Fang Qiyu, Wan Xiaoying, D'Aiello Angelica, Sun Hui, Gu Weiquing, Li Yixue, Zhou Caicun, Xie Boxiong, Deng Qinfang, Cheng Haiying, Zhou Songwen
Medical College of Soochow University, Suzhou, Jiangsu, China.
Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Front Oncol. 2023 Jul 12;13:1116809. doi: 10.3389/fonc.2023.1116809. eCollection 2023.
Despite the benefit of adjuvant systemic therapy for patients with resected non-small cell lung cancer (NSCLC), the risk of postoperative recurrence remains high. Our objective was to characterize temporal genetic heterogeneity between primary resected and recurrent tumors, and its impact on treatment outcomes.
In this study, next-generation sequencing (NGS) testing was performed on tissue specimens and circulating tumor DNA (ctDNA) collected at postoperative recurrence, and results were compared to the genotypes of initial surgical specimens.
Of forty-five patients with matched primary and post-operative recurrent tumors, EGFR status switched in 17 patients (37.8%) at post-operative recurrence and 28 patients (62.2%) had no genotype change (17 mutant, 11 wild-type). Based on the changes of EGFR status, patients were divided into 4 groups. Following subsequent treatment with EGFR TKI o chemotherapy: In group A, with sustained sensitive mutation, the percentage achieving partial response (PR) was the highest, at 72.2%, the median progression-free survival (PFS) was 17 months, and the median overall survival (OS) was 44.0 months respectively; In group B, with genotype changed from wild-type to mutant, 50% achieved PR, PFS was 10 months, and OS was 35 months; In group C, in which mutant status shifted to wild-type or new co-mutation emerged, the percentage achieving PR was 30%, PFS was 9 months, and OS was 35 months. In group D, with sustained wild type, the percentage achieving PR was 27.3%, PFS was 8 months, and OS was 22 months.
Genotypic shift between paired primary and post-operative recurrent tumors was not infrequent, and this temporal genomic heterogeneity substantially impacted subsequent treatment outcomes.
尽管辅助性全身治疗对接受手术切除的非小细胞肺癌（NSCLC）患者有益，但术后复发风险仍然很高。我们的目的是描述原发性手术切除肿瘤与复发性肿瘤之间的时间性基因异质性及其对治疗结果的影响。
在本研究中，对术后复发时收集的组织标本和循环肿瘤DNA（ctDNA）进行了二代测序（NGS）检测，并将结果与初始手术标本的基因型进行比较。
在45例原发性肿瘤与术后复发性肿瘤配对的患者中，17例（37.8%）患者术后复发时表皮生长因子受体（EGFR）状态发生改变，28例（62.2%）患者基因型未改变（17例突变型，11例野生型）。根据EGFR状态的变化，将患者分为4组。在接受EGFR酪氨酸激酶抑制剂（TKI）或化疗的后续治疗后：A组为持续敏感突变，达到部分缓解（PR）的百分比最高，为72.2%，无进展生存期（PFS）中位数为17个月，总生存期（OS）中位数为44.0个月；B组基因型从野生型变为突变型，50%达到PR，PFS为10个月，OS为35个月；C组突变状态转变为野生型或出现新的共突变，达到PR的百分比为30%，PFS为9个月，OS为35个月。D组为持续野生型，达到PR的百分比为27.3%，PFS为8个月，OS为22个月。
配对的原发性肿瘤与术后复发性肿瘤之间的基因型转变并不罕见，这种时间性基因组异质性对后续治疗结果有重大影响。
