Fig. 2.

a, b Target definition by segmentation of an unresectable bulky lung cancer (a): Segment 1- representing the contrast-enhanced (vascularized, “normoxic”) peripheral tumor segment, (GTV), Segment 2 - being the contrast-unenhanced (necrotic, “anoxic”) central tumor region, Segment 3- delineating the contrast-hypo-enhanced (hypovascularized, “hypoxic”) junctional tumor region as an up to a maximum of 5 mm junctional zone between the central-necrotic and the remaining peripheral-vascularized tumor segments, Segment 4 - representing peritumoral tissue; (b) Sparing of the peri-tumoral-surrounding immune microenvironment (thick green line) by creating as an organ at risk multiple “immune microenvironmental islands” (thick yellow line) in order to spare from radiation dose a significant volume (for ex. 2/3) of the tumor microenvironment, leaving it intact and functional