Second nonocular tumors in survivors of bilateral retinoblastoma: A possible age effect on radiation-related risk

doi:10.1016/S0161-6420(98)94006-4

Ophthalmology

Volume 105, Issue 4, 1 April 1998, Pages 573-580

Presented in part at the International Symposium on Ocular Tumors, Jerusalem, Israel, April 6–10, 1997; at the Cornell Ophthalmology Alumni Meeting, New York City, May 2, 1997; and at the Association for Research in Vision and Ophthalmology Meeting, Ft. Lauderdale, Florida, May 11–16, 1997.

https://doi.org/10.1016/S0161-6420(98)94006-4 Get rights and content

Abstract

Objective

This study aimed to investigate the relationship in bilateral retinoblastoma survivors between the incidence of second tumors and the age when external beam radiation (EBR) was used.

Design

A retrospective analysis of patients diagnosed with retinoblastoma was performed by examining records for background information and treatment information as well as reviewing documentation of patients with second nonocular tumors. Two telephone interviews were conducted for follow-up as well as inquiries directed to tumor registries and state databases.

Participants

The original study included 1729 patients treated in New York and Boston; the current study includes only the 1506 patients treated in New York. Of those, 816 patients were diagnosed with bilateral retinoblastoma, had sufficient treatment data to be useful, and survived at least 1 year from diagnosis.

Main outcome measures

The subjects were observed for evidence of the development of second nonocular tumors.

Results

There was a significant decrease in tumor-free survival among patients treated with EBR before the age of 12 months, but no significant difference between the group treated with EBR after the age of 12 months and the group not treated with EBR. For tumors in the field of radiation, patients treated with early EBR showed a significant decrease in tumor-free survival when compared to patients treated with late EBR, with no significant difference between late radiation and no radiation. There were no significant differences between groups for tumors out of the field of radiation. Significant differences attributable to the use of EBR were found only for tumors of the skull and face bones and for tumors of the soft tissue of the head.

Conclusions

The long-term effect of radiation treatment on survivors of bilateral retinoblastoma is to increase the incidence and affect the distribution of second tumors. However, no increased risk is observed for tumors out of the field of radiation among patients who underwent radiation, and the risk for tumors in the field of radiation is heavily dependent on the age at which EBR is given and may be acceptably small to the patient after the age of 12 months.

Section snippets

Methods

This study is based on a population of 1729 patients with retinoblastoma identified from medical records on file at various hos pitals and medical centers in Boston (1937–1984) and New York (1914–1984). A previous report3 contains a complete description of the methods used to locate survivors and document deaths. Briefly, information on date of birth, retinoblastoma laterality, diagnosis, treatment history, and second neoplasms was collected from patient medical charts and confirmed with

Results

Of the 816 1-year survivors of bilateral retinoblastoma, 446 (55%) were male and 370 (45%) were female. Overall followup was 90.3%, and there were no large differences in followup between groups, with the percentage that could be located or their death confirmed as 10% for patients not irradiated, 8% for patients irradiated before the age of 12 months, and 11% for patients irradiated at or after the age of 12 months. Age at follow-up ranged from 1 to 62 years, with a median of 23 years of age

Discussion

In our population of patients with bilateral retinoblastoma, more than half are estimated to develop a second primary neoplasm by the age of 50. Previous reports on this series and on other series consistently have shown an elevated risk of second nonocular tumors in patients with germinal retinoblastoma, particularly osteogenic sarcomas of the skull and long bones, soft tissue sarcomas, cutaneous melanomas, and pinealoblastomas.3, 4, 6, 8 Furthermore, a recent report on the series of which

References (25)

D.H. Abramson et al.
Second tumors in nonirradiated bilateral retinoblastoma
Am J Ophthalmol
(1979)
D.H. Abramson et al.
Second nonocular tumors in retinoblastoma survivorsare they radiation-induced?
Ophthalmology
(1984)
J.D. Roarty et al.
Incidence of second neoplasms in patients with bilateral retinoblastoma
Ophthalmology
(1988)
C. Kupfer
Retinoblastoma treated with intravenous nitrogen mustard
Am J Ophthalmol
(1953)
A.B. Reese et al.
The treatment of retinoblastoma by radiation and triethylene melamine
Am J Ophthalmol
(1957)
M.J. Greenwald et al.
Treatment of intraocular retinoblastoma with carboplatin and etoposide chemotherapy
Ophthalmology
(1996)
L.E. Blach et al.
Trilateral retinoblastoma—incidence and outcomea decade of experience
Int J Radiat Oncol Biol
(1994)
C. Eng et al.
Mortality from second tumors among long-term survivors of retinoblastoma
J Natl Cancer Inst
(1993)
A.C. Moll et al.
Second primary tumors in patients with hereditary retinoblastomaa register-based followup study, 1945-1994
Int J Cancer
(1996)
G.J. Draper et al.
Patterns of risk of hereditary retinoblastoma and applications to genetic counseling
Br J Cancer
(1992)

G.T. Lueder et al.

Second nonocular tumors in survivors of heritable retinoblastoma

Arch Ophthalmol

(1986)

D.J. DerKinderen et al.

Nonocular cancer in patients with hereditary retinoblastoma and their relatives

Int J Cancer

(1988)

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Second nonocular tumors in survivors of bilateral retinoblastoma: A possible age effect on radiation-related risk

Abstract

Objective

Design

Participants

Main outcome measures

Results

Conclusions

Section snippets

Methods

Results

Discussion

Am J Ophthalmol

Ophthalmology

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Int J Radiat Oncol Biol

Mortality from second tumors among long-term survivors of retinoblastoma

J Natl Cancer Inst

Second primary tumors in patients with hereditary retinoblastomaa register-based followup study, 1945-1994

Int J Cancer

Patterns of risk of hereditary retinoblastoma and applications to genetic counseling

Br J Cancer

Second nonocular tumors in survivors of heritable retinoblastoma

Arch Ophthalmol

Nonocular cancer in patients with hereditary retinoblastoma and their relatives

Int J Cancer