Published online Jul 27, 2026. doi: 10.4240/wjgs.v18.i7.119397
Revised: April 10, 2026
Accepted: May 18, 2026
Published online: July 27, 2026
Processing time: 132 Days and 1.3 Hours
Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Interme
To assess the short-term efficacy of TACE in conjunction with immunotherapy against TACE monotherapy in patients with intermediate-advanced HCC, while also preliminarily investigating the clinical, serological, and radiomic characteristics associated with the efficacy of the combination treatment.
This retrospective study analyzed 120 intermediate-advanced HCC patients admi
The objective response rate (36.7% vs 23.3%) and disease control rate (76.7% vs 60.0%) in the combination group were substantially higher than those in the TACE group (both P < 0.05). The combination group had superior efficacy in reducing serum tumor marker levels, suppressing angiogenic factors, upregulating cysteine aspartic protease-3 expression, and downregulating survivin expression relative to the TACE group (all P < 0.05). Moreover, the combination group’s radiomic features (including gray-level co-occurrence matrix contrast, arterial-phase entropy, and gray-level variance) were significantly correlated with clinical features, including tumor volume, number, and location (all P < 0.05). However, there were no significant differences in baseline clinical characteristics between responders and non-responders.
TACE + immunotherapy indicated improved short-term efficacy and serological molecules modulation compared with TACE monotherapy in intermediate-advanced HCC patients. Radiomic features can quantitatively reflect tumor heterogeneity and correlate with basic tumor characteristics, indicating their potential as non-invasive biomarkers. However, the predictive value of these radiomic characteristics for the effectiveness of combination therapy necessitates more validation in prospective investigations.
Core Tip: Transarterial chemoembolization + immunotherapy co-treatment can significantly improve short-term objective response rate and disease control rate in intermediate-advanced hepatocellular carcinoma patients and more effectively regulate relevant serum biomarkers. Radiomic features extracted from pre-treatment imaging can serve as a potential strategy for constructing personalized efficacy prediction models.
- Citation: Xia Q, Shan W, Yan H. Clinical and radiomic characteristics of transarterial chemoembolization combined with immunotherapy in hepatocellular carcinoma. World J Gastrointest Surg 2026; 18(7): 119397
- URL: https://www.wjgnet.com/1948-9366/full/v18/i7/119397.htm
- DOI: https://dx.doi.org/10.4240/wjgs.v18.i7.119397
Hepatocellular carcinoma (HCC) is one of the most common primary liver malignancies worldwide and represents a leading cause of cancer-related mortality[1]. Due to the lack of specific early symptoms, most patients are diagnosed at an intermediate or advanced stage, at which point curative treatments such as surgical resection or liver transplantation are no longer feasible[2,3].
Transarterial chemoembolization (TACE) is currently recommended as a standard treatment for intermediate-stage HCC patients[4]. TACE exerts its antitumor effect by delivering chemotherapeutic agents directly into the tumor-feeding arteries while simultaneously embolizing the blood supply, resulting in ischemic necrosis of tumor tissue. However, its clinical efficacy remains limited due to tumor heterogeneity, incomplete embolization, and the potential induction of hypoxia-related angiogenesis[5,6].
In recent years, cancer immunotherapy, particularly immune checkpoint inhibitors targeting programmed death-1 and programmed death ligand-1, has significantly improved the systemic treatment landscape of HCC. TACE-induced tumor necrosis may increase tumor antigen release and promote immune activation, providing a theoretical basis for synergistic effects in combination with immunotherapy[7].
This study retrospectively analyzed patients with intermediate to advanced HCC treated between January 2023 and January 2025, aiming to evaluate the short-term efficacy of TACE combined with immunotherapy compared with TACE monotherapy. This also explores potential clinical, serological, and radiomic predictors of treatment response.
This study retrospectively analyzed HCC patients treated at the General Hospital of Northern Theater Command between January 2023 and January 2025. Of these, 60 patients received TACE + immunotherapy, and the other 60 received TACE monotherapy. Clinical data, laboratory test results, and imaging data of all patients were retrieved from the hospital electronic medical record system and picture archiving and communication system. All participants willingly selected their treatment regimens and provided informed consent to participate in the trial. This study was authorized by the Institutional Review Board of our hospital.
Inclusion criteria: (1) Patients with a confirmed HCC diagnosis by histopathology or clinical diagnosis based on imaging features combined with clinical manifestations; (2) Patients who received TACE + immunotherapy as the primary treatment; (3) Patients who underwent enhanced computed tomography or magnetic resonance imaging completed before treatment, with image quality meeting the requirements for subsequent analysis; (4) Patients who had complete preoperative clinical data and laboratory test results; and (5) Patients who completed at least one post-treatment imaging follow-up to enable efficacy evaluation.
Exclusion criteria: (1) Patients with other types of malignant tumors or with extrahepatic metastases as the primary lesions; (2) Patients with a history of liver transplantation or other systemic anti-tumor therapies; (3) Patients with incomplete imaging data or poor image quality precluding further analysis; (4) Patients with missing key clinical or laboratory data; and (5) Patients with incomplete follow-up data that cannot support treatment efficacy assessment.
All enrolled patients received routine examinations before therapy, including the collection of demographic data, laboratory analyses, and imaging studies. TACE procedures were conducted by interventional physicians with considerable clinical experience. Furthermore, immunotherapy was administered in accordance with established clinical stand
Enzyme-linked immunosorbent assay was performed to assess the serum levels of α-L-fucosidase (AFU), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), cysteine aspartic protease (caspase)-4, and survivin.
Treatment responses were assessed using imaging examinations per the modified response evaluation criteria in solid tumors[1]. Complete response (CR) was defined as the elimination of all target lesions, normalization of blood tumor marker levels, and maintaining this state for a minimum of 4 weeks. A partial response (PR) is defined as a minimum 30% reduction in the aggregate maximum diameters of target lesions, and a decrease in serum tumor marker levels, main
The objective response rate (ORR) was determined as the ratio of patients attaining CR and PR to the total trial popu
Clinical and laboratory indicators included patient age, gender, AFP level, maximum tumor diameter, number of tumors, Child-Pugh classification, neutrophil-to-lymphocyte ratio, and albumin-bilirubin score.
Radiomic variables derived from pre-treatment imaging data were collected from the tumor regions of interest, primarily including entropy (indicative of tumor textural complexity), gray level variance, and tumor morphological characteristics (e.g., sphericity). These variables were employed to evaluate intratumoral heterogeneity and the morphological features of the tumors.
Primary endpoints included ORR and DCR at 3 months. Secondary endpoints included changes in serum tumor markers, angiogenic factors, and apoptosis-related biomarkers.
All statistical analyses were carried out using statistical software. Based on normality tests, continuous variables were reported as mean ± SD or median (interquartile range). Intergroup comparisons were assessed via an independent-samples t-test or a Mann-Whitney U test. Categorical variables were presented as frequencies and percentages, and their intergroup comparisons were evaluated by the χ2 test or Fisher’s exact test. All statistical tests were two-sided, and a P value < 0.05 was deemed statistically significant.
This is a retrospective study, and all the data were acquired from previously collected clinical records. The patients’ personal information was kept confidential, and the study protocol was authorized by the Institutional Review Board of our hospital. Furthermore, the requirement for individual informed consent was waived.
Baseline characteristics of the patients are summarized in Table 1. In the combination group, male patients accounted for 47.44%, whereas in the TACE group, the proportion was 57.14%, with no statistically significant difference between the groups (P = 0.310). The mean age difference between the two groups was under 2 years (59.14 ± 8.06 years vs 57.93 ± 7.01 years, t = 0.821, P = 0.413). The duration of hepatitis B virus infection was slightly prolonged in the observation group (19.22 ± 2.41 years vs 17.01 ± 3.12 years), although the difference lacked statistical significance (t = 3.214, P = 0.142). The tumor size was typically greater in the observation group (4.39 ± 2.50 cm vs 3.99 ± 1.24 cm, t = 2.581, P = 0.093). The tumor was primarily located in the right hepatic lobe, with equivalent proportions of left lobe, right lobe, and multifocal tumors between the two groups (χ2 = 1.892, P = 0.059).
| Variables | Combination group | TACE group | t/χ2 | P value |
| Gender (male/female) | 37 (47.44)/41 (52.56) | 24 (57.14)/18 (42.86) | 1.029 | 0.310 |
| Mean age (years) | 59.14 ± 8.06 | 57.93 ± 7.01 | 0.821 | 0.413 |
| Duration of hepatitis B infection (year) | 19.22 ± 2.41 | 17.01 ± 3.12 | 3.214 | 0.142 |
| Tumor size (cm) | 4.39 ± 2.50 | 3.99 ± 1.24 | 2.581 | 0.093 |
| Tumor location (left lobe/right lobe/multifocal, %) | 33.62/59.18/7.20% | 32.12/59.18/8.70% | 1.892 | 0.059 |
Imaging assessment of all measurable lesions was conducted 3 months post-treatment, in accordance with the modified response evaluation criteria in solid tumors. There were no cases of CR in either the TACE group or the combination group. The PR rate was 23.3% (14/60) in the TACE group, which increased to 36.7% (22/60) in the combination group, demonstrating a significant increase in the proportion of patients with a ≥ 30% reduction in the sum of the maximal tumor diameters after combined therapy. The percentage of SD decreased from 36.7% (22/60) in the TACE group to 20.0% (12/60) in the combination group, although the percentage of progressive disease remained comparable across the two groups (40.0% vs 43.3%). Figure 1 illustrates comparative imaging. Based on the above data, the ORR in the combination group reached 36.7%, which was significantly higher than the 23.3% in the TACE group (χ2 = 24.144, P = 0.001). Further, the DCR improved from 60.0% to 76.7%, and the difference was significant (P = 0.001) (Table 2).
| Group | Case | CR | PR | SD | PD | ORR | DCR |
| TACE group | 60 | 0 (0.0) | 14 (23.3) | 22 (36.7) | 24 (40.0) | 14 (23.3) | 36 (60.0) |
| Combination group | 60 | 0 (0.0) | 22 (36.7) | 12 (20.0) | 26 (43.3) | 22 (36.7) | 46 (76.7) |
| χ2 | - | - | - | - | - | - | 24.144 |
| P value | - | - | - | - | - | - | 0.001 |
The baseline serum marker levels were all comparable between the two groups before treatment (P > 0.05; Table 3). Post-treatment, although the levels of AFU, AFP, and CA19-9 decreased in the TACE group, they remained high (238.7 ± 21.8 U/L, 463.2 ± 25.1 ng/mL, 42.1 ± 6.8 KU/L, respectively). The reduction in levels was significantly more pronounced in the combination group, with the three markers decreased to 185.3 ± 19.2 U/L, 351.6 ± 22.0 ng/mL, and 28.4 ± 6.1 KU/L, all considerably lower than those in the TACE group at the same time point (P < 0.05). The data indicate that TACE + immunotherapy can more efficiently lower serum tumor marker levels.
It was observed that before the treatment, there were no statistically significant differences in the baseline levels of the four angiogenic factors between the two groups (P > 0.05; Table 4). Post-treatment, the concentrations of HGF, VEGF, PDGF, and bFGF in the TACE group decreased to 95.3 ± 8.9 ng/mL, 433.2 ± 41.8 ng/L, 1964.5 ± 314.2 ng/L, and 141.8 ± 15.5 ng/L, respectively, suggesting a slight decrease in magnitude. In the combination group, the reduction was more significant, with the four markers decreased to 71.8 ± 7.8 ng/mL, 304.1 ± 36.1 ng/L, 1508.2 ± 301.7 ng/L, and 101.6 ± 14.3 ng/L, respectively, all of which were much lower than those in the TACE group at the same time point (P < 0.05). The results demonstrate that TACE + immunotherapy can more efficiently inhibit the levels of angiogenic factors.
| Group | Case | HGF (ng/mL) | VEGF (ng/L) | PDGF (ng/L) | bFGF (ng/L) |
| TACE group | Before treatment | 60 | 144.2 ± 16.8 | 463.1 ± 54.7 | 2155.8 ± 350.5 |
| After treatment | 60 | 95.3 ± 8.9 | 433.2 ± 41.8 | 1964.5 ± 314.2 | |
| Combination group | Before treatment | 60 | 143.5 ± 15.9 | 462.3 ± 56.2 | 2156.5 ± 352.1 |
| After treatment | 60 | 71.8 ± 7.8a | 304.1 ± 36.1a | 1508.2 ± 301.7a |
The data revealed no statistically significant differences in the pre-treatment serum levels of caspase-3 and survivin between the two groups (P > 0.05;Table 5). However, after TACE monotherapy, caspase-3 levels increased from 28.4 ± 4.5 ng/mL to 37.5 ± 5.4 ng/mL, whereas survivin levels reduced from 33.8 ± 4.7 ng/mL to 26.3 ± 3.8 ng/mL, indicating a slight increase in apoptotic activity. In the combination group, the caspase-3 level improved to 44.3 ± 5.7 ng/mL post-treatment, whilst the survivin level decreased substantially to 21.3 ± 3.9 ng/mL; both metrics surpassed those observed in the TACE group at the same time point (P < 0.05). The results indicate that TACE + immunotherapy more efficiently activates the caspase-3-mediated apoptotic pathway and inhibits survivin expression, thus augmenting the antitumor effect.
Correlation analysis of radiomic features and clinical characteristics in 120 HCC patients indicated significant associations between certain radiomic characteristics and clinical parameters, including tumor size, location, and quantity (P < 0.05). The principal findings are detailed in Table 6.
| Clinical features | Radiomic features | Correlation coefficient (r) | P value |
| Tumor volume | GLCM contrast | -0.43 | < 0.01 |
| Tumor volume | DCE-MRI arterial phase entropy | 0.48 | < 0.01 |
| Tumor location | GLRLM SRHGE | 0.40 | < 0.05 |
| Tumor location | GLDM gray-level non-uniformity | 0.45 | < 0.01 |
| Tumor number | Gray-level variance of texture features | 0.52 | < 0.01 |
| Tumor number | GLRLM LRLGE | -0.46 | < 0.01 |
HCC ranks among the most prevalent causes of cancer-related mortality globally. In intermediate to advanced HCC patients, treatment options are substantially limited, and the prognosis is unfavorable. TACE, a frequently employed localized therapy for unresectable HCC, exhibits anticancer efficacy by inhibiting the tumor’s blood supply and administering medicines directly at the site. In recent years, systemic therapy, such as immune checkpoint inhibitors, has transformed the therapeutic paradigm of HCC. TACE-induced tumor cell necrosis may theoretically release antigens and modify the tumor immune microenvironment, thus producing a synergistic impact with immunotherapy. This retro
The data showed that TACE + immunotherapy achieved significantly higher short-term ORR and DCR than TACE monotherapy. The ORR in the combined treatment group was 36.7%, substantially higher than the 23.3% observed in the TACE group. Furthermore, the DCR also increased from 60.0% to 76.7%. This outcome corresponds to the findings of other recent prospective and retrospective investigations, validating the synergistic benefit of combination treatment in intermediate-advanced HCC[9]. Using both local control and systemic immune activation, combination treatment can more effectively inhibit tumor growth and provide enhanced therapeutic advantages to patients[10]. Moreover, the decrease in AFU, AFP, and CA19-9 levels in the combination treatment group post-treatment was considerably higher than that observed in the TACE-monotherapy group. These indicators are closely associated with tumor load, degree of differentiation, and prognosis of HCC. Their substantial decrease indicates that combination therapy may more efficiently suppress tumor activity or decrease the quantity of tumor cells[11]. Similarly, the analysis of angiogenic factors revealed that the levels of HGF, VEGF, PDGF, and bFGF in the combination treatment group post-treatment were significantly lower than those in the TACE group[12]. Angiogenesis is a crucial mechanism in the initiation, progression, and metastasis of HCC. TACE can induce ischemia and hypoxia, which could result in a temporary upregulation of some pro-angiogenic factors[13]. Immunotherapy, particularly programmed death-1/programmed death ligand-1 inhibitors, has demonstrated anti-angiogenic properties[14]. The findings of the present study indicated that the combined regimen could more effectively reduce the secretion of these factors, suggesting that combined treatment may have a more significant and persistent impact on blocking tumor blood supply and inhibiting tumor neovascularization, which might indicate its enhanced efficacy.
The analysis of apoptosis-related molecules revealed that the combined therapy group had significantly higher serum caspase-3 levels and decreased survivin levels compared to the TACE group following treatment. Caspase-3 is a crucial protease in the execution phase of apoptosis, and its elevated levels signify increased activation of the apoptotic pathway. Survivin, an essential anti-apoptotic protein, is downregulated in expression, facilitating the onset of cell apoptosis[15]. This finding indicates that TACE in conjunction with immunotherapy can more efficiently activate the intrinsic apoptotic pathway and suppress apoptosis resistance, improving the direct cytotoxic effect on tumor cells, providing molecular biological evidence for the synergistic mechanism of combined treatment[16].
This study also performed the correlation analysis between radiomic features and clinical characteristics. Preliminary data revealed that texture features reflecting tumor heterogeneity (such as gray-level co-occurrence matrix contrast and entropy) were significantly correlated with tumor volume, whereas certain morphological and gray-level distribution features (such as gray-level run-length matrix short-run high-gray-level emphasis and gray-level dependence matrix gray-level non-uniformity) were correlated with tumor location. The gray-level variation and long-run low-gray-level focus of textural features were significantly correlated with tumor quantity. The findings indicate that radiomic features derived from conventional computed tomography or magnetic resonance imaging can quantitatively represent the biological parameters of HCC, such as volume, location, quantity, and internal heterogeneity, and may function as non-invasive biomarkers[17]. This study did not perform a multivariate modeling analysis of these traits in relation to treatment efficacy; however, the previous literature suggests that HCC characterized by high tumor heterogeneity has poor treatment response and a worse prognosis[18-20]. Therefore, subsequent research should integrate these prospective radiomic features with clinical and serological markers to develop a nomogram or machine learning model to predict the efficacy of TACE + immunotherapy, thus allowing accurate identification of patients with significant benefits before treatment and mitigating the economic burden and potential adverse effects associated with ineffective interventions. This study provides preliminary evidence supporting the integration of radiomics into treatment decision-making for HCC.
Despite these findings, several limitations should be acknowledged: (1) It is a single-center, retrospective study with a relatively limited sample size, which may have selection bias; (2) The immunotherapy regimens (drug types, courses of treatment) were not uniform, which may have a certain impact on efficacy analysis; (3) The correlation analysis for radiomic features was preliminary and lacked verification with external data sets. Moreover, its predictive efficacy warrants further validation in prospective, large-sample studies; and (4) The follow-up time of this study was short, and only short-term efficacy (3 months after treatment) was evaluated. The effect of combined treatment on the long-term survival of patients, including overall survival and progression-free survival, requires extended follow-up data for clarification.
This study demonstrated that for intermediate to advanced HCC patients, TACE in conjunction with immunotherapy improved short-term ORR and DCR, while also decreasing serum tumor markers, inhibiting angiogenic factors, and modulating apoptosis-related molecules, relative to TACE monotherapy. Furthermore, radiomic properties characterizing tumor heterogeneity and morphology exhibit substantial correlations with clinical characteristics, providing a basis for the development of personalized efficacy prediction models. In the future, multi-center, prospective, large-sample randomized controlled trials, integrating multi-omics data (radiomics, genomics, immune microenvironment, etc.) should be performed to elucidate the synergistic mechanisms of combined therapies, develop and validate reliable efficacy prediction tools, and ultimately achieve precise and personalized comprehensive treatment for HCC.
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