Immunoscore Predicted by Dynamic Contrast-Enhanced Computed Tomography Can Be a Non-Invasive Biomarker for Immunotherapy Susceptibility of Hepatocellular Carcinoma
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Histological Analysis
2.3. Image Analysis
2.4. Statistical Analyses
3. Results
3.1. Cohort 1
3.1.1. Characteristics
3.1.2. Peritumoral Enhancement of CECT Findings Could Predict Immunoscore
3.2. Cohort 2
Susceptibility to Combined Immunotherapy of Nodules with Identified CECT Findings
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
HCC | hepatocellular carcinoma |
CECT | contrast-enhanced computed tomography |
PD-L1 | programmed death-ligand 1 |
TTnP | Time to nodular progression |
FFPE | formalin-fixed embedded |
TI | tumor interior |
SN | simple nodular |
SNEG | single nodular type with extranodular growth |
CMN | confluent multinodular |
LI-RADS | Liver Imaging Reporting and Data System |
non-rim APHE | non-rim arterial phase hyperenhancement |
ICI | immune checkpoint inhibitor |
EOB-MRI | gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging |
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Patient Characteristics | n = 96 |
---|---|
Age [range, SD] (years) | 72 [33–91, 9.9] |
Sex (female/male) | 20/76 |
Etiology (HBV/HCV/NBNC) | 21/27/48 |
Alcohol usage | 36 |
BMI [range, SD] (kg/m2) | 23.2 [16.1–39.0, 4.1] |
Diabetes mellitus | 31 |
Liver cirrhosis | 15 |
Child–Pugh (A/B/C) | 82/12/2 |
BCLC stage (A/B/C) | 49/30/17 |
Number of tumors [range, SD], | 1 [1–10] |
AFP [range, SD], (ng/mL) | 9 [1.5–533,413, 65,978] |
DCP [range, SD], (AU/L) | 219 [15–473,139, 58,368] |
Differentiation (wel/mod/por) | 9/69/18 |
IHC Findings | n = 96 |
TI CD3 | 58 [3–921] |
TI CD8 | 14 [0–585] |
IM CD3 | 96 [8–950] |
IM CD8 | 21 [0–671] |
Immunoscore (0/1/2/3/4-points) | 41/10/22/16/7 |
CT Findings | n = 96 |
Tumor size [range, SD] (mm) | 57 [15–160, 38] |
Gross morphology (SN/SNEG/CM) | 53/28/15 |
Non-rim APHE | 80 |
Washout | 93 |
Enhancing capsule | 78 |
Rim APHE | 15 |
Peritumoral enhancement | 40 |
Delayed enhancement | 18 |
Heterogenous enhancement | 69 |
Intralesional artery | 48 |
Necrosis | 34 |
Variables | Estimate | Standard Error | 95% CI | |t| | p-Value | VIF |
---|---|---|---|---|---|---|
Univariate | ||||||
Tumor size (mm) | 0.034 | 0.037 | 0.107 to 0.039 | 0.932 | 0.354 | - |
Gross morphology (SN vs. SNEG/CM) | −0.547 | 0.318 | −1.177 to 0.084 | 1.720 | 0.089 | - |
Nonrim APHE | −0.642 | 0.362 | 1.360 to 0.077 | 1.774 | 0.079 | - |
Washout | 0.705 | 0.503 | −0.294 to 1.703 | 1.401 | 0.165 | - |
Enhancing capsule | 0.590 | 0.355 | −0.114 to 1.294 | 1.663 | 0.100 | - |
Rim APHE | −1.002 | 0.373 | −1.742 to −0.263 | 2.690 | 0.009 ** | - |
Peritumoral enhancement | −1.076 | 0.274 | −1.621 to −0.532 | 3.928 | <0.001 ** | - |
Delayed enhancement | 0.528 | 0.383 | −0.232 to 1.289 | 1.380 | 0.171 | - |
Heterogenous enhancement | 0.047 | 0.294 | −0.536 to 0.630 | 0.162 | 0.872 | - |
Intralesional artery | 0.128 | 0.281 | −0.430 to 0.686 | 0.456 | 0.650 | - |
Necrosis | −0.250 | 0.297 | 0.839 to 0.339 | 0.842 | 0.402 | - |
Multivariate | ||||||
Intercept | 2.323 | 0.332 | 1.664 to 2.981 | 7.004 | <0.001 | |
Rim APHE | −0.432 | 0.407 | −1.240 to 0.375 | 1.063 | 0.290 | 1.289 |
Peritumoral enhancement | −0.920 | 0.311 | −1.537 to −0.302 | 2.958 | 0.004 ** | 1.289 |
Patient Characteristics | n = 40 (Patients) |
---|---|
Age [range, SD], (years) | 70 [48–83, 8] |
Sex (female/male) | 8/32 |
Etiology (HBV/HCV/NBNC) | 7/11/22 |
Child–Pugh (A/B/C) | 34/5/1 |
BCLC stage (A/B/C) | 0/21/19 |
Number of tumors enrolled [range, SD], | 2 [1–3] |
ICI treatment (Ate + Bev/Dur + Tre) | 26/14 |
CT Findings | n = 81 (Nodules) |
Tumor size [range, SD], (mm) | 39.7 [11–157, 35] |
Gross morphology (SN/SNEG/CM) | 39/25/17 |
Peritumoral enhancement | 27 |
Treatment Effect | n = 81 (Nodules) |
Best response CR/PR/SD/PD | 7/22/38/14 |
TTnP median | 294 days |
Uncensored/censored | 41/40 |
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Ueshima, E.; Sofue, K.; Komatsu, S.; Ishihara, N.; Komatsu, M.; Umeno, A.; Nishiuchi, K.; Kozuki, R.; Yamaguchi, T.; Matsuura, T.; et al. Immunoscore Predicted by Dynamic Contrast-Enhanced Computed Tomography Can Be a Non-Invasive Biomarker for Immunotherapy Susceptibility of Hepatocellular Carcinoma. Cancers 2025, 17, 948. https://doi.org/10.3390/cancers17060948
Ueshima E, Sofue K, Komatsu S, Ishihara N, Komatsu M, Umeno A, Nishiuchi K, Kozuki R, Yamaguchi T, Matsuura T, et al. Immunoscore Predicted by Dynamic Contrast-Enhanced Computed Tomography Can Be a Non-Invasive Biomarker for Immunotherapy Susceptibility of Hepatocellular Carcinoma. Cancers. 2025; 17(6):948. https://doi.org/10.3390/cancers17060948
Chicago/Turabian StyleUeshima, Eisuke, Keitaro Sofue, Shohei Komatsu, Nobuaki Ishihara, Masato Komatsu, Akihiro Umeno, Kentaro Nishiuchi, Ryohei Kozuki, Takeru Yamaguchi, Takanori Matsuura, and et al. 2025. "Immunoscore Predicted by Dynamic Contrast-Enhanced Computed Tomography Can Be a Non-Invasive Biomarker for Immunotherapy Susceptibility of Hepatocellular Carcinoma" Cancers 17, no. 6: 948. https://doi.org/10.3390/cancers17060948
APA StyleUeshima, E., Sofue, K., Komatsu, S., Ishihara, N., Komatsu, M., Umeno, A., Nishiuchi, K., Kozuki, R., Yamaguchi, T., Matsuura, T., Tada, T., & Murakami, T. (2025). Immunoscore Predicted by Dynamic Contrast-Enhanced Computed Tomography Can Be a Non-Invasive Biomarker for Immunotherapy Susceptibility of Hepatocellular Carcinoma. Cancers, 17(6), 948. https://doi.org/10.3390/cancers17060948