Single- Versus Triple-Agent Intra-Arterial Chemotherapy for Retinoblastoma

Purpose: To compare the ocular and systemic outcomes of single- (melphalan) versus triple-agent (melphalan, topotecan, carboplatin) intra-arterial chemotherapy (IAC) for retinoblastoma (RB) eye salvage.

Design: Retrospective single-institutional clinical cohort study.

Methods: Children <18 years with RB who underwent one or more IAC procedures between 2016 and 2024 with minimum 6-month follow-up were reviewed. Data included clinical features, IAC procedural details, additional eye-saving treatments, complications, and follow-up. Primary outcomes included ocular and systemic complications of IAC, intraocular recurrence, extraocular extension, metastasis, and death. Secondary outcomes were tumor response, ocular survival, and recurrence-free ocular survival. Comparative analysis was performed for single- versus triple-agent groups. A SWIMMER^rb plot graphically illustrated additional treatments following IAC.

Results: Thirty-eight eyes of 37 children (24 unilateral RB) were reviewed. Two eyes (2 children) had single- followed by multi-agent IAC and were excluded. Of 35 included children, one had bilateral triple-agent IAC. IAC (median, 3 doses; range, 1-4) was employed as primary (n = 21 eyes) or secondary (n = 15 eyes) treatment. Chemotherapy was single-agent in 13 eyes and triple-agent in 23 eyes. Following IAC, 25 eyes required additional eye-saving treatments (69% single- v 70% triple-agent, P = .983). At final follow-up, the triple-agent group was more likely to achieve very good partial or complete tumor response (91% v 62%, P = .030). Two-year recurrence-free ocular survival was 63.3% (95% CI 45.7-80.9), similar for both groups (P = .700). Globe salvage was 72%. Two-year ocular survival was 72.2% (95% CI 57.2-87.2), higher for the triple-agent group (82.6% v 53.8%; P = .059). Ocular complications occurred in 31% of eyes in the single- and 52% of eyes in the triple-agent group (P = .215). The rate of systemic complications was 38% versus 74% in the single- versus triple-agent groups, respectively (P = .036). No extraocular extension, metastasis, or death were observed at median 34.2 months (range, 14.5-87.0) follow-up.

Conclusions: Triple-agent IAC was associated with improved RB tumor response and ocular survival, though similar recurrence-free ocular survival compared to single-agent. While there were more complications with triple-agent IAC, most were mild or transient.