Adults treated for a childhood cancer in the 1970s and 1980s were three times more likely than their siblings to have developed a later, chronic health condition, according to a large study of childhood cancer survivors. While only a small percentage of survivors were affected by any one, specific chronic health condition and 26 percent reported no adverse health conditions at all, childhood cancer survivors should get close, long-term follow-up from doctors who understand what complications to look for.
New England Journal of Medicine, October 12, 2006 (see the journal abstract)
(N Engl J Med. 2006 Oct 12;355(15):1572-82)
More than 10 million cancer survivors are alive in the United States, at least 270,000 of whom were originally diagnosed when they were under the age of 21. Advances in cancer treatment have meant that today, almost 80 percent of children diagnosed with cancer are alive at least five years after diagnosis. Many ultimately will be considered cured. As a consequence, interest is growing in the long-term health of these survivors.
Health problems that develop years later as a result of a survivorâ€™s original cancer treatment are known as late effects. (For more information, see Late Effects of Treatment for Childhood Cancer.)
The Childhood Cancer Survivor Study (CCSS) was started in 1993 to better understand these late effects. More than 20,000 childhood cancer survivors who were originally diagnosed between 1970 and 1986 were identified for the study at 26 participating research centers in North America and Canada; more than 14,000 were surveyed and followed for long-term health outcomes. Researchers also gathered information from the survivorsâ€™ medical records. All had had at least one form of primary treatment â€“ surgery, radiotherapy, or chemotherapy â€“ or some combination of these. In addition, about 3,700 of their siblings were recruited as comparison (control) subjects.
The analysis described here was initially reported at the American Society of Clinical Oncology annual meeting in Orlando, Florida, in May 2005.
Researchers looked at the occurrence of chronic health conditions in 10,397 survivors and 3,034 comparison siblings participating in the CCSS. On average, survivors were about 10 years old when originally diagnosed with cancer; all were under 21 years of age. At the time they were evaluated for this late-effects analysis, survivors averaged 27 years of age, ranging from 18 to 48 years old. Those in the sibling group were, on average, a couple of years older.
The lead author of the analysis is Kevin C. Oeffinger, M.D., of Memorial Sloan-Kettering Cancer Center in New York City.
More than 200 chronic health conditions were recorded, ranging from cataracts and hearing loss to heart problems and lung disease. As adults, survivors were far more likely than their siblings who did not have cancer as children to report one or more of these conditions.
- 62.3 percent of survivors vs. 36.8 percent of siblings said they had at least one chronic condition
- 27.5 percent of survivors vs. 5.2 percent of siblings said they had a severe, disabling, or life-threatening condition
- 37.6 percent of survivors vs. 13.1 percent of siblings said they had at least two chronic conditions
- 23.8 percent of survivors vs. 5.4 percent of siblings reported having three or more chronic conditions
Most of these conditions occurred in fewer than 3 percent of the survivors, many in fewer than 1 percent. Twenty-six percent of survivors reported no chronic health conditions at all. Only a small percentage of former cancer patients was affected by any one, specific severe or life-threatening health condition.
Among the more serious conditions reported were deafness (11 siblings, or 0.36 percent vs. 204 survivors, or 1.96 percent), congestive heart failure or stroke (six siblings, or 0.20 percent vs. 162 survivors, or 1.56 percent), and blindness (21 siblings, or 0.69 percent vs. 304 survivors, or 2.92 percent).
Among the less serious conditions were cataracts (eight siblings, or 0.26 percent vs. 192 survivors, or 1.85 percent), mild to moderate hearing loss (65 siblings, or 2.14 percent vs. 345 survivors, or 3.32 percent), and problems with chewing or swallowing (29 siblings, or 0.96 percent vs. 586 survivors, or 5.64 percent).
Researchers translated the actual incidence of chronic conditions into a measure of relative risk. This showed that compared with their siblings, survivors were three times more likely to have a chronic disease; five times more likely to have two or more chronic diseases; and eight times more likely to have a severe, disabling, or life-threatening disease.
Women were about 50 percent more likely than men to have any chronic condition, two or more chronic conditions, or a severe or life-threatening condition. The risk of a severe or life-threatening chronic condition was highest for survivors of bone tumors, central nervous system (brain) tumors, and Hodgkinâ€™s disease. Survivors who had undergone certain types of treatment (in particular, combination therapies involving chest, abdominal, and pelvic radiation) had a 10-fold or greater elevated risk of having a severe or life-threatening condition.
While severe or life-threatening health conditions were not found to be common among survivors of childhood cancer, the overall risk of some kind of chronic problem is of concern. â€œ[A]dult survivors of pediatric cancer who were treated in the 1970s and 1980s are a high-risk population,â€ the study authors conclude. â€œThe incidence of health conditions reported by this population increases with time and does not appear to [level off].â€
Childhood cancer survivors should get close, long-term follow-up from doctors who â€œknow what these patients have been through and what kinds of complications to look for in the future,â€ writes Philip M. Rosoff, M.D., of Duke University School of Medicine, in an accompanying editorial. â€œSadly, such follow-up is the exception rather than the rule.â€ The complications, he continues, â€œdemand a level of knowledge that is beyond the range of the general internist or family doctorâ€¦.â€
Barry Anderson, M.D., scientific coordinator for the CCSS at the National Cancer Institute, which funded the study, agrees, adding that both survivors and their doctors need to be educated about the potential late effects of childhood cancer treatment.
Doctors usually discuss the possible long-term effects of drugs and other treatments with patients or their parents when deciding on a treatment plan, says Anderson. In addition, the near- and long-term risks of treatment are outlined in a general way in the documents that parents sign to consent to their childâ€™s treatment.
It is difficult, however, to predict what late effects any individual child may develop. And parents, understandably focused on trying to ensure that their childâ€™s cancer is successfully treated, may not fully take in information about the possible long-term risks of treatment.
To address this issue, the Childrenâ€™s Oncology Group (COG) has prepared a resource for physicians called Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers.
All of the survivors in this analysis were treated before 1986. Late effects may differ in kind or severity for childhood cancer survivors treated more recently. Better techniques have been developed for classifying patients as having a low, medium, or high risk of relapse and tailoring the intensity of their treatment accordingly, says Anderson.
In general, radiation is now used less frequently to treat children with cancer, adds Anderson. Furthermore, advances in technology now enable doctors to better focus radiation treatment on tumors and spare nearby healthy tissues.
Doctors now have a better understanding of the risks associated with high doses of chemotherapy and can design treatment plans with those dose limitations in mind. They can also prescribe additional drugs to protect tissues such as the heart.
To better understand how these changes in treatment may have altered the risks of late effects, the CCSS investigators are planning to expand their study by following a large group of survivors treated for childhood cancer between 1987 and 1999. They will also continue to follow the existing group of survivors as its members age.
The Web site of the National Cancer Institute (http://www.cancer.gov)
[ad code=1 align=center]