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Utskriftsdato (17.12.2017)

Childhood cancer

Cancer occurs in all age groups, and cancer incidence generally increases with age. There are significant differences between childhood cancers and adult cancers, with much of the difference due to the cancer cell of origin.

Childhood cancer generally originates from immature, undifferentiated cells (blastomas) or from connective tissue (sarcomas), while the majority of adult cancer usually originates from epithelial tissue (carcinomas).

In general, childhood cancer has a better prognosis than adult cancer, but there is still a large variation among cancer types. Within childhood cancer treatment, medical science has made some of its greatest recent advances, and with today's treatment methods, it is calculated that more than three out of five children with cancer are cured.

Childhood cancers consist of one third leukemia, one third in the central nervous system, and the rest in other parts of the body, all in various cancer types. The incidence of these cancer types is age-dependent; certain tumor types occur nearly exclusively in very young children. Older children and teenagers often develop cancers also occurring in adults.

Childhood cancers consist of one third leukemia, one third central nervous system tumors, and the rest various cancer types in other parts of the body. The incidence of these cancer types is age-dependent; certain tumor types occur nearly exclusively in very young children. Older children and teenagers may develop cancers that are more commonly found in adults.

Incidence

In 2014, it was estimated that 15,780 children and adolescents ages 0 to 19 years would be diagnosed with cancer in the United States. (5)

Incidence children, 0-14 years in the period 2008-2014 in Norway:

 

 

Among adults in Norway, the incidence of cancer has increased since the Cancer Registry of Norway began registering data in 1952, which is to a great degree due to lifestyle factors, but also because the population lives longer in general. Among children in other countries, an increased incidence of cancers has been reported (2,3). Nevertheless, an equivalent increase has not been found from 1980 to present in the Nordic countries (4).

The increased incidence in the first years of registering data is assumed to be due to more complete registration of data. Exogenous factors are of less etiological significance in pediatric cancers compared to adults since these exogenous factors often have a long latency time. Cancer caused by such factors will therefore appear after childhood.

 

Etiology

The cause of cancer among children is usually unknown.

In some cases, hereditary factors play a role.

Staging

See each cancer type:

 

Metastatic patterns

See each cancer type:

Symptoms

Symptoms of cancer vary depending on cancer type.

Leukemia causes symptoms which are primarily due to reduced bone marrow function. This causes vague signs and symptoms such as pallor and reduced physical capacity, fever and repeated infections, bleeding and petechiae, bruising, and possibly mucosal bleeding and gum swelling. Skeletal pain is common, possibly accompanied by swollen joints, and limping may occur.  

The symptoms of lymphoma may be due to local growth of tumor tissue in a lymph node or other organs, or general symptoms may occur.

Cancers outside the central nervous system are often discovered incidentally, for example by a lump in the abdomen. Frequently, these types of tumors are not painful but can be accompanied by, for example, constipation if the tumor presses on the colon and prevents the stool from passing, or problems when urinating. Other possible symptoms are blood in the urine caused by tumors in the urinary tract, or skeletal pain or lumps/swelling caused by tumors of the muscle/skeletal system. In general, diffuse symptoms which do not have a natural explanation, and which do not diminish after a reasonable amount of time, should be further investigated.

Symptoms from the central nervous system depend on where the tumor is localized, the growth rate of the tumor, and the age of the child.

When a brain tumor is detected in an infant's first year of life, rapid growth of the head circumference is often the only finding. Most infants with a more rapid increase in head circumference than expected do not have a brain tumor, but should still be examined more closely to find the cause. Brain tumors in children are often localized to the posterior fossa (cerebellum), which can lead to a blockage in cerebrospinal fluid followed by a pressure increase (hydrocephalus).

This causes:

  • headache
  • nausea
  • vomiting, characteristically most prominent in the morning 
  • loss of coordination

If the tumor is localized in the large brain (cerebrum), the child may have:

  • seizures (epilepsy)
  • paralysis
  • disturbances of vision 
  • hormonal disturbances

The last two symptoms occur if the tumor is located centrally in the brain.

Differential diagnoses

Childhood cancer is rare and most symptoms are nonspecific. Such symptoms are most often due to harmless disorders, and investigation is needed only if complaints persist or are unusual. 

Some general differential diagnostic alternatives:

Suspicion of leukemia

  • Infections, primarily viral. Both Epstein-Barr virus (virus causing mononucleosis) and other viruses cause changes in blood values causing suspicion of leukemia.
  • All other causes of anemia among children
  • Juvenile rheumatoid arthritis (for joint changes)
  • Bone marrow metastasis from a tumor in another location

Suspicon of central nervous system tumors

  • Injuries
  • Inflammation/infections
  • Constipation/difficulty voiding without an underlying cause 

Suspicion of lymphoma

  • Infections with enlarged lymph nodes
  • Langerhans cell histiocytosis

Suspicion of tumors in the central nervous system

  • Hydrocephalus of other etiology (especially in small children)
  • Migraines, stress headaches (older children)
  • Infections
  • Seizure disorders

Prognosis

Although cancer in children is rare, it is the leading cause of death by disease past infancy among children in the United States. In 2014 it was estimated that 1,960 would die of the disease in the United States. (5)

The prognosis varies among cancer types, from a successful cure rate of 90% for certain cancer forms (Wilms' tumor and certain lymphomas) to very poor (certain types of brain tumors).

See each cancer form:

 

References

  1. Cancer in Norway 2013, Cancer Registry of Norway, Institute of Population-based Research. Oslo, Norway.
  2. Kaatch P, Steliarova-Foucher E, Crocetti E, Magnani C, Spix C, Zambon P. Time trends of cancer incidence in European children (1978-1997): Report from the automated childhood cancer information system project. Eur J Cancer 2006; 42: 1961-71
  3. Steliarova-Foucher E, Stiller C, Kaatsch P, Berrino F, Coebergh J-W, Lacour B, Parkin M. Geographical patterns and time trends of cancer incidence and survival anomg children and adolescents in Europe since the 1970s (the ACCIS project): and epidemiological study. Lancet 2004; 364: 2097-105
  4. Hjalgrim LL, Rostgaard K, Schmiegelow K et al. Age- and sex-specific incidence of childhood leukemia by immunophenotype in the Nordic countries. J Natl Cancer Inst 2003; 95: 1539-44
  5. National Cancer Institute, Childhood Cancers. Retrieved from
    https://www.cancer.gov/types/childhood-cancers/child-adolescent-cancers-fact-sheet

Diagnostics

The diagnostic approach depends on the child's symptoms, and on a thorough examination by a general practitioner. The general practitioner will often take supplementary blood tests and sometimes X-rays, but usually will refer the child directly to a pediatrician if the child's symptoms give suspicion of a serious illness.  

If the physical examination of the child and the blood tests cause suspicion of cancer, further testing will be planned accordingly. If there is suspicion of leukemia, a bone marrow examination is performed while the child is under general anesthesia.

Tumors are always diagnosed from biopsies, and biopsies must be carefully planned. Before performing the biopsy, the tumor is examined by imaging using X-ray, ultrasound, CT, and MRI to determine the localization, size, and extensiveness of the tumor.

The medical work-up of metastasis is customized for the type of tumor, and sometimes includes plain X-rays, CT of the lungs, ultrasound of the abdomen, a bone marrow examination, and also a CNS work-up with MRI or examination of spinal fluid.

Evaluation for a brain tumor is done using MRI. In small children, the MRI must be performed under general anesthesia. Brain tumors almost never metastasize outside the central nervous system, however, the most malignant brain tumors can spread via spinal fluid to other parts of the brain or bone marrow. In such cases, an MRI of the spine must be done and sometimes a bone marrow evaluation.

Treatment

Cancer treatment in children is almost always long-term (months to years), has many side effects, and is a great burden on the family. Without comprehensive supportive care, today's cancer treatment would not be possible to complete.

Pediatricians in Norway participate in Nordic and international collaborations, as well as clinical treatment studies with Nordic and international protocols.

Treatment of cancer in children includes chemotherapy, surgery, and sometimes radiation therapy. Most cancer forms are aggressive, and in general, these cancer forms are more sensitive to chemotherapy than slow-growing tumors. Chemotherapy therefore has a greater presence in treating childhood cancer than adult cancer.

Drug therapy

Chemotherapy is the treatment form for leukemia, and is sometimes supplemented with radiation therapy of the central nervous system. A stem cell transplantation is sometimes performed.

Most tumors outside the central nervous system are treated with preoperative chemotherapy, surgery, and postoperative chemotherapy. Preoperative chemotherapy will, in most cases, reduce the size of the tumor making it easier to remove thereby reducing the extent of surgery. Radiation therapy may be included in the treatment plan for these tumors. Only a minority of tumors are treated with surgery alone. 

Surgery

Brain tumors are treated by surgical resection, both to obtain a tissue sample for histological examination and to remove as much as possible of the tumor. In the majority of children with brain tumors, surgery is the only treatment, and the patient is monitored regularly with MRI to detect recurrence. In about 1/3 of patients, the tumor is malignant and additional treatment with chemotherapy and/or radiation therapy is necessary to improve the result. Postoperative treatment with chemotherapy and radiation therapy of a typical, yet malignant tumor of childhood (medulloblastoma), has produced a dramatic improvement in survival.

Radiation therapy

In some cases, radiation therapy is used either as a supplement to chemotherapy and surgery, or as primary local treatment if the tumor is inoperable. Small children who are not able to lie still for treatment must be under general anesthesia to complete treatment. This may mean the child must be put under general anesthesia up to thirty times.

Even though radiation therapy poses a risk for delayed injury, it is an important element to improve chances of long-term survival of cancers such as medulloblastoma, manifest CNS leukemias, and intracranial germinomas. With radiation therapy, it is possible to cure other childhood malignant conditions (Hodgkin's lymphoma, sarcoma, advanced stages of Wilms' tumor and neuroblastoma, as well as localized carcinoma or other localized tumors) particularly if local treatment is not possible in the form of surgery.   

Radiation therapy is an effective local treatment for cancer. However, healthy tissue surrounding the tumor tolerates only a limited amount of radiation before the child develops a risk for delayed injury. From high doses of radiation, delayed damage may be severe.

All radiation therapy in children is a difficult balance between the risk of dying from cancer and the risk of developing permanent damage after life-saving treatment. A risk assessment of this nature raises ethical questions for parents and doctors: what extent of injury is acceptable before the price of survival is too high? Guidelines given in international treatment protocols for radiation therapy of childhood cancer are a good source for support in these difficult situations. 

Very severe cognitive damage must be expected following high doses of radiation to large parts of the brain in children younger than 3 years. Therefore, radiation therapy to the brain is avoided if at all possible in this patient group. Intense chemotherapy poses less risk for delayed damage and can replace radiation treatment for brain tumors, in very young children, in some cases.

Follow-up Care

Families of children with cancer will be offered a consultation with a social worker, psychologist, and/or child psychologist. Network groups and therapy groups are established as needed with the local hospital. School, nursery school, music and play therapy are also important factors during treatment. Parents/guardians have a right to national benefit according to the patient care right §9-11.

After treatment is concluded, the child is monitored for many years (minimum of 5), but often until the child is finished growing into an adult. 

During the first years, the goal for follow-up examinations is to find recurrence of the cancer, and also to evaluate consequent effects of the disease and treatment.  As time passes, the purpose of follow-up is to look for delayed effects of the disease and treatment.

Children treated for brain tumors are routinely checked with MRI to document control of the disease. These examinations take place either at a neurosurgical department or pediatric outpatient clinic as needed.

Delayed injury

Most children treated for cancer grow into healthy adults without severe permanent damage. It is still important to emphasize that permanent injury does occur, partly due to the disease itself and partly due to treatment. Such injuries will often gradually become worse as the child ages, and are most prominent in children treated at very young ages. For older children and adolescents, the risk for delayed injury decreases with increasing age. In Norway, there is no systematic follow-up program for adults treated for cancer during childhood.  

The tolerance for radiation treatment in children depends on these factors:

  • age of the child
  • which organ is irradiated
  • size of tissue volume to be irradiated
  • dose of radiation given per day (fraction)
  • total radiation dose

Knowledge of delayed injuries developed after children began surviving cancer, and many research studies have been performed on delayed injury after cancer treatment. It is known that most injuries are dose-dependent, occurring after a patient has received a well-defined dosage of chemotherapy (cumulative dose) or radiation. However, "safe" dosages do not exist, since there are individual differences in dosages and consequent long-term damage. 

Doctors now take into consideration cumulative doses and delayed injuries. We strive to give as small dosages of chemotherapy as possible to treat the disease without costing survival and radiation therapy in children is avoided as much as possible. For cancers that have a good prognosis, there are international studies researching reduction of treatment where possible.

Solid tumors can infiltrate and damage healthy tissue around the tumor, which can cause temporary or permanent damage of organ function. Surgical removal of a tumor with free resection margins is, in most cases, the deciding factor for curing the disease. This means that healthy tissue must also be removed, and, depending on the localization and extent of the tumor, the surgery may cause functional damage. Preoperative chemotherapy promoting tumor shrinkage may facilitate less extensive surgery, thereby preserving organ function.

Children with brain tumors often have neurological symptoms when diagnosed, which either go away or remain after treatment. Children tolerate surgery much better than adults. Children who have undergone radiation and chemotherapy in addition to complicated surgery may develop severe immediate or delayed injuries requiring help and support after treatment. Some of these injuries do not improve.

Chemotherapy causes many acute side effects, which children generally tolerate better than adults, and causes less delayed damage than radiation therapy. Some chemotherapy drugs cause fertility damage (alkylating agents) and others may damage the heart (anthracyclines). Chemotherapy can also increase the risk for developing secondary cancer, even though the increase is small and much less than the risk caused by radiation therapy.  

Radiation causes disturbances in growth locally in the irradiated area. Generalized growth may be impaired partly due to lack of growth hormone if the hypophysis is included in the radiation field. In such cases, the child is treated with growth hormone. Production of the other hypophysis hormones may be damaged and the child will need hormone substitution.  

Irradiation of the central nervous system also causes learning difficulties and loss of social skills in varying degrees. Delayed injury from radiation therapy may increase with time after treatment.