European radiology · 2025
Non-invasive PD-L1 stratification in non-small cell lung cancer using dynamic contrast-enhanced MRI.
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Messana Gaia, Bortolotto Chandra, Thulasi Seetha Sithin, Marrocco Alessandra, Pairazzi Carlotta, Sanvito Francesco, Brero Francesca, Robustelli Test Agnese, Cabini Raffaella Fiamma, Lascialfari Alessandro, Zacà Domenico, Stella Giulia Maria, Agustoni Francesco, Saddi Jessica, Filippi Andrea Riccardo, Preda Lorenzo
Аннотация
OBJECTIVES: 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.
MATERIALS AND 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.
RESULTS: 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). Ktrans median (0.25 vs. 0.12 min-¹, p = 0.02), Ktrans standard deviation (0.32 vs. 0.23 min-¹, p = 0.01) and Kep 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).
CONCLUSION: 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.
KEY POINTS: 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 Ktrans (the volume transfer rate) and Kep (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.
MATERIALS AND 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.
RESULTS: 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). Ktrans median (0.25 vs. 0.12 min-¹, p = 0.02), Ktrans standard deviation (0.32 vs. 0.23 min-¹, p = 0.01) and Kep 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).
CONCLUSION: 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.
KEY POINTS: 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 Ktrans (the volume transfer rate) and Kep (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.