小规模 ROS1 突变型非小细胞肺癌（NSCLC）患者的临床病理和分子特征。

Clinicopathologic and molecular characteristics of small-scale ROS1-mutant non-small cell lung cancer (NSCLC) patients.

机构信息

University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, Germany; Lung Cancer Group Cologne, Cologne, Germany.

University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, Germany.

出版信息

Lung Cancer. 2023 Oct;184:107344. doi: 10.1016/j.lungcan.2023.107344. Epub 2023 Aug 12.

DOI:10.1016/j.lungcan.2023.107344

PMID:37579577

Abstract

BACKGROUND

ROS1 fusions are well treatable aberrations in NSCLC. Besides solvent-front mutations (SFM) in resistance to targeted therapy, small-scale ROS1 mutations are largely unknown. We exploratively analyzed the clinical and molecular characteristics of small-scale ROS1 mutations in NSCLC patients without activating ROS1 fusions or SFMs.

METHODS

Next-generation sequencing was performed on tissue samples from NSCLC patients within the Network Genomic Medicine. Patients with ROS1 fusions and SFMs were excluded. We analyzed clinical characteristics of patients harboring small-scale ROS1-mutations, ROS1- and co-occurring mutations, and their response to systemic therapy.

RESULTS

Of 10,396 patients analyzed, 101 (1.0%) patients harbored small-scale ROS1 mutations. Most patients were male (73.3%) and smokers (96.6%). Nearly half of the patients presented with squamous-cell carcinoma (SqCC, 40.4%). Most mutations were transversions (50.5%), and 66% were in the kinase domain. Besides TP53 mutations (65.3%), KRAS (22.8%), EGFR (5.9%), PIK3CA (9.9%) and FGFR1-4 mutations (8.9%) co-occurred. In 10 (9.9%) patients, ROS1 mutation was the only aberration detected. Median overall survival (mOS) differed significantly in patients with or without KRAS co-mutations (9.7 vs 21.5 months, p = 0.02) and in patients treated with or without immune-checkpoint blockade (ICB) during treatment (21.5 vs 4.4 months, p = 0.003).

CONCLUSION

The cohort's clinical characteristics contrasted ROS1-fused cohorts. Co-occurrence of KRAS mutations led to shortened survival and patients benefited from ICB. Our data does not support the idea of ROS1 small-scale mutations as strong oncogenic drivers in NSCLC, but rather as relevant bystanders altering the efficacy of treatment approaches.

摘要

背景

ROS1 融合是 NSCLC 中可治疗的异常。除了针对靶向治疗的溶剂前沿突变（SFM）外，小规模的 ROS1 突变在很大程度上尚未被发现。我们探索性地分析了无激活 ROS1 融合或 SFM 的 NSCLC 患者中小规模 ROS1 突变的临床和分子特征。

方法

在 Network Genomic Medicine 中对 NSCLC 患者的组织样本进行下一代测序。排除具有 ROS1 融合和 SFM 的患者。我们分析了携带小规模 ROS1 突变、ROS1 和共同突变的患者的临床特征，以及他们对全身治疗的反应。

结果

在分析的 10396 名患者中，有 101 名（1.0%）患者携带小规模 ROS1 突变。大多数患者为男性（73.3%）和吸烟者（96.6%）。近一半的患者为鳞状细胞癌（SqCC，40.4%）。大多数突变是颠换（50.5%），66%发生在激酶结构域。除了 TP53 突变（65.3%）、KRAS 突变（22.8%）、EGFR 突变（5.9%）、PIK3CA 突变（9.9%）和 FGFR1-4 突变（8.9%）外，还共同发生了 KRAS 突变。在 10 名（9.9%）患者中，ROS1 突变是唯一检测到的异常。有无 KRAS 共突变的患者的中位总生存期（mOS）差异有统计学意义（9.7 与 21.5 个月，p=0.02），以及治疗期间有无免疫检查点阻断（ICB）的患者的 mOS 差异也有统计学意义（21.5 与 4.4 个月，p=0.003）。