Spatially fractionated radiotherapy for liver metastases: two cases of intrahepatic response dissociation.

Liver is a common site of metastatic involvement from non-small cell lung cancer (NSCLC). Spatially fractionated radiotherapy (SFRT) has emerged as a promising technique for controlling bulky lesions while minimizing toxicity. We report two patients with advanced NSCLC and hepatic oligoprogression who underwent SFRT to selected liver lesions. Both achieved excellent local control within the irradiated field, yet developed explosive progression in non-irradiated hepatic regions within 3 months, while extrahepatic disease remained stable. These cases highlight a striking intrahepatic response dissociation, potentially driven by intratumoral heterogeneity, clonal selection and local hepatic immune remodeling under targeted/systemic therapy. The findings underscore the need for further investigation into SFRT's immunobiology and optimal integration with systemic agents.