Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Institute of Thoracic Oncology, Fudan University, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Institute of Thoracic Oncology, Fudan University, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
J Thorac Oncol. 2021 Oct;16(10):1684-1693. doi: 10.1016/j.jtho.2021.07.006. Epub 2021 Jul 22.
We aimed to validate the use of the novel grading system proposed by the International Association for the Study of Lung Cancer pathology committee for prognosis stratification of invasive pulmonary adenocarcinomas (ADCs) in Chinese patients. Correlations between the grading system, common driver mutations, and adjuvant chemotherapy (ACT) were also investigated.
From 2008 to 2016, the histologic patterns of a large cohort of 950 patients with invasive ADCs (stage I-III) were retrospectively analyzed and classified according to the proposed grading system. Subsequently, tumor grading was correlated with genetic data, ACT, and patient outcome.
Compared with conventional predominant pattern-based groups, the novel grading system carried improved survival discrimination (area under the curve = 0.768 for recurrence-free survival and 0.775 for overall survival). The area under the curve was not further improved when incorporated lymphovascular invasion status. EGFR mutations (p < 0.001) were correlated with moderate grade, whereas KRAS mutations (p = 0.041) and ALK fusions (p = 0.021) were significantly more prevalent in poor grade. The reclassification of the grading system based on EGFR mutation status revealed excellent survival discrimination (p < 0.001). In particular, patients on stage Ib to III with novel high-grade ADCs had an improved prognosis with ACT.
The novel International Association for the Study of Lung Cancer grading system is a practical and efficient discriminator for patient prognosis and should be part of an integrated pathologic-genetic subtyping to improve survival prediction. In addition, it may support patient stratification for aggressive adjuvant chemotherapy.
我们旨在验证国际肺癌研究协会病理学委员会提出的新型分级系统在预测中国浸润性肺腺癌（ADC）患者预后中的应用。还研究了分级系统、常见驱动基因突变与辅助化疗（ACT）之间的相关性。
回顾性分析了 2008 年至 2016 年期间，一个包含 950 例浸润性 ADC（I-III 期）患者的大样本队列的组织学模式，并根据提出的分级系统进行分类。随后，将肿瘤分级与遗传数据、ACT 和患者结局进行了关联。
与传统的主要模式分组相比，新型分级系统具有更好的生存区分能力（无复发生存的曲线下面积为 0.768，总生存的曲线下面积为 0.775）。纳入脉管侵犯状态后，曲线下面积没有进一步提高。EGFR 突变（p<0.001）与中等级相关，而 KRAS 突变（p=0.041）和 ALK 融合（p=0.021）在低等级中更为常见。基于 EGFR 突变状态对分级系统进行重新分类可显著提高生存区分能力（p<0.001）。特别是，新型高等级 ADC 的 Ib 期至 III 期患者接受 ACT 治疗后预后改善。
新型国际肺癌研究协会分级系统是一种实用且有效的患者预后判别工具，应作为综合病理-遗传亚型的一部分，以提高生存预测。此外，它可能支持积极辅助化疗的患者分层。
