Tumor glycolytic profiling through ¹⁸F-FDG PET/CT predicts immune checkpoint inhibitor efficacy in advanced NSCLC

Abstract

Background: A significant proportion of patients with non-small-cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICIs). Since metabolic reprogramming with increased glycolysis is a hallmark of cancer and is involved in immune evasion, we used 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) to evaluate the baseline glycolytic parameters of patients with advanced NSCLC submitted to ICIs, and assessed their predictive value. Methods: 18F-FDG PET/CT results in the 3 months before ICIs treatment were included. Maximum standardized uptake values, whole metabolic tumor volume (wMTV), and whole-body total lesion glycolysis (wTLG) were evaluated. Cutoff values for high or low glycolytic categories were determined using receiver-operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were evaluated. Patients with a complete response and a matching group with resistance to ICIs underwent immunohistochemistry analysis. An unsupervised k-means clustering model integrating programmed cell death ligand 1 (PD-L1) expression, glycolytic parameters, and ICIs therapy was performed. Results: In all, 98 patients were included. Lower baseline 18F-FDG PET/CT parameters were associated with responses to ICIs. Patients with low wMTV or wTLG had improved PFS and OS. High wTLG, strong tumor expression of glucose transporter-1, and lack of responses were significantly associated. Patients with low glycolytic parameters benefited from ICIs, regardless of chemotherapy. Conversely, those with high parameters benefited from the addition of chemotherapy. Patients with higher wTLG and lower PD-L1 were associated with progression and worse survival to ICIs monotherapy. Conclusions: Glycolytic metabolic profiles established through baseline 18F-FDG PET/CT are useful biomarkers for evaluating ICI therapy in advanced NSCLC.

Predictive Value of Total Metabolic Tumor Burden Prior to Treatment in NSCLC Patients Treated with Immune Checkpoint Inhibition

“…In summary, our results also might suggest that the predictive power of the total metabolic tumor burden prior to ICIs might be influenced by the value of the tumor burden itself, with poorer prediction performance at very high or very low values of the metabolic tumor burden in patients with advanced NSCLC. This is very much in keeping with the results recently published by Silva et al [44]. However, this study had a fairly heterogeneous patient collective.…”

Utility of 18F-FDG uptake in predicting major pathological response to neoadjuvant immunotherapy in patients with resectable non‑small cell lung cancer

“…Furthermore, the value of 18 F-FDG PET-CT in predicting therapeutic response and prognoses in patients with advanced NSCLC who receive ICIs treatment has also been verified in several studies [ 20 , 21 ]. Glycolytic metabolic profiles based on 18 F-FDG PET-CT have been reported to be useful biomarkers for evaluating therapeutic response to ICIs in advanced NSCLC [22] . Yet, the efficiency of 18 F-FDG PET-CT for evaluating MPR to neoadjuvant immunotherapy in resectable NSCLC and the advantage of 18 F-FDG uptake over conventional methods still lacks of systematic exploration.…”