TACE Combined with Tislelizumab and Lenvatinib in the Treatment of Intermediate-to-Advanced Hepatocellular Carcinoma:A Retrospective Real-World Study

TACE Combined with Tislelizumab and Lenvatinib in the Treatment of Intermediate-to-Advanced Hepatocellular Carcinoma:A Retrospective Real-World Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article TACE Combined with Tislelizumab and Lenvatinib in the Treatment of Intermediate-to-Advanced Hepatocellular Carcinoma:A Retrospective Real-World Study Yan ze Li, Yanwei Wang, Hao Tang, Xiaolong Luo, Zujie Fan, Bo Li, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7952075/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Mar, 2026 Read the published version in BMC Cancer → Version 1 posted 13 You are reading this latest preprint version Abstract Background To evaluate the effectiveness and safety of transarterial chemoembolization (TACE) combined with tislelizumab and lenvatinib in patients with intermediate-to-advanced hepatocellular carcinoma (HCC) in real-world clinical practice. Methods Patients with intermediate-to-advanced HCC who received TACE combined with tislelizumab and lenvatinib at the Affiliated Hospital of Southwest Medical University from September 2021 to December 2023 were retrospectively enrolled. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Secondary efficacy endpoints included objective response rate (ORR) and disease control rate (DCR). Safety was evaluated based on the incidence of adverse events (AEs), with a focus on grade ≥ 3 AEs. Results By July 2025, 52 patients were included. The median follow-up time was 15 months, with median OS of 19 months and median PFS of 9 months. The best overall responses were as follows: complete response (CR) in 4 patients (7.7%), partial response (PR) in 15 patients (28.8%), stable disease (SD) in 25 patients (48.1%), and progressive disease (PD) in 8 patients (15.4%). The ORR was 36.5%, and the DCR was 84.6%. AEs of any grade occurred in 37 patients (71.1%), while grade ≥ 3 AEs were observed in 30.7% (16/52) of patients. No grade 4/5 AEs were reported. Univariate analysis indicated that tumor diameter and direct bilirubin (DBil) levels were associated with OS, while tumor diameter, DBil, and indirect bilirubin (IBil) levels were associated with PFS. Multivariate Cox regression analysis identified tumor diameter as an independent risk factor for OS (HR = 1.111; P = 0.024), and DBil level as an independent risk factor for PFS (HR = 2.368; P = 0.045). Conclusion In real-world practice, TACE combined with tislelizumab and lenvatinib demonstrated significant clinical benefits (median OS 19 months, median PFS 9 months, DCR 84.6%) with a manageable safety profile (grade ≥ 3 AE rate 30.7%, no grade 4/5 AEs). Tumor diameter was an independent risk factor for OS, and DBil level was an independent risk factor for PFS. Transarterial chemoembolization Immunotherapy Targeted therapy Systemic therapy Real-world study Hepatocellular carcinoma Figures Figure 1 Figure 2 Introduction Hepatocellular carcinoma (HCC) ranks as the sixth most common malignancy globally and represents the third leading cause of cancer-related deaths. 1 , 2 Due to its insidious onset, the majority of patients are diagnosed at an unresectable advanced stage. 3 , 4 Transarterial chemoembolization (TACE), the standard locoregional therapy for these patients, can delay tumor progression. However, the median progression-free survival (PFS) achieved with TACE is often limited to 7–8 months, accompanied by a high recurrence rate and limited long-term survival benefits . 5,6 Breakthroughs in systemic therapy have offered new hope. Among immune checkpoint inhibitors(ICIs),tislelizumab stands out as the only one demonstrating a positive outcome in a global multicenter phase III clinical trial for first-line treatment of advanced HCC. In this study, tislelizumab achieved a median overall survival (OS) of 15.9 months, with a ≥ grade 3 treatment-related adverse event (TRAE) rate of only 22.2%, providing a crucial therapeutic alternative for patients intolerant to targeted-immunotherapy combinations. 7 A synergistic effect exists between lenvatinib and tislelizumab. Mechanistically, lenvatinib inhibits VEGFR/FGFR pathways, reversing the immunosuppressive tumor microenvironment (e.g., by reducing Treg and MDSC infiltration). 8 , 9 Meanwhile, tislelizumab’s unique Fc-engineered design minimizes macrophage-mediated T cell exhaustion. 7 , 10 , 11 Collectively, they establish a complementary cycle of "anti-angiogenesis + immune activation." The BGB-A317-211 study (Phase II) conducted by Prof. Minshan Chen's team validated the clinical efficacy of this combination for first-line treatment of unresectable HCC, reporting an objective response rate (ORR) of 38.7%, a 12-month OS rate of 88.6%, and manageable ≥ grade 3 adverse events (AEs; 34.4%). 12 Further integration with locoregional therapies (e.g., TACE/Hepatic arterial infusion chemotherapy [HAIC]) demonstrates the potential to overcome efficacy limitations. In one study combining HAIC with lenvatinib and tislelizumab, median OS reached 22 months and the ORR improved to 77.1% (assessed by mRECIST criteria). 13 Moreover, the EMERALD-1 and LEAP-012 phase III trials concurrently substantiated that TACE combined with immune-targeted therapy significantly extends median PFS to 14.6–15.0 months, establishing "forward-shifted loco-systemic combination therapy" as a new paradigm. 14 , 15 However, critical evidence gaps remain: 1.Lack of regimen specificity:The EMERALD-1 and LEAP-012 trials did not evaluate the specific combination of tislelizumab plus lenvatinib; 2.Scarcity of real-world evidence (RWE): Prospective studies like BGB-A317-211 primarily enrolled patients with Child-Pugh A liver function and ECOG performance status (PS) 0–1. In contrast, real-world populations often present with complex features, including older age, compromised liver function reserve (e.g.,Child-Pugh B-C), and hepatitis B cirrhosis. The treatment tolerability and efficacy of this regimen in such diverse patients require urgent validation. This study aims to address these gaps. We retrospectively collected data from patients with intermediate-to-advanced HCC treated with TACE combined with tislelizumab and lenvatinib at the Affiliated Hospital of Southwest Medical University. We systematically assessed the effectiveness (including ORR, disease control rate [DCR], PFS, and OS) and safety (incidence and spectrum of ≥ grade 3 AEs) of this triple regimen in a real-world clinical setting. The findings will provide evidence-based support for the standardized application of this high-potential strategy in characteristic HCC populations (prevalent in hepatitis B-endemic regions with significant liver function heterogeneity), ultimately aiming to optimize individualized clinical decision-making. Material and methods Study Population​ Clinical data were collected from 52 patients with intermediate-to-advanced hepatocellular carcinoma (HCC) who were admitted to the Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University and received combination therapy with transarterial chemoembolization (TACE), tislelizumab, and lenvatinib between September 2021 and December 2023. Among the patients, 47 were male and 5 were female, with a median age of 56 years (range: 27–73 years). A total of 38 patients received 1–2 TACE sessions, and 59.6% of the patients received conventional TACE (C-TACE) (Table 1 ). This study was approved by the Ethics Committee (Approval Number: ChiECRCT20230800). Table 1 Baseline Characteristics of Patients Treated with TACE Combined with Tislelizumab and Lenvatinib (n = 52)​ Variable Category Characteristic Subgroup Value(n = 52) Demographics Sex Male 47 (90.4%) Female 5 (9.6%) Age (years) - 56 (27–73) Hypertension - 11(21.2%) Diabetes mellitus - 8 (15.4%) ​Etiology Hepatitis HBV infection 48 (92.3%) HCV infection 0(0%) Liver cirrhosis - 42 (80.7%) Tumor Morphology Location Right lobe 29 (55.8%) Left lobe 7(13.4%) Bilobar 14(26.9%) Caudate lobe 2(3.8%) Tumor number Multiple 22 (42.3%) Solitary 30(57.7%) Maximal diameter (cm) - 8.2 ± 3.86 ​Metastasis & Invasion Vascular invasion - 28 (53.8%) Extrahepatic metastasis - 14(26.9%) Laboratory Parameters AFP (µg/L) - 197.2 [966.7] PIVKA(ng/mL) - 619.58 [6839.46] Bilirubin(µmol/L) TBil 16.65 [16.5] DBil 5.8 [6.0] IBil 11.2 [9.95] ALT (U/L) - 35.25 [27.575] Albumin (g/L) - 39.1 ± 6.18 Clinical Stage Child-Pugh class A 24 (46.2%) B 28(53.8%) BCLC stage B 7 (13.5%) C 45 (86.5%) CNLC stage IIa 3 (5.8%) IIb 9 (17.3%) IIIa 24 (46.2%) IIIb 16 (30.8%) ​Treatment TACE sessions (1–2) - 38 (73.1%) TACE type C-TACE 31 (59.6%) Abbreviations: AFP,AlphaFetoprotein ;PIVKA, Protein Induced by Vitamin K Absence or Antagonist ; ALT, Alanine Aminotransferase ;BCLC,Barcelona Clinic Liver Cancer staging system ;CNLC,China Liver Cancer staging system;HBV, Hepatitis B Virus; HCV, Hepatitis C Virus; AFP, AlphaFetoprotein. TACE, transarterial chemoembolization Inclusion and Exclusion Criteria​ ​Inclusion Criteria:​ (1) Male or female patients aged between 18 and 80 years (excluding 18 and 80 years old); (2) Diagnosed with primary hepatocellular carcinoma according to the guidelines of the European Association for the Study of the Liver or the American Association for the Study of Liver Diseases; 16, 17 (3) Clinically (investigational) physician-assessed as having unresectable intermediate or advanced liver cancer, with Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC; (4) Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. ​Exclusion Criteria:​ (1) Concurrent other primary malignancies; (2) Presence of uncontrolled severe underlying diseases such as hypertension or diabetes; (3) History of gastrointestinal bleeding or definite tendency for gastrointestinal hemorrhage; (4) Participation in other drug or tumor-related clinical trials within the past 12 weeks; (5) Previous treatment with anti-tumor vaccines or other anti-tumor drugs with immunostimulatory effects; (6) Other situations judged as unsuitable for inclusion in the study. Treatment Protocol Treatment Protocol Patients first underwent the initial TACE procedure, which included conventional TACE (cTACE) or drug-eluting bead TACE (DEB-TACE), with the specific type determined by the attending physician based on the patient's individual condition. Following TACE, patients received supportive care including liver protection, hydration, analgesia, nutritional support, and other symptomatic treatments. Alkalinization of urine or albumin supplementation was administered if necessary. After 2–3 days of treatment, various clinical and laboratory indicators were rechecked. If liver function recovered adequately, oral lenvatinib was initiated on the third day after TACE (4 mg per capsule; for body weight < 60 kg, 8 mg/day; for body weight ≥ 60 kg, 12 mg/day). Within 5–10 days after TACE, tislelizumab was administered at a dose of 200 mg dissolved in 100 ml of 0.9% sodium chloride solution, via intravenous drip over 30 minutes per infusion (not less than 20 minutes, not more than 60 minutes, including the flushing phase). Follow-up Patients were scheduled for outpatient follow-up with imaging assessment within 8–12 weeks after TACE. The endpoint was defined as disease progression, initiation of other antitumor drugs, or death, whichever occurred first. During the treatment period, patients' blood test results, including complete blood count, liver function, renal function, thyroid function, and myocardial enzymes, were recorded to monitor adverse events associated with tislelizumab and lenvatinib. The documentation of adverse events was reviewed and assessed during hospitalization. Tumor markers were also evaluated, and patients underwent imaging examinations every 1 to 3 months to assess treatment efficacy. Observation Indicators and Evaluation Criteria In all cases, the decision to perform subsequent TACE was determined by the investigator based on imaging findings during follow-up visits, implementing an "on-demand TACE strategy." Repeat TACE could be administered under the following circumstances: (1) incomplete tumor necrosis; (2) regrowth of lesions; or (3) emergence of new lesions. 18 Evaluation criteria:(1) Responses were categorized per the mRECIST criteria as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). 19 CR or PR required confirmation at 3 weeks after initial assessment;(2) Overall survival (OS): defined as the time from the first drug administration to the last follow-up or death from any cause;(3) Disease control rate (DCR): (CR + PR + SD) / (CR + PR + SD + PD) × 100%;(4) Objective response rate (ORR): (CR + PR) / (CR + PR + SD + PD) × 100%;(5) Progression-free survival (PFS): the interval from treatment initiation to disease progression or death;(6) Adverse events were evaluated and recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) grading system (Grade 1–5). Statistical Analysis Statistical analysis was performed using SPSS 17.0 and RStudio 4.33. Continuous variables with a normal distribution are presented as mean ± standard deviation, while non-normally distributed variables are expressed as median and interquartile range (IQR). Categorical variables are described as frequency and percentage. Ordinal data are reported as median and IQR. The optimal cutoff value for continuous variables was determined by receiver operating characteristic (ROC) curve analysis combined with the Youden index (= sensitivity + specificity − 1) . 20 Univariate analysis of factors potentially associated with PFS and OS was conducted using the Kaplan-Meier method with log-rank testing. Variables yielding P<0.1 in univariate analysis were subsequently included in multivariate Cox proportional hazards regression models to identify independent risk factors for PFS and OS. Statistical significance was defined as P<0.05. Results​ Tumor Response Assessment​ As of July 2025, the median follow-up time for patients was 15 months. Among 52 patients, 35 died and 17 survived; 4 patients (7.7%) achieved CR, and these 4 patients underwent surgical resection after therapy; 15 patients (28.8%) achieved PR; 25 patients (48.0%) remained SD after therapy; and 8 patients (15.3%) had PD. The ORR was 36.53%, and the DCR was 84.6%. Changes in tumor diameter pre- and post-therapy are shown in Fig. 1 , and the survival curves are presented in Figs. 2 . Overall Survival (OS) The median overall survival (OS) in this study was 19 months. Univariate analysis of OS showed that tumor diameter and direct bilirubin (DBil) levels were significantly associated with patient OS. The median OS in the group with a pre-treatment tumor diameter < 10.25 cm was 20 months (95% CI: 14.774–25.226), while it was 18 months (95% CI: 8.277–27.723) in the group with a tumor diameter ≥ 10.25 cm, indicating a borderline significant difference (P = 0.062). Stratified analysis based on the initial DBil level suggested that the median OS in the group with DBil < 4.05 µmol/L was 33 months (95% CI: 14.556–51.444), which was superior to the 16 months (95% CI: 10.483–21.517) in the group with DBil ≥ 4.05 µmol/L, and this difference was statistically significant (P = 0.035). Subsequently, a multivariate COX regression analysis was performed on these potentially significant variables (P < 0.1). The results indicated that tumor diameter (HR = 1.111; P = 0.024) (Model significance: Likelihood ratio test χ²=5.197, P = 0.023) was an independent risk factor for OS (Table 2 ). Table 2 Univariate and Multivariate Regression Analysis Tables for Patient OS Univariate Analysis Multivariate Analysis Variable Group mOS (months) CI(95%) P value HR(95%CI) P value Hypertension Yes 18 4.325–31.648 0.825 No 20 16.169–23.831 Diabetes Yes 26 15.362–33.638 0.191 No 18 12.001–23.999 HBV Positive 19 15.875–22.125 0.203 Negative 8 6.040–9.960 Liver cirrhosis Yes 19 16.663–21.337 0.176 No 13 10.078–15.922 Tumor number Solitary 19 15.678–22.322 0.456 Multiple 18 4.714–31.286 Tumor diameter L[1.1-10.25) 20 14.774–25.226 0.062 1.111(1.014–1.216) 0.024 H(10.25–18.35] 18 8.277–27.723 Vascular invasion Yes 19 12.651–25.349 0.175 No 18 12.082–23.918 AFP L[1.4-21.25) 20 - 0.525 H(21.25–67001] 18 14.381–21.619 PIVKA L[1-2214.5) 20 12.033–27.967 0.184 H(2214.5-30000] 16 9.500–22.500 TBil L[4.5–14.8) 20 14.925–25.075 0.148 H(14.8–81.5] 16 10.832–21.168 DBil L[1.35–4.05) 33 14.556–51.444 0.035 - 0.063 H(4.05–41.4] 16 10.483–21.517 IBil L[3.7-15.35) 20 13.682–26.318 0.148 H(15.35-41] 14 7.763–20.237 ALT L[9.1-25.75) 23 - 0.142 H(25.75–250.1] 18 14.391-21/609 Child-Pugh class A 18 11.608–24.392 0.398 B 19 6.760–31.240 BCLC stage B 23 16.559–29.441 0.237 C 18 12.893–23.107 Notes : a) Variable selection: Forward stepwise regression (inclusion criteria: P < 0.05) ; b) "-": Variables not meeting inclusion criteria; HR and CI were not calculated. Abbreviations : AFP,AlphaFetoprotein ;PIVKA,Protein Induced by Vitamin K Absence or Antagonist; ALT,Alanine Aminotransferase;BCLC,Barcelona Clinic Liver Cancer staging system ;HBV, Hepatitis B Virus; AFP, AlphaFetoprotein; TBil,Total Bilirubin; DBil,Direct Bilirubin; IBil,Indirect Bilirubin; Progression-Free Survival (PFS) The median progression-free survival (PFS) in this study was 9 months. Univariate analysis of PFS indicated that tumor diameter, direct bilirubin (DBil), and indirect bilirubin (IDBil) levels were all associated with PFS. The median PFS in the group with a tumor diameter < 10.25 cm was 10 months (95% CI: 2.815–17.185), showing a trend towards prolongation compared to 7 months (95% CI: 5.693–8.307) in the group with a tumor diameter ≥ 10.25 cm (P = 0.076). The median PFS in the group with DBil < 4.05 µmol/L reached 19 months (95% CI: 2.817–35.183), which was higher than the 8 months (95% CI: 6.364–9.636) in the group with DBil ≥ 4.05 µmol/L (P = 0.031). Concurrently, the median PFS in the group with IDBil < 15.35 µmol/L was 15 months (95% CI: 4.606–25.394), demonstrating a trend of difference compared to 7 months (95% CI: 4.953–9.047) in the group with IDBil ≥ 15.35 µmol/L (P = 0.041). Multivariate regression analysis performed on these potentially significant variables identified DBil (HR = 2.368; P = 0.045) (Model significance: Likelihood ratio test χ²=4.028, P = 0.039) as an independent risk factor for PFS in patients receiving the combination therapy of TACE, lenvatinib, and tislelizumab (Table 3 ). Table 3 Univariate Analysis and Multivariate Regression Analysis of PFS in Patients Univariate Analysis Multivariate Analysis Variable Group mFPS (months) CI(95%) P value HR(95%CI) P value Hypertension Yes 9 0.368–17.632 0.527 No 8 5.689–10.311 Diabetes Yes 17 7.852–26.148 0.102 No 8 6.638–9.362 HBV Positive 9 6.679–11.321 0.119 Negative 5 1.173–8.267 Liver cirrhosis Yes 10 3.074–16.926 0.297 No 8 6.100–9.900 Tumor number Solitary 8 5.829–10.171 0.254 Multiple 9 0.000-21.401 Tumor diameter L[1.1-10.25) 10 2.815–17.185 0.076 - 0.097 H(10.25–18.35] 7 5.693–8.307 Intrahepatic mets Yes 15 2.155–27.845 0.183 No 8 6.276–9.724 AFP L[1.4-21.25) 7 - 0.93 H(21.25–67001] 9 6.988–11.102 PIVKA L[1-2214.5) 10 2.411–17.589 0.277 H(2214.5-30000] 8 5.573–10.472 TBil L[4.5–14.8) 10 0.810–19.190 0.192 H(14.8–81.5] 8 5.733–10.267 DBil L[1.35–4.05) 19 2.817–35.183 0.031 2.368(1.020–5.495) 0.045 H(4.05–41.4] 8 6.364–9.636 IBil L[3.7-15.35) 15 4.606–25.394 0.041 - 0.309 H(15.35-41] 7 4.953–9.047 ALT L[9.1-25.75) 10 - 0.103 H(25.75–250.1] 8 5.698–10.302 Child-Pugh class A 9 6.238–11.762 0.839 B 8 5.114–10.886 BCLC stage B 10 7.853–12.147 0.332 C 8 6.638–9.362 Notes : a) Variable selection: Forward stepwise regression (inclusion criteria: P < 0.05) ; b) "-": Variables not meeting inclusion criteria; HR and CI were not calculated. Abbreviations : AFP,AlphaFetoprotein ;PIVKA,Protein Induced by Vitamin K Absence or Antagonist; ALT,Alanine Aminotransferase;BCLC,Barcelona Clinic Liver Cancer staging system ;HBV, Hepatitis B Virus; AFP, AlphaFetoprotein; TBil,Total Bilirubin; DBil,Direct Bilirubin; IBil,Indirect Bilirubin; Safety and Adverse Reactions​ During treatment, treatment-related adverse events (AEs) were reported in 37 (71.2%) cases, with the incidence of grade ≥ 3 AEs being 30.7% (16/52) (Table 4 ). Among AEs related to targeted-immunotherapy, rash, hypertension, proteinuria, fatigue, and diarrhea were common, mostly grade 1–2. More severe grade ≥ 3 AEs primarily included hypertension, proteinuria, and rash. Common AEs associated with TACE therapy comprised fever, abdominal pain, elevated ALT, and constipation, also mostly grade 1–2; reported grade 3 events mainly involved abdominal pain and elevated liver function indices (ALT, AST, total bilirubin). No grade ≥ 4 serious AEs were documented among all reported adverse events. Table 4 Incidence of Adverse Events in Patients ​Adverse Event Any Grade, n (%)​ Grade 3, n (%)​ Rash 23(44.2) 1(1.9) Hypertension 19(36.5) 2(3.8) Proteinuria 18(34.6) 3(5.7) Fatigue 17(32.6) 1(1.9) Diarrhea 15(28.8) 0 HFSR 11(21.2) 0 Hoarseness 7(13.5) 0 Nasal/Eyelid Bleeding 7(13.5) 0 Anorexia 6 (11.5) 1(1.9) Hypothyroidism 1 (1.9) 0(0) Nausea 15(28.8) 0 Fever 26(50.0) 0 AST Elevation 23(44.2) 1(1.9) ALT Elevation 21(40.4) 2(3.8) Abdominal Pain 20(38.5) 4(7.7) Constipation 19(36.5) 0 Elevated Total Bilirubin 24(46.2) 1(1.9) Abbreviations :HFSR,Hand-Foot Skin Reaction;ALT,Alanine Aminotransferase;AST,Aspartate Aminotransferase; Discussion This real-world study prospectively evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with tislelizumab (PD-1 inhibitor) and lenvatinib as a triple therapy for unresectable advanced hepatocellular carcinoma (HCC). The study population primarily comprised BCLC stage C patients (86.5%). Results demonstrated that this combination achieved an objective response rate (ORR) of 36.53%, a disease control rate (DCR) of 84.6%, a median overall survival (OS) of 19 months, and a median progression-free survival (PFS) of 9 months. Compared with prior studies of lenvatinib combined with a single mode of local therapy: the median OS in our study (19 months) was superior to that reported in the LAUNCH phase III trial (TACE combined with lenvatinib: 17.8 months) and a study on DEB-TACE (D-TACE) combined with lenvatinib (15.9 months). 21 , 22 This advantage may stem from the synergistic effect between the PD-1 inhibitor (tislelizumab) and lenvatinib: lenvatinib reduces tumor PD-L1 levels and regulatory T cell (Treg) differentiation by blocking FGFR4, enhancing the efficacy of the PD-1 inhibitor, while the PD-1 inhibitor reverses immunosuppression, boosting immune response and anti-tumor capabilities. 23 , 24 However, the median OS (19 months) and median PFS (9 months) observed in our study were lower than those reported in some other studies. For instance, a retrospective study on TACE + sorafenib + immune checkpoint inhibitors (ICIs) (n = 22) reported a PFS of 16.26 months and OS of 23.3 months (DCR 81.82%); 25 another study on TACE + lenvatinib + PD-1 inhibitors for unresectable HCC reported superior PFS (13.3 months) and OS (23.6 months). 26 The primary reasons for the relatively lower PFS/OS in our study stem from baseline differences in the study populations: the aforementioned studies included a substantial proportion of BCLC stage B patients (approximately 50%), whereas BCLC stage B patients constituted only 13.5% of our cohort. Multiple studies indicate that BCLC stage B patients derive the greatest benefit from combination therapy, and the high proportion of BCLC stage C patients in our study likely limited the extent of survival benefit. 27 – 29 Additionally, follow-up time limitations exist in this study. Some patients were enrolled later and had insufficient follow-up time, leading to censoring of some cases (death or outcome events not yet observed). Consequently, the number of complete observation data points is relatively low, which may impact the survival assessment. Multivariate COX analysis revealed that tumor diameter is an independent risk factor for overall survival (OS) in advanced HCC patients receiving TACE combined with targeted and immunotherapeutic tri-therapy. The GUIDANCE001 study reported a 3-year OS rate of 56.2% and median PFS of 15.9 months for TACE plus targeted and immune combination therapy, concluding that AFP levels ≥ 400 ng/mL, tumor diameter ≥ 10 cm, and extrahepatic metastasis are independent risk factors for OS. 30 This aligns remarkably with our finding that tumor diameter is an independent risk factor for OS (HR = 1.111; P = 0.024). However, the impact of AFP and extrahepatic metastasis on OS was not observed in this study, likely due to limited sample size or other factors. The association between larger tumor diameter and poorer prognosis may involve the following mechanisms:①Larger tumors more readily release circulating tumor cells (CTCs) within 24h post-TACE;②Increased tumor diameter correlates with higher MVI risk, facilitating vascular invasion;③Wider microsatellite lesion distribution beyond TACE coverage in larger tumors;④Reduced response to ICIs and weaker immune infiltration in larger tumors. 31 – 33 Therefore, patients with tumor diameter ≥ 10 cm derive limited survival benefit even with TACE plus targeted-immunotherapy tri-therapy. This necessitates exploring more aggressive systemic treatments (e.g., intensified combinations or novel agents) or early intervention strategies, alongside closer monitoring. Additionally, DBil was identified as an independent risk factor for PFS in tri-therapy, consistent with LEAP-012 findings where ALBI grade 2 (poorer liver function) correlated with shorter PFS. 15 Hyperbilirubinemia potentially compromises targeted/immunotherapy drug metabolism (reducing efficacy and increasing toxicity) and promotes pro-inflammatory cytokine release (e.g.,IL-6), directly linking to hepatic dysfunction. 34 The safety profile of the combination therapy in this study was generally manageable, consistent with the known adverse reaction spectrum of each single agent, and the triple regimen did not exceed the known toxicity spectrum of the single agents. Although the incidence of any-grade AEs was high (71.2%), the incidence of grade ≥ 3 TRAEs was low, only 30.7%, and no grade 4 or 5 serious AEs were observed. These results were consistent with those reported in the EMERALD-1 and CHANCE2201 studies, which documented grade ≥ 3 TRAEs incidence rates of 26.6% and 22.2%, respectively. 14 , 35 This safety profile is crucial for intermediate to advanced stage HCC patients requiring long-term systemic therapy, demonstrating that the triple regimen is well-tolerated and manageable with controllable AEs in real-world clinical practice, thereby providing a guarantee for sustained treatment to achieve survival benefits.​ In summary, TACE combined with tislelizumab and lenvatinib demonstrated encouraging efficacy and acceptable safety in treating intermediate-to-advanced HCC patients, suggesting significant clinical value for controlling disease progression and prolonging survival in real-world advanced HCC patients. This study has several limitations. First, it was a single-center study with a relatively small sample size (n = 52), which may limit the generalizability and statistical power of the results. Second, the median follow-up duration was short (15 months), potentially resulting in immature assessment of long-term survival outcomes (e.g., OS), requiring longer-term follow-up data updates. Third, the retrospective analysis design carries inherent limitations, such as potentially incomplete data collection or bias. Conclusion​ In real-world practice, TACE combined with tislelizumab and lenvatinib demonstrated significant clinical benefit (median OS 19 months, median PFS 9 months, DCR 84.6%) with a manageable safety profile (grade ≥ 3 AE rate 30.7%, no grade 4/5 AEs) for treating intermediate-to-advanced HCC. Tumor diameter is an independent risk factor for OS, and DBil level is an independent risk factor for PFS. Declarations Statement of Ethics This research protocol adheres to the ethical principles of the 1975 Helsinki Declaration and has been approved by the Ethics Committee of the Chinese Clinical Trial Registry (approval number: ChiECRCT0380). Consent to participate Since this study is retrospective in nature and the anonymized clinical data used for analysis were obtained after written informed consent was signed by the patients or their guardians, it was exempt from obtaining additional patient consent. Competing interests The authors report no conflicts of interest in this work. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors Author Contribution (I)Conception and design: Bo Li, Xiaoli Yang; (II) Administrative support: Bo Li; (III) Provision of study materials or patients: Hao Tang, Yanze Li; (IV) Collection and assembly of data: Xiaolong Luo, Zujie Fan; (V) Data analysis and interpretation: Yanze Li, Yanwei Wang, Hao Tang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. All authors reviewed the manuscript. Acknowledgements Not applicable Data Availability Statement The data that support the ffndings of this study are available from the corresponding author upon reasonable request. References Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin. 2024;74(3):229–63. Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400(10360):1345–62. 10.1016/S0140-6736(22)01200-4 . Epub 2022 Sep 6. PMID: 36084663. Diao X, Guo C, Jin Y, Li B, Gao X, Du X, Chen Z, Jo M, Zeng Y, Ding C, Liu W, Guo J, Li S, Qiu H. Cancer situation in China: an analysis based on the global epidemiological data released in 2024. Cancer Commun (Lond). 2025;45(2):178–97. Epub 2024 Dec 10. PMID: 39659114; PMCID: PMC11833671. Brown ZJ. Tsilimigras DI,Ruff SM,Management of Hepatocellular Carcinoma:A Review[J].JAMA Surg,2023,158(4):410–20. Lu J, Zhao M, Arai Y, Zhong BY, Zhu HD, Qi XL, de Baere T, Pua U, Yoon HK, Madoff DC, Teng GJ, International Society of Multidisciplinary Interventional Oncology (ISMIO). Clinical practice of transarterial chemoembolization for hepatocellular carcinoma: consensus statement from an international expert panel of International Society of Multidisciplinary Interventional Oncology (ISMIO). Hepatobiliary Surg Nutr. 2021;10(5):661–71. 10.21037/hbsn-21-260 . PMID: 34760969; PMCID: PMC8527415. Kudo M, Ueshima K, Ikeda M, Torimura T, Tanabe N, Aikata H, Izumi N, Yamasaki T, Nojiri S, Hino K, Tsumura H, Kuzuya T, Isoda N, Yasui K, Aino H, Ido A, Kawabe N, Nakao K, Wada Y, Yokosuka O, Yoshimura K, Okusaka T, Furuse J, Kokudo N, Okita K, Johnson PJ, Arai Y. TACTICS study group. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020;69(8):1492–501. 10.1136/gutjnl-2019-318934 . Epub 2019 Dec 4. PMID: 31801872; PMCID: PMC7398460. Qin S, Kudo M, Meyer T, Bai Y, Guo Y, Meng Z, Satoh T, Marino D, Assenat E, Li S, Chen Y, Boisserie F, Abdrashitov R, Finn RS, Vogel A, Zhu AX. Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023;9(12):1651–9. 10.1001/jamaoncol.2023.4003 . PMID: 37796513; PMCID: PMC10557031. Zhao Y, Zhang YN, Wang KT, et al. Lenvatinib for hepatocellular carcinoma: From preclinical mechanisms to anti-cancer therapy[J]. Biochim Biophys Acta Rev Cancer. 2020;1874(1):188391. Kudo M, Finn RS, Qin S et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma:a randomised phase 3 non-inferiority trial[J].Lancet,2018,391(10126):1163–73. Ren Z, Ducreux M, Abou-Alfa GK, et al. Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma(RATIONALE-208): A Multicenter,Non-Randomized,Open-Label,Phase 2. Trial[J] Liver Cancer. 2023;12(1):72–84. Wang K, Liu C, Song X, Zhao N, Zheng X. Matching-adjusted indirect comparison of tislelizumab plus lenvatinib versus sintilimab plus bevacizumab biosimilar as first-line treatment for unresectable hepatocellular carcinoma. Front Immunol. 2025;16:1594935. 10.3389/fimmu.2025.1594935 . PMID: 40625746; PMCID: PMC12230042. Xu L, Chen J, Liu C, Song X, Zhang Y, Zhao H, Yan S, Jia W, Wu Z, Guo Y, Yang J, Gong W, Ma Y, Yang X, Gao Z, Zhang N, Zheng X, Li M, Su D, Chen M. Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial. BMC Med. 2024;22(1):172. 10.1186/s12916-024-03356-5 . PMID: 38650037; PMCID: PMC11036623. Zhao Y, Wen S, Xue Y, Dang Z, Nan Z, Wang D, Li X, Feng D, Chen Y. Transarterial chemoembolization combined with lenvatinib plus tislelizumab for unresectable hepatocellular carcinoma: a multicenter cohort study. Front Immunol. 2024;15:1449663. 10.3389/fimmu.2024.1449663 . PMID: 39411718; PMCID: PMC11473327. Sangro B, Kudo M, Erinjeri JP, Qin S, Ren Z, Chan SL, Arai Y, Heo J, Mai A, Escobar J, Lopez Chuken YA, Yoon JH, Tak WY, Breder VV, Suttichaimongkol T, Bouattour M, Lin SM, Peron JM, Nguyen QT, Yan L, Chiu CF, Santos FA, Veluvolu A, Thungappa SC, Matos M, Żotkiewicz M, Udoye SI, Kurland JF, Cohen GJ, Lencioni R. EMERALD-1 Investigators. Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study. Lancet. 2025;405(10474):216–32. 10.1016/S0140-6736(24)02551-0 . Epub 2025 Jan 8. PMID: 39798579; PMCID: PMC12282661. Kudo M, Ren Z, Guo Y, Han G, Lin H, Zheng J, Ogasawara S, Kim JH, Zhao H, Li C, Madoff DC, Ghobrial RM, Kawaoka T, Gerolami R, Ikeda M, Kumada H, El-Khoueiry AB, Vogel A, Peng X, Mody K, Dutcus C, Dubrovsky L, Siegel AB, Finn RS, Llovet JM. LEAP-012 investigators. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study. Lancet. 2025;405(10474):203–215. doi: 10.1016/S0140-6736(24)02575-3. Epub 2025 Jan 8. Erratum in: Lancet. 2025;405(10477):468. 10.1016/S0140-6736(25)00205-3 . PMID: 39798578. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol. 2025;82(2):315–74. 10.1016/j.jhep.2024.08.028 . Epub 2024 Dec 17. PMID: 39690085. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67(1):358–380. 10.1002/hep.29086 . PMID: 28130846. Terzi E, Golfieri R, Piscaglia F, Galassi M, Dazzi A, Leoni S, Giampalma E, Renzulli M, Bolondi L. Response rate and clinical outcome of HCC after first and repeated cTACE performed on demand. J Hepatol. 2012;57(6):1258-67. 10.1016/j.jhep.2012.07.025 . Epub 2012 Aug 4. PMID: 22871502. Llovet JM, Lencioni R. mRECIST for HCC: Performance and novel refinements. J Hepatol. 2020;72(2):288–306. 10.1016/j.jhep.2019.09.026 . PMID: 31954493. Greiner M, Pfeiffer D, Smith RD. Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests. Prev Vet Med. 2000;45(1–2):23–41. 10.1016/s0167-5877(00)00115-x . PMID: 10802332. Peng Z, Fan W, Zhu B, et al. Lenvatinib Combined With Transarterial Chemoembolization as First-Line Treatment for Advanced Hepatocellular Carcinoma:A Phase III, Randomized Clinical Trial(LAUNCH)[J]. J Clin Oncol. 2023;41(1):117–27. Xia D, Bai W, Wang E, Li J, Chen X, Wang Z, Huang M, Huang M, Sun J, Yang W, Lin Z, Wu J, Li Z, Yang S, Zhu X, Chen Z, Zhang Y, Fan W, Mai Q, Ding R, Nie C, Feng L, Li X, Huang W, Sun J, Wang Q, Lv Y, Li X, Luo B, Wang Z, Yuan J, Guo W, Li K, Li B, Li R, Yin Z, Xia J, Han G. Lenvatinib with or without Concurrent Drug-Eluting Beads Transarterial Chemoembolization in Patients with Unresectable, Advanced Hepatocellular Carcinoma: A Real-World, Multicenter, Retrospective Study. Liver Cancer. 2022;11(4):368–82. 10.1159/000523849 . PMID: 35978600; PMCID: PMC9294948. Huinen ZR, Huijbers EJM, van Beijnum JR, Nowak-Sliwinska P, Griffioen AW. Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes. Nat Rev Clin Oncol. 2021;18(8):527–40. 10.1038/s41571-021-00496-y . Epub 2021 Apr 8. PMID: 33833434. Yi C, Chen L, Lin Z, Liu L, Shao W, Zhang R, Lin J, Zhang J, Zhu W, Jia H, Qin L, Lu L, Chen J. Lenvatinib Targets FGF Receptor 4 to Enhance Antitumor Immune Response of Anti-Programmed Cell Death-1 in HCC. Hepatology. 2021;74(5):2544–60. 10.1002/hep.31921 . Epub 2021 Aug 25. PMID: 34036623. Zheng L, Fang S, Wu F et al. Efficacy and Safety of TACE Combined With Sorafenib Plus Immune Checkpoint Inhibitors for the Treatment of Intermediate and Advanced TACE-Refractory Hepatocellular Carcinoma: A Retrospective Study[J].Front Mol Biosci,2020,7:609322. Cao F, Yang Y, Si T et al. The Efficacy of TACE Combined With Lenvatinib Plus Sintilimab in Unresectable Hepatocellular Carcinoma:A Multicenter Retrospective Study[J].Front Oncol,2021,11:783480. Chen Y, Jia L, Li Y, Cui W, Wang J, Zhang C, Bian C, Luo T. Efficacy and safety of transarterial chemoembolization plus lenvatinib combined with PD-1 inhibitors versus transarterial chemoembolization plus lenvatinib for unresectable hepatocellular carcinoma: a meta-analysis. Front Immunol. 2024;15:1466113. 10.3389/fimmu.2024.1466113 . PMID: 39281676; PMCID: PMC11392794. Wang L, Lin L, Zhou W. Efficacy and safety of transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor in the treatment of advanced hepatocellular carcinoma: A meta-analysis. Pharmacol Ther. 2024;257:108634. 10.1016/j.pharmthera.2024.108634 . Epub 2024 Mar 16. PMID: 38499069. Si T, Shao Q, Jassem W, Ma Y, Heaton N. Optimal candidates and surrogate endpoints for HAIC versus Sorafenib in hepatocellular carcinoma: an updated systematic review and meta-analysis. Int J Surg. 2025;111(1):1203–13. PMID: 39093862; PMCID: PMC11745638. Yang DL, Ye L, Zeng FJ, Liu J, Yao HB, Nong JL, Liu SP, Peng N, Li WF, Wu PS, Qin C, Su Z, Ou JJ, Dong XF, Yan YH, Zhong TM, Mao XS, Wu MS, Chen YZ, Wang GD, Li MJ, Wang XY, Yang FQ, Liang YR, Chen SC, Yang YY, Chen K, Li FX, Lai YC, Pang QQ, Liang XM, You XM, Xiang BD, Yu YQ, Ma L, Zhong JH. GUIDANCE investigators. Multicenter, retrospective GUIDANCE001 study comparing transarterial chemoembolization with or without tyrosine kinase and immune checkpoint inhibitors as conversion therapy to treat unresectable hepatocellular carcinoma: Survival benefit in intermediate or advanced, but not early, stages. Hepatology. 2025;82(2):357–69. 10.1097/HEP.0000000000001229 . Epub 2025 Jan 15. PMID: 39908184. Espejo-Cruz ML, González-Rubio S, Espejo JJ, Zamora-Olaya JM, Prieto-Torre M, Linares CI, Ruiz-Ramas Á, Jiménez-Arranz Á, Guerrero-Misas M, Barrera-Baena P, Poyato-González A, Montero JL, Sánchez-Frías M, Ayllón MD, Rodríguez-Perálvarez ML, de la Mata M, Ferrín G. Early release of circulating tumor cells after transarterial chemoembolization hinders therapeutic response in patients with hepatocellular carcinoma. J Transl Med. 2025;23(1):139. 10.1186/s12967-025-06092-3 . PMID: 39885581; PMCID: PMC11783761. Men B, Cui H, Han Z, Jin X, Xu Q, Jin Y, Piao Z, Zhang S. Evaluation of the efficacy of transarterial chemoembolization combined with microwave ablation followed by adjuvant therapy in patients with hepatocellular carcinoma. Front Immunol. 2024;15:1337396. PMID: 38380330; PMCID: PMC10876829. Zhang N, Yang X, Piao M, Xun Z, Wang Y, Ning C, Zhang X, Zhang L, Wang Y, Wang S, Chao J, Lu Z, Yang X, Wang H, Zhao H. Biomarkers and prognostic factors of PD-1/PD-L1 inhibitor-based therapy in patients with advanced hepatocellular carcinoma. Biomark Res. 2024;12(1):26. 10.1186/s40364-023-00535-z . PMID: 38355603; PMCID: PMC10865587. Öcal O, Kupčinskas J, Morkunas E, Amthauer H, Schütte K, Malfertheiner P, Klümpen HJ, Sengel C, Benckert J, Seidensticker R, Sangro B, Wildgruber M, Pech M, Bartenstein P, Ricke J, Seidensticker M. Prognostic value of baseline interleukin 6 levels in liver decompensation and survival in HCC patients undergoing radioembolization. EJNMMI Res. 2021;11(1):51. 10.1186/s13550-021-00791-w . PMID: 34080071; PMCID: PMC8172845. Jin ZC, Chen JJ, Zhu XL, Duan XH, Xin YJ, Zhong BY, Chen JZ, Tie J, Zhu KS, Zhang L, Huang M, Piao MJ, Li X, Shi HB, Liu RB, Xu AB, Ji F, Wu JB, Shao GL, Li HL, Huang MS, Peng ZY, Ji JS, Yuan CW, Liu XF, Hu ZC, Yang WZ, Yin GW, Huang JH, Ge NJ, Qi X, Zhao Y, Zhou JW, Xu GH, Tu Q, Lin HL, Zhang YJ, Jiang H, Shao HB, Su YJ, Chen TS, Shi BQ, Zhou X, Zhao HT, Zhu HD, Ren ZG, Teng GJ. CHANCE2201 Investigators. Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study. EClinicalMedicine. 2024;72:102622. 10.1016/j.eclinm.2024.102622 . PMID: 38745965; PMCID: PMC11090892. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 21 Mar, 2026 Read the published version in BMC Cancer → Version 1 posted Editorial decision: Revision requested 12 Dec, 2025 Reviews received at journal 11 Dec, 2025 Reviews received at journal 09 Dec, 2025 Reviewers agreed at journal 08 Dec, 2025 Reviewers agreed at journal 08 Dec, 2025 Reviews received at journal 05 Dec, 2025 Reviewers agreed at journal 05 Dec, 2025 Reviewers agreed at journal 01 Dec, 2025 Reviewers invited by journal 02 Nov, 2025 Editor invited by journal 27 Oct, 2025 Editor assigned by journal 27 Oct, 2025 Submission checks completed at journal 27 Oct, 2025 First submitted to journal 25 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7952075","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":540098119,"identity":"6cdbac0c-ad4e-4fb2-9b7b-96149e7749ec","order_by":0,"name":"Yan ze Li","email":"","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"ze","lastName":"Li","suffix":""},{"id":540098120,"identity":"f405f12f-6fb2-462e-843b-a1693dae7aab","order_by":1,"name":"Yanwei Wang","email":"","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yanwei","middleName":"","lastName":"Wang","suffix":""},{"id":540098123,"identity":"9fd02d6e-fef3-402c-bed6-a8f09fe8991d","order_by":2,"name":"Hao Tang","email":"","orcid":"","institution":"Guangyuan Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Tang","suffix":""},{"id":540098124,"identity":"ec7f2f1e-c997-4f7a-85c1-44b73b7aca51","order_by":3,"name":"Xiaolong Luo","email":"","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaolong","middleName":"","lastName":"Luo","suffix":""},{"id":540098127,"identity":"3b1d6cab-8a4f-40ae-8221-38bc81663c8b","order_by":4,"name":"Zujie Fan","email":"","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zujie","middleName":"","lastName":"Fan","suffix":""},{"id":540098128,"identity":"067bc19e-42b0-4bc7-8043-82ab7677b53f","order_by":5,"name":"Bo Li","email":"","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Li","suffix":""},{"id":540098131,"identity":"9219b5dd-45bc-4374-8199-29423d19cf0b","order_by":6,"name":"Xiaoli Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACeYYDiQ8+GNgw87M3EKnFsPHAY8MZFWnskj0HiLXm8MFn0jxnDvEbzEggUgdj2+E0Cd62A9IGko833mCosYkmqIWd51iyhWTbHWNz6bRiC4ZjabkNBG2ZcSbxhmHbs2TL2TlmEowNhwlrYbj//oNEYtvh+g03zxCr5cCBJIkDZw4zG9zgIVKLYcOBZMOGijRmyR6gXxKI8QsoKh//AUfl4Y03PtTYEOEwJGAgkUCKcogWUnWMglEwCkbByAAAivJHibkwrKYAAAAASUVORK5CYII=","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xiaoli","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2025-10-27 11:24:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7952075/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7952075/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-026-15879-6","type":"published","date":"2026-03-21T15:59:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":95807324,"identity":"14ebbdfc-5f34-496d-b7bd-925c01e423e2","added_by":"auto","created_at":"2025-11-13 08:48:20","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":160036,"visible":true,"origin":"","legend":"","description":"","filename":"TACECombinedwithTislelizumabandLenvatinibintheTreatmentofIntermediatetoAdvancedHepatocellularCarcinomaARetrospectiveRealWorldStudy.docx","url":"https://assets-eu.researchsquare.com/files/rs-7952075/v1/ecc523f0364f2e7e68ecc2e3.docx"},{"id":95806828,"identity":"e963ac60-2f54-45bd-90d6-7d41466abff2","added_by":"auto","created_at":"2025-11-13 08:47:57","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8676,"visible":true,"origin":"","legend":"","description":"","filename":"0b745f353f5843cf8fe3e73bae7c3236.json","url":"https://assets-eu.researchsquare.com/files/rs-7952075/v1/c370ebe30da4328b4c813120.json"},{"id":95807263,"identity":"025136f3-3018-4c47-87e4-1925e291a8f1","added_by":"auto","created_at":"2025-11-13 08:48:15","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":170550,"visible":true,"origin":"","legend":"","description":"","filename":"0b745f353f5843cf8fe3e73bae7c32361enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7952075/v1/44cd68a02a15c4827dc6c64e.xml"},{"id":95806824,"identity":"2f8da129-0081-439b-b398-3ed794e79388","added_by":"auto","created_at":"2025-11-13 08:47:57","extension":"jpeg","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":256423,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7952075/v1/c47372f929f02d08a9c6edd7.jpeg"},{"id":95806892,"identity":"73d6f7d4-a6ba-43ef-9648-9fe7dbdb230d","added_by":"auto","created_at":"2025-11-13 08:47:59","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":30676,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7952075/v1/eadd91dace893e0bba4f6077.png"},{"id":95807207,"identity":"e6fbfa7b-979d-4052-bf6d-d9acd414bed7","added_by":"auto","created_at":"2025-11-13 08:48:12","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":168785,"visible":true,"origin":"","legend":"","description":"","filename":"0b745f353f5843cf8fe3e73bae7c32361structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7952075/v1/913e1c2d8e59bb7884d92602.xml"},{"id":95807288,"identity":"3bcc6c57-af08-4ea9-be11-a39acb427901","added_by":"auto","created_at":"2025-11-13 08:48:16","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":174787,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7952075/v1/82690570928abd31a51de496.html"},{"id":95807091,"identity":"4a598018-300d-4792-881f-c7d00d0f8061","added_by":"auto","created_at":"2025-11-13 08:48:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":35127,"visible":true,"origin":"","legend":"\u003cp\u003eThe waterfall plot illustrates the best percentage change from baseline in the sum of target lesion diameters for evaluable patients treated with the study regimen. The bars are color-coded to distinguish the best overall response: complete response (CR, purple), partial response (PR, green), stable disease (SD, blue), and progressive disease (PD, red).\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7952075/v1/21c328e95b490e61c7de5a4e.png"},{"id":95807024,"identity":"c1ca2603-5e0f-41db-9d12-fb801b90402d","added_by":"auto","created_at":"2025-11-13 08:48:03","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":126657,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve of overall survival (OS) and progression-free survival (PFS)\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7952075/v1/2a4569f4d78a450311a5bcc2.jpeg"},{"id":105224785,"identity":"4a17b1c2-db39-420c-9885-bcccab65cafe","added_by":"auto","created_at":"2026-03-23 16:16:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1297474,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7952075/v1/814c4b84-283d-430c-be95-1ca7ce97c516.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"TACE Combined with Tislelizumab and Lenvatinib in the Treatment of Intermediate-to-Advanced Hepatocellular Carcinoma:A Retrospective Real-World Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatocellular carcinoma (HCC) ranks as the sixth most common malignancy globally and represents the third leading cause of cancer-related deaths.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Due to its insidious onset, the majority of patients are diagnosed at an unresectable advanced stage.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Transarterial chemoembolization (TACE), the standard locoregional therapy for these patients, can delay tumor progression. However, the median progression-free survival (PFS) achieved with TACE is often limited to 7\u0026ndash;8 months, accompanied by a high recurrence rate and limited long-term survival benefits .\u003csup\u003e5,6\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eBreakthroughs in systemic therapy have offered new hope. Among immune checkpoint inhibitors(ICIs),tislelizumab stands out as the only one demonstrating a positive outcome in a global multicenter phase III clinical trial for first-line treatment of advanced HCC. In this study, tislelizumab achieved a median overall survival (OS) of 15.9 months, with a\u0026thinsp;\u0026ge;\u0026thinsp;grade 3 treatment-related adverse event (TRAE) rate of only 22.2%, providing a crucial therapeutic alternative for patients intolerant to targeted-immunotherapy combinations.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eA synergistic effect exists between lenvatinib and tislelizumab. Mechanistically, lenvatinib inhibits VEGFR/FGFR pathways, reversing the immunosuppressive tumor microenvironment (e.g., by reducing Treg and MDSC infiltration).\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Meanwhile, tislelizumab\u0026rsquo;s unique Fc-engineered design minimizes macrophage-mediated T cell exhaustion.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Collectively, they establish a complementary cycle of \"anti-angiogenesis\u0026thinsp;+\u0026thinsp;immune activation.\" The BGB-A317-211 study (Phase II) conducted by Prof. Minshan Chen's team validated the clinical efficacy of this combination for first-line treatment of unresectable HCC, reporting an objective response rate (ORR) of 38.7%, a 12-month OS rate of 88.6%, and manageable\u0026thinsp;\u0026ge;\u0026thinsp;grade 3 adverse events (AEs; 34.4%). \u003csup\u003e12\u003c/sup\u003e Further integration with locoregional therapies (e.g., TACE/Hepatic arterial infusion chemotherapy [HAIC]) demonstrates the potential to overcome efficacy limitations. In one study combining HAIC with lenvatinib and tislelizumab, median OS reached 22 months and the ORR improved to 77.1% (assessed by mRECIST criteria).\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Moreover, the EMERALD-1 and LEAP-012 phase III trials concurrently substantiated that TACE combined with immune-targeted therapy significantly extends median PFS to 14.6\u0026ndash;15.0 months, establishing \"forward-shifted loco-systemic combination therapy\" as a new paradigm.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eHowever, critical evidence gaps remain: 1.Lack of regimen specificity:The EMERALD-1 and LEAP-012 trials did not evaluate the specific combination of tislelizumab plus lenvatinib; 2.Scarcity of real-world evidence (RWE): Prospective studies like BGB-A317-211 primarily enrolled patients with Child-Pugh A liver function and ECOG performance status (PS) 0\u0026ndash;1. In contrast, real-world populations often present with complex features, including older age, compromised liver function reserve (e.g.,Child-Pugh B-C), and hepatitis B cirrhosis. The treatment tolerability and efficacy of this regimen in such diverse patients require urgent validation.\u003c/p\u003e\u003cp\u003eThis study aims to address these gaps. We retrospectively collected data from patients with intermediate-to-advanced HCC treated with TACE combined with tislelizumab and lenvatinib at the Affiliated Hospital of Southwest Medical University. We systematically assessed the effectiveness (including ORR, disease control rate [DCR], PFS, and OS) and safety (incidence and spectrum of \u0026ge;\u0026thinsp;grade 3 AEs) of this triple regimen in a real-world clinical setting. The findings will provide evidence-based support for the standardized application of this high-potential strategy in characteristic HCC populations (prevalent in hepatitis B-endemic regions with significant liver function heterogeneity), ultimately aiming to optimize individualized clinical decision-making.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Population​\u003c/h2\u003e\u003cp\u003eClinical data were collected from 52 patients with intermediate-to-advanced hepatocellular carcinoma (HCC) who were admitted to the Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University and received combination therapy with transarterial chemoembolization (TACE), tislelizumab, and lenvatinib between September 2021 and December 2023. Among the patients, 47 were male and 5 were female, with a median age of 56 years (range: 27\u0026ndash;73 years). A total of 38 patients received 1\u0026ndash;2 TACE sessions, and 59.6% of the patients received conventional TACE (C-TACE) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). This study was approved by the Ethics Committee (Approval Number: ChiECRCT20230800).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics of Patients Treated with TACE Combined with Tislelizumab and Lenvatinib (n\u0026thinsp;=\u0026thinsp;52)​\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable Category\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSubgroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eValue(n\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDemographics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e47 (90.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (9.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e56 (27\u0026ndash;73)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11(21.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (15.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e​Etiology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHepatitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHBV infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48 (92.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHCV infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLiver cirrhosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e42 (80.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor Morphology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLocation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRight lobe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29 (55.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLeft lobe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(13.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBilobar\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14(26.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCaudate lobe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2(3.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTumor number\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMultiple\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22 (42.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSolitary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30(57.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMaximal diameter (cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.86\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e​Metastasis \u0026amp; Invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVascular invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28 (53.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExtrahepatic metastasis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14(26.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLaboratory Parameters\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAFP (\u0026micro;g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e197.2 [966.7]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePIVKA(ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e619.58 [6839.46]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBilirubin(\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTBil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.65 [16.5]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDBil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.8 [6.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIBil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.2 [9.95]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eALT (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35.25 [27.575]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAlbumin (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical Stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChild-Pugh class\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 (46.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28(53.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBCLC stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (13.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e45 (86.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCNLC stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIIa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (5.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIIb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (17.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIIIa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 (46.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIIIb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (30.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e​Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTACE sessions (1\u0026ndash;2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38 (73.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTACE type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eC-TACE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e31 (59.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAbbreviations:\u0026nbsp;\u003c/strong\u003eAFP,AlphaFetoprotein\u0026nbsp;;PIVKA,\u003cem\u003eProtein Induced by Vitamin K Absence or Antagonist\u003c/em\u003e\u003cem\u003e;\u003c/em\u003e ALT,\u003cstrong\u003eAlanine Aminotransferase\u003c/strong\u003e;BCLC,Barcelona Clinic Liver Cancer staging system ;CNLC,China Liver Cancer staging system;HBV, Hepatitis B Virus; HCV, Hepatitis C Virus; AFP, AlphaFetoprotein. TACE, transarterial chemoembolization\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInclusion and Exclusion Criteria​\u003c/h3\u003e\n\u003cp\u003e​Inclusion Criteria:​ (1) Male or female patients aged between 18 and 80 years (excluding 18 and 80 years old); (2) Diagnosed with primary hepatocellular carcinoma according to the guidelines of the European Association for the Study of the Liver or the American Association for the Study of Liver Diseases;\u003csup\u003e16, 17\u003c/sup\u003e (3) Clinically (investigational) physician-assessed as having unresectable intermediate or advanced liver cancer, with Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC; (4) Eastern Cooperative Oncology Group (ECOG) performance status of \u0026le;\u0026thinsp;2.\u003c/p\u003e\u003cp\u003e​Exclusion Criteria:​ (1) Concurrent other primary malignancies; (2) Presence of uncontrolled severe underlying diseases such as hypertension or diabetes; (3) History of gastrointestinal bleeding or definite tendency for gastrointestinal hemorrhage; (4) Participation in other drug or tumor-related clinical trials within the past 12 weeks; (5) Previous treatment with anti-tumor vaccines or other anti-tumor drugs with immunostimulatory effects; (6) Other situations judged as unsuitable for inclusion in the study.\u003c/p\u003e\n\u003ch3\u003eTreatment Protocol\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eTreatment Protocol\u003c/div\u003e\u003cp\u003ePatients first underwent the initial TACE procedure, which included conventional TACE (cTACE) or drug-eluting bead TACE (DEB-TACE), with the specific type determined by the attending physician based on the patient's individual condition. Following TACE, patients received supportive care including liver protection, hydration, analgesia, nutritional support, and other symptomatic treatments. Alkalinization of urine or albumin supplementation was administered if necessary. After 2\u0026ndash;3 days of treatment, various clinical and laboratory indicators were rechecked. If liver function recovered adequately, oral lenvatinib was initiated on the third day after TACE (4 mg per capsule; for body weight\u0026thinsp;\u0026lt;\u0026thinsp;60 kg, 8 mg/day; for body weight\u0026thinsp;\u0026ge;\u0026thinsp;60 kg, 12 mg/day). Within 5\u0026ndash;10 days after TACE, tislelizumab was administered at a dose of 200 mg dissolved in 100 ml of 0.9% sodium chloride solution, via intravenous drip over 30 minutes per infusion (not less than 20 minutes, not more than 60 minutes, including the flushing phase).\u003c/p\u003e\n\u003ch3\u003eFollow-up\u003c/h3\u003e\n\u003cp\u003ePatients were scheduled for outpatient follow-up with imaging assessment within 8\u0026ndash;12 weeks after TACE. The endpoint was defined as disease progression, initiation of other antitumor drugs, or death, whichever occurred first. During the treatment period, patients' blood test results, including complete blood count, liver function, renal function, thyroid function, and myocardial enzymes, were recorded to monitor adverse events associated with tislelizumab and lenvatinib. The documentation of adverse events was reviewed and assessed during hospitalization. Tumor markers were also evaluated, and patients underwent imaging examinations every 1 to 3 months to assess treatment efficacy.\u003c/p\u003e\n\u003ch3\u003eObservation Indicators and Evaluation Criteria\u003c/h3\u003e\n\u003cp\u003eIn all cases, the decision to perform subsequent TACE was determined by the investigator based on imaging findings during follow-up visits, implementing an \"on-demand TACE strategy.\" Repeat TACE could be administered under the following circumstances: (1) incomplete tumor necrosis; (2) regrowth of lesions; or (3) emergence of new lesions.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eEvaluation criteria:(1) Responses were categorized per the mRECIST criteria as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e CR or PR required confirmation at 3 weeks after initial assessment;(2) Overall survival (OS): defined as the time from the first drug administration to the last follow-up or death from any cause;(3) Disease control rate (DCR): (CR\u0026thinsp;+\u0026thinsp;PR\u0026thinsp;+\u0026thinsp;SD) / (CR\u0026thinsp;+\u0026thinsp;PR\u0026thinsp;+\u0026thinsp;SD\u0026thinsp;+\u0026thinsp;PD) \u0026times; 100%;(4) Objective response rate (ORR): (CR\u0026thinsp;+\u0026thinsp;PR) / (CR\u0026thinsp;+\u0026thinsp;PR\u0026thinsp;+\u0026thinsp;SD\u0026thinsp;+\u0026thinsp;PD) \u0026times; 100%;(5) Progression-free survival (PFS): the interval from treatment initiation to disease progression or death;(6) Adverse events were evaluated and recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) grading system (Grade 1\u0026ndash;5).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed using SPSS 17.0 and RStudio 4.33. Continuous variables with a normal distribution are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, while non-normally distributed variables are expressed as median and interquartile range (IQR). Categorical variables are described as frequency and percentage. Ordinal data are reported as median and IQR. The optimal cutoff value for continuous variables was determined by receiver operating characteristic (ROC) curve analysis combined with the Youden index (=\u0026thinsp;sensitivity\u0026thinsp;+\u0026thinsp;specificity \u0026minus;\u0026thinsp;1) .\u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eUnivariate analysis of factors potentially associated with PFS and OS was conducted using the Kaplan-Meier method with log-rank testing. Variables yielding P\u0026lt;0.1 in univariate analysis were subsequently included in multivariate Cox proportional hazards regression models to identify independent risk factors for PFS and OS. Statistical significance was defined as P\u0026lt;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results​","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eTumor Response Assessment​\u003c/h2\u003e\u003cp\u003eAs of July 2025, the median follow-up time for patients was 15 months. Among 52 patients, 35 died and 17 survived; 4 patients (7.7%) achieved CR, and these 4 patients underwent surgical resection after therapy; 15 patients (28.8%) achieved PR; 25 patients (48.0%) remained SD after therapy; and 8 patients (15.3%) had PD. The ORR was 36.53%, and the DCR was 84.6%. Changes in tumor diameter pre- and post-therapy are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, and the survival curves are presented in Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eOverall Survival (OS)\u003c/h2\u003e\u003cp\u003eThe median overall survival (OS) in this study was 19 months. Univariate analysis of OS showed that tumor diameter and direct bilirubin (DBil) levels were significantly associated with patient OS. The median OS in the group with a pre-treatment tumor diameter\u0026thinsp;\u0026lt;\u0026thinsp;10.25 cm was 20 months (95% CI: 14.774\u0026ndash;25.226), while it was 18 months (95% CI: 8.277\u0026ndash;27.723) in the group with a tumor diameter\u0026thinsp;\u0026ge;\u0026thinsp;10.25 cm, indicating a borderline significant difference (P\u0026thinsp;=\u0026thinsp;0.062). Stratified analysis based on the initial DBil level suggested that the median OS in the group with DBil\u0026thinsp;\u0026lt;\u0026thinsp;4.05 \u0026micro;mol/L was 33 months (95% CI: 14.556\u0026ndash;51.444), which was superior to the 16 months (95% CI: 10.483\u0026ndash;21.517) in the group with DBil\u0026thinsp;\u0026ge;\u0026thinsp;4.05 \u0026micro;mol/L, and this difference was statistically significant (P\u0026thinsp;=\u0026thinsp;0.035). Subsequently, a multivariate COX regression analysis was performed on these potentially significant variables (P\u0026thinsp;\u0026lt;\u0026thinsp;0.1). The results indicated that tumor diameter (HR\u0026thinsp;=\u0026thinsp;1.111; P\u0026thinsp;=\u0026thinsp;0.024) (Model significance: Likelihood ratio test χ\u0026sup2;=5.197, P\u0026thinsp;=\u0026thinsp;0.023) was an independent risk factor for OS (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate and Multivariate Regression Analysis Tables for Patient OS\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eUnivariate Analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003eMultivariate Analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emOS (months)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCI(95%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHR(95%CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.325\u0026ndash;31.648\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.825\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.169\u0026ndash;23.831\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.362\u0026ndash;33.638\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.191\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.001\u0026ndash;23.999\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.875\u0026ndash;22.125\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.203\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.040\u0026ndash;9.960\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver cirrhosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.663\u0026ndash;21.337\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.176\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.078\u0026ndash;15.922\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor number\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSolitary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.678\u0026ndash;22.322\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.456\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMultiple\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.714\u0026ndash;31.286\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor diameter\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[1.1-10.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.774\u0026ndash;25.226\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.062\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.111(1.014\u0026ndash;1.216)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(10.25\u0026ndash;18.35]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.277\u0026ndash;27.723\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVascular invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.651\u0026ndash;25.349\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.175\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.082\u0026ndash;23.918\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAFP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[1.4-21.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.525\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(21.25\u0026ndash;67001]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.381\u0026ndash;21.619\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePIVKA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[1-2214.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.033\u0026ndash;27.967\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.184\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(2214.5-30000]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.500\u0026ndash;22.500\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTBil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[4.5\u0026ndash;14.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.925\u0026ndash;25.075\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.148\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(14.8\u0026ndash;81.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.832\u0026ndash;21.168\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDBil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[1.35\u0026ndash;4.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.556\u0026ndash;51.444\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.035\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.063\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(4.05\u0026ndash;41.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.483\u0026ndash;21.517\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIBil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[3.7-15.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.682\u0026ndash;26.318\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.148\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(15.35-41]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.763\u0026ndash;20.237\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[9.1-25.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.142\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(25.75\u0026ndash;250.1]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.391-21/609\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChild-Pugh class\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.608\u0026ndash;24.392\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.398\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.760\u0026ndash;31.240\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBCLC stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.559\u0026ndash;29.441\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.237\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.893\u0026ndash;23.107\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cb\u003eNotes\u003c/b\u003e: a) Variable selection: Forward stepwise regression (inclusion criteria: P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) ; b) \"-\": Variables not meeting inclusion criteria; HR and CI were not calculated.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cb\u003eAbbreviations\u003c/b\u003e: AFP,AlphaFetoprotein ;PIVKA,Protein Induced by Vitamin K Absence or Antagonist; ALT,Alanine Aminotransferase;BCLC,Barcelona Clinic Liver Cancer staging system ;HBV, Hepatitis B Virus; AFP, AlphaFetoprotein; TBil,Total Bilirubin; DBil,Direct Bilirubin; IBil,Indirect Bilirubin;\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eProgression-Free Survival (PFS)\u003c/h2\u003e\u003cp\u003eThe median progression-free survival (PFS) in this study was 9 months. Univariate analysis of PFS indicated that tumor diameter, direct bilirubin (DBil), and indirect bilirubin (IDBil) levels were all associated with PFS. The median PFS in the group with a tumor diameter\u0026thinsp;\u0026lt;\u0026thinsp;10.25 cm was 10 months (95% CI: 2.815\u0026ndash;17.185), showing a trend towards prolongation compared to 7 months (95% CI: 5.693\u0026ndash;8.307) in the group with a tumor diameter\u0026thinsp;\u0026ge;\u0026thinsp;10.25 cm (P\u0026thinsp;=\u0026thinsp;0.076). The median PFS in the group with DBil\u0026thinsp;\u0026lt;\u0026thinsp;4.05 \u0026micro;mol/L reached 19 months (95% CI: 2.817\u0026ndash;35.183), which was higher than the 8 months (95% CI: 6.364\u0026ndash;9.636) in the group with DBil\u0026thinsp;\u0026ge;\u0026thinsp;4.05 \u0026micro;mol/L (P\u0026thinsp;=\u0026thinsp;0.031). Concurrently, the median PFS in the group with IDBil\u0026thinsp;\u0026lt;\u0026thinsp;15.35 \u0026micro;mol/L was 15 months (95% CI: 4.606\u0026ndash;25.394), demonstrating a trend of difference compared to 7 months (95% CI: 4.953\u0026ndash;9.047) in the group with IDBil\u0026thinsp;\u0026ge;\u0026thinsp;15.35 \u0026micro;mol/L (P\u0026thinsp;=\u0026thinsp;0.041). Multivariate regression analysis performed on these potentially significant variables identified DBil (HR\u0026thinsp;=\u0026thinsp;2.368; P\u0026thinsp;=\u0026thinsp;0.045) (Model significance: Likelihood ratio test χ\u0026sup2;=4.028, P\u0026thinsp;=\u0026thinsp;0.039) as an independent risk factor for PFS in patients receiving the combination therapy of TACE, lenvatinib, and tislelizumab (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate Analysis and Multivariate Regression Analysis of PFS in Patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eUnivariate Analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003eMultivariate Analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emFPS (months)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCI(95%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHR(95%CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.368\u0026ndash;17.632\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.527\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.689\u0026ndash;10.311\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.852\u0026ndash;26.148\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.102\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.638\u0026ndash;9.362\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.679\u0026ndash;11.321\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.119\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.173\u0026ndash;8.267\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver cirrhosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.074\u0026ndash;16.926\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.297\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.100\u0026ndash;9.900\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor number\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSolitary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.829\u0026ndash;10.171\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.254\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMultiple\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.000-21.401\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor diameter\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[1.1-10.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.815\u0026ndash;17.185\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.097\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(10.25\u0026ndash;18.35]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.693\u0026ndash;8.307\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntrahepatic mets\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.155\u0026ndash;27.845\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.183\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.276\u0026ndash;9.724\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAFP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[1.4-21.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(21.25\u0026ndash;67001]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.988\u0026ndash;11.102\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePIVKA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[1-2214.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.411\u0026ndash;17.589\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.277\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(2214.5-30000]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.573\u0026ndash;10.472\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTBil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[4.5\u0026ndash;14.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.810\u0026ndash;19.190\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.192\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(14.8\u0026ndash;81.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.733\u0026ndash;10.267\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDBil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[1.35\u0026ndash;4.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.817\u0026ndash;35.183\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.368(1.020\u0026ndash;5.495)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.045\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(4.05\u0026ndash;41.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.364\u0026ndash;9.636\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIBil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[3.7-15.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.606\u0026ndash;25.394\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.041\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.309\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(15.35-41]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.953\u0026ndash;9.047\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eL[9.1-25.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eH(25.75\u0026ndash;250.1]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.698\u0026ndash;10.302\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChild-Pugh class\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.238\u0026ndash;11.762\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.839\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.114\u0026ndash;10.886\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBCLC stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.853\u0026ndash;12.147\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.332\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.638\u0026ndash;9.362\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cb\u003eNotes\u003c/b\u003e: a) Variable selection: Forward stepwise regression (inclusion criteria: P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) ; b) \"-\": Variables not meeting inclusion criteria; HR and CI were not calculated.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cb\u003eAbbreviations\u003c/b\u003e: AFP,AlphaFetoprotein ;PIVKA,Protein Induced by Vitamin K Absence or Antagonist; ALT,Alanine Aminotransferase;BCLC,Barcelona Clinic Liver Cancer staging system ;HBV, Hepatitis B Virus; AFP, AlphaFetoprotein; TBil,Total Bilirubin; DBil,Direct Bilirubin; IBil,Indirect Bilirubin;\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eSafety and Adverse Reactions​\u003c/h2\u003e\u003cp\u003eDuring treatment, treatment-related adverse events (AEs) were reported in 37 (71.2%) cases, with the incidence of grade\u0026thinsp;\u0026ge;\u0026thinsp;3 AEs being 30.7% (16/52) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Among AEs related to targeted-immunotherapy, rash, hypertension, proteinuria, fatigue, and diarrhea were common, mostly grade 1\u0026ndash;2. More severe grade\u0026thinsp;\u0026ge;\u0026thinsp;3 AEs primarily included hypertension, proteinuria, and rash. Common AEs associated with TACE therapy comprised fever, abdominal pain, elevated ALT, and constipation, also mostly grade 1\u0026ndash;2; reported grade 3 events mainly involved abdominal pain and elevated liver function indices (ALT, AST, total bilirubin). No grade\u0026thinsp;\u0026ge;\u0026thinsp;4 serious AEs were documented among all reported adverse events.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eIncidence of Adverse Events in Patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003e​Adverse Event\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAny Grade, n (%)​\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGrade 3, n (%)​\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRash\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23(44.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(1.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19(36.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(3.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProteinuria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e18(34.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(5.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFatigue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e17(32.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(1.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiarrhea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15(28.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHFSR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11(21.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHoarseness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7(13.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNasal/Eyelid Bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7(13.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnorexia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(1.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypothyroidism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (1.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNausea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15(28.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFever\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e26(50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST Elevation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23(44.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(1.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT Elevation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21(40.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(3.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal Pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20(38.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4(7.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConstipation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19(36.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eElevated Total Bilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24(46.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(1.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cb\u003eAbbreviations\u003c/b\u003e:HFSR,Hand-Foot Skin Reaction;ALT,Alanine Aminotransferase;AST,Aspartate Aminotransferase;\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis real-world study prospectively evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with tislelizumab (PD-1 inhibitor) and lenvatinib as a triple therapy for unresectable advanced hepatocellular carcinoma (HCC). The study population primarily comprised BCLC stage C patients (86.5%). Results demonstrated that this combination achieved an objective response rate (ORR) of 36.53%, a disease control rate (DCR) of 84.6%, a median overall survival (OS) of 19 months, and a median progression-free survival (PFS) of 9 months.\u003c/p\u003e\u003cp\u003eCompared with prior studies of lenvatinib combined with a single mode of local therapy: the median OS in our study (19 months) was superior to that reported in the LAUNCH phase III trial (TACE combined with lenvatinib: 17.8 months) and a study on DEB-TACE (D-TACE) combined with lenvatinib (15.9 months).\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e This advantage may stem from the synergistic effect between the PD-1 inhibitor (tislelizumab) and lenvatinib: lenvatinib reduces tumor PD-L1 levels and regulatory T cell (Treg) differentiation by blocking FGFR4, enhancing the efficacy of the PD-1 inhibitor, while the PD-1 inhibitor reverses immunosuppression, boosting immune response and anti-tumor capabilities.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e However, the median OS (19 months) and median PFS (9 months) observed in our study were lower than those reported in some other studies. For instance, a retrospective study on TACE\u0026thinsp;+\u0026thinsp;sorafenib\u0026thinsp;+\u0026thinsp;immune checkpoint inhibitors (ICIs) (n\u0026thinsp;=\u0026thinsp;22) reported a PFS of 16.26 months and OS of 23.3 months (DCR 81.82%);\u003csup\u003e25\u003c/sup\u003e another study on TACE\u0026thinsp;+\u0026thinsp;lenvatinib\u0026thinsp;+\u0026thinsp;PD-1 inhibitors for unresectable HCC reported superior PFS (13.3 months) and OS (23.6 months). \u003csup\u003e26\u003c/sup\u003e The primary reasons for the relatively lower PFS/OS in our study stem from baseline differences in the study populations: the aforementioned studies included a substantial proportion of BCLC stage B patients (approximately 50%), whereas BCLC stage B patients constituted only 13.5% of our cohort. Multiple studies indicate that BCLC stage B patients derive the greatest benefit from combination therapy, and the high proportion of BCLC stage C patients in our study likely limited the extent of survival benefit.\u003csup\u003e\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Additionally, follow-up time limitations exist in this study. Some patients were enrolled later and had insufficient follow-up time, leading to censoring of some cases (death or outcome events not yet observed). Consequently, the number of complete observation data points is relatively low, which may impact the survival assessment.\u003c/p\u003e\u003cp\u003eMultivariate COX analysis revealed that tumor diameter is an independent risk factor for overall survival (OS) in advanced HCC patients receiving TACE combined with targeted and immunotherapeutic tri-therapy. The GUIDANCE001 study reported a 3-year OS rate of 56.2% and median PFS of 15.9 months for TACE plus targeted and immune combination therapy, concluding that AFP levels\u0026thinsp;\u0026ge;\u0026thinsp;400 ng/mL, tumor diameter\u0026thinsp;\u0026ge;\u0026thinsp;10 cm, and extrahepatic metastasis are independent risk factors for OS.\u003csup\u003e30\u003c/sup\u003e This aligns remarkably with our finding that tumor diameter is an independent risk factor for OS (HR\u0026thinsp;=\u0026thinsp;1.111; P\u0026thinsp;=\u0026thinsp;0.024). However, the impact of AFP and extrahepatic metastasis on OS was not observed in this study, likely due to limited sample size or other factors. The association between larger tumor diameter and poorer prognosis may involve the following mechanisms:①Larger tumors more readily release circulating tumor cells (CTCs) within 24h post-TACE;②Increased tumor diameter correlates with higher MVI risk, facilitating vascular invasion;③Wider microsatellite lesion distribution beyond TACE coverage in larger tumors;④Reduced response to ICIs and weaker immune infiltration in larger tumors.\u003csup\u003e\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e Therefore, patients with tumor diameter\u0026thinsp;\u0026ge;\u0026thinsp;10 cm derive limited survival benefit even with TACE plus targeted-immunotherapy tri-therapy. This necessitates exploring more aggressive systemic treatments (e.g., intensified combinations or novel agents) or early intervention strategies, alongside closer monitoring. Additionally, DBil was identified as an independent risk factor for PFS in tri-therapy, consistent with LEAP-012 findings where ALBI grade 2 (poorer liver function) correlated with shorter PFS.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Hyperbilirubinemia potentially compromises targeted/immunotherapy drug metabolism (reducing efficacy and increasing toxicity) and promotes pro-inflammatory cytokine release (e.g.,IL-6), directly linking to hepatic dysfunction. \u003csup\u003e34\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe safety profile of the combination therapy in this study was generally manageable, consistent with the known adverse reaction spectrum of each single agent, and the triple regimen did not exceed the known toxicity spectrum of the single agents. Although the incidence of any-grade AEs was high (71.2%), the incidence of grade\u0026thinsp;\u0026ge;\u0026thinsp;3 TRAEs was low, only 30.7%, and no grade 4 or 5 serious AEs were observed. These results were consistent with those reported in the EMERALD-1 and CHANCE2201 studies, which documented grade\u0026thinsp;\u0026ge;\u0026thinsp;3 TRAEs incidence rates of 26.6% and 22.2%, respectively.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003eThis safety profile is crucial for intermediate to advanced stage HCC patients requiring long-term systemic therapy, demonstrating that the triple regimen is well-tolerated and manageable with controllable AEs in real-world clinical practice, thereby providing a guarantee for sustained treatment to achieve survival benefits.​\u003c/p\u003e\u003cp\u003eIn summary, TACE combined with tislelizumab and lenvatinib demonstrated encouraging efficacy and acceptable safety in treating intermediate-to-advanced HCC patients, suggesting significant clinical value for controlling disease progression and prolonging survival in real-world advanced HCC patients.\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, it was a single-center study with a relatively small sample size (n\u0026thinsp;=\u0026thinsp;52), which may limit the generalizability and statistical power of the results. Second, the median follow-up duration was short (15 months), potentially resulting in immature assessment of long-term survival outcomes (e.g., OS), requiring longer-term follow-up data updates. Third, the retrospective analysis design carries inherent limitations, such as potentially incomplete data collection or bias.\u003c/p\u003e"},{"header":"Conclusion​","content":"\u003cp\u003eIn real-world practice, TACE combined with tislelizumab and lenvatinib demonstrated significant clinical benefit (median OS 19 months, median PFS 9 months, DCR 84.6%) with a manageable safety profile (grade\u0026thinsp;\u0026ge;\u0026thinsp;3 AE rate 30.7%, no grade 4/5 AEs) for treating intermediate-to-advanced HCC. Tumor diameter is an independent risk factor for OS, and DBil level is an independent risk factor for PFS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cb\u003eStatement of Ethics\u003c/b\u003e\u003c/p\u003e\u003cp\u003e This research protocol adheres to the ethical principles of the 1975 Helsinki Declaration and has been approved by the Ethics Committee of the Chinese Clinical Trial Registry (approval number: ChiECRCT0380).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003cp\u003e Since this study is retrospective in nature and the anonymized clinical data used for analysis were obtained after written informed consent was signed by the patients or their guardians, it was exempt from obtaining additional patient consent.\u003c/p\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eThe authors report no conflicts of interest in this work.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003e(I)Conception and design: Bo Li, Xiaoli Yang; (II) Administrative support: Bo Li; (III) Provision of study materials or patients: Hao Tang, Yanze Li; (IV) Collection and assembly of data: Xiaolong Luo, Zujie Fan; (V) Data analysis and interpretation: Yanze Li, Yanwei Wang, Hao Tang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e\u003cp\u003eNot applicable\u003c/p\u003e\u003ch2\u003eData Availability Statement\u003c/h2\u003e\u003cp\u003eThe data that support the ffndings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin. 2024;74(3):229\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400(10360):1345\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(22)01200-4\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(22)01200-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2022 Sep 6. PMID: 36084663.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDiao X, Guo C, Jin Y, Li B, Gao X, Du X, Chen Z, Jo M, Zeng Y, Ding C, Liu W, Guo J, Li S, Qiu H. Cancer situation in China: an analysis based on the global epidemiological data released in 2024. Cancer Commun (Lond). 2025;45(2):178\u0026ndash;97. Epub 2024 Dec 10. PMID: 39659114; PMCID: PMC11833671.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrown ZJ. Tsilimigras DI,Ruff SM,Management of Hepatocellular Carcinoma:A Review[J].JAMA Surg,2023,158(4):410\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLu J, Zhao M, Arai Y, Zhong BY, Zhu HD, Qi XL, de Baere T, Pua U, Yoon HK, Madoff DC, Teng GJ, International Society of Multidisciplinary Interventional Oncology (ISMIO). Clinical practice of transarterial chemoembolization for hepatocellular carcinoma: consensus statement from an international expert panel of International Society of Multidisciplinary Interventional Oncology (ISMIO). Hepatobiliary Surg Nutr. 2021;10(5):661\u0026ndash;71. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.21037/hbsn-21-260\u003c/span\u003e\u003cspan address=\"10.21037/hbsn-21-260\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 34760969; PMCID: PMC8527415.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKudo M, Ueshima K, Ikeda M, Torimura T, Tanabe N, Aikata H, Izumi N, Yamasaki T, Nojiri S, Hino K, Tsumura H, Kuzuya T, Isoda N, Yasui K, Aino H, Ido A, Kawabe N, Nakao K, Wada Y, Yokosuka O, Yoshimura K, Okusaka T, Furuse J, Kokudo N, Okita K, Johnson PJ, Arai Y. TACTICS study group. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020;69(8):1492\u0026ndash;501. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/gutjnl-2019-318934\u003c/span\u003e\u003cspan address=\"10.1136/gutjnl-2019-318934\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2019 Dec 4. PMID: 31801872; PMCID: PMC7398460.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQin S, Kudo M, Meyer T, Bai Y, Guo Y, Meng Z, Satoh T, Marino D, Assenat E, Li S, Chen Y, Boisserie F, Abdrashitov R, Finn RS, Vogel A, Zhu AX. Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023;9(12):1651\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaoncol.2023.4003\u003c/span\u003e\u003cspan address=\"10.1001/jamaoncol.2023.4003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 37796513; PMCID: PMC10557031.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhao Y, Zhang YN, Wang KT, et al. Lenvatinib for hepatocellular carcinoma: From preclinical mechanisms to anti-cancer therapy[J]. Biochim Biophys Acta Rev Cancer. 2020;1874(1):188391.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKudo M, Finn RS, Qin S et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma:a randomised phase 3 non-inferiority trial[J].Lancet,2018,391(10126):1163\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRen Z, Ducreux M, Abou-Alfa GK, et al. Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma(RATIONALE-208): A Multicenter,Non-Randomized,Open-Label,Phase 2. Trial[J] Liver Cancer. 2023;12(1):72\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang K, Liu C, Song X, Zhao N, Zheng X. Matching-adjusted indirect comparison of tislelizumab plus lenvatinib versus sintilimab plus bevacizumab biosimilar as first-line treatment for unresectable hepatocellular carcinoma. Front Immunol. 2025;16:1594935. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2025.1594935\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2025.1594935\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 40625746; PMCID: PMC12230042.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu L, Chen J, Liu C, Song X, Zhang Y, Zhao H, Yan S, Jia W, Wu Z, Guo Y, Yang J, Gong W, Ma Y, Yang X, Gao Z, Zhang N, Zheng X, Li M, Su D, Chen M. Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial. BMC Med. 2024;22(1):172. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12916-024-03356-5\u003c/span\u003e\u003cspan address=\"10.1186/s12916-024-03356-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 38650037; PMCID: PMC11036623.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhao Y, Wen S, Xue Y, Dang Z, Nan Z, Wang D, Li X, Feng D, Chen Y. Transarterial chemoembolization combined with lenvatinib plus tislelizumab for unresectable hepatocellular carcinoma: a multicenter cohort study. Front Immunol. 2024;15:1449663. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2024.1449663\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2024.1449663\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 39411718; PMCID: PMC11473327.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSangro B, Kudo M, Erinjeri JP, Qin S, Ren Z, Chan SL, Arai Y, Heo J, Mai A, Escobar J, Lopez Chuken YA, Yoon JH, Tak WY, Breder VV, Suttichaimongkol T, Bouattour M, Lin SM, Peron JM, Nguyen QT, Yan L, Chiu CF, Santos FA, Veluvolu A, Thungappa SC, Matos M, Żotkiewicz M, Udoye SI, Kurland JF, Cohen GJ, Lencioni R. EMERALD-1 Investigators. Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study. Lancet. 2025;405(10474):216\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(24)02551-0\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(24)02551-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2025 Jan 8. PMID: 39798579; PMCID: PMC12282661.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKudo M, Ren Z, Guo Y, Han G, Lin H, Zheng J, Ogasawara S, Kim JH, Zhao H, Li C, Madoff DC, Ghobrial RM, Kawaoka T, Gerolami R, Ikeda M, Kumada H, El-Khoueiry AB, Vogel A, Peng X, Mody K, Dutcus C, Dubrovsky L, Siegel AB, Finn RS, Llovet JM. LEAP-012 investigators. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study. Lancet. 2025;405(10474):203\u0026ndash;215. doi: 10.1016/S0140-6736(24)02575-3. Epub 2025 Jan 8. Erratum in: Lancet. 2025;405(10477):468. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(25)00205-3\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(25)00205-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 39798578.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEuropean Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol. 2025;82(2):315\u0026ndash;74. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jhep.2024.08.028\u003c/span\u003e\u003cspan address=\"10.1016/j.jhep.2024.08.028\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2024 Dec 17. PMID: 39690085.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHeimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67(1):358\u0026ndash;380. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/hep.29086\u003c/span\u003e\u003cspan address=\"10.1002/hep.29086\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 28130846.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTerzi E, Golfieri R, Piscaglia F, Galassi M, Dazzi A, Leoni S, Giampalma E, Renzulli M, Bolondi L. Response rate and clinical outcome of HCC after first and repeated cTACE performed on demand. J Hepatol. 2012;57(6):1258-67. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jhep.2012.07.025\u003c/span\u003e\u003cspan address=\"10.1016/j.jhep.2012.07.025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2012 Aug 4. PMID: 22871502.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLlovet JM, Lencioni R. mRECIST for HCC: Performance and novel refinements. J Hepatol. 2020;72(2):288\u0026ndash;306. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jhep.2019.09.026\u003c/span\u003e\u003cspan address=\"10.1016/j.jhep.2019.09.026\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 31954493.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGreiner M, Pfeiffer D, Smith RD. Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests. Prev Vet Med. 2000;45(1\u0026ndash;2):23\u0026ndash;41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0167-5877(00)00115-x\u003c/span\u003e\u003cspan address=\"10.1016/s0167-5877(00)00115-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 10802332.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePeng Z, Fan W, Zhu B, et al. Lenvatinib Combined With Transarterial Chemoembolization as First-Line Treatment for Advanced Hepatocellular Carcinoma:A Phase III, Randomized Clinical Trial(LAUNCH)[J]. J Clin Oncol. 2023;41(1):117\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXia D, Bai W, Wang E, Li J, Chen X, Wang Z, Huang M, Huang M, Sun J, Yang W, Lin Z, Wu J, Li Z, Yang S, Zhu X, Chen Z, Zhang Y, Fan W, Mai Q, Ding R, Nie C, Feng L, Li X, Huang W, Sun J, Wang Q, Lv Y, Li X, Luo B, Wang Z, Yuan J, Guo W, Li K, Li B, Li R, Yin Z, Xia J, Han G. Lenvatinib with or without Concurrent Drug-Eluting Beads Transarterial Chemoembolization in Patients with Unresectable, Advanced Hepatocellular Carcinoma: A Real-World, Multicenter, Retrospective Study. Liver Cancer. 2022;11(4):368\u0026ndash;82. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000523849\u003c/span\u003e\u003cspan address=\"10.1159/000523849\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 35978600; PMCID: PMC9294948.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuinen ZR, Huijbers EJM, van Beijnum JR, Nowak-Sliwinska P, Griffioen AW. Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes. Nat Rev Clin Oncol. 2021;18(8):527\u0026ndash;40. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41571-021-00496-y\u003c/span\u003e\u003cspan address=\"10.1038/s41571-021-00496-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2021 Apr 8. PMID: 33833434.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYi C, Chen L, Lin Z, Liu L, Shao W, Zhang R, Lin J, Zhang J, Zhu W, Jia H, Qin L, Lu L, Chen J. Lenvatinib Targets FGF Receptor 4 to Enhance Antitumor Immune Response of Anti-Programmed Cell Death-1 in HCC. Hepatology. 2021;74(5):2544\u0026ndash;60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/hep.31921\u003c/span\u003e\u003cspan address=\"10.1002/hep.31921\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2021 Aug 25. PMID: 34036623.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZheng L, Fang S, Wu F et al. Efficacy and Safety of TACE Combined With Sorafenib Plus Immune Checkpoint Inhibitors for the Treatment of Intermediate and Advanced TACE-Refractory Hepatocellular Carcinoma: A Retrospective Study[J].Front Mol Biosci,2020,7:609322.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCao F, Yang Y, Si T et al. The Efficacy of TACE Combined With Lenvatinib Plus Sintilimab in Unresectable Hepatocellular Carcinoma:A Multicenter Retrospective Study[J].Front Oncol,2021,11:783480.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen Y, Jia L, Li Y, Cui W, Wang J, Zhang C, Bian C, Luo T. Efficacy and safety of transarterial chemoembolization plus lenvatinib combined with PD-1 inhibitors versus transarterial chemoembolization plus lenvatinib for unresectable hepatocellular carcinoma: a meta-analysis. Front Immunol. 2024;15:1466113. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2024.1466113\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2024.1466113\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 39281676; PMCID: PMC11392794.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang L, Lin L, Zhou W. Efficacy and safety of transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor in the treatment of advanced hepatocellular carcinoma: A meta-analysis. Pharmacol Ther. 2024;257:108634. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.pharmthera.2024.108634\u003c/span\u003e\u003cspan address=\"10.1016/j.pharmthera.2024.108634\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2024 Mar 16. PMID: 38499069.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSi T, Shao Q, Jassem W, Ma Y, Heaton N. Optimal candidates and surrogate endpoints for HAIC versus Sorafenib in hepatocellular carcinoma: an updated systematic review and meta-analysis. Int J Surg. 2025;111(1):1203\u0026ndash;13. PMID: 39093862; PMCID: PMC11745638.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYang DL, Ye L, Zeng FJ, Liu J, Yao HB, Nong JL, Liu SP, Peng N, Li WF, Wu PS, Qin C, Su Z, Ou JJ, Dong XF, Yan YH, Zhong TM, Mao XS, Wu MS, Chen YZ, Wang GD, Li MJ, Wang XY, Yang FQ, Liang YR, Chen SC, Yang YY, Chen K, Li FX, Lai YC, Pang QQ, Liang XM, You XM, Xiang BD, Yu YQ, Ma L, Zhong JH. GUIDANCE investigators. Multicenter, retrospective GUIDANCE001 study comparing transarterial chemoembolization with or without tyrosine kinase and immune checkpoint inhibitors as conversion therapy to treat unresectable hepatocellular carcinoma: Survival benefit in intermediate or advanced, but not early, stages. Hepatology. 2025;82(2):357\u0026ndash;69. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/HEP.0000000000001229\u003c/span\u003e\u003cspan address=\"10.1097/HEP.0000000000001229\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2025 Jan 15. PMID: 39908184.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEspejo-Cruz ML, Gonz\u0026aacute;lez-Rubio S, Espejo JJ, Zamora-Olaya JM, Prieto-Torre M, Linares CI, Ruiz-Ramas \u0026Aacute;, Jim\u0026eacute;nez-Arranz \u0026Aacute;, Guerrero-Misas M, Barrera-Baena P, Poyato-Gonz\u0026aacute;lez A, Montero JL, S\u0026aacute;nchez-Fr\u0026iacute;as M, Ayll\u0026oacute;n MD, Rodr\u0026iacute;guez-Per\u0026aacute;lvarez ML, de la Mata M, Ferr\u0026iacute;n G. Early release of circulating tumor cells after transarterial chemoembolization hinders therapeutic response in patients with hepatocellular carcinoma. J Transl Med. 2025;23(1):139. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12967-025-06092-3\u003c/span\u003e\u003cspan address=\"10.1186/s12967-025-06092-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 39885581; PMCID: PMC11783761.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMen B, Cui H, Han Z, Jin X, Xu Q, Jin Y, Piao Z, Zhang S. Evaluation of the efficacy of transarterial chemoembolization combined with microwave ablation followed by adjuvant therapy in patients with hepatocellular carcinoma. Front Immunol. 2024;15:1337396. PMID: 38380330; PMCID: PMC10876829.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang N, Yang X, Piao M, Xun Z, Wang Y, Ning C, Zhang X, Zhang L, Wang Y, Wang S, Chao J, Lu Z, Yang X, Wang H, Zhao H. Biomarkers and prognostic factors of PD-1/PD-L1 inhibitor-based therapy in patients with advanced hepatocellular carcinoma. Biomark Res. 2024;12(1):26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s40364-023-00535-z\u003c/span\u003e\u003cspan address=\"10.1186/s40364-023-00535-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 38355603; PMCID: PMC10865587.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e\u0026Ouml;cal O, Kupčinskas J, Morkunas E, Amthauer H, Sch\u0026uuml;tte K, Malfertheiner P, Kl\u0026uuml;mpen HJ, Sengel C, Benckert J, Seidensticker R, Sangro B, Wildgruber M, Pech M, Bartenstein P, Ricke J, Seidensticker M. Prognostic value of baseline interleukin 6 levels in liver decompensation and survival in HCC patients undergoing radioembolization. EJNMMI Res. 2021;11(1):51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13550-021-00791-w\u003c/span\u003e\u003cspan address=\"10.1186/s13550-021-00791-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 34080071; PMCID: PMC8172845.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJin ZC, Chen JJ, Zhu XL, Duan XH, Xin YJ, Zhong BY, Chen JZ, Tie J, Zhu KS, Zhang L, Huang M, Piao MJ, Li X, Shi HB, Liu RB, Xu AB, Ji F, Wu JB, Shao GL, Li HL, Huang MS, Peng ZY, Ji JS, Yuan CW, Liu XF, Hu ZC, Yang WZ, Yin GW, Huang JH, Ge NJ, Qi X, Zhao Y, Zhou JW, Xu GH, Tu Q, Lin HL, Zhang YJ, Jiang H, Shao HB, Su YJ, Chen TS, Shi BQ, Zhou X, Zhao HT, Zhu HD, Ren ZG, Teng GJ. CHANCE2201 Investigators. Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study. EClinicalMedicine. 2024;72:102622. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.eclinm.2024.102622\u003c/span\u003e\u003cspan address=\"10.1016/j.eclinm.2024.102622\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 38745965; PMCID: PMC11090892.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Transarterial chemoembolization, Immunotherapy, Targeted therapy, Systemic therapy, Real-world study, Hepatocellular carcinoma","lastPublishedDoi":"10.21203/rs.3.rs-7952075/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7952075/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eTo evaluate the effectiveness and safety of transarterial chemoembolization (TACE) combined with tislelizumab and lenvatinib in patients with intermediate-to-advanced hepatocellular carcinoma (HCC) in real-world clinical practice.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003ePatients with intermediate-to-advanced HCC who received TACE combined with tislelizumab and lenvatinib at the Affiliated Hospital of Southwest Medical University from September 2021 to December 2023 were retrospectively enrolled. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Secondary efficacy endpoints included objective response rate (ORR) and disease control rate (DCR). Safety was evaluated based on the incidence of adverse events (AEs), with a focus on grade\u0026thinsp;\u0026ge;\u0026thinsp;3 AEs.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eBy July 2025, 52 patients were included. The median follow-up time was 15 months, with median OS of 19 months and median PFS of 9 months. The best overall responses were as follows: complete response (CR) in 4 patients (7.7%), partial response (PR) in 15 patients (28.8%), stable disease (SD) in 25 patients (48.1%), and progressive disease (PD) in 8 patients (15.4%). The ORR was 36.5%, and the DCR was 84.6%. AEs of any grade occurred in 37 patients (71.1%), while grade\u0026thinsp;\u0026ge;\u0026thinsp;3 AEs were observed in 30.7% (16/52) of patients. No grade 4/5 AEs were reported. Univariate analysis indicated that tumor diameter and direct bilirubin (DBil) levels were associated with OS, while tumor diameter, DBil, and indirect bilirubin (IBil) levels were associated with PFS. Multivariate Cox regression analysis identified tumor diameter as an independent risk factor for OS (HR\u0026thinsp;=\u0026thinsp;1.111; P\u0026thinsp;=\u0026thinsp;0.024), and DBil level as an independent risk factor for PFS (HR\u0026thinsp;=\u0026thinsp;2.368; P\u0026thinsp;=\u0026thinsp;0.045).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn real-world practice, TACE combined with tislelizumab and lenvatinib demonstrated significant clinical benefits (median OS 19 months, median PFS 9 months, DCR 84.6%) with a manageable safety profile (grade\u0026thinsp;\u0026ge;\u0026thinsp;3 AE rate 30.7%, no grade 4/5 AEs). Tumor diameter was an independent risk factor for OS, and DBil level was an independent risk factor for PFS.\u003c/p\u003e","manuscriptTitle":"TACE Combined with Tislelizumab and Lenvatinib in the Treatment of Intermediate-to-Advanced Hepatocellular Carcinoma:A Retrospective Real-World Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-13 08:00:40","doi":"10.21203/rs.3.rs-7952075/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-12T07:01:36+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-11T08:35:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-09T13:37:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"120987116616535584947847985247811140212","date":"2025-12-09T01:29:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"72317704933054965845414219454566863514","date":"2025-12-08T11:33:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-06T04:50:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"48143620374614109677353696310103148774","date":"2025-12-05T13:58:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"173120537430011209949869942587752611765","date":"2025-12-01T06:56:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-02T16:28:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-27T17:03:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-27T05:26:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-27T05:25:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-10-25T13:46:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b9923468-f7a1-4fc2-8e07-cf2453af527f","owner":[],"postedDate":"November 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T16:14:31+00:00","versionOfRecord":{"articleIdentity":"rs-7952075","link":"https://doi.org/10.1186/s12885-026-15879-6","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2026-03-21 15:59:21","publishedOnDateReadable":"March 21st, 2026"},"versionCreatedAt":"2025-11-13 08:00:40","video":"","vorDoi":"10.1186/s12885-026-15879-6","vorDoiUrl":"https://doi.org/10.1186/s12885-026-15879-6","workflowStages":[]},"version":"v1","identity":"rs-7952075","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7952075","identity":"rs-7952075","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}