Immune Checkpoint Inhibitors in Advanced NSCLC: [18F]FDG PET/CT as a Troubleshooter in Treatment Response

Introduction: The aim of this study was to investigate whether [F-18]FDG PET/CT-derived semi-quantitative parameters can predict immunotherapy treatment response in non-small cell lung cancer (NSCLC) patients. Secondly, immune-related adverse events (irAEs) and lymphoid cell-rich organs activation were evaluated. Materials and Methods: Twenty-eight patients who underwent [F-18]FDG PET/CT scans before and at first restaging therapy with immuno-checkpoint inhibitors (ICIs) were retrospectively analyzed. PET-based semi-quantitative parameters extracted from both scans were respectively: SUVmax and SUVpeak of the target lesion, whole-body metabolic tumor volume (MTVWB), and whole-body total lesion glycolysis (TLG(WB)), as well as their interval changes (Delta SUVmaxTL, Delta SUVpeakTL, Delta MTVWB, Delta TLG(WB)). These PET-derived parameters were correlated to controlled disease (CD) assessed by RECIST 1.1. IrAEs, if present, were also described and correlated with clinical benefit (CB). SUVmax of the spleen and bone marrow at restaging scans were also correlated to CB. Results: The CD was achieved in 54% of patients. Out of 28 eligible patients, 13 (46%) experienced progressive disease (PD), 7 showed SD, 7 had PR, and only in one patient CR was achieved. Delta SUVmaxTL (p = 0.002) and Delta SUVpeakTL (p < 0.001) as well as Delta MTVWB (p < 0.001) and Delta TLG(WB) (p < 0.005) were significantly associated with PD vs. non-PD. IrAEs and lymphoid cell-rich organs activation did not correlate with CB. Conclusions: [F-18]FDG PET/CT by using interval changes of PET-derived semi-quantitative parameters could represent a reliable tool in immunotherapy treatment response evaluation in NSCLC patients.