Results
Of 550 patients with retinoblastoma encountered in this practice during the study period, our series used the 15 patients who developed a SPMN (2.7%), 2 of whom (patient 4 and 7) developed 2 distinct SPMNs. The median age at retinoblastoma diagnosis was 9.7 months (extremes 1.6 and 33.6 months). All 15 patients had a positive family history of retinoblastoma. Twelve patients were male (80%) and three were female (20%). Bilateral disease was present in 14 of the 15 (93.0%) patients, and the genetic nature of the one unilateral case (case 7, TABLE 1) was established by germline RB1 mutation on genetic analysis.
Demographics and characteristics of each patient’s retinoblastoma are presented in TABLE 1. Eleven patients received treatment prior to referral, including enucleation (11/30 eyes; 36.6%), and external beam radiation therapy (EBRT) (12/30 eyes; 40.0%). Following completion of their retinoblastoma treatment course, a total of 15/30 (50.0%) eyes were enucleated, and 14/15 (93.3%) patients underwent EBRT. In 13 patients, retinoblastoma was diagnosed, and treatment was initiated prior to the adoption of carboplatin-etoposide-vincristine (CEV) and intravenous chemotherapy at our center (in 1995). All 15 patients were diagnosed and underwent treatment for their retinoblastoma prior to the availability of selective ophthalmic intra-arterial chemotherapy at our institution (in 2008). The 2 patients diagnosed after the introduction of primary systemic chemotherapy both received intravenous chemotherapy during their treatment course. None of the patients developed metastasis from retinoblastoma and no patient died of their retinoblastoma.
The characteristics of the SPMNs are reported in TABLE 2. Thirteen of the 14 patients (92.9 %) who underwent EBRT developed their SPMN within the field of prior radiation. The histopathologic type of SPMN was osteosarcoma in 7, rhabdomyosarcoma in 3, malignant fibrous histiocytoma in 3, and a malignant astrocytoma, liposarcoma, esthesioneuroblastoma and a leiomyosarcoma in 1 case each. Treatment data for SPMN management was available for 11 of the 15 patients and included a combination of surgical resection in 11, intravenous chemotherapy in 6, and radiation therapy in 4. The median time from initial retinoblastoma diagnosis to development of SPMN was 19.0 years (extremes 3.4 and 39.4 years). The median time from retinoblastoma diagnosis to death in the 6 patients who died of their SPMN was 18.8 years (extremes 6.2 and 34.6 years), and the median interval between SPMN diagnosis and death from the neoplasm in these 6 patients was 1.2 years (extremes 0.25 and 4 years). In contrast, the median duration of follow-up after retinoblastoma in the 9 surviving patients was 32.0 years (extremes 12.5 and 39.3 years) and the median follow-up interval after diagnosis of the SPMN in these patients was 8.9 years (extremes 1.6 and 27.6 years).