CHEMOTHERAPY WITH FOCAL THERAPY CAN CURE INTRAOCULAR RETINOBLASTOMA WITHOUT RADIOTHERAPY

Background: External beam radiotherapy is standard treatment for mediu m and large, or visually threatening, intraocular retinoblastoma but m arkedly increases the risk of cosmetic deformities and second malignan t neoplasms in children with germline RBI mutations. Large tumors and those with vitreous seeds do poorly despite radiotherapy. Chemotherapy traditionally is ineffective for intraocular retinoblastoma, perhaps because many retinoblastomas overexpress the multidrug resistance prot ein, P-glycoprotein. Objective: To avoid radiotherapy in the managemen t of intraocular retinoblastoma by using chemotherapy and focal therap y. Interventions: We shrank retinoblastomas in 40 eyes of 31 patients that conventionally should be enucleated or receive radiotherapy by us ing chemotherapy (ie, vincristine-teniposide, 8 eyes; additional carbo platin, 32 eyes) combined with the administration of cyclosporine, a k nown multidrug-resistance-reversal agent. We then consolidated these r esponses to chemotherapy by subsequent 532- and 1064-nm laser therapy and cryotherapy. Results: At the median follow-up of 2/8 years (range, 1/10-43/4 years), the results of treatment were excellent. The actuar ial relapse-free rate was 89% in patients not previously treated (91% for 28 eyes) and 67% in patients treated after relapse from previous t herapy (70% for 12 eyes). For the eyes with the worst prognosis (ie, v itreous seeds), the relapse-free rate was 88%, better than previously reported. Cyclosporine is nontoxic and did not enhance the expected to xic effects of chemo therapy. Most eyes required laser therapy, cryoth erapy, or both for consolidation of tumor control. Conclusions: This p ilot study suggests that most retinoblastomas are curable by combining chemotherapy with cyclosporine therapy,laser therapy, and cryotherapy , without requiring external beam radiotherapy. We propose a randomize d trial to clarify the role of cyclosporine.