Tissue and Imaging Biomarkers of Response to Neoadjuvant Nivolumab or Nivolumab plus Ipilimumab in Patients with Resectable Hepatocellular Carcinoma

Authors

Michael LaPelusa
Shadi Chamseddine
Hop Sanderson Tran Cao
Lianchun Xiao
Elshad Hasanov
Priya Bhosale
Hesham M Amin
Yehia I Mohamed
Betul Gok Yavuz
Yara Sakr
Li Xu
Ian Hu
Sunyoung S Lee
Divya Sakamuri
Sonali Jindal
Van Nguyen
Michael A Curran
Ryan Sun
Asif Rashid
Dan Gabriel Duda
Padmanee Sharma
Aliya Qayyum
Ahmed Omar Kaseb

Publication Date

1-1-2025

Journal

Oncology

DOI

10.1159/000541250

PMID

39427654

PMCID

PMC12006443

PubMedCentral® Posted Date

10-18-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC.

Methods: Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis of more than 70%. Data comparing patients with MPR versus those without were summarized using descriptive statistics and compared using the Wilcoxon rank-sum test.

Results: Patients with MPR after neoadjuvant immunotherapy tended to have larger tumors (mean 9.52 vs. 4.99 centimeters; p = 0.050). They had a significant reduction in tumor size posttreatment (14.67% reduction vs. 9.15% increase in size; p = 0.042) and a nonsignificant decrease in serum AFP (-24.20% vs. -14.00%; p = 0.085). Further, patients with MPR had a greater increase in intratumoral expression levels of CD8 (26.92% vs. -0.04%; p = 0.026), granzyme B (15.56% vs. -2.24%; p = 0.011), and PD-1 (20.17% vs. 0.40%; p = 0.048) but not PD-L1 (7.69% vs. 0.57%; p = 0.26). For imaging biomarkers, tumor and liver fibrosis were comparable before and after neoadjuvant therapy in patients with MPR versus nonresponders.

Conclusion: Changes in tumor size, immune cell infiltration, and immune cell activation are candidate predictive markers of pathologic response to neoadjuvant immunotherapy in patients with resectable HCC.

Keywords

Humans, Nivolumab, Liver Neoplasms, Carcinoma, Hepatocellular, Male, Female, Neoadjuvant Therapy, Middle Aged, Ipilimumab, Antineoplastic Combined Chemotherapy Protocols, Aged, Biomarkers, Tumor, Adult, Treatment Outcome, Neoadjuvant immunotherapy, Hepatocellular carcinoma

Published Open-Access

yes

Recommended Citation

LaPelusa, Michael; Chamseddine, Shadi; Tran Cao, Hop Sanderson; et al., "Tissue and Imaging Biomarkers of Response to Neoadjuvant Nivolumab or Nivolumab plus Ipilimumab in Patients with Resectable Hepatocellular Carcinoma" (2025). Faculty, Staff and Student Publications. 4319.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4319