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Published on: July 21, 2018
Clinical and Imaging Features of Non-Small Cell Lung Cancer with G12C KRAS Mutation
Markus Y Wu1, Eric W Zhang1, Matthew R Strickland2
1Department of Radiology, Division of Thoracic Imaging and Intervention, Massachusetts General Hospital, Boston, MA 02114, USA.
Abstract:
KRAS G12C mutations are important oncogenic mutations that confer sensitivity to direct G12C inhibitors. We retrospectively identified patients with KRAS+ NSCLC from 2015 to 2019 and assessed the imaging features of the primary tumor and the distribution of metastases of G12C NSCLC compared to those of non-G12C KRAS NSCLC and NSCLC driven by oncogenic fusion events (RET, ALK, ROS1) and EGFR mutations at the time of initial diagnosis. Two hundred fifteen patients with KRAS+ NSCLC (G12C: 83; non-G12C: 132) were included. On single variate analysis, the G12C group was more likely than the non-G12C KRAS group to have cavitation (13% vs. 5%, p = 0.04) and lung metastasis (38% vs. 21%; p = 0.043). Compared to the fusion rearrangement group, the G12C group had a lower frequency of pleural metastasis (21% vs. 41%, p = 0.01) and lymphangitic carcinomatosis (4% vs. 39%, p = 0.0001) and a higher frequency of brain metastasis (42% vs. 22%, p = 0.005). Compared to the EGFR+ group, the G12C group had a lower frequency of lung metastasis (38% vs. 67%, p = 0.0008) and a higher frequency of distant nodal metastasis (10% vs. 2%, p = 0.02). KRAS G12C NSCLC may have distinct primary tumor imaging features and patterns of metastasis when compared to those of NSCLC driven by other genetic alterations.
Insights
KRAS G12C mutations in non-small cell lung cancer (NSCLC) show distinct imaging features and metastasis patterns. These findings differentiate G12C NSCLC from other KRAS mutations and genetic alterations.
Area of Science:
- Oncology
- Radiology
- Genetics
Background:
- KRAS G12C mutations are key drivers in non-small cell lung cancer (NSCLC).
- These mutations predict sensitivity to targeted G12C inhibitors.
- Understanding NSCLC subtypes based on genetic alterations is crucial for treatment.
Purpose of the Study:
- To compare imaging features and metastasis patterns of KRAS G12C NSCLC.
- To differentiate G12C NSCLC from non-G12C KRAS NSCLC.
- To contrast G12C NSCLC with NSCLC driven by EGFR mutations and fusion events (RET, ALK, ROS1).
Main Methods:
- Retrospective analysis of 215 NSCLC patients (2015-2019).
- Categorization into G12C (83 patients), non-G12C KRAS (132 patients), fusion rearrangements, and EGFR mutations.
- Assessment of primary tumor imaging and metastatic distribution at diagnosis.
Main Results:
- G12C NSCLC showed higher rates of cavitation and lung metastasis compared to non-G12C KRAS.
- G12C NSCLC had less pleural metastasis and lymphangitic carcinomatosis but more brain metastasis than fusion-driven NSCLC.
- G12C NSCLC exhibited lower lung metastasis and higher distant nodal metastasis rates versus EGFR-mutated NSCLC.
Conclusions:
- KRAS G12C NSCLC presents unique primary tumor imaging characteristics.
- Distinct metastatic patterns are observed in G12C NSCLC compared to other NSCLC subtypes.
- Imaging features can aid in differentiating NSCLC driven by KRAS G12C from other oncogenic drivers.
