Prospective assessment using 18 F-FDG PET/CT as a novel predictor for early response to PD-1 blockade in non-small-cell lung cancer

Anti-programmed death-1 (PD-1) blockade is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, no appropriate modality exists for monitoring its therapeutic response immediately after initiation. Therefore, we aimed to elucidate the clinical relevance of 18 F-FDG PET/CT versus CT in predicting the response to PD-1 blockade in the early phase. This prospective study included a total of 54 NSCLC patients. 18 F-FDG PET/CT was performed at 4 weeks and 9 weeks after PD-1 blockade monotherapy. Maximum standardized uptake values (SUL max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated. Among all patients, partial metabolic response and progressive metabolic disease after PD-1 blockade were observed in 35.2% and 11.1% on SUL max , 22.2% and 51.8% on MTV, and 27.8% and 46.3% on TLG, respectively, whereas a partial response (PR) and progressive disease (PD), respectively, based on RECIST v1.1 were recognized in 35.2% and 35.2%, respectively. The predictive probability of PR (MTV: 57.9% vs. 21.1%, p = 0.044; TLG: 63.2% vs. 21.1%, p = 0.020) and PD (MTV: 78.9% vs. 47.3%, p = 0.002; TLG: 73.7% vs. 21.1%, p = 0.007) detected based on RECIST at 4 weeks after PD-1 blockade initiation was significantly higher using MTV or TLG on 18 F-FDG uptake than on CT. Multivariate analysis revealed that metabolic response by MTV or TLG at 4 weeks was an independent factor for response to PD-1 blockade treatment. Metabolic assessment by MTV or TLG was superior to morphological changes on CT for predicting the therapeutic response and survival at 4 weeks after PD-1 blockade.