Purpose

Major pathological response (MPR) has become a surrogate endpoint for overall survival (OS) in non-small cell lung cancer (NSCLC) after neoadjuvant therapy, however, the prognostic histologic features and optimal N descriptor after neoadjuvant therapy are poorly defined.

Methods

We retrospectively analyzed data from 368 NSCLC patients who underwent surgery after neoadjuvant chemotherapy (NAC) from January 2010 to December 2020. The percentage of residual viable tumors in the primary tumor, lymph nodes (LN), and inflammation components within the tumor stroma were comprehensively reviewed. The primary endpoint was OS.

Results

Of the 368 enrolled patients, 12.0% (44/368) achieved MPR in the primary tumor, which was associated with significantly better OS (HR, 0.36 0.17–0.77, p = 0.008) and DFS (HR = 0.59, 0.36–0.92, p = 0.038). In patients who did not have an MPR, we identified an immune-activated phenotype in primary tumors, characterized by intense tumor-infiltrating lymphocyte or multinucleated giant cell infiltration, that was associated with similar OS and DFS as patients who had MPR. Neoadjuvant pathologic grade (NPG), consisting of MPR and immune-activated phenotype, identified 30.7% (113/368) patients that derived significant OS (HR 0.28, 0.17–0.46, p < 0.001) and DFS (HR 0.44, 0.31–0.61, p < 0.001) benefit from NAC. Moreover, the combination of NPG and the number of positive LN stations (nS) in the multivariate analysis had a higher C-index (0.711 vs. 0.663, p < 0.001) than the ypTNM Stage when examining OS.

Conclusion

NPG integrated with nS can provide a simple, practical, and robust approach that may allow for better stratification of patients when evaluating neoadjuvant chemotherapy in clinical practice.

Graphical Abstract

中文翻译：

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病理反应和肿瘤基质免疫原性特征预测新辅助化疗后非小细胞肺癌的长期生存

目的

主要病理缓解（MPR）已成为非小细胞肺癌（NSCLC）新辅助治疗后总生存（OS）的替代终点，然而，新辅助治疗后的预后组织学特征和最佳 N 描述符尚不清楚。

方法

我们回顾性分析了2010年1月至2020年12月新辅助化疗（NAC）后接受手术的368例NSCLC患者的数据。综合分析了原发肿瘤中残留存活肿瘤的百分比、淋巴结（LN）和肿瘤间质内的炎症成分。已审查。主要终点是 OS。

结果

在 368 名入组患者中，12.0% (44/368) 在原发肿瘤中实现了 MPR，这与显着改善的 OS（HR，0.36 ± 0.17–0.77，p = 0.008）和 DFS（HR = 0.59，0.36–0.92，p = 0.038）。在没有 MPR 的患者中，我们在原发性肿瘤中发现了免疫激活表型，其特征是强烈的肿瘤浸润淋巴细胞或多核巨细胞浸润，这与有 MPR 的患者相似的 OS 和 DFS 相关。新辅助病理分级 (NPG) 由 MPR 和免疫激活表型组成，确定 30.7% (113/368) 的患者获得显着的 OS（HR 0.28, 0.17–0.46，p < 0.001）和 DFS（HR 0.44, 0.31–0.61） , p < 0.001) 从 NAC 中受益。此外，在检查 OS 时，多变量分析中 NPG 和阳性 LN 站数 (nS) 的组合具有比ypTNM 分期更高的 C 指数（0.711 对比 0.663， p < 0.001）。

结论

NPG 与 nS 相结合可以提供一种简单、实用且稳健的方法，可以在临床实践中评估新辅助化疗时更好地对患者进行分层。

图形概要