Among a cohort of British survivors of childhood cancer, excess mortality from second primary cancers, as well as from cardiac and cerebrovascular diseases, continued to occur beyond 25 years from diagnosis, according to a study in the July 14 issue of Journal of the American Medical Association.
"Over recent decades, survival from childhood cancer has improved dramatically, yet mortality rates in childhood cancer survivors continue to be elevated for many years beyond five-year survival compared with the general population," the authors wrote. "Although studies have shown that the risk of death from recurrence decreases with increasing time since five-year survival, uncertainty about the long-term risks of death from other causes remains." It is also uncertain if increased mortality risks persist beyond 25 years from initial cancer diagnosis.
Raoul C. Reulen, PhD, from the Centre for Childhood Cancer Survivor Studies at the University of Birmingham in Birmingham, England, and colleagues examined the long-term cause-specific mortality among 17,981 five-year survivors of childhood cancer, who were diagnosed with cancer before age 15 years between 1940 and 1991 in Britain and followed up until the end of 2006.
Overall, there were 3,049 deaths during the study period. The researchers reported that survivors experienced 11 times the number of deaths expected from the general population (standardized mortality ratio, 10.7). The standardized mortality ratio declined with follow-up but was still three-fold higher than expected 45 years from diagnosis.
The absolute excess risk for deaths from recurrence declined from diagnosis at age five to 14 years to beyond 45 years from diagnosis, the investigators said. In contrast, during the same periods of follow-up, the absolute excess risk for deaths from second primary cancers and circulatory disease—such as from cardiac and cerebrovascular deaths—increased, with survivors after 45 years experiencing 3.6 times the number of deaths expected from the general population for a second primary cancer, and nearly 26 percent of all excess deaths beyond 45 years from diagnosis attributed to circulatory disease.
During the same periods of follow-up, according to the authors, the AER for deaths from second primary tumor, circulatory deaths and cardiac deaths increased from eight, two and one extra deaths to 58, 28 and 15 extra deaths, respectively.
"Beyond 45 years from diagnosis, recurrence accounted for 7 percent of the excess number of deaths observed while second primary cancers and circulatory deaths together accounted for 77 percent," the authors wrote.
The researchers added that the excess mortality due to second primary cancer and circulatory disease is likely attributable to late complications of treatment. "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," they wrote.
"These findings confirm the importance of very long-term outcome data and that survivors should be able to access healthcare programs even decades after treatment,” the authors concluded. “[T]he principal clinical message from these data is straightforward: 77 percent of the excess number of deaths observed among those surviving beyond 45 years from diagnosis of childhood cancer in Britain are due to second primary cancers and circulatory deaths."
They added that finding ways to “successfully intervene to reduce these potentially preventable premature deaths will be complex.”