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Originally published as JCO Early Release 10.1200/JCO.2009.27.0090 on November 15 2010

Journal of Clinical Oncology, Vol 28, No 36 (December 20), 2010: pp. 5287-5293
© 2010 American Society of Clinical Oncology.

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Pediatric Oncology

Population-Based Risks of CNS Tumors in Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study

Aliki J. Taylor, Mark P. Little, David L. Winter, Elaine Sugden, David W. Ellison, Charles A. Stiller, Marilyn Stovall, Clare Frobisher, Emma R. Lancashire, Raoul C. Reulen, Michael M. Hawkins

From the University of Birmingham, Edgbaston, Birmingham; Imperial College, Faculty of Medicine, Norfolk Place, London; Churchill Hospital; University of Oxford, Oxford, United Kingdom; St Jude Children's Research Hospital, Memphis, TN; and University of Texas M. D. Anderson Cancer Center, Houston, TX.

Corresponding author: Michael M. Hawkins, DPhil, Centre for Childhood Cancer Survivor Studies, School of Health and Population Sciences, University of Birmingham, Public Health Building, Edgbaston, Birmingham, B15 2TT, United Kingdom; e-mail: M.M.Hawkins{at}bham.ac.uk.

Purpose CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in Britain, but the relationship of risk to doses of previous radiotherapy and chemotherapy is uncertain.

Methods The British Childhood Cancer Survivor Study is a national, population-based, cohort study of 17,980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national, population-based cancer registries identified 247 SPNs of the CNS. Cohort and nested case-control studies were undertaken.

Results There were 137 meningiomas, 73 gliomas, and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly, and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01 to 9.99, 10.00 to 19.99, 20.00 to 29.99, 30.00 to 39.99 and ≥ 40 Gy had risks that were two-fold, eight-fold, 52-fold, 568-fold, and 479-fold, respectively, the risks experienced by those whose meningeal tissue was unexposed. The risk of meningioma among individuals receiving 1 to 39,40 to 69, and at least 70 mg/m2 of intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the risk experienced by those unexposed. The standardized incidence ratio for gliomas was 10.8 (95% CI, 8.5 to 13.6). The risk of glioma/primitive neuroectodermal tumors increased linearly with dose of radiation, and those who had CNS tissue exposed to at least 40 Gy experienced a risk four-fold that experienced by those who had CNS tissue unexposed.

Conclusion The largest-ever study, to our knowledge, of CNS tumors in survivors of childhood cancer indicates that the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and with increased dose of intrathecal methotrexate.

Written on behalf of the British Childhood Cancer Survivor Study Group.

Supported in part by Cancer Research UK; the Kay Kendall Leukaemia Fund; the Department of Health and Scottish Ministers; and Contract No. FP6-036465 from the European Commission (M.P.L.).

Funding sources have had no involvement in the study design, the collection, analysis, or interpretation of data; the writing of the report; or the decision to submit the paper for publication. The views expressed in this publication are those of the authors and not necessarily those of our funders.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.


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