Selective Ophthalmic artery chemotherapy with melphalan in the management of unilateral retinoblastoma: a prospective study

ABSTRACT Purpose To prospectively determine the efficacy and assess potential side effects of melphalan selective ophthalmic artery chemotherapy (SOAC) as first-line treatment for unilateral retinoblastoma. Design Phase II non-randomized prospective study. Subjects 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. Treatment Melphalan (ALKERAN®) SOAC associated with diode laser thermotherapy and/or cryotherapy, at 4-week intervals (3 to 6 cycles). For persistent vitreous seeding, intravitreal melphalan chemotherapy was also used. Main outcome measures The primary outcome was the globe preservation rate. The secondary outcomes were the tumor relapse rate, the occurrence of ocular/systemic adverse events and the measurement of the dose area product (DAP). Results Between 2012 and 2017, 39 patients (39 eyes) with unilateral retinoblastoma were prospectively included. Three included patients did not receive SOAC (2 catheterization failures, and 1 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%), and median age was 21.5 months [range: 3.2-61.6]. Median number of SOAC cycles was 3.9 [ 1 , 2 , 3 , 4 , 5 , 6 ] and median melphalan dose was 4.9 mg/procedure. The median dose area product (DAP) was 1.24 Gy.cm2/procedure. Median follow-up was 63 months [34-93]. SOAC was associated with local treatments for 31 patients (86%): diode laser thermotherapy for all of them, cryotherapy or intravitreal chemotherapy for 10 (32%) and 9 patients (25%), respectively. SOAC treatment was interrupted in 5 patients, due to severe ophthalmic (ptosis, n=2; retinal ischemia, n=2) or systemic adverse events (n=1: hypotension). At the cutoff date analysis, all patients were alive without metastasis. The 18-month eye preservation rate was 80% [68.6-94.6]. After a follow-up of at least 30 months, the ocular preservation rate was 69% (n=24 preservations). Conclusion This first prospective trial demonstrates 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.