Genomic characteristics, survival, and prognostic analysis of advanced non-small cell lung cancer with KRAS mutations and brain metastases.
- 1Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Wenzhou Medical University, Hangzhou, China.
- 2Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
- 3Phase I Clinical Trial Ward, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Abstract
The brain is a common site of metastasis in lung cancer. However, data on the incidence of brain metastases (BM) and survival outcomes among patients with non-small cell lung cancer (NSCLC) harboring KRAS mutations, particularly those receiving tyrosine kinase inhibitors (TKIs), remain limited. This single-center retrospective study aimed to characterize the incidence of BM in patients with KRAS-mutant NSCLC and identify prognostic factors associated with survival. A total of 4,021 patients with advanced NSCLC hospitalized at Zhejiang Cancer Hospital between January 2017 and December 2024 were screened. The primary endpoint was overall survival (OS), defined as the interval from BM diagnosis to death or the last follow-up. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors associated with OS were evaluated using univariable and multivariable Cox proportional hazards regression analyses. Among 301 patients with KRAS-mutant NSCLC, 57 (18.9%) had BM at initial diagnosis, and 91 (30.2%) developed BM overall. The incidence of BM according to KRAS subtypes was 36.1% (39/108) for G12C, 26.3% (10/38) for G12D, 32.4% (12/37) for G12V, and 38.1% (8/21) for G12A; no statistically significant difference was observed among these subtypes. At the follow-up cutoff date of March 5, 2026, the median OS of all patients with KRAS-mutant NSCLC was 23.5 months [95% confidence interval (CI): 21.6-29.2 months]. Among patients with BM, the median OS was 18.6 months (95% CI: 15.9-23.9 months). No significant difference in OS was observed between patients with KRAS G12C and those with other KRAS subtypes (22.4 vs. 17.4 months, P=0.18). After BM diagnosis, 70 patients received immunotherapy and 19 received TKIs. TKI therapy was not associated with an OS benefit among patients with KRAS G12C mutations (22.4 vs. 23.9 months, P=0.71). Patients with TP53 co-mutations had significantly longer OS than those without TP53 co-mutations (31.9 vs. 16.3 months, P=0.03). Patients receiving immunotherapy also had significantly longer OS (22.3 vs. 10.9 months, P<0.001). In addition, brain stereotactic radiosurgery (SRS) was associated with improved survival (23.9 vs. 13.7 months, P=0.02). Multivariate analysis identified age, immunotherapy, brain SRS, and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent predictors of OS (all P<0.05). BM is associated with an unfavorable prognosis in patients with KRAS-mutant NSCLC. TP53 co-mutations and higher diagnosis-specific graded prognostic assessment (DS-GPA) scores were associated with improved OS. Immunotherapy and brain SRS were significantly associated with prolonged survival.
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BibTeX
@article{chen2026genomic,
title = {{Genomic characteristics, survival, and prognostic analysis of advanced non-small cell lung cancer with KRAS mutations and brain metastases.}},
author = {Yi Chen and Xiheng Yu and Mengqi Bao and Xiaoqing Yu and Yuwei Li and Jing Sun and Linjing Zhou and Yunfeng Tong and Yun Fan},
journal = {Translational lung cancer research},
year = {2026},
month = sep,
doi = {10.21037/tlcr-2026-0775},
url = {https://europepmc.org/article/MED/42999419},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Genomic characteristics, survival, and prognostic analysis of advanced non-small cell lung cancer with KRAS mutations and brain metastases.
AU - Yi Chen
AU - Xiheng Yu
AU - Mengqi Bao
AU - Xiaoqing Yu
AU - Yuwei Li
AU - Jing Sun
AU - Linjing Zhou
AU - Yunfeng Tong
AU - Yun Fan
PY - 2026
DA - 2026/09/29
JO - Translational lung cancer research
DO - 10.21037/tlcr-2026-0775
UR - https://europepmc.org/article/MED/42999419
AB - The brain is a common site of metastasis in lung cancer. However, data on the incidence of brain metastases (BM) and survival outcomes among patients with non-small cell lung cancer (NSCLC) harboring KRAS mutations, particularly those receiving tyrosine kinase inhibitors (TKIs), remain limited. This single-center retrospective study aimed to characterize the incidence of BM in patients with KRAS-mutant NSCLC and identify prognostic factors associated with survival. A total of 4,021 patients with advanced NSCLC hospitalized at Zhejiang Cancer Hospital between January 2017 and December 2024 were screened. The primary endpoint was overall survival (OS), defined as the interval from BM diagnosis to death or the last follow-up. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors associated with OS were evaluated using univariable and multivariable Cox proportional hazards regression analyses. Among 301 patients with KRAS-mutant NSCLC, 57 (18.9%) had BM at initial diagnosis, and 91 (30.2%) developed BM overall. The incidence of BM according to KRAS subtypes was 36.1% (39/108) for G12C, 26.3% (10/38) for G12D, 32.4% (12/37) for G12V, and 38.1% (8/21) for G12A; no statistically significant difference was observed among these subtypes. At the follow-up cutoff date of March 5, 2026, the median OS of all patients with KRAS-mutant NSCLC was 23.5 months [95% confidence interval (CI): 21.6-29.2 months]. Among patients with BM, the median OS was 18.6 months (95% CI: 15.9-23.9 months). No significant difference in OS was observed between patients with KRAS G12C and those with other KRAS subtypes (22.4 vs. 17.4 months, P=0.18). After BM diagnosis, 70 patients received immunotherapy and 19 received TKIs. TKI therapy was not associated with an OS benefit among patients with KRAS G12C mutations (22.4 vs. 23.9 months, P=0.71). Patients with TP53 co-mutations had significantly longer OS than those without TP53 co-mutations (31.9 vs. 16.3 months, P=0.03). Patients receiving immunotherapy also had significantly longer OS (22.3 vs. 10.9 months, P<0.001). In addition, brain stereotactic radiosurgery (SRS) was associated with improved survival (23.9 vs. 13.7 months, P=0.02). Multivariate analysis identified age, immunotherapy, brain SRS, and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent predictors of OS (all P<0.05). BM is associated with an unfavorable prognosis in patients with KRAS-mutant NSCLC. TP53 co-mutations and higher diagnosis-specific graded prognostic assessment (DS-GPA) scores were associated with improved OS. Immunotherapy and brain SRS were significantly associated with prolonged survival.
SN - 2218-6751
SN - 2226-4477
ER -