Journal of the National Cancer Institute Advance Access originally published online on April 7, 2009
JNCI Journal of the National Cancer Institute 2009 101(8):581-591; doi:10.1093/jnci/djp046
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Published by Oxford University Press 2009.
ARTICLES |
Cause-Specific Mortality in Long-Term Survivors of Retinoblastoma
Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD (C-LY, MAT, JFF, RAK); Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (DHA); Department of Statistics, Radiation Effects Research Foundation, Hiroshima, Japan (KF); Ophthalmic Epidemiology & Genetics Service, Tufts-New England Medical Center, Boston, MA (JMS); Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (MS)
Correspondence to: Chu-Ling Yu, ScD, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Blvd MSC 7238, Rockville, MD 20892-7238 (e-mail: yuchu{at}mail.nih.gov).
Background: Subsequent malignant neoplasms are a major cause of premature death in survivors of hereditary retinoblastoma. Radiotherapy further increases the risk of death. Mortality information is limited among long-term survivors who were irradiated for hereditary retinoblastoma.
Methods: We examined cause-specific mortality among 1854 retinoblastoma survivors who were diagnosed from January 1, 1914, through December 31, 1996, at two US institutions. Standardized mortality ratios (SMRs) were calculated by use of US mortality data to estimate expected numbers of deaths. The relative rates (RRs) of mortality due to subsequent malignant neoplasms associated with multiple risk factors were evaluated with Poisson regression models. Cumulative mortality from subsequent malignant neoplasms was calculated by treating other causes of death as competing risks.
Results: A total of 151 deaths due to subsequent malignant neoplasms occurred among 1092 hereditary retinoblastoma survivors (SMR = 35, 95% confidence interval [CI] = 30 to 41) compared with 12 deaths among 762 nonhereditary retinoblastoma survivors (SMR = 2.5, 95% CI = 1.3 to 4.4). In this extended follow-up of retinoblastoma survivors, we found no evidence of excess mortality from non-neoplastic causes compared with the general population. However, excess mortality from subsequent malignant neoplasms (particularly sarcomas, melanomas, and cancers of the brain and other parts of the nervous system) among hereditary retinoblastoma survivors extended beyond 40 years after retinoblastoma diagnosis. The additional 13 years of follow-up since our last mortality study revealed a previously unreported increased risk of death due to cancers of the corpus uteri (primarily sarcomas) and confirmed the previously reported elevated risk of death from lung cancer among hereditary retinoblastoma survivors. Among hereditary and nonhereditary retinoblastoma survivors, the relative rates of mortality from subsequent malignant neoplasm were higher in those who had been treated with radiotherapy than in those who had not. Cumulative mortality from subsequent malignant neoplasms at 50 years after retinoblastoma diagnosis was 25.5% (95% CI = 20.8% to 30.2%) for hereditary retinoblastoma survivors and 1.0% (95% CI = 0.2% to 1.8%) for nonhereditary retinoblastoma survivors.
Conclusions: The temporal patterns of site-specific excess risks of subsequent malignant neoplasms in retinoblastoma survivors should inform screening programs designed for the early detection and treatment of subsequent malignant neoplasms.
| CONTEXT AND CAVEATS Prior knowledge Many survivors of hereditary retinoblastoma (ie, survivors who carry a germline mutation in the retinoblastoma [RB1] gene) die prematurely from subsequent malignant neoplasms, and those who were treated with radiotherapy have an even higher risk of premature death from subsequent malignant neoplasms compared with the general population. Study design Mortality data for 1854 long-term survivors of hereditary and nonhereditary retinoblastoma were used to quantify cause-specific mortality and to evaluate interactions between hereditary status and treatment with radiotherapy. Contribution Compared with the general population, hereditary retinoblastoma survivors had increased risks of death from subsequent malignant neoplasms (particularly sarcomas, melanomas, and cancers of the brain and other parts of the nervous system) that extended beyond 40 years after retinoblastoma diagnosis, as well as for cancers of the corpus uteri (primarily sarcomas), and lung cancer. Among hereditary and nonhereditary retinoblastoma survivors, the relative rates of mortality from subsequent malignant neoplasm were higher in those who had been treated with radiotherapy than in those who had not. Implications The temporal patterns of site-specific excess risks of subsequent malignant neoplasms in retinoblastoma survivors should inform screening programs designed for the early detection and treatment of subsequent malignant neoplasms. Limitations In some cases, the cause of death listed on death certificates may have been inaccurate and nonfatal cancers could have been missed. From the Editors
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Manuscript received July 17, 2008; revised January 21, 2009; accepted February 12, 2009.
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J Natl Cancer Inst 2009 101: 539.