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

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.

Intracranial Efficacy of Adagrasib in Patients From the KRYSTAL-1 Trial With KRASG12C-Mutated Non–Small-Cell Lung Cancer Who Have Untreated CNS Metastases

“…4 CNS metastases are observed at diagnosis in 27%-42% of patients with KRAS G12C -mutated NSCLC. [5][6][7][8] Patients with KRAS-mutated NSCLC and CNS metastases have a worse prognosis and higher rates of CNS failure compared with patients without KRAS mutations. [9][10][11] Adagrasib (MRTX849), a KRAS G12C inhibitor that selectively and irreversibly binds the switch II pocket of KRAS G12C , 12 has demonstrated CNS penetration, intracranial (IC) tumor regression, and increased survival in multiple preclinical models.…”

Magnetic resonance imaging characteristics of brain metastases in small cell lung cancer

“…This is also true for research on BM of SCLC and NSCLC. Numerous imaging characteristics of NSCLC have been established based on radionics and machine deep learning 15,16 . However, due to the low incidence of BMs of SCLC, their features have not been comprehensively evaluated.…”

Characteristics and Treatment Outcomes in Advanced-Stage Non-Small Cell Lung Cancer Patients with a KRAS G12C Mutation: A Real-World Study

“…These challenges in treating this population may have possibly added to their overall poor prognosis. Previous data have shown that patients with KRAS G12C mutations have a lower frequency of lung metastasis than EGFR -positive patients do (38% vs. 67%) and a high prevalence of brain metastases (28% at diagnosis and 40% during follow-up) [ 27 , 29 ]. We found that 28% of the patients had pulmonal and 24% had intracranial metastases at diagnosis of advanced-stage KRAS G12C -mutated NSCLC.…”