KRAS mutation subtypes in metastatic non-small cell lung cancer.

IF 2.9 3区医学 Q2 ONCOLOGY

American journal of cancer research Pub Date : 2025-07-15 eCollection Date: 2025-01-01 DOI:10.62347/GYHT4724

Ali Aytac, Bilgin Demir, Onur Yazdan Balcik, Tuba Ugur Tuzcu, Esin Oktay, Ibrahim Halil Erdogdu, Ozgur Tanriverdi, Ozan Yazici

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Abstract

The aim of this study is to determine the clinicopathologic features of KRAS mutant metastatic non-small cell lung cancer (NSCLC) patients and to determine the clinical, prognostic and survival differences between subtypes and their relationship with response to treatment. A total of 101 patients with KRAS mutant metastatic non-small cell lung cancer treated in 3 oncology centers between 2013 and 2024 were included in this retrospective, multicenter study conducted in Turkey. Molecular analysis was confirmed by next generation sequencing (NGS; QIAGEN Clinical Insight Interpretation, United States). The Kaplan-Meier method was used to compare progression-free (PFS) and overall survival (OS) times between KRAS subgroups. KRAS G12C mutation was detected in 69 (68.3%) and KRAS non-G12C mutation in 32 (31.7%) patients. In both groups, the majority of patients were male (91.3% vs. 84.4%), smokers or former smokers (92.8% vs. 90.6%) and histologically had adenocarcinoma subtype (88.4% vs. 81.3%). There was no statistically significant difference in PD-L1 expression (21.7% vs. 34.4%, P: 0.132). In the KRAS non-G12C group, the most common mutations were G12V 15 (14.8%) and G12D 6 (5.9%). The most common co-mutation accompanying KRAS G12C mutation was TP53 (23%), while the most common co-mutation accompanying KRAS non-G12C was Rictor (36.3%). While 23 (33.3%) patients with KRAS G12C mutation developed brain metastasis, this rate was 14 (43.8%) in the KRAS non-G12C mutation group (P=0.312). Median follow-up was 15.30 (0.3-112.0) months. The objective response rate (ORR) with first-line treatment was 47.5% in the KRAS G12C group and 48.3% in the KRAS non-G12C group (P: 0.657). Median PFS was 4.46 (2.85-6.08) months in the KRAS G12C group and 5.23 (3.46-6.99) months in the KRAS non-G12C group (P: 0.852). Median overall survival was 14.46 (8.34-20.58) months in the KRAS G12C group and 15.36 (5.01-25.71) months in the KRAS non-G12C group (P: 0.201). In KRAS mutant metastatic NSCLC patients, no significant difference was found between KRAS subtypes (G12C vs. non-G12C) in terms of clinical, prognostic and survival data.

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转移性非小细胞肺癌的KRAS突变亚型。

本研究的目的是确定KRAS突变转移性非小细胞肺癌（NSCLC）患者的临床病理特征，确定亚型之间的临床、预后和生存差异及其与治疗反应的关系。这项在土耳其进行的多中心回顾性研究纳入了2013年至2024年间在3个肿瘤中心接受治疗的101例KRAS突变转移性非小细胞肺癌患者。通过下一代测序(NGS；QIAGEN Clinical Insight Interpretation，美国)。采用Kaplan-Meier法比较KRAS亚组间的无进展（PFS）和总生存（OS）时间。KRAS G12C突变69例（68.3%），KRAS非G12C突变32例（31.7%）。在两组中，大多数患者为男性（91.3% vs. 84.4%），吸烟者或前吸烟者（92.8% vs. 90.6%），组织学上患有腺癌亚型（88.4% vs. 81.3%）。两组PD-L1表达差异无统计学意义（21.7% vs. 34.4%, P: 0.132）。在KRAS非g12c组中，最常见的突变是g12v15（14.8%）和g12d6（5.9%）。KRAS G12C突变最常见的共突变是TP53 (23%)， KRAS非G12C突变最常见的共突变是Rictor（36.3%）。KRAS G12C突变组有23例（33.3%）发生脑转移，而KRAS非G12C突变组有14例（43.8%）发生脑转移（P=0.312）。中位随访时间为15.30（0.3-112.0）个月。一线治疗的客观缓解率（ORR） KRAS G12C组为47.5%，KRAS非G12C组为48.3% （P: 0.657）。KRAS G12C组的中位PFS为4.46（2.85-6.08）个月，KRAS非G12C组的中位PFS为5.23（3.46-6.99）个月（P: 0.852）。KRAS G12C组的中位总生存期为14.46（8.34-20.58）个月，KRAS非G12C组的中位总生存期为15.36（5.01-25.71）个月（P: 0.201）。在KRAS突变的转移性NSCLC患者中，在临床、预后和生存数据方面，KRAS亚型（G12C与非G12C）之间没有发现显著差异。

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来源期刊

American journal of cancer research ONCOLOGY-

自引率

3.80%

发文量

263

期刊介绍： The American Journal of Cancer Research (AJCR) (ISSN 2156-6976), is an independent open access, online only journal to facilitate rapid dissemination of novel discoveries in basic science and treatment of cancer. It was founded by a group of scientists for cancer research and clinical academic oncologists from around the world, who are devoted to the promotion and advancement of our understanding of the cancer and its treatment. The scope of AJCR is intended to encompass that of multi-disciplinary researchers from any scientific discipline where the primary focus of the research is to increase and integrate knowledge about etiology and molecular mechanisms of carcinogenesis with the ultimate aim of advancing the cure and prevention of this increasingly devastating disease. To achieve these aims AJCR will publish review articles, original articles and new techniques in cancer research and therapy. It will also publish hypothesis, case reports and letter to the editor. Unlike most other open access online journals, AJCR will keep most of the traditional features of paper print that we are all familiar with, such as continuous volume, issue numbers, as well as continuous page numbers to retain our comfortable familiarity towards an academic journal.