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Childhood Cancers: Questions and Answers
- What are the most common types of childhood cancer?
Among the 12 major types of childhood cancers, leukemias (blood cell cancers)
and cancers of the brain and central nervous system account for more than
half of the new cases. About one-third of childhood cancers are leukemias.
The most common type of leukemia in children is acute lymphoblastic leukemia.
The most common solid tumors are brain tumors (e.g., gliomas and medulloblastomas),
with other solid tumors (e.g., neuroblastomas, Wilms tumors, and sarcomas
such as rhabdomyosarcoma and osteosarcoma) being less common.
- How many children are diagnosed with cancer in the
United States annually?
In the United States in 2007, approximately 10,400 children under age 15
were diagnosed with cancer and about 1,545 children will die from the disease
(1). Although this makes cancer the leading cause of death
by disease among U.S. children 1 to 14 years of age, cancer is still relatively
rare in this age group. On average, 1 to 2 children develop the disease
each year for every 10,000 children in the United States (2).
- How have childhood cancer incidence and survival
rates changed over the years?
Over the past 20 years, there has been some increase in the incidence of
children diagnosed with all forms of invasive cancer, from 11.5 cases per
100,000 children in 1975 to 14.8 per 100,000 children in 2004. During this
same time, however, death rates declined dramatically and 5-year survival
rates increased for most childhood cancers. For example, the 5-year survival
rates for all childhood cancers combined increased from 58.1 percent in
1975–77 to 79.6 percent in 1996–2003 (2).
This improvement in survival rates is due to significant advances in treatment,
resulting in a cure or long-term remission for a substantial proportion
of children with cancer.
Long-term trends in incidence for leukemias and brain tumors, the most
common childhood cancers, show patterns that are somewhat different from
the others. Incidence of childhood leukemias appeared to rise in the early
1980s, with rates increasing from 3.3 cases per 100,000 in 1975 to 4.6 cases
per 100,000 in 1985. Rates in the succeeding years have shown no consistent
upward or downward trend and have ranged from 3.7 to 4.9 cases per 100,000
(2).
For childhood brain tumors, the overall incidence rose from 1975 through
2004, from
2.3 to 3.2 cases per 100,000 (2), with the greatest increase
occurring from l983 through l986. An article in the September 2, 1998, issue
of the Journal of the National Cancer Institute suggests that the rise in
incidence from 1983 through 1986 may not have represented a true increase
in the number of cases, but may have reflected new forms of imaging equipment
(magnetic resonance imaging or MRI) that enabled visualization of brain
tumors that could not be easily visualized with older equipment (3).
Other important developments during this time period included the changing
classification of brain tumors, which resulted in tumors previously designated
as “benign” being reclassified as “malignant,” and
improvements in neurosurgical techniques for biopsying brain tumors. Regardless
of the explanation for the increase in incidence that occurred from 1983
to 1986, childhood brain tumor incidence has been essentially stable since
the mid-1980s.
A monograph based on data from the National Cancer Institute’s (NCI)
Surveillance, Epidemiology, and End Results (SEER) Program was published
in 1999 on U.S. trends in incidence, mortality, and survival rates of childhood
cancers. This monograph, Cancer Incidence and Survival Among Children and
Adolescents: United States SEER Program 1975–1995, is available at
http://seer.cancer.gov/publications/childhood/
on the Internet. In 2006, SEER published another monograph, Cancer Epidemiology
in Older Adolescents and Young Adults 15 to 29 Years of Age, Including SEER
Incidence and Survival: 1975–2000. This monograph is the first to
collect detailed information about cancer incidence and outcomes in adolescents
and young adults (AYA). It provides population-based incidence, mortality,
and survival data specific to cancers that occur in the AYA population,
along with epidemiological data and risk factors for the development of
age-specific cancers. This resource is available at http://seer.cancer.gov/publications/aya/
on the Internet. More recent cancer statistics for children ages 0–14
and 0–19 are available in sections 28 and 29 of the SEER Cancer Statistics
Review, 1975–2004 at http://seer.cancer.gov/csr/1975_2004/sections.html
on the Internet.
- What are the known or suspected causes of childhood
cancer?
The causes of childhood cancers are largely unknown. A few conditions,
such as Down syndrome, other specific chromosomal and genetic abnormalities,
and ionizing radiation exposures, explain a small percentage of cases.
Environmental causes of childhood cancer have long been suspected by many
scientists but have been difficult to pin down, partly because cancer in
children is rare and because it is difficult to identify past exposure levels
in children, particularly during potentially important periods such as pregnancy
or even prior to conception. In addition, each of the distinctive types
of childhood cancers develops differently—with a potentially wide
variety of causes and a unique clinical course in terms of age, race, gender,
and many other factors. Possible risk factors for specific childhood cancers
are discussed in the SEER monograph mentioned above. It can be found at
http://seer.cancer.gov/publications/childhood/
on the Internet.
A number of studies are examining suspected or possible risk factors for
childhood cancers, including early-life exposures to infectious agents;
parental, fetal, or childhood exposures to environmental toxins such as
pesticides, solvents, or other household chemicals; parental occupational
exposures to radiation or chemicals; parental medical conditions during
pregnancy or before conception; maternal diet during pregnancy; early postnatal
feeding patterns and diet; and maternal reproductive history. Researchers
are also studying the risks associated with maternal exposures to oral contraceptives,
fertility drugs, and other medications; familial and genetic susceptibility;
and risk associated with exposure to the human immunodeficiency virus (HIV).
- What have studies shown about the possible causes
of childhood cancer?
For several decades, the NCI, a part of the National Institutes of Health
(NIH), has supported national and international collaborations devoted to
studying the causes of cancer in children. Key findings from this research
include the following:
• High levels of ionizing radiation from accidents or from radiotherapy
have been linked with increased risk of some childhood cancers.
• Children with cancer treated with chemotherapy and/or radiation
therapy may be at increased risk for developing a second primary cancer.
For example, certain types of chemotherapy, including alkylating agents
or topoisomerase II inhibitors (e.g., epipodophyllotoxins), can cause an
increased risk of leukemia.
• Recent research has shown that children with AIDS (acquired immunodeficiency
syndrome), like adults with AIDS, have an increased risk of developing certain
cancers, predominantly non-Hodgkin lymphoma and Kaposi sarcoma. These children
also have an additional risk of developing leiomyosarcoma (a type of muscle
cancer).
• Certain genetic syndromes (e.g., Li-Fraumeni syndrome, neurofibromatosis,
and Gorlin syndrome) have been linked to an increased risk of specific childhood
cancers.
• Children with Down syndrome have an increased risk of developing
leukemia.
• Low levels of radiation exposure from indoor radon have not been
significantly associated with childhood leukemias.
• Ultrasound use during pregnancy has not been linked with childhood
cancer in numerous large studies.
• Residential magnetic field exposure from power lines has not been
significantly associated with childhood leukemias.
• Pesticides have been suspected to be involved in the development
of certain forms of childhood cancer based on interview data. However, interview
results have been inconsistent and have not yet been validated by physical
evidence of pesticides in the child’s body or environment.
• No consistent findings have been observed linking specific occupational
exposures of parents to the development of childhood cancers.
• Several studies have found no link between maternal cigarette smoking
before pregnancy and childhood cancers, but increased risks have been related
to the father’s smoking habits in studies in the United Kingdom and
China.
• Little evidence has been found to link specific viruses or other
infectious agents to the development of most types of childhood cancers,
though investigators worldwide are exploring the role of exposures of very
young children to some common infectious agents that may protect children
from, or put them at risk for, developing certain leukemias.
- What research is NCI currently doing on childhood
cancer?
The NCI is funding a large portfolio of studies (http://researchportfolio.cancer.gov/)
looking at the causes of and the most effective treatments for childhood
cancers. Ongoing investigations include:
• Studies to identify causes of the cancers that develop
in children: The Children’s Oncology Group (COG) (http://www.childrensoncologygroup.org)
is evaluating potential risk factors for a variety of childhood cancers.
Very large studies have been completed of childhood acute lymphoblastic
leukemia, acute myeloid leukemia, non-Hodgkin lymphoma, primitive neuroectodermal
tumors of the brain, astrocytoma, neuroblastoma, and germ cell tumors. One
large study, the Childhood Cancer Survivor Study, is evaluating the risks
of second cancers related to radiation therapy and chemotherapy received
by survivors of childhood cancer as part of treatment for their primary
cancer (see below).
COG has also established a Childhood Cancer Research Network that creates
a national registry of children with cancer. This initiative builds upon
the unique NCI-supported national clinical trials system for treating children
with cancer.
• Monitoring of U.S. and international trends in incidence
and mortality rates for childhood cancers: By identifying places
where high or low cancer rates occur, researchers can uncover patterns of
cancer that provide important clues for further in-depth studies into the
causes and control of cancer.
• Studies to better understand the biology of childhood cancer,
with the hope that this understanding will lead to new treatment approaches
that target critical cellular processes required for cancer cell growth and
survival: The Childhood Cancer Therapeutically Applicable Research
to Generate Effective Treatments (TARGET) Initiative was established by the
NCI and the Foundation for the National Institutes of Health to identify and
validate therapeutic targets in childhood cancers. The first TARGET project
focuses on targets for high-risk acute lymphoblastic leukemia and the second
TARGET project focuses on neuroblastoma. More information about the TARGET
Initiative can be found in the article “Initiative TARGETs Childhood
Cancer” at http://www.cancer.gov/NCICancerBulletin/NCI_Cancer_Bulletin_112106
on the Internet.
• Preclinical studies (animal studies) of new agents to identify
promising anticancer drugs that can be evaluated in clinical trials:
The NCI-supported Pediatric Preclinical Testing Program (PPTP) systematically
evaluates new drugs and substances using animal models (animals with a cancer
similar to or the same as a cancer found in children) to find the drugs
most likely to have significant anticancer effects in clinical trials. The
program is based on a large amount of research showing that animal models
imitate the effects of proven anticancer drugs and can be used to prospectively
identify new drugs that are effective against childhood cancers in subsequent
patient studies. More information about the PPTP is available at http://pptp.stjude.org/
on the Internet. Questions concerning the PPTP can be addressed to the PPTP
Project Officer, Dr. Malcolm Smith (smithm@ctep.nci.nih.gov).
• Projects designed to improve the health status of survivors
of childhood cancers: The NCI funds the Childhood Cancer Survivor
Study (CCSS), a study coordinated by St. Jude Children’s Research Hospital. The CCSS has
over 25 sites across the country at medical institutions with doctors specializing
in long-term care for children and young adults. This study was created
to gain new knowledge and to educate cancer survivors about the long-term
effects of cancer and cancer treatment. Information about the study is available at http://www.stjude.org/stjude/v/index.jsp?vgnextoid=0d5dd3ce38e70110VgnVCM100
0001e0215acRCRD&vgnextchannel=cc66c08e1f5d3110VgnVCM1000001e0215acRCRD on the Internet.
• Clinical trials to identify superior treatments for childhood
cancers, thereby leading to improved survival rates for children with cancer:
Each year about 4,000 children enter 1 of approximately 100 ongoing clinical
trials sponsored by the NCI. The following groups are conducting these trials:
The COG, with support from the NCI, conducts clinical trials devoted exclusively
to children and adolescents with cancer at more than 200 member institutions,
including cancer centers of all major universities, teaching hospitals throughout
the United States and Canada, and sites in Europe and Australia. COG was
formed in 2000 by the merger of four children’s cancer cooperative
groups to accelerate the search for a cure for childhood cancers and to
make it possible for children with cancer, regardless of where they live,
to have access to state-of-the-art therapies and the collective expertise
of world-renowned pediatric specialists.
The Pediatric Brain Tumor Consortium (PBTC) (http://www.pbtc.org) includes
10 leading academic institutions with extensive experience in the design
and conduct of clinical trials for children with brain tumors. The group’s
primary objective is to rapidly conduct phase I and II clinical evaluations
of new therapeutic drugs, treatment delivery technologies, new biological
therapies, and radiation treatment strategies in children up to age 21 with
primary central nervous system (CNS) tumors. Another objective of the PBTC
is to develop and coordinate innovative neuroimaging techniques. Results
from PBTC studies are made available to large international collaborative
groups for confirmatory phase II and multiagent phase III clinical trials.
New Approaches to Neuroblastoma Therapy (NANT) (http://www.nant.org) is
a consortium of university and children’s hospitals funded by the
NCI to test promising new therapies for neuroblastoma. NANT members constitute
a group of closely collaborating investigators linked with laboratory programs
where novel therapies for high-risk neuroblastoma are being developed. The
group conducts early clinical trials to test new drugs and new combinations
of drugs so promising therapies can be tested nationally.
The Pediatric Oncology Branch (POB) (http://home.ccr.cancer.gov/oncology/pediatric/)
of the NCI’s Center for Cancer Research conducts basic, preclinical,
and clinical studies of childhood cancer at the NIH Clinical Center in Bethesda,
MD. Basic studies include analyses of genetic and biological characteristics
of childhood cancers, as well as the study of immune system interactions
with these cancers and the effects of chemotherapy on the immune system.
Preclinical studies by the POB identify new drugs and types of immunotherapy
(treatment to boost the immune system’s ability to fight cancer),
as well as agents to control infectious diseases that occur in childhood
cancer patients. An active clinical trial program includes phase I and phase
II studies of new agents to treat childhood cancers, with a focus on molecularly
targeted therapy and immunotherapy, as well as bone marrow transplantation
and the development of immunotoxins (antibodies linked to a toxic substance
that bind to cancer cells and kill them) to treat childhood leukemia. The
POB also develops and tests new treatments for tumors associated with genetic
predisposition syndromes such as neurofibromatosis type 1 and multiple endocrine
neoplasia.
• Evaluations of new drugs that may be more effective against
childhood cancers and that may have less toxicity for children: The
COG Phase I/Pilot Consortium is a major component of the NCI’s pediatric
drug development program. The primary objective of the consortium is to develop
and implement pediatric phase I and pilot studies to promote the integration
of advances in cancer biology and therapy into the treatment of childhood
cancer. The consortium includes approximately 20 institutions that carefully
monitor the drugs for toxicity and safety. After their initial evaluation
for safety in children by the consortium, the agents and regimens can then
be studied within the larger group of COG institutions to determine their
role in the treatment of specific childhood cancers.
Selected References
- American Cancer Society. Cancer Facts and Figures
2007. Atlanta, GA: American Cancer Society. Retrieved December 26, 2007,
from http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf.
- Ries LAG, Melbert D, Krapcho M, et al. SEER Cancer
Statistics Review, 1975–2004. Bethesda, MD: National Cancer Institute.
Retrieved December 26, 2007, from http://seer.cancer.gov/csr/1975_2004.
- Smith MA, Freidlin B, Ries LA, Simon R. Trends in reported
incidence of primary malignant brain tumors in children in the United States.
Journal of the National Cancer Institute 1998; 90(17):1269–1277..
# # #
Related NCI materials and Web pages:
For more help, contact:
- NCI's Cancer Information Service
Telephone
(toll-free): 1-800-4-CANCER (1-800-422-6237) TTY (toll-free):
1-800-332-8615 LiveHelp® online chat: https://cissecure.nci.nih.gov/livehelp/welcome.asp
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