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Updated: Jan 28, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Imaging characteristics of BRAF-mutant non-small cell lung cancer by functional class
Dexter P Mendoza1, Ibiayi Dagogo-Jack2, Tianqi Chen3
1Department of Radiology, Massachusetts General Hospital, United States.
Objectives:
Mutations in the BRAF gene have emerged as a validated molecular target in the treatment of non-small cell lung cancer (NSCLC). These mutations can be classified into three functional classes based on their mechanisms of oncogenesis. The relationship between these functional classes and their imaging features has not been systematically investigated. The goal of this work is to determine if imaging features of the primary tumor and the pattern of metastasis correlate with the functional class of BRAF mutation.
Methods:
We reviewed pre-treatment computed tomography (CT) images of patients with BRAF-mutated NSCLC with known functional class. We assessed and recorded the features of the primary tumor and the patterns of lymphadenopathy and distant metastasis. Wilcoxon rank-sum test and Kruskal-Wallis test were performed to compare continuous characteristics, and Fisher's exact test was used to compare categorical features between groups.
Results And Conclusions:
105 patients with BRAF-mutant NSCLC had pre-treatment imaging available for review (n = 43 class I, n = 40 class II, and n = 22 class III). Approximately half of the primary tumors were considered masses (n = 54/105, 51%) and most were solid (n = 81/105, 77%). There were no statistically significant differences in imaging features of the primary tumor among the three functional classes. Intrathoracic metastases occurred more frequently in class I tumors compared to tumors with class II and III mutations (p = 0.03). The odds of class I mutation were higher among tumors involving the pleural space (OR: 4.39, 95% CI: 1.11-17.4) and lower among tumors disseminating to the abdomen (OR: 0.25, 95% CI: 0.07-0.92). Our findings suggest that class I (V600) mutated NSCLC may be more likely to have intrathoracic metastases, while classes II and III (non-V600) mutated NSCLC may be more likely to have intra-abdominal metastases at the time of presentation.
Insights
Imaging features of BRAF-mutant non-small cell lung cancer (NSCLC) can predict metastasis patterns. Class I BRAF mutations are linked to intrathoracic spread, while Classes II and III suggest intra-abdominal metastasis.
Area of Science:
- Oncology
- Radiology
- Genetics
Background:
- BRAF gene mutations are key targets in non-small cell lung cancer (NSCLC) treatment.
- BRAF mutations are categorized into three functional classes based on oncogenic mechanisms.
- The correlation between BRAF mutation functional classes and their corresponding imaging features remains underexplored.
Purpose of the Study:
- To investigate if primary tumor imaging characteristics and metastasis patterns correlate with the functional class of BRAF mutations in NSCLC.
- To establish a link between specific BRAF mutation subclasses and their propensity for distinct metastatic sites.
Main Methods:
- Retrospective review of pre-treatment computed tomography (CT) scans from 105 patients with BRAF-mutant NSCLC.
- Assessment of primary tumor features, lymphadenopathy, and distant metastasis patterns.
- Statistical analysis using Wilcoxon rank-sum, Kruskal-Wallis, and Fisher's exact tests to compare groups.
Main Results:
- No significant differences in primary tumor imaging features were observed across the three BRAF functional classes.
- Class I BRAF-mutated NSCLC showed a higher frequency of intrathoracic metastases (p=0.03).
- Class I mutations were associated with pleural space involvement, while Classes II and III were linked to abdominal dissemination.
Conclusions:
- Imaging features of primary tumors do not reliably differentiate BRAF mutation functional classes in NSCLC.
- Metastasis patterns differ significantly based on BRAF mutation class, with Class I favoring intrathoracic spread and Classes II/III favoring intra-abdominal spread.
- These findings may aid in predicting metastatic behavior in BRAF-mutant NSCLC based on imaging.
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