Non-invasive PD-L1 stratification in non-small cell lung cancer using dynamic contrast-enhanced MRI.

Abstract

This study aimed to assess whether pharmacokinetic parameters derived from DCE-MRI can stratify Programmed Death-Ligand 1 (PD-L1) expression in NSCLC. The secondary aim was to identify a suitable pharmacokinetic model configuration for anisotropic temporally-spaced DCE-MRI sequences, considering Tofts variants, population-averaged arterial input functions (AIF), and bolus arrival time (BAT) estimation methods. From April 2021 to May 2023, patients with locally advanced non-small cell lung cancer (NSCLC) were prospectively enrolled. Tumors were categorized based on: PD-L1 absence/presence (threshold 1%) and hyperexpression/hypoexpression (threshold 50%). Pharmacokinetic parameters were extracted using several candidate configurations; fit quality was evaluated using coefficient of determination (R²). Mann-Whitney U-test and ROC-AUC were used to assess correlation with PD-L1 for the best-fit configuration. Thirty-eight patients (mean age 68 ± 9 years, 28 men) were included. PD-L1 expression was present in 25 patients (66%) and absent in 13 (34%). PD-L1 was hyperexpressed in 13 (34%) patients and hypoexpressed in 25 (66%). Voxel-wise pharmacokinetic parameters were extracted using the best-fit configuration-extended Tofts model (ETM) with Georgiou AIF and Peak-Gradient (PG) BAT estimation (R² = 0.79). K^trans median (0.25 vs. 0.12 min^-¹, p = 0.02), K^trans standard deviation (0.32 vs. 0.23 min^-¹, p = 0.01) and K_ep median (1.09 vs. 0.59 min^-¹, p = 0.02) were significantly higher in PD-L1 < 50% group (ROC-AUC 0.71-0.76). DCE-MRI pharmacokinetic parameters could stratify PD-L1 hypo/hyperexpression in NSCLC. The ETM with PG BAT estimation method and Georgiou AIF was the best-performing pharmacokinetic configuration. Question Could Dynamic Contrast-Enhanced (DCE) MRI offer a safe and non-invasive way to assess Programmed Death-Ligand 1 (PD-L1) expression? Findings Quantitative DCE-MRI parameters K^trans (the volume transfer rate) and K_ep (the efflux rate constant) show potential for distinguishing PD-L1 hyperexpression from hypoexpression. Clinical relevance Preliminary results suggest that DCE-MRI could be a safe method to stratify PD-L1 hypo/hyperexpression in non-small cell lung cancer, potentially optimizing treatment decisions, given the high cost of immunotherapy.