BACKGROUND: Access to intra-arterial chemotherapy for retinoblastoma in low- and middle-income countries (LMICs) is limited. There is a need to optimize the efficacy of systemic chemotherapy for advanced intraocular retinoblastoma, particularly in LMICs. The aim was to compare the efficacy of standard versus higher dose carboplatin-based intravenous chemotherapy for group D and E retinoblastoma.
METHODS: The single-center, single-blinded, randomized study was conducted during 2019-2021. Patients with newly diagnosed group D or E retinoblastoma were randomized to receive vincristine, etoposide, and standard versus higher dose (<36 months: 18.6 vs. 28 mg/kg; ≥36 months: 560 vs. 840 mg/m2 ) carboplatin. Examination under anesthesia and ultrasonography was performed at diagnosis and following three cycles of chemotherapy. Group E eyes with poor likelihood of globe/vision salvage at diagnosis were excluded.
RESULTS: Thirty-two eyes of 30 patients were analyzed: 17 group D and 15 group E eyes. The tumor response to chemotherapy with regards to regression pattern (p = .72), tumor shrinkage (diameter: p = .11, height: p = .96), subretinal seeds (p = .91), and vitreous seeds (p = .9) were comparable between the two treatment arms. The globe salvage (group D [82% vs. 67%; p = .58]; group E [12.5% vs. 29%; p = .57]) and salvage of meaningful vision (group D [100% vs. 75%; p = .13]; group E [100% vs. 50%; p = .48]) were comparable between standard and higher dose arms. No excess treatment-related toxicity was observed in the higher dose arm.
CONCLUSIONS: Higher dose carboplatin-based intravenous chemotherapy did not result in superior globe or vision salvage in group D or E retinoblastoma.

Retinoblastoma, an intraocular cancer primarily affecting children, interacts with surrounding intraocular and extraocular structures in the development and progression. Subretinal and vitreous seeds are characteristic features of retinoblastoma, which result from the interaction between the tumor and its environment at the levels of tissue and microenvironment. The retina and vitreous affect the disease course and responses to treatment options. Also, neighboring cells in the retina and physicochemical properties of the tumor microenvironment are related to the biological activities of retinoblastoma tumors. Researches focusing on the tumor environment of retinoblastoma will lead to the development of more effective treatment options, which can revolutionize the prognosis of patients with retinoblastoma.