Combining spatially fractionated radiation therapy (SFRT) and immunotherapy opens new rays of hope for enhancing therapeutic ratio

Spatially Fractionated Radiation Therapy (SFRT) is a form of radiotherapy that delivers a single large dose of radiation within the target volume in a heterogeneous pattern with regions of peak dosage and regions of under dosage. SFRT types can be defined by how the heterogeneous pattern of radiation is obtained. Immune checkpoint inhibitors (ICIs) have been approved for various malignant tumors and are widely used to treat patients with metastatic cancer. The efficacy of ICI monotherapy is limited due to the "cold" tumor microenvironment. Fractionated radiotherapy can achieve higher doses per fraction to the target tumor, and induce immune activation (immodulate tumor immunogenicity and microenvironment). Therefore, coupling ICI therapy and fractionated radiation therapy could significantly improve the outcome of metastatic cancer. This review focuses on both preclinical and clinical studies that use a combination of radiotherapy and ICI therapy in cancer.