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

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.