Radiotherapy Dose in Patients Receiving Immunotherapy

There is significant rationale for combining radiation therapy (RT) and immuno-oncology (IO) agents, but the optimal radiation parameters are unknown. This review summarizes key trials in the RT and IO space with a focus on RT dose. Very low RT doses solely modulate the tumor immune microenvironment, intermediate doses both modulate the tumor immune microenvironment and kill some fraction of tumor cells, and ablative doses eliminate the majority of target tumor cells and also possess immunomodulatory effects. Ablative RT doses may have high toxicity if targets are adjacent to radiosensitive normal organs. The majority of completed trials have been conducted in the setting of metastatic disease and direct RT to a single lesion with the goal of generating systemic antitumor immunity termed the abscopal effect. Unfortunately, reliable generation of an abscopal effect has proved elusive over a range of radiation doses. Newer trials are exploring the effects of delivering RT to all or most sites of metastatic disease, with dose personalization based on the number and location of lesions. Additional directions include testing RT and IO in earlier stages of disease, sometimes in further combination with chemotherapy and surgery, where lower doses of RT may still contribute substantially to pathologic responses.