What are childhood cancers?

Related conditions:
Leukemia, lymphoma, brain cancer, osteosarcoma

Definition:
Childhood cancers are cancers that occur in a person from infancy through age nineteen. The twelve major types of childhood cancers vary by type of histology, site of origin, race, sex, and age. They are leukemias, lymphomas, brain and spinal tumors, sympathetic nervous system tumors, retinoblastomas, kidney tumors, liver tumors, bone tumors, soft-tissue sarcomas, gonadal and germ-cell tumors, epithelial tumors, and other and unspecified malignant tumors. The most common types are leukemias and lymphomas.

Risk factors: Childhood cancers result from noninherited mutations or changes in the genes of developing cells. Some risk factors have been associated with different types of childhood cancers such as acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML). If a child has an identical twin who was diagnosed with ALL or AML before the age of six, the child has a 20 to 25 percent greater risk of developing the illness. Nonidentical twins and other siblings of children with leukemia have two to four times the average risk of developing the illness. Children with Down syndrome, Klinefelter syndrome, or other genetic syndromes and those who have received drugs following organ transplants also are at greater risk of developing leukemia. Children who have received radiation therapy or chemotherapy for other types of cancer have an increased risk of developing leukemia within an eight-year period following treatment.

Etiology and the disease process: In childhood leukemia, an abnormal amount of white blood cells, or leukocytes, is produced in the bone marrow; these cells invade the bloodstream and deplete the body’s ability to fight infection. As the disease progresses, it affects the body’s ability to produce red blood cells and platelets, resulting in anemia, bleeding disorders, and continued risk of infection from the overproduction of white blood cells.

Lymphocytes are infection-fighting white blood cells that are made and stored in the lymph nodes (organs in the neck, groin, abdomen, chest, and armpits), spleen, thymus, tonsils, and bone marrow. In lymphoma, the white blood cells of the lymphatic system grow abnormally, producing cancerous cells called Reed-Sternberg cells. Although Hodgkin disease is most often seen in children aged fifteen or older, nodular lymphocyte predominance (LP) is more common in younger children, accounting for about one-fifth of the incidence of most Hodgkin disease in children. Non-Hodgkin lymphoma (NHL) occurs more often in boys than girls and most often between the ages of two and ten. Unlike the non-Hodgkin lymphoma seen in adults, most cases of NHL in children are of the fast-growing, aggressive type (such as Burkitt lymphoma, non-Burkitt lymphoma, and lymphoblastic lymphoma).

Another common type of childhood cancer, neuroblastomas (solid tumors), often begins in one of the adrenal glands above the kidneys; the tumors can also can arise in nerve tissues in the neck, abdomen, pelvis, or chest. While the cause of neuroblastomas is unknown, they are believed to arise from anomalies during the normal development of the adrenal glands.

Incidence: Childhood cancer is the leading cause of death in the United States in children from infancy to fourteen years of age. However, childhood cancer is relatively rare; each year 1 to 2 children per 10,000 children in the United States will be diagnosed with cancer. Childhood cancer is estimated to occur at the rate of 17 per 100,000 children through the age of nineteen. Incidence is higher for boys than girls, and cancer rates are higher for children under five years of age and those between the ages of fifteen and nineteen. The National Cancer Institute (NCI) estimates that, in 2014, 15,780 children and adolescents up to nineteen years old in the United States will be diagnosed with cancer and 1,980 will die of the disease.

According to an NCI study from 1975 to 1995, 25 to 30 percent of cancers occurring in childhood were leukemias. Of these, 60 percent were cases of ALL, and 38 percent were acute AML. The next most common type was miscellaneous intracranial and intraspinal neoplasms (mostly solid, typically brain tumors involving the cerebellum or brain stem) at 16.7 percent, followed by lymphomas at 15.5 percent. Leukemias are the most common cancer in those under age five (and decrease proportionally in those over age five), and lymphomas are most common in those fifteen to nineteen years old. Hodgkin disease occurs at a rate of 12.6 per 1 million children, while non-Hodgkin lymphoma occurs at a rate of 10.5 per 1 million children.

NCI's SEER Cancer Statistics Review 1975–2011 reported that from 2007 to 2011, the incidence of leukemia (except for myelodysplastic syndromes) was 49.4 cases per million for individuals from zero to nineteen years old. For the same age group and time period, the incidence of Hodgkin lymphoma was 12.4 per million and the incidence of non-Hodgkin lymphoma (except Burkitt lymphoma) was 8.6 per million. For the same age group and time period, the incidence of CNS and miscellaneous intracranial and intraspinal neoplasms was 45.1 per million.

Other types of childhood cancer include Wilms’ tumor, affecting one or both kidneys and seen in children between two and three years of age; neuroblastoma, the most common form of solid tumor occurring outside the brain in children, often diagnosed by one year of age; retinoblastoma, or eye cancer; rhabdomyosarcoma, developing in cells that become mature voluntary muscle (the most common soft-tissue sarcoma seen in children); and primary bone cancer (osteosarcoma).

The NCI reported in 2014 that mortality for childhood cancers declined more than 50 percent between 1975–1977 and 2007–2010, largely because of early detection and advances in treatment. However, the incidence of all types of invasive cancer in children has increased from 11.5 cases per 100,000 children in 1975 to 14.5 cases per 100,000 in 2004.

The reasons for this increase in incidence are unclear. However, the increase in the incidence of childhood brain tumors may be attributed to advances in early detection, as technologies such as magnetic resonance imaging (MRI) allow more accurate and differential diagnosing of tumors, and advances in neurosurgical techniques allow for biopsies of brain tumors. These advances in detection methods have resulted in an increase in discovery and diagnosis of malignant tumors.

Symptoms: The symptoms of childhood cancer vary by type, may mimic symptoms of other illnesses, and may include unexplained weight loss; headaches and vomiting; increased swelling or pain in bone, joints, back, or legs; a detectable lump or mass in the abdomen, pelvis, chest, armpit, or neck; unusual bleeding, bruising, or rash; recurring infections; sudden and persistent eye or vision changes; nausea or vomiting without nausea; a whitish color behind the pupil; tiredness or pallor; and recurring and persistent fevers. A child in the early stages of leukemia may not have these symptoms but may exhibit other changes in behavior, such as lacking the usual energy to engage in activities.

A painless swelling of the lymph nodes, fever, and fatigue are often symptoms of both Hodgkin disease and non-Hodgkin lymphoma. The type of Hodgkin disease most often seen in young adults ages fifteen and older is associated with these symptoms: swollen lymph node in the neck, groin, or armpit; lethargy and weakness; facial swelling; night sweats; unexplained fever and weight loss; abdominal pain or swelling; difficulty breathing; and pain. Non-Hodgkin lymphoma may progress quickly in children, with many initially diagnosed at Stage III or IV, so these children may first complain of abdominal pain, fever, or constipation or decreased appetite originating from an abdominal mass.

Neuroblastoma, or a cancer of the sympathetic nervous system, the most common type of cancer in infants, is usually seen as a lump or mass in the abdomen causing swelling, discomfort, pain, or a feeling of fullness. A neuroblastoma can also occur in the pelvis, neck, or eye. Often the neuroblastoma may spread to bone, causing pain, limping, weakness, numbness, or inability to walk. In about one-quarter of cases, the child may develop fever; less common symptoms include rapid heartbeat, flushed skin, sweating, irritability, high blood pressure, and diarrhea.

Screening and diagnosis: There are no tests that screen for childhood cancers such as leukemia or lymphoma; however, there are standard tests for diagnosing. Typically, a parent notices a change in a child’s behavior and brings the child to the doctor, who will conduct a complete physical and examine the child for enlargement of the lymph nodes, liver, or spleen. If a blood cancer such as leukemia is suspected, the doctor will order a complete blood count (CBC) with differential. A fraction of patients with leukemia may have a normal blood test result when diagnosed. Suspicious cases must have a bone marrow test to confirm the diagnosis of leukemia.

If Hodgkin disease or non-Hodgkin lymphoma is suspected, the doctor will do a thorough exam and order a CBC and a chest x-ray. If the diagnosis of lymphoma is confirmed, the doctor may refer the child to a specialist, such as a pediatric hematologist or oncologist, for further diagnostic tests such as a biopsy of the tumor to differentially diagnose the type of lymphoma, a bone marrow aspirate, or an imaging test such as a computed tomography (CT) scan.

Neuroblastomas are relatively rare, and screening for them in children with no symptoms is not believed to decrease mortality from the disease, so no screening test is conventionally used. Most neuroblastomas are detected within the first six months of life. A doctor who suspects an infant of having a neuroblastoma will order a urinalysis, which will reveal a higher-than-normal concentration of metabolites from the body’s breakdown of catecholamine neurotransmitters. If the physical exam and urine chemistry results indicate a neuroblastoma, the doctor will proceed to order other tests, such as an x-ray, CT scan, abdominal ultrasound, CBC, blood test of liver and kidney function, bone scan, metaiodobenzylguanidine (MIBG) scan, and bone marrow aspiration.

Staging is used to describe the disease at the time of diagnosis and to help the doctor determine the type of therapy, its course, and its prognosis. Leukemia, unlike other childhood cancers, is staged based on its presence and proliferation in organs other than its presence in the bone marrow and blood. Other factors in staging include sex, race, organ spread, types of leukemic cells, presence of abnormal chromosomes, and response to treatment within seven to fourteen days of inception. Staging to assess a child’s prognosis seems to be more important in children with ALL than in those with AML. Age and white blood cell count (WBCC) are important factors in staging ALL, with children younger than one and older than ten at highest risk (having a high white blood cell count of 50,000 cells per cubic millimeter).

Lymphoma is staged based on the extent of the disease. Stage I lymphoma is limited to one primary area of the lymph node or organ, while Stage IV indicates the lymphoma has spread to one or more tissues or organs outside the lymphatic system.

Neuroblastomas are staged I to IV-S, with Stage I being a tumor that is visible, is localized, and can be removed, and Stage IV being a cancer that has spread to distant lymph nodes or other parts of the body. In Stage IV-S, limited to a child under one year of age, the cancer has spread to skin, liver, or bone marrow but not to bone. Alternatively, neuroblastomas may be staged on the basis of low, intermediate, and high risk, depending on the features of the cancer cells, the age at which the child is diagnosed, and the stage of the disease.

Treatment and therapy: Childhood cancers are treated with surgery, chemotherapy, radiation therapy, or a combination of two or more therapies. Cancers in children, unlike those in many adults, typically are fast growing and respond well to chemotherapy. Children are often treated in children’s cancer centers, which tend to offer new therapies and the latest treatment with clinical trials. The NCI recommends that children with cancer be treated by a multidisciplinary team consisting of a pediatric oncologist and other specialists and that all children be considered for clinical trials to test the effectiveness of existing treatments and evaluate the benefits and side effects of experimental treatments. The American Cancer Society (ACS) recommends that parents ask their pediatric cancer team about the potential side effects of treatment before the regimen begins. Side effects include hair loss, fatigue, risk of infection, easy bruising or bleeding, vomiting, diarrhea, bone marrow changes leading to anemia, lower white blood cell counts leading to reduced ability to fight infections, and a reduction in platelet production leading to easy bleeding and bruising.

Treatment for the most common forms of cancer seen in children, acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML), consists of three phases: induction, consolidation, and maintenance. Once the cancer is staged by risk group, induction therapy is designed to induce remission such that leukemic cells are no longer present in bone marrow, normal cells return, and blood counts return to normal. The month-long treatment, often performed in the hospital, is intense because of the risk of serious infection, but more than 95 percent children with ALL who receive this treatment experience remission. Although the cancer is in remission, consolidation treatment lasting four to six months and maintenance therapy lasting at least two years are required to destroy all cancerous cells. These intravenous chemotherapies are coupled with intrathecal chemotherapy (drugs injected into the fluid surrounding the brain and spinal cord) to destroy cancer cells that may have spread to the central nervous system. In addition, radiation therapy may be directed at the brain or spinal cord if the leukemia was present in cerebrospinal fluid at the time of diagnosis; however, the side effects and long-term effects of radiation to the brain are such that this type of radiation therapy is avoided whenever possible. Low-risk ALL has the highest cure rate, 85 to 95 percent of all cases.

The three main types of therapy for Hodgkin disease are radiation therapy to decrease tumors and destroy cancerous cells; chemotherapy or systemic drug therapy; and bone marrow and peripheral blood transplants, particularly for those whose disease recurs. The four types of non-Hodgkin lymphoma seen in children (Burkitt, lymphoblastic, anaplastic large-cell lymphoma, and large B-cell lymphoma) may be localized in a swollen lymph node, but often the disease has spread to other organs at the time of diagnosis.

Some neuroblastomas go away without treatment, while others commonly require surgery. Approximately half of the tumors spread to bone and bone marrow, requiring chemotherapy, radiation therapy, stem cell transplantation, or immunotherapy. The location of the tumor, age of the child, and diffusion of the tumor are factors in determining the recommended treatment.

Prognosis, prevention, and outcomes: Overall, death rates have declined and five-year survival rates have increased for most types of childhood cancers. In 2014 the NCI reported that between 2004 and 2010, more than 80 percent of children diagnosed with cancer before the age of twenty survived at least five years, up from a survival rate of just over 50 percent in 1975. The increase in survival rates is attributable to new treatments resulting in cures or long-term remission for many children with cancer. Although the majority of cancers respond well to treatment, some will recur and require the child’s doctor to develop a new treatment plan. The most commonly reported longevity statistic is the five-year survival rate, or the percentage of children with cancer who live at least five years after diagnosis. According to the SEER Cancer Statistics Review 1975–2011, from 2004 to 2010 the five-year relative survival rate for cancer patients ages zero to nineteen was 82.5 percent for all International Classification of Childhood Cancer groups combined , 82.1 percent for leukemia, 96.4 percent for Hodgkin lymphoma, 86.5 percent for non-Hodgkin lymphoma, and 78.6 percent for neuroblastoma and other peripheral nervous cell tumors.

Children with cancer respond to chemotherapies and tolerate treatment better than adults do, making their prognoses bright. However, children who survive cancer may have long-term effects that require lifelong follow-up. These late or delayed effects can include hormonal disturbances in the endocrine system causing short stature, problems in puberty, thyroid or fertility disturbances, secondary learning difficulties, and other health consequences of the disease or treatment. Published data on long-term survivors of childhood cancers indicate that those most at risk of developing secondary sarcomas (cancers of connective or supportive tissue such as in bone, fat, or muscle) are children whose primary cancer was in soft tissue, bone, or renal tissue, or was Hodgkin disease. Because sarcomas can occur anywhere in the body and are more difficult to detect, long-term aggressive follow-up of childhood cancer patients is critical to their staying healthy.

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