Artificial intelligence (AI)-powered tumor microenvironment (TME) analysis to identify potential biomarkers for ICIs with or without bevacizumab in hepatocellular carcinoma (HCC).

Authors

Hong Jae Chon

Hong Jae Chon

Department of Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea

Hong Jae Chon , Gwangil Kim , Beodeul Kang , Jung Yong Hong , Haeyoun Kang , Sohyun Hwang , Sung Hwan Lee , Sanghoon Jung , Chansik An , Won Suk Lee , Seulki Kim , Yoojoo Lim , Siraj Mahamed Ali , Chan-Young Ock , Ho Yeong Lim , Chan Kim

Organizations

Department of Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea, Department of Pathology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea, Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, Department of Pathology, CHA Bundang Medical Center, Seongnam, South Korea, CHA University School of Medicine, Seongnam, South Korea, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea, Department of Radiology, CHA Bundang Medical Center, Seongnam, South Korea, CHA Bundang Medical Center, CHA University, Seongnam, South Korea, CHA Bundang Medical Center, Seongnam, South Korea, Lunit Inc., Seoul, South Korea

Research Funding

No funding sources reported

Background: While immunotherapies have been approved for use in HCC patients, there is a need for validated predictive biomarkers that correlate with treatment outcomes. We investigated whether AI-powered spatial analysis of non-cancerous cells within the TME can be potential biomarkers for ICIs with or without bevacizumab in advanced HCC. Methods: Analysis of images of H&E-stained slides was conducted by an AI model, Lunit SCOPE IO in pre-treatment tumor samples of 163 HCC patients treated with atezolizumab plus bevacizumab as first-line (n=82), or monotherapies of nivolumab or pembrolizumab as ≥ second-line (n=81) at CHA Bundang Medical Center or Samsung Medical Center. We analyzed the correlation between clinical outcomes after the treatment and AI-powered TME-related variables, including TILs and endothelial cells, within intratumoral or stromal areas. Inflamed immune phenotype (IIP) was defined as cases exhibiting enrichment of intratumoral TILs. Results: Baseline characteristics, including Child-Pugh liver classification, Barcelona Clinic Liver Cancer stage, and hepatitis B virus, were well-balanced between treatment regimens. IIP was predictive of longer progression-free survival (PFS) of nivolumab or pembrolizumab monotherapy (median PFS 4.7 months for IIP vs. 2.2 months for non-IIP; hazard ratio [HR] 0.50; 95% confidence interval [CI] 0.25-0.99; p=0.042), but not PFS of atezolizumab plus bevacizumab (median PFS 6.8 months vs. 6.2 months; HR 0.92; 95% CI 0.50-1.69; p=0.762). PFS of atezolizumab plus bevacizumab was significantly longer in cases harboring intratumoral endothelial cell density in the highest quartile (median PFS 6.7 months for upper 25% vs. 3.9 months for lower 75%; HR 0.51; 95% CI 0.27-0.97; p=0.037), while there was no significant difference in PFS of pembrolizumab or nivolumab monotherapy (median PFS 2.3 months vs. 2.8 months; HR 1.02; 95% CI 0.59-1.77; p=0.935). Conclusions: AI-powered TME analysis shows IIP is predictive of longer PFS with ICI monotherapies, whereas intratumoral endothelial cell density is specifically associated with PFS of atezolizumab plus bevacizumab in advanced HCC. The latter finding may suggest efficacy of combined VEGFRi and ICI activity is dependent on the amount of baseline tumor vasculature.

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Abstract Details

Meeting

2024 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Track

Pancreatic Cancer,Hepatobiliary Cancer,Neuroendocrine/Carcinoid,Small Bowel Cancer

Sub Track

Tumor Biology, Biomarkers, and Pathology

Citation

J Clin Oncol 42, 2024 (suppl 3; abstr 549)

DOI

10.1200/JCO.2024.42.3_suppl.549

Abstract #

549

Poster Bd #

F16

Abstract Disclosures