Towards a personalized utilization of stereotactic body radiotherapy for the management of liver metastases in solid tumors

The presence of liver metastases in solid tumors is associated with poor prognosis. This adverse impact on patient outcomes may partly stem from the highly immunosuppressive environment commonly found within hepatic lesions, often resulting in a "cold" immune phenotype less responsive to immunotherapy. Despite this observation, the immune microenvironment of liver metastases is more complex and heterogeneous. Both intra- and inter-tumor heterogeneity are frequently observed in liver metastases. While multiple-site biopsies could potentially evaluate this heterogeneity, such procedures are invasive, time-consuming, and resource-intensive. Additionally, liquid biopsies based on circulating tumor DNA fail to provide insights into the immune landscape of individual lesions. The challenge of accurately evaluating the immune microenvironment of liver lesions at the individual level contributes to the variability in responses to immunotherapy-based treatments. Recent advances offer new opportunities to personalize the treatment of liver metastases. Radiomic signatures, in particular, offer a non-invasive means of assessing individual lesions' tumor texture, heterogeneity, and immune cell infiltration, such as the presence of CD8⁺ effector T cells. These advancements pave the way for a tailored use of stereotactic-body radiotherapy (SBRT) for the treatment of liver metastases. Thus, SBRT could be selectively delivered to “cold” liver lesions to stimulate an anti-tumor immune response. After describing the general aspects of the synergy between immunotherapy and radiotherapy in solid tumors, as well as the specific immune landscape of liver lesions that may dampen the efficacy of immunotherapy, this review discusses the potential role of SBRT, combined with non-invasive tools as radiomics, in improving outcomes for patients with liver metastases.