One of the growing challenges in medicine is providing appropriate health care for survivors of childhood and adolescent cancer. They have an excess risk for early mortality due to second cancers and cardiac or pulmonary disease.1 Studies estimate that two thirds of survivors have at least one chronic or late-occurring complication (late effect) of their cancer therapy, with about one third having serious or life-threatening complications.2–6, , , ,  Nearly one half of young adult survivors of childhood cancer have at least one major adverse outcome of their health status as a result of their cancer therapy.7 The incidence of most late effects increases with age, often becoming clinically apparent decades after therapy.
This high-risk population, currently numbering about 270,000 in the United States, interfaces with many health care professionals, including oncologists, medical and pediatric specialists, surgeons, primary care physicians, nurses, psychologists, and social workers.8 Table 1 provides the distribution of survivors by cancer group.9 Examples are innumerable: the pregnant Ewing's sarcoma survivor referred by an obstetrician to a cardiologist for shortness of breath; the primary care physician evaluating a leukemia survivor for dyslipidemia and insulin resistance; a surgeon assessing a breast mass in a Hodgkin disease (HD) survivor who had mantle radiation; the school nurse working with the family of a medulloblastoma survivor with seizures and cognitive limitations. The challenge arises from the heterogeneity of this population treated with evolving cancer therapies amid a rapidly advancing understanding of the late effects of therapy.
|Cancer Group||Distribution at Cancer Diagnosis (2000) (%)||Five-year Survival Rates (1992 to 1999) (%)||Predicted Distribution of Five-year or More Survivors† (%)|
|Brain and other nervous||18.5||70.8||16.8|
|Kidney and renal pelvis||4.8||74.2||4.5|
|Bone and joint||4.8||68.1||4.2|
Faced with these risks and challenges, how can the health care delivered to these relatively young survivors be optimized? Many of the late effects can be lessened by prevention or by early diagnosis with therapeutic intervention. In the past 10 years, the concept of risk-based health care of survivors has evolved. The term “risk-based health care,” coined by Meadows, Oeffinger, and Hudson, refers to a conceptualization of lifelong health care that integrates the cancer and survivorship experience in the overall health care needs of the individual.10 A systematic plan for lifelong screening, surveillance, and prevention that incorporates risks based on the previous cancer, cancer therapy, genetic predispositions, lifestyle behaviors, and comorbid health conditions should be developed for all survivors. The fundamental tenets of risk-based health care are provided in Table 2. Possibly up to one third of this population experience relatively few minor complications and will face minimal long-term risks. It is difficult to fully appreciate risk, however, because the effect of chemotherapy, radiation therapy, and surgery on the aging of different organ systems will only become evident as the population ages.
|• Longitudinal care that is considered a continuum from cancer diagnosis to eventual death, regardless of age|
|• Continuity of care consisting of a partnership between the survivor and a single health care provider who can coordinate necessary services|
|• Comprehensive, anticipatory, proactive care that includes a systematic plan of prevention and surveillance|
|• Multidisciplinary team approach with communication between the primary health care provider, specialists of pediatric and adult medicine, and allied/ancillary service providers|
|• Health care of the whole person, not a specific disease or organ system, that includes the individual's family and his or her cultural and spiritual values|
|• Sensitivity to the issues of the cancer experience, including expressed and unexpressed fears of the survivor and his or her family/spouse|
Apart from academic centers, few health care professionals see more than a handful of survivors, each with different cancers, treatment exposures, and health risks. Thus, it is a daunting task for the clinician to deliver appropriate care. The aims of this review are to (1) convey a sense of the risk faced by survivors to clinicians unfamiliar with the population; (2) provide an up-to-date tool for clinicians, regardless of specialty or discipline, when providing care for a survivor; and (3) complement the recently completed recommendations for screening, prevention, and management of childhood cancer survivors described in the next section. Recognizing the diversity of readership of this journal, we have attempted to balance the details of late effects while maintaining the “big picture,” with the intent of providing a useful foundation for delivering risk-based health care to this vulnerable population.
Organizational Approach of the Review
In presenting this information, one can approach late effects from three different vantage points: the specific type of cancer, the organ system affected, or the therapeutic exposure. Each has its advantages and limitations. We have chosen to organize this review by therapeutic exposures and believe this approach will be useful to clinicians regardless of specialty or discipline. By knowing the treatment exposures, the clinician can then determine what late effects the survivor faces. This review does not presume to be exhaustive; rather, it describes the more common or serious problems experienced by survivors. Because risk that is associated with one exposure may be modified by other therapies, where appropriate, these modifying risks are included.
This review is intended to complement the recently released “Children's Oncology Group (COG) Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers,” which can be found on the Children's Oncology Group Web site (http://www.survivorshipguidelines.org). These guidelines were produced through a multidisciplinary effort, cochaired by one of the authors (MMH) and Wendy Landier, RN, MSN, CPNP. A Web-based interactive and user-friendly format of these guidelines, targeted for health care professionals and survivors, is under development.
Childhood Cancer Survivor Study
A major contributor to the literature is the Childhood Cancer Survivor Study (CCSS).11 Briefly, this longitudinal cohort study, supported through the National Cancer Institute and directed through the University of Minnesota, is tracking the outcomes of over 14,000 long-term survivors of childhood cancer. Five-year or more survivors who were diagnosed with cancer at one of 26 participating institutions from 1970 to 1986 were eligible for enrollment. Survivors were diagnosed before the age of 21 with one of the following: leukemia, central nervous system (CNS) tumor, HD, non-Hodgkin lymphoma (NHL), Wilms tumor, neuroblastoma, soft tissue sarcoma, or bone tumor. The participating institutions abstracted extensive information regarding the cancer diagnosis and treatment exposures. For comparisons with many of the outcomes, a random sample of siblings was enrolled. The primary limitation of CCSS is that many of the outcomes are self-reported. The main strength of the CCSS is the large geographically and ethnically diverse population with extensive demographic and treatment exposure data, allowing in-depth analysis of factors associated with various outcomes. As this cohort is followed longitudinally, reports from CCSS will continue to enhance our understanding of the cancer and survivor experience and long-term effects of chemotherapy, radiotherapy, and surgery.