Efficacy and Toxicity of Second-Course Ophthalmic Artery Chemosurgery for Retinoblastoma

Abstract

Objective Assess the utility of second-course ophthalmic artery chemosurgery (OAC) for patients with intra-ocular retinoblastoma that recurred following prior ophthalmic artery chemosurgery. This study evaluates the efficacy and toxicity of second-course OAC. Design Single-arm, retrospective study of 29 eyes in 30 patients treated with second-course OAC at Memorial Sloan-Kettering Cancer Center between May 2006 and July 2013, with a median 25.9 months follow-up. Participants Retinoblastoma patients who underwent a course of OAC, with a minimum of 2 months of progression-free follow-up at monthly examinations, but who subsequently received additional OAC for recurrent tumor. Methods Efficacy- Kaplan-Meier survival estimates were generated and the Mantel-Cox test was used to compare curves. Toxicity- Electroretinogram (ERG) amplitudes were measured in response to 30-Hz photopic flicker stimulation before and after OAC treatment; systemic adverse events were graded according to CTCAE 4.0. Main Outcome Measure Efficacy- Ocular progression free survival, ocular event (enucleation, external beam radiation or intravitreal melphalan) free survival and ocular survival. Toxicity- Peak-to-peak comparisons between ERG studies before and after OAC treatment; CTCAE 4.0 graded systemic adverse events. Results 50% of all recurrences were within 4.4 months and 90% were within 16 months of completion of first course OAC. The 2-year Kaplan-Meier ocular survival, event free survival and progression free survival estimates following second-course OAC were 82.8% (95% confidence interval [CI], 60.1–93.2%), 57.3% (95%CI, 36.1–73.7%) and 26.5% (95% confidence interval [CI], 11.0–45.0%), respectively. All eyes without vitreous seeding are progression free, while eyes with vitreous seeding were significantly associated with worse ocular survival following second- course OAC (p=0.03). Following second-course OAC, 90% of eyes had stable or improved electroretinogram responses. Of all evaluable cases, there was no increased risk of systemic toxicity during second course compared to initial course OAC. Conclusions Retinoblastoma eyes requiring second-course OAC following initial OAC treatment have good salvage rates and the treatment has an acceptable ocular and systemic toxicity profile. However, these eyes often require additional (third or fourth-course) OAC or other treatment modalities due to progression of disease after second-line OAC, particularly if vitreous seeds are present at the time of initial OAC failure.

Retinoblastoma

“…A range of modalities is appropriate, but each subsequent plan has a lower success rate 114 and long drawn out attempts to salvage an eye incur high risks for the child and family, including metastasis and death. 108,115,116 …”

“…Second line treatment options include focal therapies, repeated systemic chemotherapy, 117,118 IAC, 114,119 brachytherapy (internal radiotherapy), 120,121 , EBRT 122–124 and whole-eye 121 or proton beam 125 radiation. Criteria for secondary enucleation are not well defined but are dominated by refractory subretinal and vitreous seeding, vitreous haemorrhage and secondary neovascular glaucoma, 117,126 and socio-economic and psychological fatigue to save an eye with poor vision.…”

“…136 A combination of repeat IAC and intravitreal chemotherapy may play an important part in saving eyes that have failed IVC, radiation or IAC 119,130,131 However, in general, extensive treatments over a long time to save an eye may increase family stress, decrease family resources, 108 and risk metastases and death. 114,116,129 …”

Rescue intra-arterial chemotherapy following retinoblastoma recurrence after initial intra-arterial chemotherapy

“…Francis et al reported on the efficacy of a second course of IAC and found 24 month Kaplan Meier ocular survival at 83% and progression-free survival at 26% [26]. These findings indicate that these eyes are still ''at risk'' for tumor progression even after the second round of IAC as 74% of patients in that series, particularly those with vitreous seeding, showed further disease requiring treatment.…”

Diagnosis and management of secondary epipapillary retinoblastoma

“…It was successfully used in five cases in the present study, alone or in conjunction with IAC. IAC is rapidly gaining popularity as first-line and second-line treatment,3 and we can now show its value in salvage following Rb recurrence after initial IAC 12 13. In the present study, IAC for secondary epipapillary involvement was successfully used in five cases, in four of which following recurrence after previous IAC.…”