare bone cancer that usually occurs in teenagers. It is more common in girls than in boys, and often starts in the femur (thighbone). Between 50 and 60% of children with Ewing's sarcoma will survive up to five years.
Retinoblastoma is a cancer that arises in the cells of the retinas of the eyes. It is a disease of young children and has been diagnosed at birth. It can occur in both eyes in an inherited syndrome, and siblings of children with retinoblastoma in both eyes need to be screened. First symptoms include a sudden onset of squinting or crossed eyes. Radiation therapy will cure the disease in about 90% of children and, although most will suffer some visual changes, few lose their eyesight.
Germ cell cancers
These include teratomas, choriocarcinomas, embryonal carcinomas, and germinomas. These are all cancers of stem cells—cells that represent the earliest, or embryonal, stages of cell development and which have the potential to develop into mature cells. Some germ cell tumors are benign; others are malignant. They arise in the ovaries, testes, or sites along the midline of the interior of the body. Symptoms vary with the site of origin. Testicular masses are usually painless; ovarian masses can be accompanied by abdominal pain and swelling. Midline germ cell cancers can cause constipation or urinary retention as they grow and block internal organs. They are treated with surgery, radiation, and chemotherapy, and long-term survival rates are as high as 80% percent.
Hepatic (liver) cancers are rare but not unheard of in children. There are two types of liver cancer in children.
The second type is hepatocellular carcinoma, which accounts for about one-third of the cases of liver cancer in children, and its incidence has been falling. Hepatocellular carcinoma has been associated with hepatitis B and C, exposure to anabolic steroids, aflatoxins (food contaminants), pesticides, and vinyl chloride.
Treatment of both of these cancers includes surgical removal of the cancer and chemotherapy, although hepatoblastoma is more responsive to chemotherapy than is hepatocellular carcinoma.
Alternative and complementary therapies
Alternative and complementary treatments have not been studied extensively in children, and some have been proven harmful. Herbal remedies can be particularly dangerous, in that children have very different metabolisms from adults and relatively benign treatments for adults can be fatal in children. For example, jin bu hua, a traditional Chinese medicine, can produce heart problems or difficulty breathing. Life root or comfrey might cause fatal liver damage in children.
Techniques such as guided imagery can be adapted for children. Providing favorite toys or videotapes can serve as focal points for children to distract them from painful or frightening procedures.
Late effects of treatment
The high cure rates for children with cancer have not come without a price. While chemotherapeutic drugs and radiation are highly toxic to cancer cells, they are highly toxic to healthy cells and organs, as well. Most organ systems can be affected by cancer treatment, and children who have been cured of cancer frequently face lifelong consequences of those treatments.
CENTRAL NERVOUS SYSTEM.
Children who receive radiation therapy to their brains often experience a decline in scores on cognitive tests. More than one-half of the children who receive high-dose brain radiation have IQ scores below 90. Children with acute leukemia who are given chemotherapeutic agents directly into their spinal fluid are also at risk for developing learning disabilities and other neurologic effects.
EYES AND VISION.
Both radiation to the brain and chemotherapy can cause damage to vision. If the eyes are included in a radiation field, the child can develop radiation cataracts. The long-term use of steroids, which are part of most chemotherapeutic regimens and used after bone marrow transplant, can also cause cataracts.
Both radiation and the drug, cisplatin, can cause hearing loss.
TEETH AND SALIVARY GLANDS.
Radiation therapy to the head and neck can damage permanent teeth and salivary glands. The chemotherapy administered to very young children with acute lymphoblastic leukemia can also cause damage to the teeth.
Heart damage can occur from the toxic effects of radiation therapy and from certain chemotherapeutic drugs. That damage can be centered in the heart muscle, the pericardium (lining) of the heart, or the coronary arteries. The drugs most noted for causing heart damage are daunorubicin and doxorubicin. They do particular damage to the left ventricle, the main pumping chamber of the heart. This can lead to congestive heart failure, in which the heart fails to pump blood effectively throughout the body. This might not appear until later life, precipitated by such stressors as vigorous exercise or pregnancy. Some survivors of childhood (and adult) cancers eventually come to require heart transplant.
Bleomycin and carmustine, two chemo-therapeutic drugs, can cause inflammation of the lungs with later scarring and decrease in lung function. Radiation treatment of the chest can also impair lung function.
The kidneys can be damaged by radiation therapy to the abdomen or by a number of chemotherapeutic drugs. Some of those drugs are cisplatin, BCNU, ifosfamide, methotrexate, vinblastine, and bleomycin. Children treated for Wilms' tumors can develop kidney disease in the unaffected kidney years after treatment.
Liver damage can occur with radiation or with chemotherapy. The agents used to treat leukemias are particularly known for their liver toxicity. BCNU is another agent with known liver toxicity.
Because so many children receive transfusions of blood products, they are at risk for developing transfusion-related hepatitis, which can progress to cirrhosis in a few cases. Blood products are now screened for the presence of hepatitis B and C viruses, but many older surviving children received transfusions before the screening tests were available.
Radiation can cause an acute inflammation of the intestines with vomiting and diarrhea. Some children go on to develop scarring of the intestines that can lead to blockages requiting surgical repair.
Radiation to the spine, sometimes used for children with Hodgkin's disease or medulloblastoma, can produce curvature of the spine, in the form of kyphosis, or hunchback, or scoliosis, an S-shaped curve of the spine. Radiation to the hips can cause damage to the hipbones. The two most common forms of that damage are slipped capital femoral epiphysis and avascular necrosis, both of which involve damage to the end of the thighbone where it meets the pelvic bones.
Loss of the necessary minerals within the bones can be seen in children who have been treated for brain cancers, acute lymphoblastic leukemia, lymphoma and some solid tumors. Long-term use of steroids or methotrexate is a common cause of this. These children are at risk of fractures.
The endocrine system is the group of glands responsible for the production of hormones. Almost any gland can be affected.
Pituitary gland: Brain radiation can cause growth hormone deficiency. Even when normal levels of growth hormone are found, children who have undergone brain radiation are often obese and fail to achieve their expected height. Those whose levels are low will grow when growth hormone injections are administered.
Thyroid gland: The thyroid gland can be damaged by radiation treatment that involves the neck, typically becoming underactive. This might not occur until several years after treatment, and is treated with oral thyroid hormone.
Reproductive function: Radiation therapy and chemotherapy can both damage the ovaries, causing loss of hormones, lack of periods and infertility. The testes are less easily damaged and adult male survivors often have normal hormonal levels and sexual function, but might be sterile. Adolescents might be offered the opportunity to bank sperm before treatment to ensure that they might have future children through artificial insemination. Those who have had surgery to remove internal nodes involved in testicular cancer might be impotent as adults due to damage to the nerves that control sexual function.
Concerns have been raised that since chemotherapeutic agents can cause genetic mutations, those survivors whose fertility has been preserved might be at risk of giving birth to children with birth defects. This has not been observed yet, but children of women treated for Wilms' tumors often have low birth weights.
The most serious late effect of successful treatment for childhood cancer is a second cancer. Second Cancers are a different type and are related to either inherited factors or far more often to late effects of treatments.
About fifty percent of those who have been treated for the hereditary form of retinoblastoma develop a second cancer at some point in their lives.
Children with cancers that obstruct the flow of urine sometimes require a procedure called ureterosigmoidostomy. In this, the ureter, which carries urine from the kidney to the bladder, is attached instead to the sigmoid colon. Such children have a significant risk of developing adenocarcinoma of the colon at the site of the connection in adulthood.
Radiation to the neck can cause later thyroid cancer. Radiation to the brain can cause later brain tumors, such as meningiomas or gliomas. This was once fairly common in children treated for leukemia and given prophylactic radiation therapy to prevent central nervous system relapse. Bone sarcomas are possible after radiation treatment of retinoblastomas or Ewing's sarcoma. The risk of later breast cancer is increased in those who were treated with radiation for Hodgkin's disease in childhood.
Etoposide and teniposide, chemotherapeutic drugs known as epipodophyllins, are associated with a risk of developing acute myelogenous leukemia in the years after initial treatment for cancer. These are used in treatment of some germ cell tumors, ALL, and non-Hodgkin's lymphoma.
To prevent rejection, children who undergo bone marrow transplant receive drugs to suppress their immune systems. Long-term use of these medications is associated with a risk of developing cancer that originates in the white blood cells known as B cells.
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National Childhood Cancer Foundation. 440 E. Huntington Drive, P.O. Box 60012, Arcadia, CA 91066-6012. (626)447-1674. <http://www.nccf.org>
Childhood Cancer Ombudsman Program. P.O. Box 595, Burgess, VA 22432. Fax: (804)580-2502
American Cancer Society. 1599 Clifton Road, Atlanta, GA, 30329. (800)ACS-2345. <http://www.cancer.org>
The Leukemia and Lymphoma Society of America (formerly The Leukemia Society of America). 1311 Mamaroneck Avenue, White Plains, NY 10605. (914)949-5213. <http://www.leukemia-lymphoma.org/>
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Cancer Care, Inc. 1180 Avenue of the Americas, New York, NY10036. (212)302-2400 or (800)813-4673. <http://www.cancercare.org>
National Marrow Donor Program. Suite 500, 3001 Broadway Street NE, Minneapolis, MN 55413-1753. (800)MARROW2 (800-627-7692). <http://www.marrow.org/>
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Marianne Vahey, M.D.
—An inherited disorder of abnormal gait, skin lesions, and respiratory infections associated with a greater-than-average risk of developing childhood cancer.
—An inherited disorder featuring skin abnormalities with a higher-than-average risk of childhood cancers.
—Those parts of the body that give it structure and form, including bones, joints, muscles, tendons, and ligaments.
—An inherited disorder featuring multiple polyps in the colon with a very high likelihood of developing colon cancer by age 40; also associated with a greater-than-average risk of developing childhood cancer.
Fetal alcohol syndrome
—A variety of birth defects that occur in children of mothers who abuse alcohol while pregnant, including mental retardation and facial abnormalities. Children with this syndrome have a higher than average risk of developing liver cancer.
—An inherited disorder characterized by skin lesions, including brown spots called café au lait spots, small to large skin tumors, and neurofibromas, tumors within nerves. This carries a higher than average risk of developing childhood cancer.
—The gland that produces multiple hormones that in turn affect other glands. The pituitary influences the nerves, the thyroid gland, the adrenal glands, and the ovaries and testes.
—An inherited disorder that includes skin abnormalities, mental retardation, and seizures, and carries a higher-than-average risk of childhood cancer.
—A surgical procedure that reroutes the ureters, the tubes that carry urine from the kidneys to the bladder, by implanting them instead into the sigmoid colon.
—Spaces within the body. In the brain, these are spaces filled with cerebrospinal fluid. In the heart, these are the largest pumping chambers.
QUESTIONS TO ASK THE DOCTOR
- What type of cancer does my child have?
- What characteristics of my child's illness are favorable? Which are unfavorable?
- What course of therapy do you recommend?
- What medications will you use and what side effect should we anticipate?
- Will my child require surgery?
- Will my child need radiation therapy?
- Will my child need to be hospitalized for treatments?
- Should my child be enrolled in a clinical trial?
- Should my child be treated at a pediatric oncology center?
- Can my child continue to go to school?
- Can I stay with my child for procedures; for hospitalizations?
- How and what should we tell our child about the illness?
- What should we tell our other children?
- What should we expect after treatment is finished?