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

Abstract

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 18F-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. 18F-FDG PET/CT was performed at 4 weeks and 9 weeks after PD-1 blockade monotherapy. Maximum standardized uptake values (SULmax), 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 SULmax, 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 18F-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.

Comparative analysis of different response criteria at early phase after PD-1 blockade in non-small lung cancer

“…The present study design has been previously reported [ 4 ]. This study was a multicenter prospective investigation in which eight Japanese institutions participated.…”

“…Even though many investigations have attempted to identify an optimal predictor of PD-1 blockade, the confirmation of established biomarkers has failed, aside from the expression of PD-L1 within tumor cells [ 3 ]. Therefore, we prospectively examined the prognostic significance of metabolic activity to determine whether 2-deoxy-2-[fluorine-18]-fluoro- d -glucose ( 18 F-FDG) positron emission tomography (PET) can predict the efficacy of PD-1 blockade in the early phase after its initiation [ 4 ]. It was confirmed that 18 F-FDG PET was superior to computed tomography (CT) for the detection of responders and non-responders 1 month after PD-1 blockade administration [ 4 ].…”

“…Therefore, we prospectively examined the prognostic significance of metabolic activity to determine whether 2-deoxy-2-[fluorine-18]-fluoro- d -glucose ( 18 F-FDG) positron emission tomography (PET) can predict the efficacy of PD-1 blockade in the early phase after its initiation [ 4 ]. It was confirmed that 18 F-FDG PET was superior to computed tomography (CT) for the detection of responders and non-responders 1 month after PD-1 blockade administration [ 4 ]. In our previous study, the PET Response Criteria in Solid Tumors (PERCIST) was adopted as a therapeutic response criterion for 18 F-FDG PET [ 5 ].…”

“…Based on this background, we compared RECIST, irRECIST, PERCIST, iPERCIST, and EORTC criteria for the evaluation of therapeutic response and outcome in the early phase (4 weeks) after PD-1 blockade monotherapy, using a sample from our previous study [ 4 ]. As a result, we assessed which response criteria can be used to predict therapeutic efficacy within 1 month of ICI initiation.…”

Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021

“…Typically, non-small cell lung cancer (NSCLC) occupies 80% of lung cancer cases [ 31 ]. Recently, great progress has been made in identifying novel diagnostic and prognostic biomarkers for lung cancer, including RBR E3 ubiquitin ligase [ 32 ], prostaglandin E synthase 3 (PTGES3) [ 33 ], fibroblast activation protein (FAP) [ 34 ], checkpoint inhibitor immunotherapy targeting programmed cell death 1 (PD1), and programmed death ligand 1 (PDL1) pathways [ 35 , 36 ]. However, the 5-year overall survival rate of lung cancer remains low among all the cancer types, and its high mortality can be ascribed to the fact that most patients are diagnosed at an advanced stage and the treatment options are thereby limited, with a 5-year survival rate of only 4% [ 37 ].…”