Background

PD-L1 expression determination defines eligibility for treatment with pembrolizumab in patients with advanced non-small cell lung cancer (NSCLC). This study was designed to better define which value across core biopsies from the same case more closely reflects the PD-L1 expression status on whole sections and how many biopsies are needed for confident classification of tumors in terms of PD-L1 expression.

Materials and Methods

We built tissue microarrays as surrogate of biopsies collecting 5 cores per case from 268 cases and compared PD-L1 staining results using validated clone SP263 with tumor whole sections.

Results

We found an overall positivity in 39% of cases at 1% cutoff and 10% of cases at 50% cutoff. The maximum value across cores was associated with high concordance between cores and whole sections and the lowest number of false negative cases overall. In order to reach high concordance with whole sections, 4 and 3 cores are necessary at 1% and 50% cutoff, respectively. Importantly, with 20% as cutoff on biopsies, less than 3 cores showed high sensitivity and specificity in identifying cases with ≥50% of tumor cells positive for PD-L1 on whole sections.

Specifically, for PD-L1 values of 20-49% on cores, the probability of tumor specimen expressing PD-L1 in ≥ 50% of cells on whole section is 46% and 24% with 1 and 2 biopsies, respectively.

Conclusions

An accurate definition of the criteria to determine the PD-L1 status of a given tumor may greatly help to select those patients who could benefit from anti-PD1/PD-L1 treatment.

中文翻译：

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非小细胞肺癌中PD-L1表达异质性：定义活检组织和整个切片之间协调的标准

背景

PD-L1表达的确定定义了使用pembrolizumab治疗晚期非小细胞肺癌（NSCLC）患者的资格。这项研究旨在更好地确定来自同一病例的所有核心活检中的哪个值更紧密地反映了整个切片上PD-L1的表达状态，以及根据PD-L1表达对肿瘤进行可靠分类所需的活检数。

材料和方法

我们建立了组织微阵列作为活检的替代物，从268例病例中每例收集了5个核心，并使用经过验证的SP263克隆与肿瘤整个切片比较了PD-L1染色结果。

结果

我们发现，在1％截止水平时有39％的病例和在50％截止水平时有10％的病例的总体阳性率。核心之间的最大值与核心与整个部分之间的高度一致性以及总的假阴性案例数最少有关。为了与整个截面保持高度一致性，分别需要4％和3％的磁芯（截止频率为1％）。重要的是，以20％作为活检的截止值，少于3个核心显示出高的敏感性和特异性，可用于鉴定整个切片中≥50％的PD-L1阳性肿瘤细胞的情况。

具体而言，对于核心上的PD-L1值为20-49％，在进行1次和2次活检时，肿瘤标本在整个切片中≥50％的细胞中表达PD-L1的可能性分别为46％和24％。

结论

确定给定肿瘤的PD-L1状态的标准的准确定义可能会极大地帮助选择那些可以从抗PD1 / PD-L1治疗中受益的患者。