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© The Author 2007. Published by Oxford University Press.
ARTICLES |
Risk of Second Malignant Neoplasms After Childhood Leukemia and Lymphoma: An International Study
Affiliations of authors: Childhood Cancer Registry of Piedmont, Cancer Epidemiology Unit, Centro di Riferimento per l’Epidemiologia e la Prevenzione Oncologica in Piemonte, Centro di Ricerca in Medicina Sperimentale, University of Turin, Turin, Italy (MM, GP, FM); Division of Pediatrics, Department of Medical Sciences, University of Eastern Piedmont at Novara, Novara, Italy (GP); International Agency for Research on Cancer, Lyon, France (GS, P. Brennan, P. Boffetta); Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany (KH); Center of Family Medicine, Karolinska Institutet, Huddinge, Sweden (KH); New South Wales Cancer Registry, Eveleigh, New South Wales, Australia (ET); Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland (RS); The Cancer Registry of Norway, Oslo, Norway (EW); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (EW); Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark (JHO); British Columbia Cancer Agency, Vancouver, BC, Canada (MLM); Scottish Cancer Registry, Information Services Division, NHS National Services Scotland, Edinburgh, UK (DHB); Cancer Registry of Slovenia, Institute of Oncology, Ljubljana, Slovenia (VPK); Epidemiology and Cancer Registry, CancerCare Manitoba, Winnipeg, MB, Canada (EVK); Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada (EVK); Center for Molecular Epidemiology, Singapore (KSC); Singapore Cancer Registry, Singapore (KSC); Saskatchewan Cancer Agency, Regina, SK, Canada (JMT); Cancer Registry of Zaragoza, Health Department of Aragon Government, Zaragoza, Spain (CM); Icelandic Cancer Registry, Icelandic Cancer Society, Reykjavik, Iceland (JGJ); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (JGJ)
Correspondence to: Milena Maule, PhD, Childhood Cancer Registry of Piedmont, Cancer Epidemiology Unit, CPO Piemonte, CeRMS, University of Turin, Via Santena 7, 10126, Turin, Italy (e-mail: milena.maule{at}unito.it).
Background: Survivors of childhood leukemia and lymphoma experience high risks of second malignant neoplasms. We quantified such risk using a large dataset from 13 population-based cancer registries.
Methods: The registries provided individual data on cases of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma occurring in children aged 0–14 years and on subsequent second malignant neoplasms for different time periods from 1943 to 2000. Risks of second malignant neoplasms were assessed through standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs), using the incidence rates in the general populations covered by the registries as a reference. Cumulative absolute risks were also calculated.
Results: A total of 133 second malignant neoplasms were observed in 16 540 patients (12 731 leukemias, 1246 Hodgkin lymphomas, and 2563 non-Hodgkin lymphomas) after an average follow-up of 6.5 years. The most frequent second malignancies after leukemia were brain cancer (19 cases, SIR = 8.52, 95% CI = 5.13 to 13.3), non-Hodgkin lymphoma (nine cases, SIR = 9.41, 95% CI = 4.30 to 17.9), and thyroid cancer (nine cases, SIR = 18.8, 95% CI = 8.60 to 35.7); the most frequent after Hodgkin lymphoma were thyroid cancer (nine cases, SIR = 52.5, 95% CI = 24.0 to 99.6), breast cancer (six cases, SIR = 20.9, 95% CI = 7.66 to 45.4), and neoplasms of skin (non-melanoma) (six cases, SIR = 34.0, 95% CI = 12.5 to 74.0); and the most frequent after non-Hodgkin lymphoma were thyroid cancer (six cases, SIR = 40.4, 95% CI = 14.8 to 88.0) and brain cancer (four cases, SIR = 6.97, 95% CI = 1.90 to 17.9). Cumulative incidence of any second malignant neoplasm was 2.43% (95% CI = 1.09 to 3.78), 12.7% (95% CI = 8.29 to 17.2), and 2.50% (95% CI = 1.04 to 3.96) within 30 years from diagnosis of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma, respectively.
Conclusions: This population-based study provides, to our knowledge, the most precise and up-to-date estimates for relative and absolute risks of second malignant neoplasms after childhood leukemia and lymphoma.
| CONTEXT AND CAVEATS Prior knowledge The population of survivors of childhood cancer is growing and aging. Hematolymphopoietic malignancies are among the most common cancers of childhood. Study design Population-based registry study in which 13 registries from around the world provided individual data on more than 16500 survivors of childhood leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma. Rates of second malignancies in survivors were compared with those in the general populations covered by the registries. Contributions After an average follow-up of 6.5 years, survivors had almost seven times the risk of a second malignant neoplasm than the general population. The most frequent second malignancies after leukemia were brain cancer, non-Hodgkin lymphoma, and thyroid cancer; after Hodgkin lymphoma were thyroid cancer, female breast cancer, and nonmelanoma skin cancer; and after non-Hodgkin lymphoma were thyroid cancer and brain cancer. Cumulative incidence of any second cancer 30 years after diagnosis of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma was 2.4%, 12.7%, and 2.5%, respectively. Implications Survivors of hematolymphopoietic neoplasms are at increased risk of second cancers, with survivors of Hodgkin lymphoma at particularly high risk. Both relative and absolute risks could be evaluated in this large and geographically diverse study. Limitations Individual treatment information was not available from the registries. Because of small numbers and multiple comparisons, some associations may have arisen by chance. Some misclassification is possible.
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Manuscript received July 21, 2006; revised February 15, 2007; accepted March 27, 2007.
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J Natl Cancer Inst 2007 99: 741.
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