Incidence and Risk Factors of Second Primary Cancers in Patients with Retinoblastoma: A Single Center Study from South Korea

Background: Retinoblastoma (RB) is a rare childhood malignancy with a favorable prognosis; however, second primary cancers (SPCs) are a growing concern.This study aimed to analyze the incidence of SPCs in patients with RB and sought to identify the risk factors associated with their development.Methods: This retrospective cohort study included data from 85 patients diagnosed with RB between 2001 and 2023 extracted from the Yonsei University Health System in South Korea.Patient characteristics, family history, tumor laterality, RB1 mutation, treatment, and the occurrence of SPCs were analyzed.Statistical analyses were performed using Pearson's chi-squared test and Kaplan-Meier survival curves.Results: Of the 85 patients with RB, 43 (50.6%) had heritable RB and 42 (49.4%)had nonheritable RB.Seven SPCs developed in six patients, all of whom had heritable RB.SPCs included hematologic malignancies (two leukemias and two lymphomas) and sarcomas (three osteosarcomas).A significant association was observed between heritable status and SPCs development (P=0.018).A higher frequency of hematologic malignancies was observed among patients who received ≥10 cycles of chemotherapy compared with those who received ＜10 cycles (P=0.039).Conclusion: Patients with heritable RB are at higher risk of developing SPCs.In this cohort, hematologic malignancies occurred more frequently than sarcomas, which have been reported as the predominant SPCs in previous studies.This likely reflects the increased use of chemotherapy.Future long-term cohort studies are needed to clarify the role of chemotherapy in the development of SPCs.Additionally, tailored surveillance protocols may optimize early detection and follow-up strategies based on SPCs type.