This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kleinerman, R. A. Articles by Fraumeni, J. F. Search for Related Content PubMed PubMed Citation Articles by Kleinerman, R. A. Articles by Fraumeni, J. F., Jr

Risk of New Cancers After Radiotherapy in Long-Term Survivors of Retinoblastoma: An Extended Follow-Up

From the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services; International Epidemiology Institute, Rockville, MD; Ophthalmic Oncology Service, Memorial Sloan- Kettering Cancer Center, New York, NY; Massachusetts Eye and Ear Infirmary; Dana-Farber Cancer Institute, Boston, MA; and Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX

Address reprint requests to Ruth A. Kleinerman, MPH, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, EPS 7044, 6120 Executive Blvd, Rockville, MD 20852-7362; e-mail: Kleinerr{at}mail.nih.gov

PURPOSE: Many children diagnosed with retinoblastoma (Rb) survive into adulthood and are prone to subsequent cancers, particularly hereditary patients, who have germline Rb-1 mutations. We have extended the follow-up of a large cohort of Rb patients for 7 more years to provide new information on the risk of additional cancers after radiotherapy in long-term survivors.

PATIENTS AND METHODS: We analyzed the risk of new cancers through 2000 in 1,601 Rb survivors, diagnosed from 1914 to 1984, at two US medical centers. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cancers after hereditary and nonhereditary Rb to the expected number from the Connecticut Tumor Registry. The cumulative incidence of a new cancer after hereditary and nonhereditary Rb and radiotherapy was calculated with adjustment for competing risk of death.

RESULTS: Subsequent cancer risk in 963 hereditary patients (SIR, 19; 95% CI, 16 to 21) exceeded the risk in 638 nonhereditary Rb patients (SIR, 1.2; 95% CI, 0.7 to 2.0). Radiation further increased the risk of another cancer in hereditary patients by 3.1-fold (95% CI, 2.0 to 5.3). Hereditary patients continued to be at significantly increased risk for sarcomas, melanoma, and cancers of the brain and nasal cavities. The cumulative incidence for developing a new cancer at 50 years after diagnosis of Rb was 36% (95% CI, 31% to 41%) for hereditary and 5.7% (95% CI, 2.4% to 11%) for nonhereditary patients.

CONCLUSION: Hereditary Rb predisposes to a variety of new cancers over time, with radiotherapy further enhancing the risk of tumors arising in the radiation field.

Supported by N02-CP-81121 (National Cancer Institute) to Westat Inc (for field work), Rockville, MD.

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

This article has been cited by other articles:

				M. J. Eliason, C. B. Hansen, M. Hart, P. Porter-Gill, W. Chen, R. A. Sturm, G. Bowen, S. R. Florell, R. M. Harris, L. A. Cannon-Albright, et al. Multiple Primary Melanomas in a CDKN2A Mutation Carrier Exposed to Ionizing Radiation Arch Dermatol, November 1, 2007; 143(11): 1409 - 1412. [Abstract] [Full Text] [PDF]

				M. Chintagumpala, P. Chevez-Barrios, E. A. Paysse, S. E. Plon, and R. Hurwitz Retinoblastoma: Review of Current Management Oncologist, October 1, 2007; 12(10): 1237 - 1246. [Abstract] [Full Text] [PDF]

				S. Lee, J. Jeong, T. Majewski, S. E. Scherer, M.-S. Kim, T. Tuziak, K. S. Tang, K. Baggerly, H. B. Grossman, J.-H. Zhou, et al. Forerunner genes contiguous to RB1 contribute to the development of in situ neoplasia PNAS, August 21, 2007; 104(34): 13732 - 13737. [Abstract] [Full Text] [PDF]

				S. Guerin, M. Hawkins, A. Shamsaldin, C. Guibout, I. Diallo, O. Oberlin, L. Brugieres, and F. de Vathaire Treatment-Adjusted Predisposition to Second Malignant Neoplasms After a Solid Cancer in Childhood: A Case-Control Study J. Clin. Oncol., July 1, 2007; 25(19): 2833 - 2839. [Abstract] [Full Text] [PDF]

				E. M. Chung, C. S. Specht, and J. W. Schroeder From the Archives of the AFIP: Pediatric Orbit Tumors and Tumorlike Lesions: Neuroepithelial Lesions of the Ocular Globe and Optic Nerve RadioGraphics, July 1, 2007; 27(4): 1159 - 1186. [Abstract] [Full Text] [PDF]

				A. T. Meadows Retinoblastoma Survivors: Sarcomas and Surveillance J Natl Cancer Inst, January 3, 2007; 99(1): 3 - 5. [Full Text] [PDF]

				R. A. Kleinerman, M. A. Tucker, D. H. Abramson, J. M. Seddon, R. E. Tarone, and J. F. Fraumeni Jr Risk of Soft Tissue Sarcomas by Individual Subtype in Survivors of Hereditary Retinoblastoma J Natl Cancer Inst, January 3, 2007; 99(1): 24 - 31. [Abstract] [Full Text] [PDF]

				A. T. Meadows Pediatric Cancer Survivorship: Research and Clinical Care J. Clin. Oncol., November 10, 2006; 24(32): 5160 - 5165. [Abstract] [Full Text] [PDF]

				J. R. Elison, D. Cobrinik, N. Claros, D. H. Abramson, and T. C. Lee Small Molecule Inhibition of HDM2 Leads to p53-Mediated Cell Death in Retinoblastoma Cells. Arch Ophthalmol, September 1, 2006; 124(9): 1269 - 1275. [Abstract] [Full Text] [PDF]

				M. C. Foster, R. A. Kleinerman, D. H. Abramson, J. M. Seddon, R. E. Tarone, and M. A. Tucker Tobacco Use in Adult Long-term Survivors of Retinoblastoma. Cancer Epidemiol. Biomarkers Prev., August 1, 2006; 15(8): 1464 - 1468. [Abstract] [Full Text] [PDF]

				N. Gonin-Laurent, A. Gibaud, M. Huygue, S. H. Lefevre, M. Le Bras, L. Chauveinc, X. Sastre-Garau, F. Doz, L. Lumbroso, S. Chevillard, et al. Specific TP53 mutation pattern in radiation-induced sarcomas Carcinogenesis, June 1, 2006; 27(6): 1266 - 1272. [Abstract] [Full Text] [PDF]

				L. B. Travis, C. S. Rabkin, L. M. Brown, J. M. Allan, B. P. Alter, C. B. Ambrosone, C. B. Begg, N. Caporaso, S. Chanock, A. DeMichele, et al. Cancer Survivorship--Genetic Susceptibility and Second Primary Cancers: Research Strategies and Recommendations J Natl Cancer Inst, January 4, 2006; 98(1): 15 - 25. [Abstract] [Full Text] [PDF]

				D. H. Abramson Retinoblastoma in the 20th Century: Past Success and Future Challenges The Weisenfeld Lecture Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2684 - 2691. [Full Text] [PDF]