Cancer mortality in long-term survivors of retinoblastoma
Introduction
Retinoblastoma is a rare childhood cancer of the eye. The disease is caused by a RB1 gene mutation in all patients with bilateral retinoblastoma, as well as in 10% of those with unilateral retinoblastoma.1 Nowadays children diagnosed with retinoblastoma in the western world have excellent cure rates (up to 99%).2 However, hereditary retinoblastoma survivors are at an exceptionally high risk of developing subsequent primary malignancies in childhood and adolescence.3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 So far, little information is available on long-term excess mortality among survivors of retinoblastoma.7, 14, 15 Published studies include few patients with more than 50 years of follow-up, implying that mortality risk of retinoblastoma survivors has been hardly examined at ages during which death rates increase in the general population.
The national retinoblastoma registry of the Netherlands includes 1068 retinoblastoma patients diagnosed since 1862. Therefore, the registry offers a unique opportunity to analyse cause-specific mortality after long-term follow-up in a large group of retinoblastoma survivors, according to treatment and heredity.
Section snippets
Study population
The cohort analysed in this study has been described previously.13 In brief, the cohort includes 1068 Dutch retinoblastoma patients diagnosed from 1862 to 2005. For each patient data were collected concerning demography, family history of retinoblastoma, tumour laterality, treatment for retinoblastoma (including radiotherapy fields and energy type, and chemotherapeutic agents), second and subsequent cancers and date and (underlying) cause of death. If a cohort member had died, the date, the
Results
Table 1 shows the general characteristics of the study population; retinoblastoma patients diagnosed between 1862 and 2005, who were at risk of death between January 1901 and June 2007. The median follow-up time for hereditary retinoblastoma survivors was 25.8 years (range = 0.13–79.9 years). For non-hereditary retinoblastoma survivors, the median follow-up was 34.2 years (range = 0.01–89.7 years). Most of the hereditary patients (56.2%) were treated with radiotherapy for their retinoblastoma,
Discussion
To our knowledge, this is the first study that evaluates mortality among retinoblastoma patients in a nationwide cohort with very long-term follow-up and near complete cause of death information. Statistically significantly elevated risks of death were only found for second malignancies among hereditary retinoblastoma survivors, with an almost 13-fold increase of second malignancy death compared with general population expectations. During follow-up, the AER increased and amounted to 23.2
Conflict of interest statement
None declared.
Acknowledgements
We are grateful to Drs. Willem J. Klokman, senior statistical analyst, for his statistical support. We thank Prof. Dr. Johan P. Mackenbach for the historical mortality reference rates.
The study was supported by award VU 2004-3046 from the Dutch Cancer Society. The Dutch Cancer Society had no role in the design and conduct of the study, the collection, management, analysis and interpretation of the data, or in the preparation, review and approval of the manuscript, other than with respect to the
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