Comparative effectiveness and safety of intra-arterial chemotherapy and intravenous chemotherapy for retinoblastoma: A systematic review and meta-analysis.
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Intra-arterial chemotherapy (IAC) has emerged as a targeted alternative to intravenous chemotherapy (IVC) for retinoblastoma; however, the comparative effectiveness and safety of these approaches remain incompletely defined. We performed a systematic review and meta-analysis to evaluate whether IAC-based regimens are associated with improved clinical outcomes compared with IVC in pediatric retinoblastoma. Twelve studies were included. Comparative studies contributed to the quantitative synthesis, whereas selected non comparative IAC series were summarized qualitatively to provide contextual evidence. Overall survival demonstrated a consistent association favoring IAC across both early and advanced disease categories, with a pooled effect estimate of OR 4.72 (95% CI 2.69-8.28). In early-stage disease, the pooled OR was 12.61 (95% CI 3.82-41.58), while advanced-stage disease showed a pooled OR of 3.56 (95% CI 1.88-6.74). Heterogeneity was negligible within subgroups (I² = 0%). Event-free survival favored IAC-based treatment overall with a pooled RR of 1.36 (95% CI 1.13-1.62). When stratified by treatment approach, IAC alone showed a pooled RR of 1.30 (95% CI 1.01-1.66) with moderate heterogeneity (I² = 61%), whereas IAC combined with IVC sequencing demonstrated a pooled RR of 1.43 (95% CI 1.10-1.86) with no heterogeneity (I² = 0%). Globe salvage outcomes were improved with IAC, with a pooled RR of 1.33 (95% CI 1.23-1.42; I² = 9%). Avoidance of enucleation also favored IAC overall, with a pooled RR of 1.69 (95% CI 1.34-2.12). Subgroup analyses indicated a modest and non-significant effect in early-stage disease (RR 1.27, 95% CI 0.89-1.80) and a clearer effect in advanced-stage disease (RR 2.08, 95% CI 1.54-2.80), with minimal heterogeneity (I² = 0%). Metastatic events were rare across studies; nevertheless, pooled analysis suggested lower odds of metastasis in IAC-based regimens compared with IVC (OR 0.42, 95% CI 0.19-0.91; I² = 0%), with no evidence of subgroup differences between IAC alone and IAC plus IVC sequencing. In conclusion, IAC-based strategies were associated with favorable outcomes in survival, disease control, globe salvage, and avoidance of enucleation compared with IVC, with consistently low heterogeneity across major endpoints and metastatic events remaining uncommon in both arms. These findings support the role of IAC as an important component of contemporary retinoblastoma management, particularly in settings with appropriate technical expertise and multidisciplinary resources.