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Childhood cancer treatment leads to complications later in life
Cancer survivors were 3.3 times more likely than their siblings to have a chronic health condition as adults.
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Survivors of childhood cancer must face a price for the eradication of their disease: They experience significant illness due to chronic health conditions as adults, according to a special report from the Childhood Cancer Survivor Study.
“Thirty years after a diagnosis of cancer, almost three-fourths of survivors had a chronic health condition, more than 40% had a serious health problem and one-third had multiple conditions,” said lead researcher Kevin C. Oeffinger, MD, from the department of pediatrics at the Memorial Sloan-Kettering Cancer Center in New York.
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“It is important for survivors to know the details of their treatment as patients,” Oeffinger told Hem/Onc Today. “We encourage patients to either be followed at a cancer center by a physician who is familiar with their special risks, or by a physician who is in communication with a cancer center.”
Following survivors
“These findings imply that vigorous and long-term monitoring of young cancer survivors, accompanied by early intervention when problems arise, is mandatory,” wrote Philip M. Rosoff, MD, associate professor of pediatric hematology/oncology at Duke University School of Medicine in Durham, N.C., in a supplementary editorial. Both Oeffinger’s report and Rosoff’s editorial appeared in The New England Journal of Medicine.
Rosoff suggested incorporating specific training on cancer survivorship in the residency programs in internal medicine, pediatrics and family medicine. “As an alternative, we could develop a postgraduate training fellowship in an adult subspecialty, analogous to the fellowships in adult congenital heart disease that are common in most major academic medical centers,” he said.
Max J. Coppes, MD, PhD, MBA, Hem/Onc Today’s section editor for Childhood Cancers, said that there is a lack of structural support to follow survivors.
“This specialty need not be restricted to adult childhood cancer survivors but could include the follow up and management of all cancer survivors,” said Coppes, who is executive director of the Center for Cancer and Blood Disorders and the Children’s National Medical Center in Washington.
“Once they reach 18 years, most of the survivors leave the children’s facility where they were treated and fall into a vacuum: Some are followed by a family physician, some by an internist and others are not really followed until they develop complications,” he said.
Oeffinger agreed that more physicians from different specialties are needed to work in this area of survivorship care and research. “They need to communicate with primary care physicians and specialists of adult medicine that are seeing these survivors in the community.”
According to Oeffinger, the number of long-term follow-up programs has continued to increase within the last eight to ten years. “More than half of cancer centers or children’s hospitals in the United States have long-term follow-up programs and we want all centers to implement such programs,” Oeffinger said. Unfortunately, few of these programs follow patients past 25 years of age, which is why patients need to keep records of their history, he said.
To prevent survivors from falling into this vacuum, the Children’s Oncology Group developed the Long-Term Follow-up Guidelines, a resource for clinicians who provide ongoing health care to survivors of pediatric malignancies. The guidelines can be viewed at www.survivorshipguidelines.org.
CCSS cohort
Oeffinger and colleagues assessed the long-term morbidity that follows the treatment of childhood cancer by determining the incidence and severity of chronic health conditions among adult survivors. They followed patients enrolled in the CCSS, an NCI-funded cohort study of individuals who survived five or more years after treatment for the eight major groups of cancer diagnosed during childhood or adolescence. The CCSS includes more than 14,000 childhood cancer survivors who initially were diagnosed between 1970 and 1986. The researchers also enrolled about 4,000 siblings of survivors as a comparative group. Publication of initial findings is in progress and follow-up is ongoing.
For the current report, the researchers assessed 10,397 adult survivors and 3,034 siblings from the CCSS. The most common diagnoses were leukemia, Hodgkin’s lymphoma, central nervous system tumors and bone tumors, representing 29.5%, 18%, 12.7% and 10.9% of the cohort, respectively. The remaining diagnoses each representing less than 10% of the cohort included: sarcoma, non-Hodgkin’s lymphoma, Wilms’ tumor and neuroblastoma.
At enrollment, survivors and siblings completed a 289-item survey that included questions regarding their physical health conditions. Investigators graded a total of 137 conditions based on the Common Terminology Criteria for Adverse Events (grade 1 through grade 5) and determined the incidence and prevalence of chronic conditions among survivors and siblings.
Chronic conditions
Twenty-five years following a cancer diagnosis, the cumulative incidence was 66.8% for any chronic conditions and 33.1% for a chronic condition of grade 3 or higher, according to the study. The risk of chronic health conditions was particularly higher for second cancers, cardiovascular disease, renal dysfunction, severe musculoskeletal problems and endocrinopathies.
“Moreover, the incidence of chronic conditions, including these five groups of serious outcomes, increases over time and does not appear to plateau,” the researchers wrote.
Among the survivors, 62.3% reported having at least one chronic health condition, with 27.5% reporting a grade-3 or -4 condition. About 38% of survivors reported at least two conditions and 24% reported three or more conditions.
Among siblings of survivors, 36.8% reported a chronic health condition, with 5.2% reporting severe or life-threatening/disabling conditions. Of these siblings, 13.1% reported at least two conditions and 5.4% reported three or more conditions, according to the study.
Cancer survivors were 3.3 times as likely as siblings to have a chronic health condition (95% CI, 3.0-3.5). This risk increased 8.2-fold when researchers assessed the likelihood of developing a grade-3 or -4 condition (95% CI, 6.9-9.7), such as myocardial infarction, congestive heart failure, premature gonadal failure, second cancers and severe cognitive dysfunction.
Survivor groups at the highest risk for developing a grade-3 or -4 condition were survivors of bone tumors (RR=38.9; 95% CI, 31.2-48.5), CNS tumors (RR=12.6; 95% 10.3-15.5) and Hodgkin’s lymphoma (RR=10.2; 95% CI, 8.3-12.5).
High-risk therapies included radiation-based treatment: Chest radiation plus bleomycin was associated with a 13.6-fold risk (95% CI, 9.8-18.7), chest radiation plus an anthracycline was associated with a 13-fold risk (95% CI, 10.4-16.3), chest radiation plus abdominal or pelvic irradiation was associated with a 10.9-fold risk (95% CI, 8.9-13.2) and abdominal or pelvic irradiation plus an alkylating agent was associated with a 10-fold risk of developing a chronic condition (95% CI, 8.2-12.1). Combining an anthracycline and an alkylating agent increased the risk of an acute condition, as well (RR=10.9; 95% CI, 8.9-13.2).
“An increase in the cumulative dose of an alkylating agent was associated with an increased risk of any condition or multiple conditions,” Oeffinger said. “In a similar way, an increase in the cumulative dose of an alkylating agent in combination with any type of irradiation was associated with an increased risk.” The cumulative dose of an anthracycline did not increase the likelihood the developing a grade-1 to -4 chronic condition, the researchers said.
Survivor characteristics associated with a chronic condition of grade 3 or higher were the female sex and an older age at initial diagnosis.
Rosoff noted a limitation in the study: All patients received treatment prior to 1986, and there have been considerable changes in therapy for most childhood cancers during the subsequent 20 years.
“It would be expected that patients who were treated more recently might have an analogous but different array of long-term complications,” he said. Researchers should establish another cohort for future study, according to Rosoff.
“We hope that the trends for chronic conditions in patients being treated today will be lower than with this cohort,” Oeffinger said. “Though some therapies have been altered over the last 10 to 15 years, there are still older therapies that are quite effective and we have not found less aggressive treatments to replace them. The first goal is still to cure the cancer.” – by Rebekah Cintolo
For more information:
- Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355:1572-1582.
- Rosoff PM. The two-edged sword of curing childhood cancer. N Engl J Med. 2006;355:1522-1523.
- www.survivorshipguidelines.org