Radiation and Immunotherapy for Sarcoma

Almost half of all cancer patients receive radiation therapy [1]. Radiotherapy is used for localized cancers to achieve local control and for metastatic tumors to palliate symptoms, and is estimated to contribute to approximately 40% of cancer cures [2]. For patients with large and/or high-grade soft tissue sarcomas, radiation therapy is frequently used in the neoadjuvant or adjuvant setting to improve local control [3–5], but small randomized studies suggest that radiation therapy does not alter the rate of metastasis compared to surgery alone [6, 7]. However, the addition of immunotherapy to neoadjuvant radiation therapy has the potential to activate a systemic antitumor response and eliminate micrometastases, which could improve survival for patients with sarcoma. This hypothesis will be tested in two clinical trials that are currently ongoing–the NEXIS trial (NCT03116529) and SU2C-SARC032 (NCT03092323). This chapter provides the rationale for this treatment strategy, as well as a summary of ongoing clinical trials testing the combination of radiation therapy and immune checkpoint blockade.