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Intra-arterial Chemotherapy for Retinoblastoma A Systematic Review

Yacoub A. Yousef, MD1,2; Sameh E. Soliman, MD1,3; Paulita Pamela P. Astudillo, MD1,4; Priya Durairaj, MD1; Helen Dimaras, PhD1; Helen S. L. Chan, MBBS5,6; Elise Héon, MD1,7; Brenda L. Gallie, MD1,7,8; Furqan Shaikh, MD5,6
[+] Author Affiliations
1Department of Ophthalmology and Vision Sciences, Hospital for Sick Children, Toronto, Ontario, Canada
2Department of Surgery, King Hussein Cancer Center, Amman, Jordan
3Department of Ophthalmology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
4Angeles University Foundation Medical Center, Philippines
5Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
6Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada
7Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
8Department of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
JAMA Ophthalmol. 2016;134(5):584-591. doi:10.1001/jamaophthalmol.2016.0244.
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Importance  Intra-arterial chemotherapy has emerged as a treatment for intraocular retinoblastoma and has been quickly adopted by centers worldwide.

Objective  To conduct a systematic review and attempt a meta-analysis to summarize the reported outcomes of intra-arterial chemotherapy.

Evidence Review  In January 2015, we performed comprehensive searches in Medline, Embase, Cochrane, and Web of Science from inception through January 2015, including any peer-reviewed English-language publication that described outcomes related to toxicity or efficacy in at least 4 patients.

Findings  From a total of 208 identified publications, 28 met inclusion criteria. Twelve reports with discernable nonduplicative information were included, reporting 655 patients, 757 eyes, and 2350 catheterizations. All were single-arm case series, and 67% (8 of 12) were retrospective. Across all studies, globe salvage was achieved for 502 (66%) of all eyes. Most common reported toxicities were chorioretinal atrophy and vascular occlusions. There were at least 13 reports of children with metastases. After publication, 7 additional children had metastases. The 4 different classification systems used challenged the comparison of disease severity at presentation. Visual outcome was not addressed in most studies. Meta-analyses were not possible because no study had a comparative group. Assessment of risk of bias was not possible because no validated tool for single-arm studies was available.

Conclusions and Relevance  Intra-arterial chemotherapy is a promising new treatment associated with high rates of globe salvage. However, the literature is limited by the predominance of retrospective case series, absence of comparison groups, short median follow-up, heterogeneous definitions and tumor classifications, and frequent duplicate reporting. Metastases have been observed, and long-term follow-up is needed. Until the results of clinical, prospective studies are available, it is recommended that intra-arterial chemotherapy be offered selectively among other options, with fully informed discussion about all possible risks, benefits, and uncertainties.

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