Intra-Arterial Chemotherapy (Ophthalmic Artery Chemosurgery) for Group D Retinoblastoma.

David H Abramson,Anthony B Daniels,Ira J Dunkel,Jasmine H Francis,Y Pierre Gobin,Scott E Brodie,Brian P Marr,Demetrios Vavvas

doi:10.1371/journal.pone.0146582

Abstract

PurposeTo report globe salvage rates, patient survival and adverse events of ophthalmic artery chemosurgery (OAC) for International Classification of Retinoblastoma (ICRB) group D retinoblastoma (naive and after prior failures).MethodsSingle institution retrospective review of all Group D eyes treated with OAC from 5/2006-12/2012. Patients were treated according to our previously-published techniques. Primary outcome was globe retention without need for external beam radiotherapy (EBRT). Demographics, prior treatments, OAC agents used, and adverse events were also recorded.Results112 group D eyes (103 patients) that underwent OAC were included (average follow-up was 34 months, range: 2–110 months). 47 eyes were treatment-naïve, 58 eyes received prior treatments elsewhere, and 7 young infants (7 eyes) underwent our published “bridge therapy” (single agent intravenous carboplatin) until old enough to undergo OAC. Median number of OAC sessions/eye was 3 (range 1–9). 110/112 eyes received intra-arterial melphalan, but only 31 eyes received melphalan alone. 43 eyes received carboplatin, and 78 eyes received topotecan (never as a single agent). 80/112 eyes received >1 drug over their treatment course, and 39 eyes received all three agents. 24 eyes (16 pretreated, 7 treatment-naïve, 1 bridge) failed treatment and required enucleation during the study period. Enucleation and EBRT were avoided in 88/112 eyes (78.6%; including 40/47 [85.1%] treatment-naïve eyes, 42/58 [72.4%] previously-treated eyes, and 6/7 eyes [85.7%] among bridge patients). By Kaplan-Meier survival analysis, globe salvage rate was 74% at 110 months among all patients, and 85% at 110 months in the treatment-naïve subgroup. Transient grade 3/4 neutropenia was more common in patients receiving OAC bilaterally. No child died of metastatic disease.ConclusionsOAC is effective for curing group D retinoblastoma, achieving rates of globe salvage many times higher than systemic chemotherapy (10–47%), even in eyes that previously failed other treatments. OAC can be performed multiple times, using multiple agents, on one or both eyes of patients.

Highlights

Over the past two decades, the introduction of systemic chemotherapy for the management of intraocular retinoblastoma has enabled globe retention for these children without the need for external beam radiation or enucleation.[1,2,3] Using primary systemic chemotherapy, most of the successes have been in children with International Classification of Retinoblastoma (ICRB) groups A, B and C eyes.[4]
Enucleation and external beam radiotherapy (EBRT) were avoided in 88/112 eyes (78.6%; including 40/47 [85.1%] treatment-naïve eyes, 42/58 [72.4%] previously-treated eyes, and 6/7 eyes [85.7%] among bridge patients)
ophthalmic artery chemosurgery (OAC) is effective for curing group D retinoblastoma, achieving rates of globe salvage many times higher than systemic chemotherapy (10–47%), even in eyes that previously failed other treatments

Summary

Introduction

Over the past two decades, the introduction of systemic chemotherapy for the management of intraocular retinoblastoma has enabled globe retention for these children without the need for external beam radiation or enucleation.[1,2,3] Using primary systemic chemotherapy, most of the successes have been in children with International Classification of Retinoblastoma (ICRB) groups A, B and C eyes.[4]. Since the previous standard of care, systemic chemotherapy, had relatively poor success at saving group D eyes, we wanted to assess our success rates in treating these eyes using our OAC technique. Intravenous chemotherapy is associated with many systemic side effects, including neutropenia during treatment and possibly secondary acute myelogenous leukemia (sAML) years later.[1, 5, 11, 16,17,18] complications related to OAC have likewise been reported by various authors.[19, 20] Here we report our success rates with OAC both as primary treatment, as well as for patients who had previously failed other forms of treatment, for group D retinoblastoma. We demonstrate rates of globe salvage with OAC that are much higher than those reported previously using other previous treatment modalities

Methods

Results

Conclusion