Second malignant neoplasms following chemoreduction with carboplatin, etoposide, and vincristine in 245 patients with intraocular retinoblastoma

Abstract

BACKGROUND: To evaluate the occurrence of second malignant neoplasms (SMN) following chemoreduction (CRD) with carboplatin, vincristine, and etoposide (CEV) as frontline therapy in patients with retinoblastoma (RB). PRODECURE: We conducted a two-institution retrospective chart review of 245 patients with intraocular RB treated with six cycles of vincristine, carboplatin, and etoposide for treatment of intraocular retinoblastoma. Cumulative incidence of SMN was calculated with adjustment for the competing risk of death. RESULTS: There were 187 patients with germline retinoblastoma and 58 with non-germline disease. External beam radiotherapy was subsequently utilized in 46 (24%) of germline cases and six (10%) of non-germline cases. Mean follow-up of germline and non-germline patients was 80 and 70 months, respectively. Seven subsequent cancers were found in six patients for an overall incidence of 3% at a mean of 11 years. For germline cases, following CEV alone (n = 156), SMN were found in 4% following the RB diagnosis. We found no SMN in patients with non-germline RB. One patient developed pineoblastoma. SMN included osteosarcoma (n = 3), rhabdomyosarcoma (n = 1), orbital and conjunctival melanoma (n = 1), low-grade glioma (n = 1), and acute promyeloctic leukemia (n = 1). Five of the six patients with a second malignancy survive at mean of 46 months (range 15-71 months). CONCLUSIONS: At a mean of 11 years, 4% of children with germline RB treated with CEV as frontline therapy developed SMN's. No SMN was found in non-germline patients. Concerns regarding CEV-induced second cancers should not deter clinicians from using life and vision preserving therapy in patients with retinoblastoma.