© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 8, 618-629,
April 18, 2001
© 2001 Oxford University Press
Second Malignant Neoplasms in Five-Year Survivors of Childhood Cancer: Childhood Cancer Survivor Study
Affiliations of authors: J. P. Neglia, A. C. Mertens, L. L. Robison, Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis; D. L. Friedman, Department of Pediatrics, University of Washington School of Medicine, and Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle; Y. Yasui, Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center; S. Hammond, Department of Pathology, Ohio State University School of Medicine, Columbus; M. Stovall, The University of Texas M. D. Anderson Cancer Center, Houston; S. S. Donaldson, Department of Radiation Oncology, Stanford University Medical Center, Palo Alto, CA; A. T. Meadows, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia.
Correspondence to: Joseph P. Neglia, M.D., M.P.H., MMC #484, 420 Delaware St., S.E., Minneapolis, MN 55455 (e-mail: jneglia{at}tc.umn.edu).
Background: Because survival rates among childhood cancer patients are increasing, assessing the risk of second and subsequent malignant neoplasms (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort, we identified the risk of SMNs. Methods: A retrospective cohort of 13 581 children diagnosed with common cancers before age 21 years and surviving at least 5 years was constructed with the use of data from patients treated at 25 U.S. and Canadian institutions. SMNs were ascertained through self-administered questionnaires and verified by pathology reports. Information on therapeutic exposures was abstracted from medical records. The risk of SMN was evaluated by standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple regression models were used to assess the impact of host and therapy factors on the risk of developing SMNs. All statistical tests were two-sided. Results: In 298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to 20.83], respectively). A statistically significant excess of SMNs followed all childhood cancers. In multivariate regression models adjusted for therapeutic radiation exposure, SMNs of any type were independently associated with female sex (P<.001), childhood cancer at a younger age (P for trend <.001), childhood Hodgkin's disease or soft-tissue sarcoma (P<.001 and P = .01, respectively), and exposure to alkylating agents (P for trend = .02). Twenty years after the childhood cancer diagnosis, the cumulative estimated SMN incidence was 3.2%. However, only 1.88 excess malignancies occurred per 1000 years of patient follow-up. Conclusions: Success in treating children with cancer should not be overshadowed by the incidence of SMNs. However, patients and health-care providers must be aware of risk factors for SMNs so that surveillance is focused and early prevention strategies are implemented.
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F. E. van Leeuwen, W. J. Klokman, M. Stovall, E. C. Dahler, M. B. van't Veer, E. M. Noordijk, M. A. Crommelin, B. M. P. Aleman, A. Broeks, M. Gospodarowicz, et al. Roles of Radiation Dose, Chemotherapy, and Hormonal Factors in Breast Cancer Following Hodgkin's Disease J Natl Cancer Inst, July 2, 2003; 95(13): 971 - 980. [Abstract] [Full Text] [PDF]
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P. S. Rosenberg, M. H. Greene, and B. P. Alter Cancer incidence in persons with Fanconi anemia Blood, February 1, 2003; 101(3): 822 - 826. [Abstract] [Full Text] [PDF]
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K. M. Emmons, R. M. Butterfield, E. Puleo, E. R. Park, A. Mertens, E. R. Gritz, M. Lahti, and F. P. Li Smoking Among Participants in the Childhood Cancer Survivors Cohort: The Partnership for Health Study J. Clin. Oncol., January 15, 2003; 21(2): 189 - 196. [Abstract] [Full Text] [PDF]
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O. Oberlin When Quality of Life Is the Major Challenge J. Clin. Oncol., July 15, 2002; 20(14): 3051 - 3053. [Full Text] [PDF]
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C. A. Sklar, A. C. Mertens, P. Mitby, G. Occhiogrosso, J. Qin, G. Heller, Y. Yasui, and L. L. Robison Risk of Disease Recurrence and Second Neoplasms in Survivors of Childhood Cancer Treated with Growth Hormone: A Report from the Childhood Cancer Survivor Study J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3136 - 3141. [Abstract] [Full Text] [PDF]
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S. Bhatia, H. N. Sather, O. B. Pabustan, M. E. Trigg, P. S. Gaynon, and L. L. Robison Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983 Blood, May 29, 2002; 99(12): 4257 - 4264. [Abstract] [Full Text] [PDF]
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N. S. Kadan-Lottick, L. L. Robison, J. G. Gurney, J. P. Neglia, Y. Yasui, R. Hayashi, M. Hudson, M. Greenberg, and A. C. Mertens Childhood Cancer Survivors' Knowledge About Their Past Diagnosis and Treatment: Childhood Cancer Survivor Study JAMA, April 10, 2002; 287(14): 1832 - 1839. [Abstract] [Full Text] [PDF]
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D. J. Vaughn and A. T. Meadows Cancer Survivorship Research: The Best Is Yet to Come J. Clin. Oncol., February 15, 2002; 20(4): 888 - 890. [Full Text] [PDF]
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A. C. Mertens, Y. Yasui, J. P. Neglia, J. D. Potter, M. E. Nesbit Jr, K. Ruccione, W. Anthony Smithson, and L. L. Robison Late Mortality Experience in Five-Year Survivors of Childhood and Adolescent Cancer: The Childhood Cancer Survivor Study J. Clin. Oncol., July 1, 2001; 19(13): 3163 - 3172. [Abstract] [Full Text] [PDF]
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