Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation

doi:10.1016/j.ophtha.2004.04.016

Ophthalmology

Volume 111, Issue 10, October 2004, Pages 1917-1924

https://doi.org/10.1016/j.ophtha.2004.04.016 Get rights and content

Abstract

Purpose

To evaluate the causes of chemoreduction failure in retinoblastoma and to analyze the associated factors for eventual treatment with external beam radiotherapy and enucleation.

Design

Prospective noncomparative case series.

Participants

Seventy-one patients with 105 eyes with intraocular retinoblastoma that underwent chemoreduction therapy between October 1998 and January 2003.

Intervention

A 6-treatment cycle of chemoreduction therapy with vincristine, etoposide, and carboplatin was administered at monthly intervals. Unresponsive disease was defined as persistence of retinal tumors, vitreous seeds, or subretinal seeds after the second treatment cycle, with no appreciable sign of regression. Eyes with unresponsive disease were enucleated after the second treatment. Eyes that responded to chemoreduction therapy received focal treatment, including indirect laser photocoagulation, transpupillary thermotherapy, cryotherapy, and ruthenium 106 episcleral plaque radiotherapy after the second chemoreduction treatment, if necessary, to achieve complete tumor regression. Recurrence was defined as the regrowth of retinal tumors, vitreous or subretinal seeds after an initial favorable response, and regression. Recurrent retinal tumor, vitreous seeds, or subretinal seeds were treated with focal treatments and 2 to 3 additional chemoreduction treatments. When these methods failed or were not applicable, external beam radiotherapy and/or enucleation was administered.

Main outcome measures

The use of external beam radiotherapy and enucleation for chemoreduction failure, which was defined as unresponsive or recurrent disease.

Results

The mean follow-up was 25.7 months (range: 6–49). Ten of 105 eyes (9.5%) with unresponsive disease were enucleated after the second treatment. Of the remaining 95 eyes, 42 (44.2%) developed recurrence after chemoreduction. Recurrent disease failing to be treated successfully by other methods was treated with external beam radiotherapy in 26 of 95 eyes (27.4%) and enucleation in 22 of 95 eyes (23.2%). External beam radiotherapy was successful in preventing enucleation in 20 of 26 eyes (76.9%). Overall, the globe salvage rate was 69.5%, ranging from 36.1% for Reese–Ellsworth group V disease to 87.0% for groups I to IV disease. Histopathologically, 29 of 31 enucleated eyes (93.5%) had poorly differentiated or moderately differentiated retinoblastoma. Using multivariate logistic regression analysis, factors predictive of eventual treatment with external beam radiotherapy were female gender (P = 0.010), presence of subretinal seeds (P = 0.023), and a greater number of chemoreduction treatments (P = 0.027). By multivariate analysis, the factors associated with the need for eventual treatment with enucleation were recurrence of retinal tumors (P = 0.004), presence of vitreous seeds (P = 0.008), greater tumor thickness (P = 0.015), presence of subretinal fluid (P = 0.040), and older patient age (P = 0.042).

Conclusions

Chemoreduction failure in this article was defined as unresponsive or, more commonly, recurrent retinoblastoma. Older patient age, greater tumor thickness, presence of vitreous seeds and subretinal fluid at baseline, and retinal tumor recurrence after chemoreduction were factors associated with the need for enucleation.

Section snippets

Materials and methods

Between October 1998 and January 2003, 105 eyes of 71 patients with intraocular retinoblastoma underwent chemoreduction treatment. The chemoreduction protocol was approved by the pediatric oncology review board. Informed consent was obtained from all patients. The chemotherapeutic agents employed in the protocol included IV vincristine, etoposide, and carboplatin, as shown in Table 1. Chemoreduction therapy consisted of 6 treatments administered at monthly intervals. Examination under

Results

Of the 71 patients included in this study, 40 had bilateral retinoblastoma, and 31 had unilateral retinoblastoma. A total of 105 eyes were included in the study. Ten patients had a family history of retinoblastoma. Six eyes of 6 patients with bilateral retinoblastoma had been enucleated elsewhere because of advanced intraocular disease before being referred to us. Of the 71 patients, 35 were male and 36 were female. The mean age of the patients was 20.8 months (range: 2–96).

The distribution of

Discussion

The use of chemotherapy in the treatment of intraocular retinoblastoma dates back nearly 50 years. Intravenous nitrogen mustard was the first chemotherapeutic drug used in the management of this condition.15, 16 Later, improved ocular salvage rates using intracarotid triethylenemelamine in combination with external beam radiotherapy were reported.17 Since that time, there have been several reports on the use of chemotherapy, particularly for extraocular retinoblastoma.18, 19, 20 The use of

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Original articleCauses of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation☆

Abstract

Purpose

Design

Participants

Intervention

Main outcome measures

Results

Conclusions

Section snippets

Materials and methods

Results

Discussion

Ophthalmology

Ophthalmology

Surv Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Chemoreduction in the initial management of intraocular retinoblastoma

Arch Ophthalmol

Chemotherapy plus local treatment in the management of intraocular retinoblastoma

Arch Ophthalmol

Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy

Arch Ophthalmol

Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma

Arch Ophthalmol

Role of chemotherapy alone or in combination with hyperthermia in the primary treatment of intraocular retinoblastomapreliminary results

Br J Ophthalmol

First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma

J Clin Oncol

External beam radiotherapy for retinoblastoma. II. Lens sparing technique

Br J Ophthalmol

Factors predictive of recurrence of retinal tumors, vitreous seeds, and subretinal seeds following chemoreduction for retinoblastoma

Arch Ophthalmol

Recent developments in the management of retinoblastoma

J Pediatr Ophthalmol Strabismus

External beam radiotherapy for retinoblastomaI. Whole eye technique

Br J Ophthalmol

Histopathologic risk factors in retinoblastoma. A retrospective study of 172 patients treated in a single institution

Cancer

Multiagent chemotherapy as neoadjuvant treatment for multifocal intraocular retinoblastoma

Ophthalmology

Original article
Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation☆