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Late Effects in Childhood Cancer Survivors: The New Epidemic
by
M. Fatih Okcu, M.D., M.P.H.
Although
cancers that occur in children and adolescents younger than 20
years of age are relatively rare (comprising only one percent of
all cancers diagnosed), 1 in 300 children will develop cancer
before age 21. The fact that more than 70% of children diagnosed
with cancer are surviving leads to a remarkable statistic: by
2010, it is estimated that in the U.S. one of every 250 people
ages 20 to 39 years will be a pediatric cancer survivor! Those
projections, coupled with the recent understanding that two of
three survivors will carry one or more chronic late effects
secondary to cancer therapy, forecasts an important public
health impact from this population.
Late
effects of childhood cancer include complications, disabilities
or adverse outcomes that are the result of the disease process,
its treatment or both. Patterns of late effects have emerged
among groups of childhood cancer survivors that have contributed
to an appreciation of cancer as a chronic disease with
implications for continuing care. As many as two-thirds of
childhood cancer survivors are likely to experience at least one
late effect, with one-fourth experiencing a late effect that is
severe or life threatening. The seriousness of late effects is
illustrated by the recent finding of a 10.8-fold increase in
mortality in survivors diagnosed between 1970 and 1986. While
most of these deaths were due to recurrence of the primary
cancer, 21.3 percent were caused by treatment-related secondary
cancers, heart toxicity, lung complications and other adverse
effects.
The
emergence of late effects depends on a number of factors such as
age at diagnosis and therapy, severity of the initial disease,
types and dosages of chemotherapy, radiation fields and doses
and individual patient susceptibilities. Complicating the
management of late effects is their variable nature. Some late
effects are identified early in follow-up during childhood and
adolescence and resolve without consequence. Others may persist
or develop in adulthood to become chronic problems or influence
the progression of other diseases. Understanding late effects is
complicated by the constant evolution of treatments over the
years. Groups of patients, representing different treatment
eras, may experience unique sets of effects. At present, at the
time of diagnosis, we do not have the ability to predict which
children with cancer will develop which late effects.
Selected late effects are listed in
table
1 (pdf). One of the most debilitating of these is cognitive
impairment among children whose cancer or its treatment involved
the central nervous system. This particularly includes children
with brain tumors and those with leukemia or lymphoma who
received specific radiation therapy or chemotherapy to their
central nervous system. These patients may experience learning
impairments, social difficulties, behavioral adjustment
problems, and long-term education and vocational handicaps.
Since leukemias and lymphomas account for about 40 percent of
childhood cancer and tumors of the central nervous system
account for nearly 20 percent, some 60 percent of children are
at risk for neurocognitive damage, especially those who are
young when treated or who receive particularly intense or
prolonged treatment. Impairment may become apparent over time
and may include loss of IQ, deficits in short-term memory,
processing speed, visual motor integration, attention and
concentration. Other important late effects include psychosocial
limitations, like poor adjustment, depression and diminished
functioning in the area of social contacts and friendships.
While we
cannot predict which childhood cancer survivors will develop
which specific late effect our understanding of the potential
late effects for each survivor based on disease and treatment
history is increasing. In an effort initiated by the Children’s
Oncology Group (COG) Late Effects Committee, multiple disease
specific task forces have developed guidelines to provide
recommendations for screening and management of late effects
that may potentially arise as a result of therapeutic exposures
used during treatment for pediatric malignancies. These
guidelines represent a statement of consensus from a panel of
experts in the late effects of pediatric cancer treatment. The
recommendations are based on a thorough review of the literature
as well as the collective clinical experience of the task force
members, panel of experts and multidisciplinary review panel
(including nurses, physicians, behavioral specialists and
patient/parent advocates). Implementation of these guidelines is
intended to increase awareness of potential late effects and to
standardize and enhance follow-up care provided to survivors of
pediatric malignancies throughout the lifespan. These guidelines
are an extremely important resource. They can be viewed online
at
http://www.survivorshipguidelines.org. In collaboration with
the COG, David Poplack, M.D. and coworkers at the Texas
Children’s Cancer Center and the Baylor College of Medicine’s
Center for Collaborative and Interactive Technology are
developing the Passport for Care; an online resource for
survivors of childhood cancer. The Passport will provide the
survivor with a synopsis of their cancer and treatment history,
individualized lists of potential late effects and guidelines
for surveillance. Additional features of the Passport will
include individualized information resources of particular
interest to the survivor as well as a survivor forum. More
information about the Passport for Care can be found at
www.txccc.org/pfc.
The key to predicting late effects and
ultimately reducing or eliminating them is understanding
individual patient susceptibilities to treatment side effects.
Translational studies aimed at identifying potential biological
markers that can help to predict development of certain late
effects are an exciting area of research. Individual variation
in the response to chemotherapeutic agents and radiation based
on patient biological differences is an area of active study.
This variability in drug response is, in part, determined
genetically. It has been proposed that host germline variability
determines the biological consequences of cancer treatment;
particularly development of short and long-term various late
effects. As we gain more information from this pharmacogenetic
research, genetic testing for this variability may facilitate
the development of better strategies for planning an
individualized treatment approaches for pediatric and adult
cancer patients that will maximize the potential for cure and
minimize chronic side effects.
M.
Fatih Okcu, M.D., M.P.H., an assistant professor of
pediatrics at Baylor College of Medicine is a pediatric
oncologist/hematologist and director of research in the Texas
Children’s Cancer Center’s Long Term Survivor Program. His
research interests include the genetic polymorphisms that
determine the effects of cancer treatment.
References
Childhood Cancer Survivorship: Improving Care and Quality of
Life. National Cancer Policy Board, Weiner SL, Simone JV, Hewitt
M. Washington, DC: The National Academies Press, 2003.
Oeffinger KC, Eshelman DA, Tomlinson GE, Buchanan GR, Foster BM.
Grading of late effects in young adult survivors of childhood
cancer followed in an ambulatory adult setting. Cancer. 2000 Apr
1;88(7):1687-95.
Mertens AC, Yasui Y, Neglia JP,
Potter JD, Nesbit ME Jr, Ruccione K, Smithson WA, Robison LL.
Late mortality experience in five-year survivors of childhood
and adolescent cancer: the Childhood Cancer Survivor Study. J
Clin Oncol. 2001 Jul 1;19(13):3163-72.
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