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Purpose: To evaluate the efficacy of primary chemotherapy combined with local therapy in the treatment of retinoblastomas not treatable with a single therapeutic method. Methods: We performed a retrospective chart review of 227 patients diagnosed with retinoblastoma. Sixty-five eyes in 52 patients had tumors not treatable with a single therapeutic method and received primary chemotherapy combined with local therapy as needed. Results: Tumor control and eye salvage was achieved in 34 of the 65 eyes; the probability of ocular survival was 46.56% using the Kaplan-Meier method. Forty-three of the 65 eyes were group D or E tumors, in which tumor control and eye salvage was achieved in 16 eyes. Twenty eyes were treated with chemotherapy only, while 28 eyes received one additional modality of local therapy, and 17 eyes received two modalities of local therapy. Of the eyes treated with chemotherapy only, tumor control was achieved in 5 eyes. Conclusions: Primary chemotherapy combined with local therapy can be effective and safe in the treatment of retinoblastomas otherwise untreatable with other therapeutic methods, such as group D and E retinoblastomas. More vigorous treatment with more local therapeutic methods combined may yield even better results.

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