Thoracic: Lung Cancer: Basic Science
Prognostic value of KRAS G12C mutation in lung adenocarcinoma stratified by stages and radiological features

https://doi.org/10.1016/j.jtcvs.2023.04.037Get rights and content

Abstract

Objectives

The role of KRAS G12C is of particular interest given the promising clinical activity of KRAS G12C-specific inhibitors. This study comprehensively investigated the clinicopathological characteristics and prognostic value of KRAS G12C mutation in patients with surgically resected lung adenocarcinoma.

Methods

Data were collected on 3828 patients with completely resected primary lung adenocarcinomas who underwent KRAS mutation analysis between 2008 and 2020. The association between KRAS G12C and clinicopathologic characteristics, molecular profiles, recurrence patterns, and postoperative outcome were explored.

Results

Two hundred seventy-five patients (7.2%) were confirmed to harbor a KRAS mutation, of whom 83 (30.2%) had the G12C subtype. KRAS G12C was more frequent in men, former/current smokers, radiologic solid nodules, invasive mucinous adenocarcinoma, and solid predominant tumors. KRAS G12C tumors had more lymphovascular invasion and higher programmed death-ligand 1 expression than KRAS wild-type tumors. TP53 (36.8%), STK11 (26.3%), and RET (18.4%) mutations were the 3 most frequent in the KRAS G12C group. Logistic regression analysis showed patients with KRAS G12C mutation were prone to experience early recurrence and locoregional recurrence. KRAS G12C mutation was found to be significantly associated with poor survival after propensity score matching. Stratified analysis showed that the KRAS G12C was an independent prognostic factor in stage I tumors and part-solid lesions, respectively.

Conclusions

The KRAS G12C mutation had a significant prognostic value in stage I lung adenocarcinomas as well as in part-solid tumors. Furthermore, it exhibited a potentially aggressive phenotype associated with early and locoregional recurrence. These findings might be relevant as better KRAS treatments are developed for clinical application.

Section snippets

Patients and Clinicopathologic Characteristics

From January 2008 to December 2020, we collected patients with lung adenocarcinoma who underwent surgical resection at the Department of Thoracic Surgery, Fudan University Shanghai Cancer Center. All the identified patients underwent complete surgical resection with negative margins, and patients who received neoadjuvant chemotherapy were excluded. This study was approved by the Ethics Committee and Institutional Review Boards of Fudan University Shanghai Cancer Center (IRB2008223-9, Date: July

KRAS G12C Mutation and Patient Characteristics

This study cohort enrolled 3829 patients with a mean age of 59 years, among whom 275 (7.2%) were harboring KRAS mutations with 83 (30.2%) cases presenting the KRAS G12C mutation subtype. About 58.4% were women and 27.6% were former or current smokers in the overall cohort. Adjuvant therapy was administered to 923 patients. Regimens included chemotherapy only (n = 816) and chemoradiation (n = 107). Other clinicopathologic characteristics were listed in Table 1. Among the 275 KRAS mutation cases,

Discussion

Clinicopathologic characteristics and analysis of long-term outcomes in patients with surgically resected KRAS G12C-mutation adenocarcinoma are now required due to the recent development of KRAS G12C inhibitors and their encouraging early results in clinical trials. Therefore, we undertook a comprehensive investigation of the intrinsic prognostic value of KRAS G12C mutations in patients with surgically resected lung adenocarcinoma (Figure 5). In this study, KRAS G12C mutations were more

Conclusions

The KRAS G12C mutation had a significant prognostic value in stage I lung adenocarcinomas as well as in part-solid tumors. In addition, it exhibited a potentially aggressive phenotype associated with early and locoregional recurrence. These findings might be relevant as better KRAS treatments are developed for clinical application.

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    • Cited by (0)

    Supported by the National Natural Science Foundation of China (No. 81930073), the Shanghai Science and Technology Innovation Action Project (No. 20JC1417200), and the Cooperation Project of Conquering Major Diseases in Xuhui District (N. XHLHGG202101).

    Drs Chen and Zhang contributed equally to this article as co-senior authors.

    Drs Cao and Ma contributed equally to this article.

    This study was approved by the Ethics Committee and Institutional Review Boards of Shanghai Cancer Center, Fudan University (IRB2008223-9, Date: July 14, 2020). Informed consent was waived because of its retrospective nature.

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