Sarcoma risk after radiation exposure

Sarcomas are a rare but highly fatal outcome of radiation exposure. The first case reports of bone sarcomas in patients who had received radiotherapy for benign bone conditions were published as early as 1922 [1], making it one of the first solid cancers to be linked to radiation. Martland’s famous report of bone sarcomas in the jaws of radium-dial painters followed in 1929 [2]. In the last few decades much has been learned about the relationship by studying the occurrence of sarcomas after radiotherapy treatment for both benign and malignant diseases. Nevertheless, because radiation-related sarcoma is a very rare event, studies have generally been small, and many questions remain about the relationship. Uncertainties include the shape of the dose–response relationship, particularly at lower (<5？Gy (Gray)) and very high absorbed doses (20？+？Gy), the impact of factors such as age at exposure, time since exposure, sex and genetic susceptibility on risk as well as understanding variation in risk by sarcoma subtype. Attempts to find a radiation-signature are also currently underway and sarcomas are one of the cancers that have been targeted for these studies.In this article we review the epidemiological evidence on the association between radiation exposure and development of sarcoma, including both bone and connective tissue sarcomas but differentiating where possible. We focus on studies of radiotherapy for malignant conditions, especially those with individual estimates of absorbed radiation dose to the site of the sarcoma (unless otherwise specified this is the dose that we refer to throughout the article). Treatment of benign conditions has mostly been discontinued and little new data are available since previous reviews [3]. However, we briefly review the findings from these studies and other non-medical populations, especially where there are gaps in the evidence from the studies of treatment for malignant disease. We include assessment of potential effect modifi