Not all sarcomas developed in irradiated tissue are necessarily radiation-induced – Spectrum of disease and treatment characteristics

Background: Sarcomas in irradiated tissue (SITs) are often considered with second cancers, although they usually present distinct dose-response, genetic and clinical patterns. The contribution of radiation in SIT development is likely, but remains unproven in many cases.Materials and methods: We reviewed the literature for published data on SITs.Results: SITs incidence ranged between 0.03% and 0.2%. Median latency was 15 years. Angiosarcoma was the second most common subtype after undifferentiated sarcomas of malignant fibrous histiocytoma (MFH). C-Myc overexpression can be used to identify radiation-induced angiosarcoma, and a recently described transcriptomic signature of genes involved in chronic oxidative stress and mitochondrial dysfunction may indicate radiation causality. Osteosarcomas were often associated with genetic predisposition. Five-year survival rates rarely exceeded 30% because the therapeutic possibilities were often limited by the first cancer. Chemotherapy response may differ from that of de novo sarcomas.Conclusion: SITs present different characteristics from non-sarcomatoid second cancers. Reporting of SIT cases and the establishment of tissue and serum banks is necessary to better understand and validate the recently discovered radiation signature.