Prognostic significance of volume-based 18F-FDG PET/CT parameters and correlation with PD-L1 expression in patients with surgically resected lung adenocarcinoma

Abstract

The aim of this study was to retrospectively analyze 18F-FDG positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic variables, programmed death-ligand 1 (PD-L1) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) tumor expression, and other factors as predictors of disease-free survival (DFS) in patients with lung adenocarcinoma (LUAD) (stage IA-IIIA) who underwent surgical resection. We still lack predictor of immune checkpoint (programmed cell death-1 [PD-1]/PD-L1) inhibitors. Herein, we investigated the correlation between metabolic parameters from 18F-FDG PET/CT and PD-L1 expression in patients with surgically resected LUAD.Seventy-four patients who underwent 18F-FDG PET/CT prior to treatment were consecutively enrolled. The main 18F-FDG PET/CT-derived variables were primary tumor maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Surgical tumor specimens were analyzed for PD-L1 and p-STAT3 expression using immunohistochemistry. Correlations between immunohistochemistry results and 18F-FDG PET/CT-derived variables were compared. Associations of PD-L1 and p-STAT3 tumor expression, 18F-FDG PET/CT-derived variables, and other factors with DFS in resected LUAD were evaluated.All tumors were FDG-avid. The cutoff values of low and high SUVmax, MTV, and TLG were 12.60, 14.87, and 90.85, respectively. The results indicated that TNM stage, PD-L1 positivity, and high 18F-FDG PET/CT metabolic volume parameters (TLG ≥90.85 or MTV ≥14.87) were independent predictors of worse DFS in resected LUAD. No 18F-FDG metabolic parameters associated with PD-L1 expression were observed (chi-square test), but we found that patients with positive PD-L1 expression have significantly higher SUVmax (P = .01), MTV (P = .00), and TLG (P = .00) than patients with negative PD-L1 expression.18F-FDG PET/CT metabolic volume parameters (TLG ≥90.85 or MTV ≥14.87) were more helpful in prognostication than the conventional parameter (SUVmax), PD-L1 expression was an independent predictor of DFS in patients with resected LUAD. Metabolic parameters on 18F-FDG PET/CT have a potential role for 18F-FDG PET/CT in selecting candidate LUAD for treatment with checkpoint inhibitors.

Figure 1

ROC curve for the determination of the most discriminative cutoff point for SUVmax, metabolic tumor volume-MTV, and total lesion glycolysis-TLG in primary tumors. The optimal cutoff values for SUVmax, MTV, and TLG were 12.60, 14.87, and 90.58, respectively. SUVmax = maximum standardized uptake value.

Figure 2

A typical case of PET/CT volumetric metabolic parameters. The patient was a 55-year-old male with stage IIA moderately differentiated adenocarcinoma. PET/CT metabolic parameters were: SUVmax, 13.45; metabolic tumor volume (MTV), 5.61; and total lesion glycolysis (TLG), 34.68. Disease-free survival (DFS) was 50.5 months. PET/CT = positron emission tomography/computed tomography, SUVmax = maximum standardized uptake value.

Figure 3

A typical case of PET/CT volumetric metabolic parameters. A 61-year-old male with stage IIA poorly differentiated adenocarcinoma. PET/CT metabolic parameters were: SUVmax, 14.26; metabolic tumor volume (MTV), 36.90; and total lesion glycolysis (TLG), 319.23. DFS was 20.8 months. DFS = disease-free survival, PET/CT = positron emission tomography/computed tomography, SUVmax = maximum standardized uptake value.

Figure 4

IHC staining for PD-L1/p-STAT3 in pulmonary adenocarcinoma specimens. (A) Positive expression of PD-L1 in pulmonary adenocarcinoma. (B) Positive expression of p-STAT3 in pulmonary adenocarcinoma. (C) Negative. The magnification is ×200. PD-L1 = programmed death-ligand 1, p-STAT3 = phosphorylated signal transducer and activator of transcription 3.

Figure 5

Kaplan-Meier curve analyses of disease-free survival (DFS) of 74 patients with resected lung adenocarcinoma. (A) DFS according to staging. (B) Kaplan-Meier analysis of DFS according to PD-L1 expression. (C) Kaplan-Meier analysis of DFS according to the total lesion glycolysis (TLG). (D) Kaplan-Meier analysis of DFS according to the metabolic tumor volume (MTV). PD-L1 = programmed death-ligand 1.