Wolf J L, Trandafir T E, Akram F, Andrinopoulou E R, Maat A W P M, Mustafa D A M, Kros J M, Stubbs A P, Dingemans A C, von der Thüsen J H
Department of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Lung Cancer. 2023 Feb;176:112-120. doi: 10.1016/j.lungcan.2022.12.018. Epub 2022 Dec 30.
Since lung adenocarcinoma (LUAD) biopsies are usually small, it is questionable if their prognostic and predictive information is comparable to what is offered by large resection specimens. This study compares LUAD biopsies and resection specimens for their ability to provide prognostic and predictive parameters.
We selected 187 biopsy specimens with stage I and II LUAD. In 123 cases, subsequent resection specimens were also available. All specimens were evaluated for growth pattern, nuclear grade, fibrosis, inflammation, and genomic alterations. Findings were compared using non-parametric testing for categorical variables. Model performance was assessed using the area under the curve for both biopsies and resection specimens, and overall (OS) and disease-free survival (DFS) was calculated.
The overall growth pattern concordance between biopsies and resections was 73.9%. The dominant growth pattern correlated with OS and DFS in resected adenocarcinomas and for high-grade growth pattern in biopsies. Multivariate analysis of biopsy specimens revealed that T2-tumors, N1-status, KRAS mutations and a lack of other driver mutations were associated with poorer survival. Model performance using clinical, histological and genetic data from biopsy specimens for predicting OS and DSF demonstrated an AUC of 0.72 and 0.69, respectively.
Our data demonstrated the prognostic relevance of a high-grade growth pattern in biopsy specimens of LUAD. Combining clinical, histological and genetic information in one model demonstrated a suboptimal performance for DFS prediction and good performance for OS prediction. However, for daily practice, more robust (bio)markers are required to predict prognosis and stratify patients for therapy and follow-up.
由于肺腺癌（LUAD）活检样本通常较小，其预后和预测信息是否与大的切除标本相当尚存在疑问。本研究比较了LUAD活检样本和切除标本提供预后和预测参数的能力。
我们选取了187例I期和II期LUAD活检标本。其中123例随后也获得了切除标本。对所有标本评估生长模式、核分级、纤维化、炎症和基因组改变。使用非参数检验对分类变量的结果进行比较。使用活检标本和切除标本的曲线下面积评估模型性能，并计算总生存期（OS）和无病生存期（DFS）。
活检标本和切除标本的总体生长模式一致性为73.9%。在切除的腺癌中，主要生长模式与OS和DFS相关，在活检标本中与高级别生长模式相关。对活检标本的多变量分析显示，T2期肿瘤、N1状态、KRAS突变以及缺乏其他驱动基因突变与较差的生存率相关。使用活检标本的临床、组织学和基因数据预测OS和DSF的模型性能显示，曲线下面积（AUC）分别为0.72和0.69。
我们的数据证明了LUAD活检标本中高级别生长模式的预后相关性。将临床、组织学和基因信息整合到一个模型中，对DFS预测表现欠佳，对OS预测表现良好。然而，在日常实践中，需要更可靠的（生物）标志物来预测预后，并对患者进行治疗和随访分层。
