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. 2021 Jul 16;13(14):3572.
doi: 10.3390/cancers13143572.

Clinical and Imaging Features of Non-Small Cell Lung Cancer with G12C KRAS Mutation

Markus Y Wu  1 , Eric W Zhang  1 , Matthew R Strickland  2 , Dexter P Mendoza  1 , Lev Lipkin  3 , Jochen K Lennerz  3 , Justin F Gainor  2 , Rebecca S Heist  2 , Subba R Digumarthy  1
Affiliations

Clinical and Imaging Features of Non-Small Cell Lung Cancer with G12C KRAS Mutation

Markus Y Wu et al. Cancers (Basel). .

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.

Keywords: KRAS mutation; lung cancer; radiology; targeted therapy.

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Conflict of interest statement

M.Y.W., E.W.Z., D.P.M., L.L., J.K.L. and M.R.S.: None. J.F.G.: Consultant or received honoraria from Bristol-Myers Squibb, Genentech/Roche, Takeda, Loxo, Lilly, EMD Serono, Glyde Bio, Blueprint, Mirati, AstraZeneca, Pfizer, Novartis, Merck, Agios, Amgen, Helsinn, Regeneron, Oncorus, and Jounce, research support from Novartis, Genentech/Roche, and Ariad/Takeda, and institutional research support from Bristol-Myers Squibb, Tesaro, Moderna, Blueprint, Jounce, Array Biopharma, Merck, Adaptimmune, Novartis, and Alexo. Immediate family member who is an employee of Ironwood Pharmaceuticals. R.S.H.: Consulting honoraria from Boehringer Ingelheim, Novartis, Apollomics, Tarveda, Daichii Sankyo, EMD Serono. Research funding (to institution, not to self): Abbvie, Daichii Sankyo, Agios, Novartis, Corvus, Genentech/Roche, Mirati, Millenium, Exelixis, Celgene, Lilly. S.R.D.: Provides independent image analysis for hospital contracted clinical research trials programs for Merck, Pfizer, Bristol Mayer Squibb, Novartis, Roche, Polaris, Cascadian, Abbvie, Gradalis, Clinical Bayer, Janssen, Zai laboratories. Received honorarium from Siemens Healthineers (not related to work) and research funding from Lunit Inc.

Figures

Figure 1
Figure 1
Inclusion and exclusion of patient cohorts.
Figure 2
Figure 2
Representative imaging features in a 64-year-old male prior smoker with G12C KRAS NSCLC. Pretreatment CT images show a solid mass in the right lower lobe ((A), black arrow) and associated septal and peribronchial thickening consistent with lymphangitic carcinomatosis ((A), black arrowheads). There was extensive mediastinal and hilar lymphadenopathy ((B), white arrows), bilateral adrenal metastases ((C), white arrows), brain metastasis ((D), white arrow), soft tissue metastasis ((E), white arrow), and a lytic osseous metastasis of the first lumbar vertebral body ((F), white arrow).
Figure 3
Figure 3
Frequencies of various metastatic sites in G12C KRAS+ NSCLC and in other genetic alterations.
See this image and copyright information in PMC

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