Second neoplasms in patients with hereditary retinoblastoma.

Abstract

10620 Background: Patients with hereditary retinoblastoma have an increased risk of developing second tumors during adolescence and adulthood. The incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the leading cause of death in these patients. This risk is increased in patients who have received external radiation therapy as part of treatment but is also increased in non-radiated patients. Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established. Methods: We present a cohort of patients with hereditary retinoblastoma assessed in our multidisciplinary pediatric and adult genetic predisposition cancer unit (UPGeCI) from September 2018 to December 2023. During this period, 62 patients with retinoblastoma were attended, all with RB1 gene mutation. Of these, 84% of patients had bilateral retinoblastoma, and 16% had unilateral retinoblastoma. They ranged in age from 6 months to 55 years (median 13 years). 18 patients (29%) were treated with external beam radiation therapy. Clinical follow-up and orbital magnetic resonance imaging were performed every two years. Results: Six cases of SMNs were detected in 5 patients (9.3%), all soft tissue sarcomas. The mortality rate was 60% (3/5 patients). Four patients (80%) had received external radiotherapy as part of the treatment of retinoblastoma. Three patients presented 3 sarcomas in the facial region within the irradiated area, of which one was an osteosarcoma and the other two leiomyosarcomas. Two of them presented in adulthood, and one at 9 years old. One of the patients died, the other two are living disease-free. The fourth patient who had received external radiotherapy presented with osteosarcoma of the femur at 15 years of age. She died of septic shock. The patient who had not received external radiotherapy presented with osteosarcoma of the tibia at 6 years of age and later with osteosarcoma of the contralateral femur at 10 years of age. She died of progression. Conclusions: There is an increased risk of SMNs in patients with hereditary retinoblastoma, mainly soft tissue sarcomas, with high mortality. This risk increases if they have received external radiation therapy. Therefore, screening for SMNs is essential for of follow-up in patients with heritable retinoblastoma.