The Late Effects on Childhood Cancer Survivors

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Modern therapies and supportive care have increased the number of the childhood cancer survivors (CCS); as well, there has also been an increase in the late effects such as endocrine impairments and neuropsychological problems. These late effects often do not become clinically apparent until decades after cancer therapy. Unfortunately, over time the likelihood of medical follow-up decreases. Therefore, it is important for physicians to be aware of the late effects facing this population over their lifetime and the need to recall CCS patients for follow-up. However, where and by whom the follow-up of CCS can best be done is still a question that remains to be answered. Dickerman has set forth the recommendations for monitoring the late effects of CCS. He listed in a table both radiation-therapy site and chemotherapeutic agents along with the late effects that result from their use. These include: hypopituitarism, growth problems, hypogonadism, neurocognitive defects, coronary artery disease, caridiomyopathy, lung fibrosis, interstitial pneumonitis, breast cancer, nephropathy, muscle atrophy, osteoporosis, and second cancers. He recommended that in addition to being followed by a primary care physician, all CCS patients should also attend a specialized late-effects clinic on a yearly basis. At that specialized clinic, CCS patients would be evaluated by a member of the oncology team and subspecialists such as an endocrinologist, psychologist and neurologist. Ideally, such clinics should be located in the same center in which the patient was initially treated and be available on or near the site of residence.

Dickerman JD. The late effects of childhood cancer therapy. Pediatrics. 2007;119:554-68.

Editor’s Comment

This is a very special review article which provides important information for physicians who care for CCS patients. The survival rate of childhood cancer patients has markedly improved, thus the long-term late effects, such as endocrine impairments and neuropsychological problems, have become increasingly important. These alterations may result many years after conclusion of the cancer treatment. Currently, 10 million individuals in the US are living with a cancer diagnosis, 3 times the number of survivors in decades past. In the near future 1 of 450 individuals in the population will be a long-term CCS. The 5-year survival rate of children with cancer is 80% to 85%; presently 1 in 640 individuals between 20 and 39 years of age is a CCS. Approximately 270,000 in the US present long-term morbidity of CCS.

In another paper, Oeffinger et al1 recently reported the chronic health conditions (late effects) in adults following the treatment of childhood cancer. Their retrospective cohort study tracked the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compared the results with those of siblings of the patients. They calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings (mean ages 26.6 years and 29.2 years, respectively, at the time of the study). In 62.3% of the cancer survivors there was at least one chronic condition; 27.5% had a severe or life-threatening condition. The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition (Table). Thus, CCS have a high rate of illness owing to chronic health conditions that occurred long after the cancer was treated. There are many long-term CCS who were treated in the last 50 years, and these patients still need monitoring.

The late effects resulting from current treatment will likely decrease with improved radiotherapy being delivered with newer equipment in better fractionation schedules, along with the replacement of, or the use of, reduced doses of second-cancer-inducing chemotherapy. However, new cancer therapies used now or in the future will, in all likelihood, be associated with their own late effects. The patients who are treated with these new therapies must also be monitored closely to assess the magnitude of any late effects. It is necessary for physicians, as well as patients and family members, to know that late effects of a cancer survivor can occur even after many years following cancer treatment. The signs and symptoms of late effects of CCS are often nonspecific and may be masked by the sequela of chemotherapy, radiation therapy, and/or surgery, and may not be clinically evident until much later in life. Therefore, they are likely to be overlooked if late effects are not actively searched for through regular follow-up. In previous issues of GGH there were 4 reviews of papers dealing with the long-term complications of CCS addressing height,2 premature menopause,3 growth hormone therapy and secondary neoplasms,4 growth hormone deficiency, quality of life and neuropsychological function.5 A clinic based model for survivors of childhood cancer has been proposed by Hinkle et al.6

Yoshikazu Nishi, MD

References - (linked to )

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Last Updated: 04/30/2008