Correlation between genetic biomarkers and response to Yttrium-90 radioembolization in hepatic metastatic colorectal cancer

Wednesday, April 2, 2025

11:06 AM – 11:15 AM CT

Location: Music City Center, 209 ABC

Presenting Author(s)

Erez Klein, MD

Interventional Radiology faculty
Moffitt Cancer Center, United States

Author/Co-author(s)

HN

Hoang Ngo, B.S.

Medical Student
University of South Florida Morsani College of Medicine, United States
Altan Ahmed, MD

Assistant Member, Department of Diagnostic Imaging and Interventional Radiology
H. Lee Moffitt Cancer Center & Research Institute, United States

Purpose: To investigate the association between specific genetic mutations and the response to Y90 radioembolization in patients with metastatic colorectal cancer to the liver. The study aims to identify potential genetic biomarkers that predict treatment response and survival outcomes.

Materials and Methods: A retrospective single tertiary cancer center study identified 35 patients between the years 2011-2021 who underwent genetic mutation testing prior to radioembolization treatment. Mutational status of KRAS, BRAF, NRAS, MMR, PIK3CA, EGFR, TP53, APC, SMAD4, ERBB2, ERBB3, FGFR1, MYC was then correlated with Y90 treatment response (Pearson’s chi-square or Fisher’s exact test) and survival (Mann-Whitney U test). Treatment response was evaluated as complete response (CR), stable disease (SD), Partial Response (PR) or Progressive Disease (PD) at 1,3- and 6-months post treatment.

Results: 35 patients who underwent a total of 65 Y90 radioembolization procedures were identified. 24 (68.5%) patients underwent bilobar treatment. KRAS and TP53 mutation status is significantly associated with response to Y90 treatment at 1 month. 71.4% and 87.5% of non-responsive patients had a KRAS (P = 0.014) and TP3 (P=0.030) mutations, respectively. While a greater proportion of responding patients were MMR wild-type/proficient, the association did not reach statistical significance at 1, 3, or 6 months. PIK3CA wild-type is associated with response at 6 months post treatment (0.021) There is an association between BRAF mutation status and Y90 response at 3 months post treatment (P = 0.025), with 96% of responsive patients having a wild-type genotype. Other mutations did not show significant associations with Y90 response in this cohort. KRAS mutation is associated with significantly lower mOS from the time of diagnosis 22.2 months (13.0, 30.6) and first radioembolization 6.6 months (4.0, 9.2).

Conclusion:

The data highlights key mutations that may predict Y90 radioembolization treatment response and survival. KRAS and TP53 mutations, in particular, are linked to poor response to radioembolization. These may be potential biomarkers for prognostication and stratification in Y90 treatment planning.