Incidence and outcomes of radiation-induced sarcomas following radiotherapy for low-grade non-Hodgkin lymphomas: A population-based study

PURPOSE: Radiation-induced sarcomas are a rare but serious long-term complication of radiotherapy. While radiotherapy is an effective treatment for low-grade non-Hodgkin lymphomas, the incidence and characteristics of radiation-induced sarcomas in this setting have not been previously described. The purpose of this study was to analyse the incidence and outcomes of radiation-induced sarcomas following radiotherapy for low-grade non-Hodgkin lymphomas. PATIENTS AND METHODS: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database (17 registries, 2024 submission) to identify patients diagnosed with follicular or marginal zone lymphoma between 2000 and 2022 who received radiotherapy. Cases of subsequently histologically-confirmed sarcoma were screened and classified as confirmed or possible radiation-induced sarcomas based on anatomical localization and a minimum latency of 3 years. Clinical characteristics, treatments, latency intervals, and survival outcomes were analysed. RESULTS: Among 18,293 patients with low-grade non-Hodgkin lymphomas treated with radiation, 19 developed sarcomas (0.10 %). Ten cases were excluded (eight due to anatomical mismatch, two due to insufficient latency). Of the nine remaining cases, six met criteria for confirmed radiation-induced sarcomas. The median age at lymphoma diagnosis was at least 70years, and the median latency to radiation-induced sarcoma was 12years (range: 3-20years). All sarcomas were localized and treated surgically; three patients also received radiotherapy. After a median follow-up of 78months, the 5-year overall survival rate was estimated at 83.3 % (95 % confidence interval: 43.6 %-97.0 %). One patient died from lymphoma progression. CONCLUSION: Radiation-induced sarcomas following radiotherapy for low-grade non-Hodgkin lymphomas is extremely rare, with favourable outcomes when it occurs. These results provide reassuring data supporting the long-term safety of modern radiotherapy for low-grade non-Hodgkin lymphomas and underscore the importance of continued surveillance and treatment planning in patients with prolonged life expectancy.