Journal of the National Cancer Institute Advance Access published online on May 26, 2009
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djp104
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Lifelong Cancer Incidence in 47 697 Patients Treated for Childhood Cancer in the Nordic Countries
Affiliations of authors: Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark (JHO, JFW, JC); Southern Swedish Regional Tumour Registry, Lund, Sweden (TM); Department of Cancer Epidemiology, Lund University, Lund, Sweden (HA); Cancer Registry of Norway, Oslo, Norway (FL); Finnish Cancer Registry, Helsinki, Finland (RS); Icelandic Cancer Registry, Reykjavik, Iceland (LT); Department of Pediatrics, Rigshospitalet, Copenhagen, Denmark (CR); Children's Hospital, Landspitalinn, Reykjavik, Iceland (GJ); Childhood Cancer Research Center, University Children's Hospital, Lund, Sweden (SG)
Correspondence to: Jørgen H. Olsen, MD, DMSc, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark (e-mail: jorgen{at}cancer.dk).
Background: The pattern of cancer in long-term survivors from childhood cancer has not been investigated comprehensively.
Methods: We obtained a cohort of 47 697 children and adolescents aged 0–19 years with cancer as defined by the country-wide cancer registries of Denmark, Finland, Iceland, Norway, and Sweden during 1943–2005. Cohort members were followed through age 79 years for subsequent primary cancers notified to the registries, and the age-specific risk pattern of the survivors was compared with that of the national populations using country and sex standardized incidence ratios (SIRs). We used a multiplicative Poisson regression model to estimate relative risk of cancer for attained age, with adjustment for calendar period and age at diagnosis of primary cancer. We also calculated excess absolute risk (EAR) attributable to status as childhood cancer survivor and determined the cumulative incidence of second primary cancer as a function of attained age for three subcohorts defined by period of treatment for childhood cancer.
Results: A total of 1180 asynchronous second primary cancers were observed in 1088 persons, yielding an overall SIR of 3.3 (95% confidence interval = 3.1 to 3.5). The relative risk was statistically significantly increased in all age groups, even for cohort members approaching 70 years of age. The EAR for second primary cancer among survivors increased gradually from one additional case per 1000 person-years of observation in early life to six additional cases per 1000 person-years in the age group 60–69 years. For children treated in the prechemotherapy era (1943–1959), the cumulative risk for a second primary cancer reached 18%, 34%, and 48% at ages 60, 70, and 80 years, respectively. The age-specific incidence rates were highest for cohort members treated in the era of intensive, multiple-agent chemotherapy (1975–2005).
Conclusion: Survivors of childhood cancer have a persistent excess risk for a second primary cancer throughout their lives, accompanied by continuous changes in the risk of cancers at specific sites.
| CONTEXT AND CAVEATS Prior knowledge The long-term risks of second primary cancers in survivors of childhood malignancies were not known. Study design Incidence of second primary cancers was determined based on data from national registries of the Nordic countries. Risk patterns of survivors were compared with the populations of these countries using standardized incidence ratios. Cumulative risks of a second malignancy were calculated separately for those treated in the prechemotherapy era, the first-generation chemotherapy era, and the era of combination chemotherapy. Contribution This study quantified long-term temporal patterns of increased risk of cancer at specific sites in survivors of childhood cancer. The results may be useful in the screening and care of these individuals. Cumulative risks in survivors appeared somewhat higher in those treated in the era of intensive multiple-agent chemotherapy. Implications Survivors of childhood cancers are at increased risk for second primary malignancies throughout their lives. Limitations The registries lacked data on treatment variables that might have allowed the investigators to analyze risks of second cancers associated with different types and doses of treatment. From the Editors
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The funding source was not involved in decisions regarding study design or data collection, analyses, or interpretation. All authors had final responsibility for writing of the manuscript and the decision to submit for publication.
We thank Andrea Bautz and Nick Martinussen for help with computing.
Manuscript received October 10, 2008; revised March 9, 2009; accepted March 30, 2009.
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J Natl Cancer Inst 2009 101: 769.
J Natl Cancer Inst 2009 101: 769.