After Childhood Cancer, Long-Term Mortality Risks Remain

July 13, 2010— -- Survivors of childhood cancer remain at risk for premature death 25 years after their initial cancer diagnosis, largely as a consequence of their treatment, according to a large British study.

The data, culled from a study of almost 18,000 five-year survivors of childhood cancers, found that overall this group experienced 11 times the number of deaths that could be expected in the general population, according to Raoul C. Reulen of the University of Birmingham and colleagues.

The good news for these patients is that rates of early death in a given year declined as more time went by. However, their risk of dying earlier than their peers who had never had cancer remained significantly elevated even after 45 years, the researchers reported in the July 14 Journal of the American Medical Association.

Previous research has pointed to increased mortality linked to second cancers and other diseases through the first two decades after five-year survival from childhood cancer, but until now little has been known about risks and causes beyond 25 years.

"Investigations into long-term cause-specific mortality are important because any excess mortality may be related to long-term complications of treatment," wrote Reulen and colleagues.

In the largest analysis of long-term mortality among childhood cancer survivors thus far, the investigators obtained data from the British Childhood Cancer Survivor Study, which includes 17,981 five-year survivors of cancers diagnosed between 1940 and 1991.

Patients were followed through the end of 2006, by which time 3,049 -- 17 percent -- of the patients had died.

At 50 years, 19 percent of these patients had died from a cause other than recurrence of their primary cancer, compared with the 6.3 percent rate expected in the general population. The cause of death in most of these cases was often tied to another type of cancer, circulatory disorders like cardiac and cerebrovascular diseases, and respiratory causes.

Death from a second primary cancer was a particular area of interest to the researchers, particularly since they suggested the second cancers could be related to the treatment for the childhood cancers.

Among patients whose deaths were attributed to a second primary cancer, treatment with radiotherapy had a two-fold elevation in mortality.

Treatment for Childhood Cancer May Lead to Later Problems

"Second primary cancers are a recognized late complication of childhood cancer, largely due to exposure to radiation during treatment, but specific cytotoxic drugs also have been implicated in the development of second primary cancers," the authors wrote.

Treatment for childhood cancer may alse be to blame for the elevated risk of death from circulatory disorders that the researchers found. Survivors who had been treated with radiotherapy were at a twofold increased risk of circulatory death compared with survivors who had not received radiotherapy.

Death from respiratory causes also was elevated up to 45 years after a patient's initial cancer diagnosis. These deaths were particularly pronounced for patients who had been treated with chemotherapy; these patients faces a 3-fold risk of death from these causes compared with cancer survivors who had not undergone chemotherapy.

Cranial and chest irradiation have been associated with stroke and heart disease, respectively, and cancer drugs known as anthracyclines can cause cardiotoxicity.

"Finding ways to successfully intervene to reduce these potentially preventable premature deaths will be complex," the investigators warned.

They noted that a potential limitation of their study was a lack of detailed data on radiation and chemotherapy, including treatment intensity. In addition, modern anticancer treatments are considerably different than those used during the earlier years of the study, which may have influenced the results -- which means that more study will be needed to more accurately assess risks for patients treated in recent decades.