36: KRAS-G12V and TP53 But Not KRAS-G12V Mutation Alone Is Associated with Worse Survival in Patients with Resected Colorectal Liver Metastasis

Friday, March 24, 2023

3:22 PM – 3:34 PM

Location: Veterans Memorial Auditorium

Abstract Presenter(s)

Reed I. Ayabe, MD

Complex General Surgical Oncology Fellow
MD Anderson Cancer Center
Houston, Texas, United States

Disclosure(s): No financial relationships to disclose

Author(s)

HM

Harufumi Maki, MD

Postdoctoral Fellow
MD Anderson Cancer Center, United States

Disclosure information not submitted.
YN

Yujiro Nishioka, MD

Postdoctoral Fellow
MD Anderson Cancer Center, United States

Disclosure information not submitted.
Timothy E. Newhook, MD, FACS

Assistant Professor
MD Anderson Cancer Center
Houston, Texas, United States

Disclosure(s): No financial relationships to disclose
Hop S. Tran Cao, MD (he/him/his)

Associate Professor of Surgery
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States

Disclosure(s): Intuitive Surgical: Research Grant (Ongoing)
YC

Yun Shin Chun, MD, FACS

Associate Professor
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States

Disclosure information not submitted.
Ching-Wei D. Tzeng, MD (he/him/his)

Associate Professor
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States

Disclosure(s): Panther: Consultant (Ongoing)
Jean-Nicolas Vauthey, MD (he/him/his)

Professor of Surgery
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States

Disclosure information not submitted.

Disclosure(s):

Reed I. Ayabe, MD: No financial relationships to disclose

Timothy E. Newhook, MD, FACS: No financial relationships to disclose

Hop S. Tran Cao, MD: Intuitive Surgical: Research Grant (Ongoing)

Ching-Wei D. Tzeng, MD: Panther: Consultant (Ongoing)

Introduction: The oncologic significance of specific KRAS point mutations for patients with colorectal liver metastases (CLM) remains uncertain, with prior studies suggesting reduced survival associated with a G12V substitution. The purpose of this study was to assess the prognostic impact of KRAS point mutations in a large cohort of patients who underwent curative-intent surgery for CLM.

Methods: Patients who underwent curative-intent surgery for CLM from January 2001 to December 2020 were selected. KRAS point mutations and other clinicopathologic variables were examined for association with survival.

Results: A total of 798 patients were classified into 5 groups by KRAS mutation status: wild-type (412, 51.6%), G12D (123, 15.4%), G12V (88, 11.0%), G13D (61, 7.6%), and other mutations (114, 14.3%). The different KRAS point mutations were not significantly associated with overall survival (OS) or relapse-free survival. In multivariate analysis, TP53 mutation was associated with worse OS in patients with G12V substitutions (hazard ratio [HR]: 2.66, p = 0.04) but was not associated with a survival difference in the other 4 groups. Patients with KRAS-G12V/TP53 co-mutations had median OS of 4.4 years and a 5-year OS rate of 39.8%. In contrast, patients with KRAS-G12V mutation and wild-type TP53 had median OS of 7.3 years and a 5-year OS rate of 75.9%, which was similar to the survival of patients with wild-type KRAS. Multivariate analysis showed that KRAS-G12V/TP53 co-mutations were independently associated with worse OS in the whole cohort (HR: 2.36, p = 0.007).

Conclusions: Prognosis after surgery for CLM should not be stratified by KRAS mutational site alone. KRAS-G12V mutation is associated with worse OS only in the setting of TP53 co-mutation.

Learning Objectives:

Upon completion, participants will be able to explain the implications of KRAS mutation in metastatic colorectal cancer.
Upon completion, participants will be able to list the most common KRAS point mutations associated with colorectal liver metastases.
Upon completion, participants will be able to describe the significance of KRAS G12V and TP53 co-mutation as it pertains to overall and recurrence-free survival in colorectal liver metastases.