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Cited by 286Ocular Oncology and TreatmentsMultiple and Secondary Primary CancersChildhood Cancer Survivors' Quality of Life

Risk of Second Malignancies in Survivors of Retinoblastoma: More Than 40 Years of Follow-up

Marees, Tamara, Moll, Annette C., Imhof, Saskia M., de Boer, Michiel R., Ringens, Peter J., van Leeuwen, Flora E.·2008·JNCI: Journal of the National Cancer Institute
DOI 10.1093/jnci/djn394
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Abstract

BACKGROUND: Survivors of hereditary retinoblastoma have an elevated risk of developing second malignancies, but data on the risk in middle-aged retinoblastoma survivors (ie, those with more than 40 years of follow-up) are scarce. METHODS: Data from the Dutch retinoblastoma registry were used to analyze risks of second malignancies in 668 retinoblastoma survivors, diagnosed from 1945 to 2005 (median age = 24.9 years) and classified as having had hereditary or nonhereditary disease based on the presence of family history, bilateral disease, or a germline RB1 mutation. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) of subsequent cancers in patients with hereditary and nonhereditary disease were estimated by comparison with Dutch sex-, age-, and calendar year-specific rates. Multivariable Cox regression and competing risk analyses were used to determine associations of treatment with risks of second malignancies. All statistical tests were two-sided. RESULTS: After a median follow-up of 21.9 years, the risk of second malignancies in survivors of hereditary retinoblastoma (SIR = 20.4, 95% confidence interval [CI] = 15.6 to 26.1) far exceeded the risk of survivors of nonhereditary retinoblastoma (SIR = 1.86, 95% CI = 0.96 to 3.24). Among patients with hereditary disease, treatment with radiotherapy was associated with a further increase in the risk of a subsequent cancer (hazard ratio = 2.81, 95% CI = 1.28 to 6.19). After 30 years of follow-up, elevated risks of epithelial cancers (lung, bladder, and breast) were observed among survivors of hereditary retinoblastoma. After 40 years of follow-up, the AER of a second malignancy among survivors of hereditary retinoblastoma had increased to 26.1 excess cases per 1000 person-years. The cumulative incidence of any second malignancy 40 years after retinoblastoma diagnosis was 28.0% (95% CI = 21.0% to 35.0%) for patients with hereditary disease. CONCLUSION: Our analysis of middle-aged hereditary retinoblastoma survivors suggests that these individuals have an excess risk of epithelial cancer. Lifelong follow-up studies are needed to evaluate the full spectrum of subsequent cancer risk in hereditary retinoblastoma survivors.

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Crossref · 10.1093/jnci/djn394

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  • Patients with germline TP53 mutations and hereditary retinoblastoma are at particularly high risk for developing radiation-associated sarcomas.

    “Patients with germline TP53 mutations as well as hereditary retinoblastoma are at particularly high risk for developing radiation-associated sarcomas and, therefore, radiation should be avoided in these individuals 123,124 .”

    From Osteosarcoma (2022) · cites this paper as [123]

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Authors
Marees, T., Moll, A. C., Imhof, S. M., de Boer, M. R., Ringens, P. J., & van Leeuwen, F. E.
Affiliations
Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
ORCID
Venue
JNCI: Journal of the National Cancer Institute
Publisher
Oxford University Press (OUP)
Published
2008-12-17
Volume
100
Issue
24
Pages
1771-1779
ISSN
  • 0027-8874 (ISSN-L)
  • 1460-2105
DOI
10.1093/jnci/djn394
OpenAlex
W2140618265
Cited by
286
References
52
Citations by year
2026: 5 · 2025: 13 · 2024: 12 · 2023: 7 · 2022: 9 · 2021: 24 · 2020: 15 · 2019: 14 · 2018: 16 · 2017: 15 · 2016: 21 · 2015: 21 · 2014: 26 · 2013: 17 · 2012: 14
FWCI
19.23
Type
journal article
Language
en
Open access
closed
Locations
  • JNCI Journal of the National Cancer Institute (publishedVersion)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • VU Research Portal (publishedVersion)
  • Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
  • Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Childhood Cancer Survivors' Quality of Life
Keywords
retinoblastoma survivors, secondary malignancies, hereditary retinoblastoma, radiotherapy, cancer risk, epithelial cancers, lung cancer, bladder cancer, breast cancer, long-term follow-up, cumulative incidence, competing risks, treatment-related cancer risk
MeSH terms
Adolescent, Adult, Aged, Urinary Bladder Neoplasms, Breast Neoplasms, Carcinoma, Female, Follow-Up Studies, Humans, Lung Neoplasms, Male, Middle Aged, Netherlands, Radiotherapy, Registries, Retinoblastoma, Risk Factors, Time Factors, Confounding Factors, Epidemiologic, Incidence, Multivariate Analysis, Confidence Intervals, Proportional Hazards Models, Odds Ratio, Retinoblastoma Protein, Neoplasms, Second Primary, Survivors, Germ-Line Mutation, Risk Assessment, Retinal Neoplasms, Genetic Predisposition to Disease, Young Adult

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