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Original Contribution
July 14, 2010

Long-term Cause-Specific Mortality Among Survivors of Childhood Cancer

Author Affiliations

Author Affiliations: Centre for Childhood Cancer Survivor Studies, School of Health and Population Sciences, University of Birmingham, Edgbaston, United Kingdom (Drs Reulen, Frobisher, Lancashire, and Hawkins and Mr Winter); Childhood Cancer Research Group, University of Oxford, Oxford, United Kingdom (Mr Stiller); Children's Hospital for Wales, Cardiff, United Kingdom (Dr Jenney); Department of Paediatric and Adolescent Oncology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (Dr Skinner); and Institute of Child Life and Health, University of Bristol, Bristol, United Kingdom (Dr Stevens).

JAMA. 2010;304(2):172-179. doi:10.1001/jama.2010.923

Context Survivors of childhood cancer are at increased risk of premature mortality compared with the general population, but little is known about the long-term risks of specific causes of death, particularly beyond 25 years from diagnosis at ages when background mortality in the general population starts to increase substantially.

Objective To investigate long-term cause-specific mortality among 5-year survivors of childhood cancer in a large-scale population-based cohort.

Design, Setting, and Patients British Childhood Cancer Survivor Study, a population-based cohort of 17 981 5-year survivors of childhood cancer diagnosed with cancer before age 15 years between 1940 and 1991 in Britain and followed up until the end of 2006.

Main Outcome Measures Cause-specific standardized mortality ratios (SMRs) and absolute excess risks (AERs).

Results Overall, 3049 deaths were observed, which was 11 times the number expected (SMR, 10.7; 95% confidence interval [CI], 10.3-11.1). The SMR declined with follow-up but was still 3-fold higher than expected (95% CI, 2.5-3.9) 45 years from diagnosis. The AER for deaths from recurrence declined from 97 extra deaths (95% CI, 92-101) per 10 000 person-years at 5 to 14 years from diagnosis, to 8 extra deaths (95% CI, 3-22) beyond 45 years from diagnosis. In contrast, during the same periods of follow-up, the AER for deaths from second primary cancers and circulatory causes increased from 8 extra deaths (95% CI, 7-10) and 2 extra deaths (95% CI, 2-3) to 58 extra deaths (95% CI, 38-90) and 29 extra deaths (95% CI, 16-56), respectively. Beyond 45 years from diagnosis, recurrence accounted for 7% of the excess number of deaths observed while second primary cancers and circulatory deaths together accounted for 77%.

Conclusion Among a cohort of British survivors of childhood cancer, excess mortality from second primary cancers and circulatory diseases continued to occur beyond 25 years from diagnosis.