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Objectives <p>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.</p> Materials and methods <p>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 (<i>R</i>²). Mann–Whitney U-test and ROC-AUC were used to assess correlation with PD-L1 for the best-fit configuration.</p> Results <p>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 (<i>R</i><sup>2</sup> = 0.79). K<sup>trans</sup> median (0.25 vs. 0.12 min<sup>−</sup>¹, <i>p</i> = 0.02), K<sup>trans</sup> standard deviation (0.32 vs. 0.23 min<sup>−</sup>¹, <i>p</i> = 0.01) and K<sub>ep</sub> median (1.09 vs. 0.59 min<sup>−</sup>¹, <i>p</i> = 0.02) were significantly higher in PD-L1 &lt; 50% group (ROC-AUC 0.71–0.76).</p> Conclusion <p>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.</p> Key Points <p><Emphasis Type="BoldItalic">Question</Emphasis> <i>Could Dynamic Contrast-Enhanced (DCE) MRI offer a safe and non-invasive way to assess Programmed Death-Ligand 1 (PD-L1) expression?</i></p> <p><Emphasis Type="BoldItalic">Findings</Emphasis> <i>Quantitative DCE-MRI parameters K</i><sup>trans</sup> (the volume transfer rate) and K<sub>ep</sub> (the efflux rate constant) show potential for distinguishing PD-L1 hyperexpression from hypoexpression.</p> <p><Emphasis Type="BoldItalic">Clinical relevance</Emphasis> <i>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.</i></p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月27日

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  • Gaia Messana,
  • Chandra Bortolotto,
  • Sithin Thulasi Seetha,
  • Alessandra Marrocco,
  • Carlotta Pairazzi,
  • Francesco Sanvito,
  • Francesca Brero,
  • Agnese Robustelli Test,
  • Raffaella Fiamma Cabini,
  • Alessandro Lascialfari,
  • Domenico Zacà,
  • Giulia Maria Stella,
  • Francesco Agustoni,
  • Jessica Saddi,
  • Andrea Riccardo Filippi,
  • Lorenzo Preda

摘要

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.

Graphical Abstract