Selective Ophthalmic Artery Chemotherapy with Melphalan in the Management of Unilateral Retinoblastoma: A Prospective Study

Abstract

To determine prospectively the efficacy and to assess potential side effects of melphalan selective ophthalmic artery chemotherapy (SOAC) as first-line treatment for unilateral retinoblastoma. Phase 2 nonrandomized, prospective study. Patients with unilateral retinoblastoma group B, C, or D of the International Classification for Intraocular Retinoblastoma (IRC). Group D eyes with massive vitreous seeding were not eligible. Melphalan SOAC associated with diode laser thermotherapy, cryotherapy, or both at 4-week intervals (3-6 cycles). For persistent vitreous seeding, intravitreal melphalan chemotherapy also was used. The primary outcome was globe preservation rate. Secondary outcomes were tumor relapse rate, occurrence of ocular or systemic adverse events, and measurement of the dose area product (DAP). Between 2012 and 2017, 39 patients (39 eyes) with unilateral retinoblastoma were included prospectively. Three included patients did not receive SOAC (2 catheterization failures and 1 case of viral syndrome) and were considered failures. At diagnosis, IRC groups for the 36 treated patients were: B, n= 4 (11%); C, n= 13 (36%); and D, n= 19 (53%); median age was 21.5 months (range, 3.2-61.6 months). Median number of SOAC cycles was 3.9 (range, 1-6 cycles), and median melphalan dose was 4.9 mg/procedure. The median DAP was 1.24 Gy.cm2/procedure. Median follow-up was 63 months (range, 34-93 months). SOAC was associated with local treatments for 31 patients (86%): diode laser thermotherapy for all of them and cryotherapy or intravitreal chemotherapy for 10 (32%) and 9 patients (25%), respectively. SOAC treatment was interrupted in 5 patients because of severe ophthalmic (ptosis, n= 2; retinal ischemia, n= 2) or systemic (hypotension, n= 1) adverse events. At the cutoff date analysis, all patients were alive without metastasis. The 18-month eye preservation rate was 80% (range, 68.6%-94.6%). After a follow-up of at least 30 months, the ocular preservation rate was 69% (n= 24 preservations). This first prospective trial demonstrated that SOAC with melphalan alone as first-line treatment for retinoblastoma is efficient and well tolerated with no metastatic events, although ocular ischemic complications were observed.