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通过对转移性非小细胞肺癌中程序性死亡受体配体1(PD-L1)表达进行定量连续评分来优化患者选择,用于免疫肿瘤治疗。

Enhanced patient selection with quantitative continuous scoring of PD-L1 expression for IO treatment in metastatic NSCLC.

作者信息

Lesniak J, Schick M, Kunzke T, Pollastri F, Vigueras-Guillén J P, Hessel H, Haneder S, Sontakke P, DaCosta K, Alleze R, Zimmermann J, Kapil A, Brieu N, Shumilov A, Sade H, Barrett J C, Schmidt G, Stewart R

机构信息

AstraZeneca Computational Pathology GmbH, Munich, Germany.

AstraZeneca Early Oncology Translational Medicine, Oncology R&D, Gaithersburg, MD, USA.

出版信息

NPJ Precis Oncol. 2025 Sep 18;9(1):315. doi: 10.1038/s41698-025-01107-0.

Abstract

Immune checkpoint inhibitors targeting PD-1/PD-L1 are approved for metastatic non-small-cell lung cancer treatment. In clinical practice, the treatment choice depends on visual scoring of PD-L1, which is subjective and semi-quantitative. In this work, we present PD-L1 Quantitative Continuous Scoring (PD-L1 QCS), a computer vision system for granular cell-level quantification of PD-L1 staining intensity in digitized whole slide images (WSI). We derived a biomarker which captures the percentage of tumor cells (TC) with medium to strong staining intensity (PD-L1 QCS-PMSTC) and classifies patients with ≥0.575% as biomarker positive (BM+). Its effectiveness was examined against visual scoring of %TC ≥ 50 in 768 WSI from the MYSTIC trial (NCT02453282). Considering anti-PD-L1 treatment (N = 256) vs. chemotherapy (N = 246), visual scoring resulted in a hazard ratio (HR) of 0.69 (CI 0.46-1.02) with a 29.7% prevalence of the BM+ group. With PD-L1 QCS-PMSTC, a similar HR of 0.62 (CI 0.46-0.82) with an increased prevalence of 54.3% was obtained.

摘要

靶向PD-1/PD-L1的免疫检查点抑制剂已被批准用于转移性非小细胞肺癌的治疗。在临床实践中,治疗选择取决于PD-L1的视觉评分,这是主观的且半定量的。在这项工作中,我们提出了PD-L1定量连续评分(PD-L1 QCS),这是一种用于在数字化全切片图像(WSI)中对PD-L1染色强度进行颗粒细胞水平定量的计算机视觉系统。我们得出了一种生物标志物,它可以捕获中等至强染色强度的肿瘤细胞(TC)百分比(PD-L1 QCS-PMSTC),并将≥0.575%的患者分类为生物标志物阳性(BM+)。在来自MYSTIC试验(NCT02453282)的768张WSI中,针对%TC≥50的视觉评分检验了其有效性。考虑抗PD-L1治疗组(N = 256)与化疗组(N = 246),视觉评分得出的风险比(HR)为0.69(CI 0.46 - 1.02),BM+组的患病率为29.7%。使用PD-L1 QCS-PMSTC,得到了相似的HR为0.62(CI 0.46 - 0.82),患病率增加到54.3%。

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