In addition to bTMB estimation, cfDNA analysis using plasma NGS panels might provide additional useful information, as the concomitant presence of somatic mutations that have been associated in tissue with primary resistance to PD(L)-1-based therapies (i.e., STK11, KEAP1) [67,68] or with improved outcomes with PD-1 plus CTLA-4 blockage (i.e., ARIAD1) [68], as well as might rescue a significant proportion of oncogene-addicted NSCLC patients with incomplete molecular profiling [69] that can derive less benefit from ICB. This evidence concerns the gene CD274 and non-small cell lung carcinoma.