Circulating Tumor DNA (ctDNA) as a Biomarker of Response to Therapy in Advanced Hepatocellular Carcinoma Treated With Nivolumab

Authors

Yehia I Mohamed
Sunyoung S Lee
Tarik Demir
Shadi Chamseddine
Zishuo Ian Hu
Lianchun Xiao
Khaled Elsayes
Jeffrey S Morris
Robert A Wolff
Rikita Hiatia
Aliya Qayyum
Asif Rashid
Dan G Duda
James C Yao
Michael LaPelusa
Eugene J Koay
Armeen Mahvash
Ahmed Al Azzam
Ecaterina E Dumbrava
Manal Hassan
Hesham M Amin
Ahmed Omar Kaseb

Language

English

Publication Date

1-1-2024

Journal

Cancer Biomarkers

DOI

10.3233/CBM-230431

PMID

39269823

PMCID

PMC11491993

PubMedCentral® Posted Date

9-19-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).

Objective: This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.

Methods: We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.

Results: Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04).

Conclusions: ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.

Keywords

Humans, Male, Circulating Tumor DNA, Nivolumab, Female, Liver Neoplasms, Aged, Biomarkers, Tumor, Carcinoma, Hepatocellular, Middle Aged, Prognosis, Aged, 80 and over, Mutation, Antineoplastic Agents, Immunological, Adult, ctDNA, hepatocellular carcinoma, immunotherapy, nivolumab, biomarker

Published Open-Access

yes

Recommended Citation

Mohamed, Yehia I; Lee, Sunyoung S; Demir, Tarik; et al., "Circulating Tumor DNA (ctDNA) as a Biomarker of Response to Therapy in Advanced Hepatocellular Carcinoma Treated With Nivolumab" (2024). Faculty, Staff and Student Publications. 5264.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5264