TACE and tyrosine kinase inhibitors with or without PD-1 inhibitors as first-line therapy for intermediate-advanced HCC: a multicenter real-world cohort study

TACE and tyrosine kinase inhibitors with or without PD-1 inhibitors as first-line therapy for intermediate-advanced HCC: a multicenter real-world cohort 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 and tyrosine kinase inhibitors with or without PD-1 inhibitors as first-line therapy for intermediate-advanced HCC: a multicenter real-world cohort study Xue-Gang Yang, Li-Wei Deng, Yong Zhao, Bo Peng, Bin Liu, Shi-Feng Feng, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8029505/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Feb, 2026 Read the published version in Hepatology International → Version 1 posted 5 You are reading this latest preprint version Abstract Background and aims This study aimed to evaluate the efficacy and safety of combining transarterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs), with or without programmed death-1 (PD-1) inhibitors (ICI), as first-line therapy for intermediate-advanced hepatocellular carcinoma (HCC) in a real-world setting. Methods This multicentre retrospective cohort study enrolled patients with intermediate-advanced HCC who received either TACE combined with TKIs and PD-1 inhibitors (TACE-TKI-ICI) or TACE plus TKIs (TACE-TKI) from January 2019 to December 2023. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Propensity score matching (PSM) was used to reduce bias. Results A total of 514 patients with intermediate-advanced HCC were analyzed, 263 patients in the TACE-TKI-ICI group and 251 patients in the TACE-TKI group. After PSM (1:1), 241 patients were included in each group. The TACE-TKI-ICI group had significantly longer median PFS (13.8 vs. 10.8 months; hazard ratio [HR] = 0.73; 95% confidence interval [CI], 0.58–0.91; p = 0.005) and OS (22.6 vs. 16.7 months; HR = 0.71; 95% CI, 0.55–0.91; p = 0.006) than the TACE-TKI group. The ORR was also better (58.9% vs. 41.5%, p < 0.001) in the TACE-TKI-ICI group. The incidence of grade 3/4 adverse events was 10.8% in the TACE-TKI-ICI group and 8.3% in the TACE-TKI group. Conclusion Adding PD-1 inhibitors to TACE and TKIs as first-line therapy for intermediate-advanced HCC can improve PFS, OS, and ORR, while being well tolerated. Hepatocellular carcinoma Transarterial chemoembolization Tyrosine kinase inhibitors Immunologic checkpoint inhibitors Programmed cell death 1 receptor (PD-1) Figures Figure 1 Figure 2 Figure 3 Introduction Hepatocellular carcinoma (HCC) ranks as the sixth most common cancer globally and the third leading cause of cancer-related mortality 1 . A significant proportion of patients—approximately 70% are diagnosed at intermediate or advanced stages of disease (Barcelona Clinic Liver Cancer [BCLC] stage B or C), rendering them ineligible for curative treatments such as surgical resection or ablation 2 – 4 . Transarterial chemoembolisation (TACE) as first-line therapy is used for patients with intermediate-advanced stage HCC 2 , 3 , 5 , 6 . Increasing evidence suggests that combining TACE with tyrosine kinase inhibitors (TKIs) (sorafenib or Lenvatinib) can synergistically enhance treatment efficacy and prolong survival 7 , 8 . For example, the TACTICS trial demonstrated that TACE plus sorafenib significantly improved progression-free survival (PFS) compared to TACE alone in patients with unresectable HCC 7 . Systemic therapy is the cornerstone of treatment for advanced-stage HCC 2 , 9 . Immune checkpoint inhibitors (ICIs), particularly programmed death-(ligand) 1 (PD-[L]1) inhibitors, have transformed the therapeutic landscape. First-line therapies, including atezolizumab (PD-L1 inhibitors) plus bevacizumab (anti-vascular endothelial growth factor [anti-VEGF] antibody), nivolumab (PD-1 inhibitors) plus ipilimumab, camrelizumab (PD-1 inhibitors) plus apatinib (TKIs), and tremelimumab plus durvalumab (PD-L1 inhibitors), have improved overall survival. 10 – 13 Based on this growing body of evidence, immunotherapy-based combinations are now preferred options for first-line therapy in many patients with intermediate-advanced stage disease 14 . The biological rationale for combining locoregional and systemic therapies is compelling. TACE induces tumor necrosis and the release of tumor-associated antigens, potentially enhancing immune responses. Concurrent use of TKIs can normalize tumor vasculature and counteract the pro-angiogenic effects of TACE, while ICIs may potentiate anti-tumor immunity 9 , 15 . The interim analysis of LEAP-012 study showed that the addition of lenvatinib and pembrolizumab (PD-1 inhibitor) to TACE could significantly improve PFS in patients with unresectable HCC 16 . The large-scale real-world studies have explored these regimens in diverse patient populations, showing improved outcomes for combinations of TACE with TKIs and ICIs compared to TACE alone or anti-VEGF antibodies/TKIs plus ICIs in predominantly intermediate-advanced HCC 17 , 18 . We hypothesized that adding PD-1 inhibitors to TACE and TKIs might improve treatment outcomes in patients with intermediate-advanced HCC. In this study, we conducted a multicenter, real-world, propensity score-matched cohort study to evaluate the efficacy and safety of TACE plus TKIs with or without PD-1 inhibitors as first-line therapy for intermediate-advanced HCC. Material and methods Study design This multicentre retrospective cohort study included patients with intermediate-advanced HCC between January 2019 and December 2023 at four participating centers in China. Ethical approval was granted by the Ethics Committee of Sichuan Cancer Hospital (SCCHEC-02-2022-113), and the study protocol was also approved by the institutional review boards of the other three centers. Due to the retrospective nature of the study, informed consent was waived. The inclusion criteria were as follows: (1) HCC diagnosis confirmed either histologically/cytologically or by clinical criteria in accordance with the American Association for the Study of Liver Diseases (AASLD) guidelines 19 ; (2) age between 18 and 80 years; (3) at least one measurable intrahepatic lesion per modified RECIST (mRECIST) criteria; (4) BCLC stage B or C; (5) Child–Pugh class A or B; (6) Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1; and (7) patients received TACE combined with TKIs and PD-1 inhibitors (TACE-TKI-ICI) or TACE with TKIs (TACE-TKI) as first-line therapy. More specifically, patients have received either first-line TKIs, or TKIs-ICI performed either concurrently with, or up to one month before or after TACE. Patients in the TACE-TKI-ICI group underwent at least one round of TKI and ICI therapy following their initial TACE session. The exclusion criteria included: (1) prior systemic or locoregional therapy (hepatic resection, ablation, or radiotherapy) for HCC; (2) concurrent or previous malignancies other than HCC; (3) Child–Pugh class C; (4) treatment with bevacizumab or its biosimilar; and (5) incomplete data. We gathered the baseline details for each patient, including age, gender, ECOG PS, cirrhosis, AFP levels, HBV infection status, BCLC stage, Child–Pugh class, type of TACE, and lab results. Tumour information included tumour number, size, distribution, macroscopic portal vein invasion, and extrahepatic spread. TACE procedures TACE was performed by experienced interventional radiologists (minimum 5 years of experience) at each centre, following established guidelines 20 . Superselective catheterization and embolization techniques were employed using microcatheters. Repeat TACE sessions were performed as clinically indicated based on multidisciplinary team (MDT) assessments of residual viable tumour or intrahepatic recurrence. Detailed procedural protocols are provided in the Supplementary treatment protocol . TKIs and ICIs administration In the TACE-TKI-ICI group, patients received first-line TKIs plus PD-1 inhibitors, whereas the TACE-TKI group received first-line TKIs alone. The specific agents, dosages, and administration schedules are detailed in Supplementary Tables 1 and 2 . TKIs dose reductions were permitted in the event of treatment-related adverse events (TRAEs), but dose reductions were not allowed for PD-1 inhibitors. However, temporary treatment interruptions for both TKIs and PD-1 inhibitors due to toxicity were allowed. Treatment continued until disease progression, occurrence of unacceptable toxicity, or death. Follow-up Patients were first assessed four to six weeks following the initial TACE treatment and subsequently monitored every four to twelve weeks until death or study dropout. Follow-up evaluations included laboratory testing, assessment of TRAEs, and contrast-enhanced abdominal CT or MRI. Tumour response was independently reviewed by two radiologists, each with over eight years of experience, using mRECIST criteria. The final follow-up date was April 30, 2024. Outcomes PFS was defined as the interval from treatment initiation to either tumour progression (per mRECIST) or death from any cause. Overall survival (OS) was defined as the time from treatment initiation to death or last follow-up; the best objective response rate (ORR), defined as the proportion of patients achieving complete or partial response; and safety, assessed throughout the treatment and follow-up periods. TRAEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analysis Statistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA) and R software version 4.2.1. To minimize potential confounding and baseline imbalances between groups, propensity score matching (PSM) was performed using a 1:1 nearest-neighbor method without replacement and a caliper width of 0.05. Variables included in the propensity score model were age, gender, ECOG PS, AFP, cirrhosis, BCLC stage, HBV status, Child–Pugh class, tumour size, tumour number, tumour distribution, macroscopic portal vein invasion, and extrahepatic spread. Covariate balance after matching was evaluated using standardized mean differences (Supplementary Fig. 1) . Continuous variables were summarized as medians with interquartile ranges (IQRs), while categorical variables were compared using Pearson’s χ² test or Fisher’s exact test, as appropriate. Kaplan–Meier survival analysis with log-rank testing was used to compare PFS and OS between treatment groups. Cox proportional hazards models were applied for univariate and multivariate analyses in both unmatched and matched cohorts. Variables with p < 0.05 in univariate analysis were included in multivariate models to identify independent predictors of survival. All tests were two-sided, and p < 0.05 were considered statistically significant. Results Patient characteristics A total of 747 patients with intermediate-advanced HCC were included from January 2019 to December 2023. After applying exclusion criteria, 263 patients in the TACE-TKI-ICI group and 251 patients in the TACE-TKI group. After PSM (1:1), 241 patients were included in each group. (Fig. 1 ). After PSM, baseline characteristics including age, gender, cirrhosis status, liver function (Child-Pugh class, ALBI grade), tumour (size, number, distribution, portal vein invasion), BCLC stage, treatment factors (TACE type, number of sessions), and tumour biology (AFP level, extrahepatic spread, up-to-seven criteria) were well balanced with no significant differences (all p > 0.05, Table 1 ). These matched cohorts were used for the primary analyses. Analyses conducted before PSM showed similar baseline trends. Table 1 Baseline characteristics of patient in the two groups before and after PSM. Characteristics Before PSM After PSM TACE-TKI-ICI (n = 263) TACE-TKI (n = 251) P value TACE-TKI-ICI (n = 241) TACE-TKI (n = 241) P value Age (years) 55 (49.0–64.0) 56 (55.0–65.0) 0.111 55.0 (49.0–64.0) 56.0 (50.0–65.0) 0.508 < 60 175 (66.5) 150 (59.8) 156 (64.7) 149 (61.8) ≥ 60 88 (33.5) 101 (40.2) 85 (35.3) 92 (38.2) Sex 0.100 0.338 Male 235 (89.4) 212 (84.5) 214 (88.8) 207 (85.9) Female 28 (10.6) 39 (15.5) 27 (11.2) 34 (14.1) Cirrhosis 0.513 0.498 Absent 84 (31.9) 87 (34.7) 76 (31.5) 83 (34.4) Present 179 (68.1) 164 (65.3) 165 (68.5) 158 (65.6) BCLC stage 0.695 0.826 B 58 (22.1) 59 (23.5) 54 (22.4) 52 (21.6) C 205 (77.9) 192 (76.5) 187 (77.6) 189 (78.4) Tumour size (cm) 9.4 (6.4–12.6) 9.4 (6.5–12.2) 0.677 9.3 (6.4–12.5) 9.4 (6.6–12.2) 0.693 < 5 39 (14.8) 34 (13.5) 35 (14.5) 32 (13.3) ≥ 5 224 (85.2) 217 (86.5) 206 (85.5) 209 (86.7) Tumour distribution 0.104 0.457 Single lobe 116 (44.1) 93 (37.1) 100 (41.5) 92 (38.2) Multiple lobes 147 (55.9) 158 (62.9) 141 (58.5) 149 (61.8) Tumour number 0.708 0.853 ≤ 3 108 (41.1) 99 (39.4) 98 (40.7) 96 (39.8) > 3 155 (58.9) 152 (60.6) 143 (59.3) 145 (60.2) Macroscopic portal vein invasion 0.863 0.926 Absent 107 (40.7) 104 (41.4) 96 (39.8) 97 (40.2) Present 156 (59.3) 147 (58.6) 145 (60.2) 144 (59.8) Extrahepatic spread 0.845 0.643 Absent 156 (59.3) 151 (60.2) 146 (60.6) 141 (58.5) Present 107 (40.7) 100 (39.8) 95 (39.4) 100 (41.5) Etiology 0.356 0.307 HBV 212 (80.6) 194 (77.3) 197 (81.7) 188 (78.0) Others 51 (19.4) 57 (22.7) 44 (18.3) 53 (22.0) Child-Pugh class 0.158 0.225 A 224 (85.2) 202 (80.5) 205 (85.1) 195 (80.9) B 39 (14.8) 49 (19.5) 36 (14.9) 46 (19.1) ALBI grade 0.489 0.296 1 63 (24) 54 (21.5) 61 (25.3) 51 (21.2) 2 193 (73.4) 186 (74.1) 174 (72.2) 179 (74.3) 3 7 (2.7) 11 (4.4) 6 (2.5) 11 (4.6) ECOG PS 0.101 0.313 0 129 (49.0) 105 (41.8) 113 (46.9) 102 (42.3) 1 134 (51.0) 146 (58.2) 128 (53.1) 139 (57.7) TACE type 0.753 0.648 cTACE 120 (45.6) 118 (47) 108 (44.8) 113 (46.9) DEB-TACE 143 (54.4) 133 (53) 133 (55.2) 128 (53.1) AFP (ng/mL) 0.082 0.411 < 400 114 (43.3) 128 (51.0) 109 (45.2) 118 (49.0) ≥ 400 149 (56.7) 123 (49.0) 132 (54.8) 123 (51.0) Up-to-seven criteria 0.237 0.386 Within 35 (13.3) 25 (10.0) 30 (12.4) 24 (10.0) Beyond 228 (86.7) 226 (90.0) 211 (87.6) 217 (90.0) TACE sessions 0.402 0.465 1–2 137 (52.1) 140 (55.8) 126 (52.3) 134 (55.6) ≥ 3 126 (47.9) 111 (44.2) 115 (47.7) 107 (44.4) Data were median (interquartile range) or n (%). Abbreviations: PSM, propensity score matching; TACE-TKI-ICI, transarterial chemoembolization plus tyrosine kinase inhibitors with immune checkpoint inhibitors; TACE-TKI, transarterial chemoembolisation plus tyrosine kinase inhibitors; BCLC, Barcelona Clinic Liver Cancer; HBV, Hepatitis B virus; ALBI, albumin-bilirubin; ECOG PS, Eastern Cooperative Oncology Group performance status; cTACE, conventional transarterial chemoembolisation; DEB-TACE, drug-eluting beads transarterial chemoembolisation; AFP, alpha-fetoprotein. In this study, TKIs and PD-1 inhibitors were summarized in Supplementary Tables 1 and 2 . Subsequent therapies, such as conversion surgeries and radiotherapy were more frequent in the TACE-TKI-ICI group than TACE-TKI group ( Supplementary Table 3 ). Outcomes Progression-Free survival Before PSM, the TACE-TKI-ICI group had significantly longer median PFS than the TACE-TKI group (13.9 vs. 10.8 months; hazard ratio [HR] = 0.71; 95% confidence interval [CI], 0.57–0.88; p = 0.002; Supplementary Fig. 2 ). Univariate and multivariate analyses supported treatment with TACE-TKI-ICI as an independent favourable predictor of PFS ( Supplementary Table 4 ). After PSM, median PFS result was consistent with before PSM finding (13.8 vs. 10.8 months; HR = 0.73; 95% CI, 0.58–0.91; p = 0.005; Fig. 2 A). The PFS benefits of TACE-TKI-ICI therapy were generally consistent across various clinical subgroups (Fig. 3 A). Multivariate analysis showed that ECOG PS of 0 and TACE-TKI-ICI therapy were associated with better PFS (Table 2 ). Table 2 Predictors of progression-free survival and overall survival after PSM. Characteristics Univariate analysis Multivariate analysis HR 95%CI P value HR 95%CI P value PFS analyses Cirrhosis (Present vs. Absent) 0.98 0.77–1.24 0.853 BCLC stage (C vs. B) 1.39 1.05–1.83 0.021 1.08 0.81–1.45 0.588 Tumour size (cm) (≥ 5 vs. <5) 2.08 1.42–3.05 3 vs. ≤3) 1.37 1.08–1.72 0.008 1.20 0.92–1.56 0.186 Macroscopic portal vein invasion (Present vs. Absent) 1.22 0.97–1.54 0.085 Extrahepatic spread (Present vs. Absent) 1.16 0.93–1.45 0.198 Etiology (HBV vs. Others) 1.05 0.80–1.38 0.707 Child-Pugh class (B vs. A) 1.48 1.12–1.96 0.006 1.31 0.98–1.75 0.064 ALBI grade (2 + 3 vs. 1) 1.38 1.05–1.83 0.022 1.14 0.85–1.52 0.380 ECOG PS (1 vs. 0) 2.21 1.75–2.80 < 0.001 1.96 1.54–2.51 < 0.001 TACE type (DEB-TACE vs. cTACE) 0.87 0.70–1.09 0.238 AFP (ng/mL) (≥ 400 vs. <400) 1.44 1.15–1.81 0.001 1.22 0.96–1.55 0.097 Up-to-seven criteria (Beyond vs. Within) 2.01 1.31–3.08 0.001 1.03 0.53-2.00 0.929 TACE sessions (≥ 3 vs. 1–2) 0.88 0.71–1.11 0.278 Treatment (TACE-TKI-ICI vs. TACE-TKI) 0.73 0.58–0.91 0.005 0.72 0.57–0.90 0.004 OS analyses Cirrhosis (Present vs. Absent) 0.95 0.74–1.23 0.705 BCLC stage (C vs. B) 2.12 1.54–2.94 < 0.001 1.39 0.83–2.33 0.217 Tumour size (cm) (≥ 5 vs. <5) 2.49 1.61–3.86 3 vs. ≤3) 1.33 1.04–1.71 0.023 1.23 0.92–1.65 0.154 Macroscopic portal vein invasion (Present vs. Absent) 1.55 1.21–1.99 < 0.001 1.08 0.75–1.56 0.667 Extrahepatic spread (Present vs. Absent) 1.51 1.19–1.92 < 0.001 1.12 0.82–1.53 0.476 Etiology (HBV vs. Others) 0.98 0.74–1.31 0.894 Child-Pugh class (B vs. A) 1.33 0.98–1.81 0.063 ALBI grade (2 + 3 vs. 1) 1.31 0.98–1.76 0.071 ECOG PS (1 vs. 0) 3.13 2.41–4.06 < 0.001 2.58 1.97–3.38 < 0.001 TACE type (DEB-TACE vs. cTACE) 0.85 0.66–1.08 0.173 AFP (ng/mL) (≥ 400 vs. <400) 1.66 1.30–2.12 < 0.001 1.35 1.04–1.74 0.022 Up-to-seven criteria (Beyond vs. Within) 1.78 1.14–2.78 0.011 1.85 0.92–3.70 0.087 TACE sessions (≥ 3 vs. 1–2) 0.61 0.48–0.78 < 0.001 0.75 0.59–0.96 0.024 Treatment (TACE-TKI-ICI vs. TACE-TKI) 0.71 0.56–0.91 0.006 0.67 0.53–0.85 0.001 PSM, propensity score matching; HR, hazard ratio; CI, confidence intervals; PFS, progression-free survival; OS, overall survival; BCLC, Barcelona Clinic Liver Cancer; HBV, Hepatitis B virus; ALBI, albumin-bilirubin; ECOG PS, Eastern Cooperative Oncology Group performance status; TACE, transarterial chemoembolisation; cTACE, conventional transarterial chemoembolisation; DEB-TACE, drug-eluting beads transarterial chemoembolisation; AFP, alpha-fetoprotein; TACE-TKI-ICI, transarterial chemoembolisation and tyrosine kinase inhibitors with immune checkpoint inhibitors; TACE-TKI, transarterial chemoembolisation and tyrosine kinase inhibitors. Overall survival Before PSM, the TACE-TKI-ICI group had significantly longer median OS than the TACE-TKI group (22.9 vs. 16.7 months; HR = 0.69; 95% CI, 0.55–0.88; p = 0.002; Supplementary Fig. 3 ). Univariate and multivariate analyses supported treatment with TACE-TKI-ICI as an independent favourable predictor of OS ( Supplementary Table 4 ). After PSM, median OS result was consistent with before PSM finding (22.6 vs. 16.7 months; HR = 0.71; 95% CI, 0.56–0.91; p = 0.006) (Fig. 2 B). The OS benefits of TACE-TKI-ICI therapy were generally consistent across various clinical subgroups (Fig. 3 B). Multivariate analysis confirmed that tumour size < 5 cm, ECOG PS of 0, AFP < 400 ng/mL, TACE sessions ≥ 3, and TACE-TKI-ICI therapy were associated with better OS (Table 2 ). Objective response rate After PSM, the TACE-TKI-ICI group showed significantly higher ORR (58.9% vs. 41.5%, p < 0.001) and disease control rate (DCR) (84.6% vs. 76.8%, p = 0.028) than the TACE-TKI group (Supplementary Table 5) . These findings were consistent with analyses conducted before PSM (Supplementary Table 5) . Safety The safety profiles of both treatment groups were evaluated after PSM. The overall incidence of any-grade TRAEs was comparable between the TACE-TKI-ICI group and the TACE-TKI group (66.8% vs. 61.8%, p = 0.254). Most TRAEs were grade 1/2 in severity, with grade 3/4 events being infrequent in both groups (10.8% vs. 8.3%, p = 0.352). The most common TRAEs in the TACE-TKI-ICI group included increased AST (28.6%), increased ALT (22.4%), and pain (22.0%). In the TACE-TKI group, the most frequent events were increased AST (25.3%), pain (18.3%), and hyperbilirubinemia (16.2%). Hypertension, fatigue, and decreased appetite were also observed with similar frequencies in both groups. Notably, hypothyroidism was significantly more common in the TACE-TKI-ICI group than in the TACE-TKI group (11.6% vs. 0.8%, p < 0.001). The incidence of serious adverse events (grade 3/4) remained low and did not differ significantly between groups for most TRAEs. No treatment-related deaths were reported ( Table 3 ) . Table 3 Treatment-related adverse events after PSM. Events, n (%) TACE-TKI-ICI (N = 241) TACE-TKI (N = 241) P value Any grade Grade 1/2 Grade 3/4 Any grade Grade 1/2 Grade 3/4 Any grade Grade 1/2 Grade 3/4 Any TRAE 161 (66.8) 158 (65.6) 26 (10.8) 149 (61.8) 148 (61.4) 20 (8.3) 0.254 0.344 0.352 Fatigue 41 (17.0) 40 (16.6) 1 (0.4) 31 (12.9) 31 (12.9) 0 (0.0) 0.201 0.247 0.317 Decreased appetite 37 (15.4) 37 (15.4) 0 (0.0) 30 (12.4) 30 (12.4) 0 (0.0) 0.357 0.357 - Pain 53 (22.0) 52 (21.6) 1 (0.4) 44 (18.3) 44 (18.3) 0 (0.0) 0.307 0.362 0.317 Diarrhea 43 (17.8) 42 (17.4) 1 (0.4) 33 (13.7) 32 (13.3) 1 (0.4) 0.211 0.206 > 0.999 Nausea 31 (12.9) 30 (14.5) 1 (0.4) 37 (15.4) 35 (14.5) 2 (0.8) 0.432 0.505 0.562 Hand and foot syndrome 35 (14.5) 31 (12.9) 4 (1.7) 31 (12.9) 28 (11.6) 3 (1.2) 0.596 0.677 0.703 Gastrointestinal hemorrhage 20 (8.3) 18 (7.5) 2 (0.8) 18 (7.5) 18 (7.5) 0 (0.0) 0.735 > 0.999 0.156 Gingival bleeding 13 (5.4) 12 (5.0) 1 (0.4) 7 (2.9) 7 (2.9) 0 (0.0) 0.171 0.242 0.317 Dysphonia 2 (0.8) 2 (0.8) 0 (0.0) 4 (1.7) 4 (1.7) 0 (0.0) 0.411 0.411 - Hypothyroidism 28 (11.6) 26 (10.8) 2 (0.8) 2 (0.8) 2 (0.8) 0 (0.0) < 0.001 < 0.001 0.156 Fever 49 (20.3) 48 (19.9) 1 (0.4) 38 (15.8) 38 (15.8) 0 (0.0) 0.193 0.234 0.317 Hypertension 37 (15.4) 33 (13.7) 4 (1.7) 31 (12.9) 29 (12.0) 2 (0.8) 0.432 0.586 0.411 Proteinuria 32 (13.3) 32 (13.3) 0 (0.0) 30 (12.4) 29 (12.0) 1 (0.4) 0.786 0.681 0.317 Hyperbilirubinemia 47 (19.5) 41 (17.0) 6 (2.5) 39 (16.2) 35 (14.5) 4 (1.7) 0.341 0.453 0.523 Hypoalbuminemia 46 (19.1) 42 (17.4) 4 (1.7) 41 (17.0) 39 (16.2) 2 (0.8) 0.554 0.715 0.411 Increased ALT 54 (22.4) 49 (20.3) 5 (2.1) 40 (16.6) 38 (15.8) 2 (0.8) 0.108 0.193 0.253 Increased AST 69 (28.6) 62 (25.7) 7 (2.9) 61 (25.3) 55 (22.8) 6 (2.5) 0.412 0.457 0.779 Neutropenia 19 (7.9) 19 (7.9) 0 (0.0) 21 (8.7) 21 (8.7) 0 (0.0) 0.714 0.741 - Thrombocytopenia 26 (10.8) 24 (10.0) 2 (0.8) 23 (9.5) 21 (8.7) 2 (0.8) 0.651 0.639 > 0.999 PSM, propensity score matching; TACE-TKI-ICI, transarterial chemoembolisation plus tyrosine kinase inhibitors with immune checkpoint inhibitors; TACE-TKI, transarterial chemoembolisation plus tyrosine kinase inhibitors; TRAEs, Treatment-Related Adverse Events; ALT, alanine transaminase; AST, aspartate aminotransferase. Discussion This multicentre, retrospective, matched cohort study evaluated the clinical outcomes of adding PD-1 inhibitors to the combination of TACE and TKIs as first-line therapy for intermediate-advanced HCC. The results indicated that TACE-TKI-ICI group significantly improved PFS, OS, and ORR, without increasing TRAEs compared to TACE-TKI group. Multivariate analysis further confirmed TACE-TKI-ICI as an independent predictor for prolonging PFS and OS. The CHANCE001 study was a retrospective, matched cohort study showed that TACE plus PD-(L)1 inhibitors and molecular targeted therapies in patients with intermediate-advanced HCC improved survival outcomes compared to TACE alone 17 . In CHANCE001 study, the immunotherapeutic agents included PD-L1 inhibitors and PD-1 inhibitors, while the targeted drugs cover TKIs and anti-VEGF antibody (bevacizumab), resulting in a more diverse range of drug types. In our study, only PD-1 inhibitors and TKIs were included, PD-L1 inhibitors and anti-VEGF antibody not being included, in contrast to CHANCE001 study. The CHANCE2211 study showed that TACE plus camrelizumab (PD-1 inhibitors) and apatinib (TKIs) in patients with intermediate-advanced HCC improved survival outcomes compared to TACE alone 21 . The sample size of the CHANCE2211 study is relatively small. The control group of the CHANCE001 and CHANCE2211 studies was TACE alone, while the control group of our study was TACE plus TKIs. The data from our study further enriches the real-world evidence on the treatment of intermediate-advanced HCC with TACE combined with TKIs and ICIs. The LEAP-012 trial demonstrated that adding lenvatinib and pembrolizumab to TACE improved median PFS compared to TACE alone in patients with unresectable, non-metastatic HCC, and median OS was not disclosed 16 . Our study showed that adding PD-1 inhibitors to TACE plus TKIs improved median PFS and OS compared to TACE plus TKIs in patients with intermediate-advanced HCC. The median OS was reached in our study. This result fills the data gaps in the LEAP-012 study by leveraging real-world data. Another retrospective study showed that TACE plus lenvatinib and PD-1 inhibitor in patients with advanced HCC improved PFS and OS compared to TACE plus lenvatinib 22 . That study was only included advanced (BCLC C) HCC. TACE induces immunogenic cell death and enhances the release of tumor antigens, thereby eliciting an immune response. Nevertheless, it concurrently triggers VEGF upregulation and immunosuppression, which may contribute to disease progression 9 , 23 . TKIs are capable of normalizing tumor vasculature, reducing microvessel density, lowering intratumoural interstitial pressure, mitigating VEGF-induced immune evasion, and remodelling the tumor microenvironment 9 , 24 . The combination of TKIs and TACE essentially resolves the predicament of "efficacy limitation due to abnormal blood vessels" in TACE treatment by optimizing the tumour microenvironment 25 , 26 . Therefore, adding ICIs to TACE plus TKIs is a treatment strategy for HCC that aims to augment tumor immune infiltration and therapeutic efficacy. This study showed that the TACE-TKI-ICI group had comparable overall TRAE rates (66.8% vs. 61.8%) and grade 3/4 TRAE rates (10.8% vs. 8.3%) to the TACE-TKI-ICI group. TACE-TKI-ICI group had 28 (11.6%) of patients suffered from hypothyroidism, which was probably attributable to TKIs and PD-1 inhibitors. The TACE-TKI-ICI group exhibited comparable overall TRAE rates and even lower grade 3/4 AEs compared to LEAP-012 trial 16 . This could reflect differences in AE reporting, possibly influenced by healthcare access disruptions during the COVID-19 pandemic. This study had several limitations. First, being a retrospective study, there is a potential for selection bias, which we attempted to mitigate through PSM. Second, the inclusion of multiple different TKIs and PD-1 inhibitors, based on both Western and Chinese guidelines, adds variability to our results. The treatment selection process was influenced by the patient's health status, financial considerations, and preferences, making it difficult to standardize therapy across the cohort. Future studies should evaluate more uniform combination protocols to better assess the optimal treatment strategy. Finally, over 70% of the patients in our study had HBV-related HCC, limiting the generalizability of our findings to other aetiologies of liver-related HCC. In conclusion, adding PD-1 inhibitors to TACE and TKIs as first-line therapy for intermediate-advanced HCC can improve PFS, OS, and ORR, without significantly increasing treatment-related adverse events, compared to TACE and TKIs alone. A prospective, multicentre, large-sample study is needed to validate these findings. Declarations Declarations of competing interest All authors declare that they have no competing interests. Ethics approval and consent to participate The study was approved by the Ethics Committee of Sichuan Cancer Hospital (SCCHEC-02-2022-113), and the study protocol was also approved by the institutional review boards of the other three centers. Due to the retrospective nature of the study, informed consent was waived. Funding This study was supported by the Natural Science Foundation of Sichuan (No. 2025ZNSFSC0239), and Beijing Hepatobiliary Harmony Public Welfare Foundation (No. iGandanF-1082025-YLPS013), Zhongguancun Precision Medicine Foundation (No. GXZBD07). Acknowledgements We thank the patients and investigators in this study. Data availability The data supporting the findings of this study are not publicly available due to regulations under the Personal Information Protection Act. 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Une N, Takano-Kasuya M, Kitamura N, et al. The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors. Med Oncol. 2021;38(6):60. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307(5706):58–62. Supplementary Files Supplementarymaterials.docx Cite Share Download PDF Status: Published Journal Publication published 17 Feb, 2026 Read the published version in Hepatology International → Version 1 posted Editorial decision: Major Revisions Needed 27 Nov, 2025 Reviewers agreed at journal 10 Nov, 2025 Reviewers invited by journal 10 Nov, 2025 Editor assigned by journal 05 Nov, 2025 First submitted to journal 04 Nov, 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. 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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-8029505","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":542730849,"identity":"4faae48a-31db-40aa-a83e-92d91c7a5021","order_by":0,"name":"Xue-Gang Yang","email":"","orcid":"","institution":"Sichuan Cancer Hospital and Research Institute: Sichuan Cancer Hospital and Institute","correspondingAuthor":false,"prefix":"","firstName":"Xue-Gang","middleName":"","lastName":"Yang","suffix":""},{"id":542730850,"identity":"dfc842d8-b2a1-40d7-92d3-3d2036fa7537","order_by":1,"name":"Li-Wei Deng","email":"","orcid":"","institution":"Sichuan 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01:06:26","extension":"html","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":155538,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8029505/v1/dc3b76e7834f2e9f73deab25.html"},{"id":96421766,"identity":"8f59be60-5e25-41a5-b98a-2cbc435c4c58","added_by":"auto","created_at":"2025-11-21 01:06:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":846454,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of the study.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHCC, hepatocellular carcinoma; TACE, transarterial chemoembolisation; TKIs, tyrosine kinase inhibitors; ICIs, programmed death-1 inhibitors; BCLC, Barcelona Clinic Liver Cancer; TACE-TKI-ICI, TACE and tyrosine kinase inhibitors with programmed death-1 inhibitors; TACE-TKI, TACE and tyrosine kinase inhibitors.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8029505/v1/80083e99bcffb4f64c8884b2.png"},{"id":96455165,"identity":"8899c4f5-6483-402c-9071-69499d579501","added_by":"auto","created_at":"2025-11-21 10:03:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2150926,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier curves of progression-free survival (A) and overall survival (B) in the two groups after propensity score matching.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTACE-TKI-ICI, TACE and tyrosine kinase inhibitors with programmed death-1 inhibitors; TACE-TKI, TACE and tyrosine kinase inhibitors.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8029505/v1/438e91cd60eb8d5e3bf74aba.png"},{"id":96421777,"identity":"cd4d15b1-fcc4-4d28-b99d-6224bed9c799","added_by":"auto","created_at":"2025-11-21 01:06:26","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":5308389,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSubgroup analysis of progression-free survival (A) and overall survival (B) after propensity score matching.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTACE, transarterial chemoembolisation; cTACE, conventional transarterial chemoembolisation; DEB-TACE, drug-eluting beads transarterial chemoembolisation; HR, hazard ratio; CI, confidence interval; BCLC, Barcelona Clinic Liver Cancer; ALBI, albumin-bilirubin; ECOG PS, Eastern Cooperative Oncology Group performance status; TACE-TKI-ICI, TACE and tyrosine kinase inhibitors with programmed death-1 inhibitors; TACE-TKI, TACE and tyrosine kinase inhibitors.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8029505/v1/eb79b79197b053f44d6ba4d5.png"},{"id":103251010,"identity":"04478cc3-bca2-4c40-952c-3265aebe4d52","added_by":"auto","created_at":"2026-02-23 16:00:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":11431178,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8029505/v1/e89743a6-217d-498b-a39e-9efb696b1ab0.pdf"},{"id":96421782,"identity":"06f6d21c-ee4f-445e-8d8f-0ab09ee81da0","added_by":"auto","created_at":"2025-11-21 01:06:26","extension":"docx","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":192728,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-8029505/v1/99e5bca1aeb4894233ab7820.docx"}],"financialInterests":"","formattedTitle":"TACE and tyrosine kinase inhibitors with or without PD-1 inhibitors as first-line therapy for intermediate-advanced HCC: a multicenter real-world cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatocellular carcinoma (HCC) ranks as the sixth most common cancer globally and the third leading cause of cancer-related mortality\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. A significant proportion of patients\u0026mdash;approximately 70% are diagnosed at intermediate or advanced stages of disease (Barcelona Clinic Liver Cancer [BCLC] stage B or C), rendering them ineligible for curative treatments such as surgical resection or ablation\u003csup\u003e\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTransarterial chemoembolisation (TACE) as first-line therapy is used for patients with intermediate-advanced stage HCC\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Increasing evidence suggests that combining TACE with tyrosine kinase inhibitors (TKIs) (sorafenib or Lenvatinib) can synergistically enhance treatment efficacy and prolong survival\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. For example, the TACTICS trial demonstrated that TACE plus sorafenib significantly improved progression-free survival (PFS) compared to TACE alone in patients with unresectable HCC\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eSystemic therapy is the cornerstone of treatment for advanced-stage HCC\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Immune checkpoint inhibitors (ICIs), particularly programmed death-(ligand) 1 (PD-[L]1) inhibitors, have transformed the therapeutic landscape. First-line therapies, including atezolizumab (PD-L1 inhibitors) plus bevacizumab (anti-vascular endothelial growth factor [anti-VEGF] antibody), nivolumab (PD-1 inhibitors) plus ipilimumab, camrelizumab (PD-1 inhibitors) plus apatinib (TKIs), and tremelimumab plus durvalumab (PD-L1 inhibitors), have improved overall survival.\u003csup\u003e\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Based on this growing body of evidence, immunotherapy-based combinations are now preferred options for first-line therapy in many patients with intermediate-advanced stage disease \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe biological rationale for combining locoregional and systemic therapies is compelling. TACE induces tumor necrosis and the release of tumor-associated antigens, potentially enhancing immune responses. Concurrent use of TKIs can normalize tumor vasculature and counteract the pro-angiogenic effects of TACE, while ICIs may potentiate anti-tumor immunity\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. The interim analysis of LEAP-012 study showed that the addition of lenvatinib and pembrolizumab (PD-1 inhibitor) to TACE could significantly improve PFS in patients with unresectable HCC\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe large-scale real-world studies have explored these regimens in diverse patient populations, showing improved outcomes for combinations of TACE with TKIs and ICIs compared to TACE alone or anti-VEGF antibodies/TKIs plus ICIs in predominantly intermediate-advanced HCC\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. We hypothesized that adding PD-1 inhibitors to TACE and TKIs might improve treatment outcomes in patients with intermediate-advanced HCC. In this study, we conducted a multicenter, real-world, propensity score-matched cohort study to evaluate the efficacy and safety of TACE plus TKIs with or without PD-1 inhibitors as first-line therapy for intermediate-advanced HCC.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003e This multicentre retrospective cohort study included patients with intermediate-advanced HCC between January 2019 and December 2023 at four participating centers in China. Ethical approval was granted by the Ethics Committee of Sichuan Cancer Hospital (SCCHEC-02-2022-113), and the study protocol was also approved by the institutional review boards of the other three centers. Due to the retrospective nature of the study, informed consent was waived.\u003c/p\u003e\u003cp\u003eThe inclusion criteria were as follows: (1) HCC diagnosis confirmed either histologically/cytologically or by clinical criteria in accordance with the American Association for the Study of Liver Diseases (AASLD) guidelines \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e; (2) age between 18 and 80 years; (3) at least one measurable intrahepatic lesion per modified RECIST (mRECIST) criteria; (4) BCLC stage B or C; (5) Child\u0026ndash;Pugh class A or B; (6) Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1; and (7) patients received TACE combined with TKIs and PD-1 inhibitors (TACE-TKI-ICI) or TACE with TKIs (TACE-TKI) as first-line therapy. More specifically, patients have received either first-line TKIs, or TKIs-ICI performed either concurrently with, or up to one month before or after TACE. Patients in the TACE-TKI-ICI group underwent at least one round of TKI and ICI therapy following their initial TACE session.\u003c/p\u003e\u003cp\u003eThe exclusion criteria included: (1) prior systemic or locoregional therapy (hepatic resection, ablation, or radiotherapy) for HCC; (2) concurrent or previous malignancies other than HCC; (3) Child\u0026ndash;Pugh class C; (4) treatment with bevacizumab or its biosimilar; and (5) incomplete data.\u003c/p\u003e\u003cp\u003eWe gathered the baseline details for each patient, including age, gender, ECOG PS, cirrhosis, AFP levels, HBV infection status, BCLC stage, Child\u0026ndash;Pugh class, type of TACE, and lab results. Tumour information included tumour number, size, distribution, macroscopic portal vein invasion, and extrahepatic spread.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eTACE procedures\u003c/h3\u003e\n\u003cp\u003eTACE was performed by experienced interventional radiologists (minimum 5 years of experience) at each centre, following established guidelines\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Superselective catheterization and embolization techniques were employed using microcatheters. Repeat TACE sessions were performed as clinically indicated based on multidisciplinary team (MDT) assessments of residual viable tumour or intrahepatic recurrence. Detailed procedural protocols are provided in the \u003cb\u003eSupplementary treatment protocol\u003c/b\u003e.\u003c/p\u003e\n\u003ch3\u003eTKIs and ICIs administration\u003c/h3\u003e\n\u003cp\u003eIn the TACE-TKI-ICI group, patients received first-line TKIs plus PD-1 inhibitors, whereas the TACE-TKI group received first-line TKIs alone. The specific agents, dosages, and administration schedules are detailed in \u003cb\u003eSupplementary Tables\u0026nbsp;1 and 2\u003c/b\u003e.\u003c/p\u003e\u003cp\u003eTKIs dose reductions were permitted in the event of treatment-related adverse events (TRAEs), but dose reductions were not allowed for PD-1 inhibitors. However, temporary treatment interruptions for both TKIs and PD-1 inhibitors due to toxicity were allowed. Treatment continued until disease progression, occurrence of unacceptable toxicity, or death.\u003c/p\u003e\n\u003ch3\u003eFollow-up\u003c/h3\u003e\n\u003cp\u003ePatients were first assessed four to six weeks following the initial TACE treatment and subsequently monitored every four to twelve weeks until death or study dropout. Follow-up evaluations included laboratory testing, assessment of TRAEs, and contrast-enhanced abdominal CT or MRI. Tumour response was independently reviewed by two radiologists, each with over eight years of experience, using mRECIST criteria. The final follow-up date was April 30, 2024.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003ePFS was defined as the interval from treatment initiation to either tumour progression (per mRECIST) or death from any cause. Overall survival (OS) was defined as the time from treatment initiation to death or last follow-up; the best objective response rate (ORR), defined as the proportion of patients achieving complete or partial response; and safety, assessed throughout the treatment and follow-up periods. TRAEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA) and R software version 4.2.1. To minimize potential confounding and baseline imbalances between groups, propensity score matching (PSM) was performed using a 1:1 nearest-neighbor method without replacement and a caliper width of 0.05. Variables included in the propensity score model were age, gender, ECOG PS, AFP, cirrhosis, BCLC stage, HBV status, Child\u0026ndash;Pugh class, tumour size, tumour number, tumour distribution, macroscopic portal vein invasion, and extrahepatic spread. Covariate balance after matching was evaluated using standardized mean differences \u003cb\u003e(Supplementary Fig.\u0026nbsp;1)\u003c/b\u003e.\u003c/p\u003e\u003cp\u003eContinuous variables were summarized as medians with interquartile ranges (IQRs), while categorical variables were compared using Pearson\u0026rsquo;s χ\u0026sup2; test or Fisher\u0026rsquo;s exact test, as appropriate. Kaplan\u0026ndash;Meier survival analysis with log-rank testing was used to compare PFS and OS between treatment groups. Cox proportional hazards models were applied for univariate and multivariate analyses in both unmatched and matched cohorts. Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in univariate analysis were included in multivariate models to identify independent predictors of survival. All tests were two-sided, and p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003ePatient characteristics\u003c/h2\u003e\u003cp\u003eA total of 747 patients with intermediate-advanced HCC were included from January 2019 to December 2023. After applying exclusion criteria, 263 patients in the TACE-TKI-ICI group and 251 patients in the TACE-TKI group. After PSM (1:1), 241 patients were included in each group. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAfter PSM, baseline characteristics including age, gender, cirrhosis status, liver function (Child-Pugh class, ALBI grade), tumour (size, number, distribution, portal vein invasion), BCLC stage, treatment factors (TACE type, number of sessions), and tumour biology (AFP level, extrahepatic spread, up-to-seven criteria) were well balanced with no significant differences (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These matched cohorts were used for the primary analyses. Analyses conducted before PSM showed similar baseline trends.\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 patient in the two groups before and after PSM.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\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\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eBefore PSM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u003cp\u003eAfter PSM\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTACE-TKI-ICI (n\u0026thinsp;=\u0026thinsp;263)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTACE-TKI (n\u0026thinsp;=\u0026thinsp;251)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTACE-TKI-ICI (n\u0026thinsp;=\u0026thinsp;241)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eTACE-TKI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;241)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\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\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55 (49.0\u0026ndash;64.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56 (55.0\u0026ndash;65.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.111\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e55.0 (49.0\u0026ndash;64.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e56.0 (50.0\u0026ndash;65.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.508\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e175 (66.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e150 (59.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e156 (64.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e149 (61.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e88 (33.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e101 (40.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e85 (35.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e92 (38.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.100\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.338\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e235 (89.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e212 (84.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e214 (88.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e207 (85.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (10.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39 (15.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27 (11.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e34 (14.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCirrhosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.513\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.498\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e84 (31.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e87 (34.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e76 (31.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e83 (34.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e179 (68.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e164 (65.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e165 (68.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e158 (65.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.695\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.826\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58 (22.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59 (23.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e54 (22.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e52 (21.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e205 (77.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e192 (76.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e187 (77.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e189 (78.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumour size (cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.4 (6.4\u0026ndash;12.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.4 (6.5\u0026ndash;12.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.677\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9.3 (6.4\u0026ndash;12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9.4 (6.6\u0026ndash;12.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.693\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39 (14.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34 (13.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e35 (14.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e32 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e224 (85.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e217 (86.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e206 (85.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e209 (86.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumour distribution\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.104\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.457\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSingle lobe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e116 (44.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93 (37.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e100 (41.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e92 (38.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMultiple lobes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e147 (55.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e158 (62.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e141 (58.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e149 (61.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumour number\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.708\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.853\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e108 (41.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e99 (39.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e98 (40.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e96 (39.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e155 (58.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e152 (60.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e143 (59.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e145 (60.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMacroscopic portal vein invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.863\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.926\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e107 (40.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e104 (41.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e96 (39.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e97 (40.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e156 (59.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e147 (58.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e145 (60.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e144 (59.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtrahepatic spread\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.845\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.643\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e156 (59.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e151 (60.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e146 (60.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e141 (58.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e107 (40.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100 (39.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e95 (39.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e100 (41.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEtiology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.356\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.307\u003c/p\u003e\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\u003e212 (80.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e194 (77.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e197 (81.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e188 (78.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51 (19.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57 (22.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e44 (18.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e53 (22.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.158\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.225\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e224 (85.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e202 (80.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e205 (85.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e195 (80.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39 (14.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49 (19.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e36 (14.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e46 (19.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALBI grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.489\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.296\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e63 (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54 (21.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e61 (25.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e51 (21.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e193 (73.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e186 (74.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e174 (72.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e179 (74.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (2.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (4.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (2.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11 (4.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECOG PS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.101\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.313\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e129 (49.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e105 (41.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e113 (46.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e102 (42.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e134 (51.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e146 (58.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e128 (53.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e139 (57.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTACE type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.753\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.648\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecTACE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e120 (45.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e118 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e108 (44.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e113 (46.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDEB-TACE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e143 (54.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e133 (53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e133 (55.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e128 (53.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAFP (ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.082\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.411\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;400\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e114 (43.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e128 (51.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e109 (45.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e118 (49.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;400\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e149 (56.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e123 (49.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e132 (54.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e123 (51.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUp-to-seven criteria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.237\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.386\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWithin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25 (10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e30 (12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e24 (10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBeyond\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e228 (86.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e226 (90.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e211 (87.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e217 (90.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTACE sessions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.402\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.465\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u0026ndash;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e137 (52.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e140 (55.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e126 (52.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e134 (55.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e126 (47.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e111 (44.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e115 (47.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e107 (44.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003eData were median (interquartile range) or n (%). Abbreviations: PSM, propensity score matching; TACE-TKI-ICI, transarterial chemoembolization plus tyrosine kinase inhibitors with immune checkpoint inhibitors; TACE-TKI, transarterial chemoembolisation plus tyrosine kinase inhibitors; BCLC, Barcelona Clinic Liver Cancer; HBV, Hepatitis B virus; ALBI, albumin-bilirubin; ECOG PS, Eastern Cooperative Oncology Group performance status; cTACE, conventional transarterial chemoembolisation; DEB-TACE, drug-eluting beads transarterial chemoembolisation; AFP, alpha-fetoprotein.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn this study, TKIs and PD-1 inhibitors were summarized in \u003cb\u003eSupplementary Tables\u0026nbsp;1 and 2\u003c/b\u003e. Subsequent therapies, such as conversion surgeries and radiotherapy were more frequent in the TACE-TKI-ICI group than TACE-TKI group (\u003cb\u003eSupplementary Table\u0026nbsp;3\u003c/b\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eOutcomes\u003c/h2\u003e\u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\u003ch2\u003eProgression-Free survival\u003c/h2\u003e\u003cp\u003eBefore PSM, the TACE-TKI-ICI group had significantly longer median PFS than the TACE-TKI group (13.9 vs. 10.8 months; hazard ratio [HR]\u0026thinsp;=\u0026thinsp;0.71; 95% confidence interval [CI], 0.57\u0026ndash;0.88; p\u0026thinsp;=\u0026thinsp;0.002; \u003cb\u003eSupplementary Fig.\u0026nbsp;2\u003c/b\u003e). Univariate and multivariate analyses supported treatment with TACE-TKI-ICI as an independent favourable predictor of PFS (\u003cb\u003eSupplementary Table\u0026nbsp;4\u003c/b\u003e).\u003c/p\u003e\u003cp\u003eAfter PSM, median PFS result was consistent with before PSM finding (13.8 vs. 10.8 months; HR\u0026thinsp;=\u0026thinsp;0.73; 95% CI, 0.58\u0026ndash;0.91; p\u0026thinsp;=\u0026thinsp;0.005; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). The PFS benefits of TACE-TKI-ICI therapy were generally consistent across various clinical subgroups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Multivariate analysis showed that ECOG PS of 0 and TACE-TKI-ICI therapy were associated with better PFS (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\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\u003ePredictors of progression-free survival and overall survival after PSM.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\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\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eUnivariate analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" 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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95%CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95%CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\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\u003ePFS analyses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCirrhosis (Present vs. Absent)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.77\u0026ndash;1.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.853\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBCLC stage (C vs. B)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.05\u0026ndash;1.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.81\u0026ndash;1.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.588\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumour size (cm) (\u0026ge;\u0026thinsp;5 vs. \u0026lt;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.42\u0026ndash;3.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.93\u0026ndash;3.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.086\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumour distribution\u003c/p\u003e\u003cp\u003e(Multiple lobes vs. Single lobe)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.02\u0026ndash;1.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.85\u0026ndash;1.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.497\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumour number (\u0026gt;\u0026thinsp;3 vs. \u0026le;3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.08\u0026ndash;1.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.92\u0026ndash;1.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.186\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMacroscopic portal vein invasion (Present vs. Absent)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.97\u0026ndash;1.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.085\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtrahepatic spread (Present vs. Absent)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.93\u0026ndash;1.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.198\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEtiology (HBV vs. Others)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.80\u0026ndash;1.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.707\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChild-Pugh class (B vs. A)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.12\u0026ndash;1.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.98\u0026ndash;1.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.064\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALBI grade (2\u0026thinsp;+\u0026thinsp;3 vs. 1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.05\u0026ndash;1.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.85\u0026ndash;1.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.380\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECOG PS (1 vs. 0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.75\u0026ndash;2.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.54\u0026ndash;2.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTACE type (DEB-TACE vs. cTACE)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.70\u0026ndash;1.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.238\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAFP (ng/mL) (\u0026ge;\u0026thinsp;400 vs. \u0026lt;400)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.15\u0026ndash;1.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.96\u0026ndash;1.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.097\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUp-to-seven criteria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e(Beyond vs. Within)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.31\u0026ndash;3.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.53-2.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.929\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTACE sessions (\u0026ge;\u0026thinsp;3 vs. 1\u0026ndash;2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.71\u0026ndash;1.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.278\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003cp\u003e(TACE-TKI-ICI vs. TACE-TKI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.58\u0026ndash;0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.57\u0026ndash;0.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOS analyses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCirrhosis (Present vs. Absent)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.74\u0026ndash;1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.705\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBCLC stage (C vs. B)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.54\u0026ndash;2.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.83\u0026ndash;2.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.217\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumour size (cm) (\u0026ge;\u0026thinsp;5 vs. \u0026lt;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.61\u0026ndash;3.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.28\u0026ndash;5.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumour distribution\u003c/p\u003e\u003cp\u003e(Multiple lobes vs. Single lobe)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.04\u0026ndash;1.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.90\u0026ndash;1.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.225\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumour number (\u0026gt;\u0026thinsp;3 vs. \u0026le;3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.04\u0026ndash;1.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.92\u0026ndash;1.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.154\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMacroscopic portal vein invasion\u003c/p\u003e\u003cp\u003e(Present vs. Absent)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.21\u0026ndash;1.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.75\u0026ndash;1.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.667\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtrahepatic spread (Present vs. Absent)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.19\u0026ndash;1.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.82\u0026ndash;1.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.476\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEtiology (HBV vs. Others)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.74\u0026ndash;1.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.894\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChild-Pugh class (B vs. A)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.98\u0026ndash;1.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.063\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALBI grade (2\u0026thinsp;+\u0026thinsp;3 vs. 1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.98\u0026ndash;1.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.071\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECOG PS (1 vs. 0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.41\u0026ndash;4.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.97\u0026ndash;3.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTACE type (DEB-TACE vs. cTACE)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.66\u0026ndash;1.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.173\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAFP (ng/mL) (\u0026ge;\u0026thinsp;400 vs. \u0026lt;400)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.30\u0026ndash;2.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.04\u0026ndash;1.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUp-to-seven criteria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e(Beyond vs. Within)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.14\u0026ndash;2.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.92\u0026ndash;3.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.087\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTACE sessions (\u0026ge;\u0026thinsp;3 vs. 1\u0026ndash;2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.48\u0026ndash;0.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.59\u0026ndash;0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\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\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e(TACE-TKI-ICI vs. TACE-TKI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.56\u0026ndash;0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.53\u0026ndash;0.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003ePSM, propensity score matching; HR, hazard ratio; CI, confidence intervals; PFS, progression-free survival; OS, overall survival; BCLC, Barcelona Clinic Liver Cancer; HBV, Hepatitis B virus; ALBI, albumin-bilirubin; ECOG PS, Eastern Cooperative Oncology Group performance status; TACE, transarterial chemoembolisation; cTACE, conventional transarterial chemoembolisation; DEB-TACE, drug-eluting beads transarterial chemoembolisation; AFP, alpha-fetoprotein; TACE-TKI-ICI, transarterial chemoembolisation and tyrosine kinase inhibitors with immune checkpoint inhibitors; TACE-TKI, transarterial chemoembolisation and tyrosine kinase inhibitors.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eOverall survival\u003c/h2\u003e\u003cp\u003eBefore PSM, the TACE-TKI-ICI group had significantly longer median OS than the TACE-TKI group (22.9 vs. 16.7 months; HR\u0026thinsp;=\u0026thinsp;0.69; 95% CI, 0.55\u0026ndash;0.88; p\u0026thinsp;=\u0026thinsp;0.002; \u003cb\u003eSupplementary Fig.\u0026nbsp;3\u003c/b\u003e). Univariate and multivariate analyses supported treatment with TACE-TKI-ICI as an independent favourable predictor of OS (\u003cb\u003eSupplementary Table\u0026nbsp;4\u003c/b\u003e).\u003c/p\u003e\u003cp\u003eAfter PSM, median OS result was consistent with before PSM finding (22.6 vs. 16.7 months; HR\u0026thinsp;=\u0026thinsp;0.71; 95% CI, 0.56\u0026ndash;0.91; p\u0026thinsp;=\u0026thinsp;0.006) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). The OS benefits of TACE-TKI-ICI therapy were generally consistent across various clinical subgroups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). Multivariate analysis confirmed that tumour size\u0026thinsp;\u0026lt;\u0026thinsp;5 cm, ECOG PS of 0, AFP\u0026thinsp;\u0026lt;\u0026thinsp;400 ng/mL, TACE sessions\u0026thinsp;\u0026ge;\u0026thinsp;3, and TACE-TKI-ICI therapy were associated with better OS (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eObjective response rate\u003c/h2\u003e\u003cp\u003eAfter PSM, the TACE-TKI-ICI group showed significantly higher ORR (58.9% vs. 41.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and disease control rate (DCR) (84.6% vs. 76.8%, p\u0026thinsp;=\u0026thinsp;0.028) than the TACE-TKI group \u003cb\u003e(Supplementary Table\u0026nbsp;5)\u003c/b\u003e. These findings were consistent with analyses conducted before PSM \u003cb\u003e(Supplementary Table\u0026nbsp;5)\u003c/b\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eSafety\u003c/h2\u003e\u003cp\u003eThe safety profiles of both treatment groups were evaluated after PSM. The overall incidence of any-grade TRAEs was comparable between the TACE-TKI-ICI group and the TACE-TKI group (66.8% vs. 61.8%, p\u0026thinsp;=\u0026thinsp;0.254). Most TRAEs were grade 1/2 in severity, with grade 3/4 events being infrequent in both groups (10.8% vs. 8.3%, p\u0026thinsp;=\u0026thinsp;0.352).\u003c/p\u003e\u003cp\u003eThe most common TRAEs in the TACE-TKI-ICI group included increased AST (28.6%), increased ALT (22.4%), and pain (22.0%). In the TACE-TKI group, the most frequent events were increased AST (25.3%), pain (18.3%), and hyperbilirubinemia (16.2%). Hypertension, fatigue, and decreased appetite were also observed with similar frequencies in both groups. Notably, hypothyroidism was significantly more common in the TACE-TKI-ICI group than in the TACE-TKI group (11.6% vs. 0.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eThe incidence of serious adverse events (grade 3/4) remained low and did not differ significantly between groups for most TRAEs. No treatment-related deaths were reported \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\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\u003eTreatment-related adverse events after PSM.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"23\"\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\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c19\" colnum=\"19\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c20\" colnum=\"20\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c21\" colnum=\"21\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c22\" colnum=\"22\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c23\" colnum=\"23\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEvents, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e\u003cp\u003eTACE-TKI-ICI (N\u0026thinsp;=\u0026thinsp;241)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"6\" nameend=\"c14\" namest=\"c9\"\u003e\u003cp\u003eTACE-TKI (N\u0026thinsp;=\u0026thinsp;241)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"6\" nameend=\"c22\" namest=\"c17\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eAny\u003c/p\u003e\u003cp\u003egrade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eGrade\u003c/p\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGrade 3/4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003eAny\u003c/p\u003e\u003cp\u003egrade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003eGrade\u003c/p\u003e\u003cp\u003e1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003eGrade\u003c/p\u003e\u003cp\u003e3/4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003eAny grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003eGrade 1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003eGrade\u003c/p\u003e\u003cp\u003e3/4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAny TRAE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e161 (66.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e158 (65.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e26 (10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e149 (61.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e148 (61.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e20 (8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.254\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.344\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.352\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFatigue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (17.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e40 (16.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e31 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e31 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.201\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.247\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDecreased appetite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e37 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e30 (12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e30 (12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.357\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.357\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53 (22.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e52 (21.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e44 (18.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e44 (18.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.307\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.362\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiarrhea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43 (17.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e42 (17.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e33 (13.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e32 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.211\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.206\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNausea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e30 (14.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e37 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e35 (14.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.432\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.505\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.562\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHand and foot syndrome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (14.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e31 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e4 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e31 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e28 (11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e3 (1.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.596\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.677\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.703\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastrointestinal hemorrhage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e18 (7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e18 (7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e18 (7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.735\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.156\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGingival bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (5.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e12 (5.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e7 (2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e7 (2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.171\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.242\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDysphonia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e4 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e4 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.411\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.411\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypothyroidism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e26 (10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.156\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFever\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e49 (20.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e48 (19.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e38 (15.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e38 (15.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.193\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.234\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\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\u003e37 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e33 (13.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e4 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e31 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e29 (12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.432\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.586\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.411\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProteinuria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e32 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e30 (12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e29 (12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.786\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.681\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHyperbilirubinemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47 (19.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e41 (17.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e6 (2.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e39 (16.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e35 (14.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e4 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.341\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.453\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.523\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypoalbuminemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (19.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e42 (17.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e4 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e41 (17.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e39 (16.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.554\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.715\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.411\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIncreased ALT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54 (22.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e49 (20.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e5 (2.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e40 (16.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e38 (15.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.108\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.193\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.253\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIncreased AST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e69 (28.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e62 (25.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e7 (2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e61 (25.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e55 (22.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e6 (2.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.412\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.457\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e0.779\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutropenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (7.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e19 (7.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003e21 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003e21 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003e0.714\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u003cp\u003e0.741\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c22\" namest=\"c21\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c23\" namest=\"c23\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThrombocytopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e26 (10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e24 (10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u003cp\u003e23 (9.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e\u003cp\u003e21 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c15\" namest=\"c14\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c17\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c19\" namest=\"c18\"\u003e\u003cp\u003e0.651\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c21\" namest=\"c20\"\u003e\u003cp\u003e0.639\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c23\" namest=\"c22\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"23\"\u003ePSM, propensity score matching; TACE-TKI-ICI, transarterial chemoembolisation plus tyrosine kinase inhibitors with immune checkpoint inhibitors; TACE-TKI, transarterial chemoembolisation plus tyrosine kinase inhibitors; TRAEs, Treatment-Related Adverse Events; ALT, alanine transaminase; 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 multicentre, retrospective, matched cohort study evaluated the clinical outcomes of adding PD-1 inhibitors to the combination of TACE and TKIs as first-line therapy for intermediate-advanced HCC. The results indicated that TACE-TKI-ICI group significantly improved PFS, OS, and ORR, without increasing TRAEs compared to TACE-TKI group. Multivariate analysis further confirmed TACE-TKI-ICI as an independent predictor for prolonging PFS and OS.\u003c/p\u003e\u003cp\u003eThe CHANCE001 study was a retrospective, matched cohort study showed that TACE plus PD-(L)1 inhibitors and molecular targeted therapies in patients with intermediate-advanced HCC improved survival outcomes compared to TACE alone\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. In CHANCE001 study, the immunotherapeutic agents included PD-L1 inhibitors and PD-1 inhibitors, while the targeted drugs cover TKIs and anti-VEGF antibody (bevacizumab), resulting in a more diverse range of drug types. In our study, only PD-1 inhibitors and TKIs were included, PD-L1 inhibitors and anti-VEGF antibody not being included, in contrast to CHANCE001 study. The CHANCE2211 study showed that TACE plus camrelizumab (PD-1 inhibitors) and apatinib (TKIs) in patients with intermediate-advanced HCC improved survival outcomes compared to TACE alone\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. The sample size of the CHANCE2211 study is relatively small. The control group of the CHANCE001 and CHANCE2211 studies was TACE alone, while the control group of our study was TACE plus TKIs. The data from our study further enriches the real-world evidence on the treatment of intermediate-advanced HCC with TACE combined with TKIs and ICIs.\u003c/p\u003e\u003cp\u003eThe LEAP-012 trial demonstrated that adding lenvatinib and pembrolizumab to TACE improved median PFS compared to TACE alone in patients with unresectable, non-metastatic HCC, and median OS was not disclosed\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Our study showed that adding PD-1 inhibitors to TACE plus TKIs improved median PFS and OS compared to TACE plus TKIs in patients with intermediate-advanced HCC. The median OS was reached in our study. This result fills the data gaps in the LEAP-012 study by leveraging real-world data. Another retrospective study showed that TACE plus lenvatinib and PD-1 inhibitor in patients with advanced HCC improved PFS and OS compared to TACE plus lenvatinib\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. That study was only included advanced (BCLC C) HCC.\u003c/p\u003e\u003cp\u003eTACE induces immunogenic cell death and enhances the release of tumor antigens, thereby eliciting an immune response. Nevertheless, it concurrently triggers VEGF upregulation and immunosuppression, which may contribute to disease progression\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. TKIs are capable of normalizing tumor vasculature, reducing microvessel density, lowering intratumoural interstitial pressure, mitigating VEGF-induced immune evasion, and remodelling the tumor microenvironment\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. The combination of TKIs and TACE essentially resolves the predicament of \"efficacy limitation due to abnormal blood vessels\" in TACE treatment by optimizing the tumour microenvironment\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Therefore, adding ICIs to TACE plus TKIs is a treatment strategy for HCC that aims to augment tumor immune infiltration and therapeutic efficacy.\u003c/p\u003e\u003cp\u003eThis study showed that the TACE-TKI-ICI group had comparable overall TRAE rates (66.8% vs. 61.8%) and grade 3/4 TRAE rates (10.8% vs. 8.3%) to the TACE-TKI-ICI group. TACE-TKI-ICI group had 28 (11.6%) of patients suffered from hypothyroidism, which was probably attributable to TKIs and PD-1 inhibitors. The TACE-TKI-ICI group exhibited comparable overall TRAE rates and even lower grade 3/4 AEs compared to LEAP-012 trial\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. This could reflect differences in AE reporting, possibly influenced by healthcare access disruptions during the COVID-19 pandemic.\u003c/p\u003e\u003cp\u003eThis study had several limitations. First, being a retrospective study, there is a potential for selection bias, which we attempted to mitigate through PSM. Second, the inclusion of multiple different TKIs and PD-1 inhibitors, based on both Western and Chinese guidelines, adds variability to our results. The treatment selection process was influenced by the patient's health status, financial considerations, and preferences, making it difficult to standardize therapy across the cohort. Future studies should evaluate more uniform combination protocols to better assess the optimal treatment strategy. Finally, over 70% of the patients in our study had HBV-related HCC, limiting the generalizability of our findings to other aetiologies of liver-related HCC.\u003c/p\u003e\u003cp\u003eIn conclusion, adding PD-1 inhibitors to TACE and TKIs as first-line therapy for intermediate-advanced HCC can improve PFS, OS, and ORR, without significantly increasing treatment-related adverse events, compared to TACE and TKIs alone. A prospective, multicentre, large-sample study is needed to validate these findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDeclarations of competing interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no competing interests.\u003c/p\u003e\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\u003cp\u003e The study was approved by the Ethics Committee of Sichuan Cancer Hospital (SCCHEC-02-2022-113), and the study protocol was also approved by the institutional review boards of the other three centers. Due to the retrospective nature of the study, informed consent was waived.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was supported by the Natural Science Foundation of Sichuan (No. 2025ZNSFSC0239), and Beijing Hepatobiliary Harmony Public Welfare Foundation (No. iGandanF-1082025-YLPS013), Zhongguancun Precision Medicine Foundation (No. GXZBD07).\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e\u003cp\u003eWe thank the patients and investigators in this study.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of this study are not publicly available due to regulations under the Personal Information Protection Act. However, they 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. 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Liver Cancer. 2020;9(6):682\u0026ndash;720.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLu J, Zhao M, Arai Y, et al. 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.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKudo M, Ueshima K, Ikeda M, et al. 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.\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 Clin Oncol. 2023;41(1):117\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLlovet JM, De Baere T, Kulik L, et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021;18(5):293\u0026ndash;313.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSangro B, Sarobe P, Hervas-Stubbs S, Melero I. Advances in immunotherapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021;18(8):525\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFinn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894\u0026ndash;905.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQin S, Chan SL, Gu S, et al. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet. 2023;402(10408):1133\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022;1(8):EVIDoa2100070.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen JJ, Jin ZC, Luo B, et al. New First-line Immunotherapy-based Therapies for Unresectable Hepatocellular Carcinoma: A Living Network Meta-analysis. J Clin Transl Hepatol. 2024;12(1):15\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhong BY, Fan W, Guan JJ, et al. Combination locoregional and systemic therapies in hepatocellular carcinoma. Lancet Gastroenterol Hepatol. 2025;10(4):369\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKudo M, Ren Z, Guo Y, et al. 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;15.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhu HD, Li HL, Huang MS, et al. Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001). Signal Transduct Target Ther. 2023;8(1):58.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJin ZC, Chen JJ, Zhu XL, et al. 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Nat Rev Clin Oncol. 2018;15(5):325\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUne N, Takano-Kasuya M, Kitamura N, et al. The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors. Med Oncol. 2021;38(6):60.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307(5706):58\u0026ndash;62.\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":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"hepatology-international","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"hepi","sideBox":"Learn more about [Hepatology International](https://www.springer.com/journal/12072)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/hepi/default.aspx","title":"Hepatology International","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Hepatocellular carcinoma, Transarterial chemoembolization, Tyrosine kinase inhibitors, Immunologic checkpoint inhibitors, Programmed cell death 1 receptor (PD-1)","lastPublishedDoi":"10.21203/rs.3.rs-8029505/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8029505/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground and aims\u003c/h2\u003e\u003cp\u003eThis study aimed to evaluate the efficacy and safety of combining transarterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs), with or without programmed death-1 (PD-1) inhibitors (ICI), as first-line therapy for intermediate-advanced hepatocellular carcinoma (HCC) in a real-world setting.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis multicentre retrospective cohort study enrolled patients with intermediate-advanced HCC who received either TACE combined with TKIs and PD-1 inhibitors (TACE-TKI-ICI) or TACE plus TKIs (TACE-TKI) from January 2019 to December 2023. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Propensity score matching (PSM) was used to reduce bias.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 514 patients with intermediate-advanced HCC were analyzed, 263 patients in the TACE-TKI-ICI group and 251 patients in the TACE-TKI group. After PSM (1:1), 241 patients were included in each group. The TACE-TKI-ICI group had significantly longer median PFS (13.8 vs. 10.8 months; hazard ratio [HR]\u0026thinsp;=\u0026thinsp;0.73; 95% confidence interval [CI], 0.58\u0026ndash;0.91; p\u0026thinsp;=\u0026thinsp;0.005) and OS (22.6 vs. 16.7 months; HR\u0026thinsp;=\u0026thinsp;0.71; 95% CI, 0.55\u0026ndash;0.91; p\u0026thinsp;=\u0026thinsp;0.006) than the TACE-TKI group. The ORR was also better (58.9% vs. 41.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in the TACE-TKI-ICI group. The incidence of grade 3/4 adverse events was 10.8% in the TACE-TKI-ICI group and 8.3% in the TACE-TKI group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eAdding PD-1 inhibitors to TACE and TKIs as first-line therapy for intermediate-advanced HCC can improve PFS, OS, and ORR, while being well tolerated.\u003c/p\u003e","manuscriptTitle":"TACE and tyrosine kinase inhibitors with or without PD-1 inhibitors as first-line therapy for intermediate-advanced HCC: a multicenter real-world cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-21 01:06:21","doi":"10.21203/rs.3.rs-8029505/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revisions Needed","date":"2025-11-27T11:54:02+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-11-10T14:38:17+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-10T14:00:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-05T05:47:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"Hepatology International","date":"2025-11-04T08:24:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"hepatology-international","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"hepi","sideBox":"Learn more about [Hepatology International](https://www.springer.com/journal/12072)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/hepi/default.aspx","title":"Hepatology International","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3350bb36-fdd5-4b63-8179-ff5d996bf5ab","owner":[],"postedDate":"November 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T15:59:56+00:00","versionOfRecord":{"articleIdentity":"rs-8029505","link":"https://doi.org/10.1007/s12072-026-11052-0","journal":{"identity":"hepatology-international","isVorOnly":false,"title":"Hepatology International"},"publishedOn":"2026-02-17 15:56:54","publishedOnDateReadable":"February 17th, 2026"},"versionCreatedAt":"2025-11-21 01:06:21","video":"","vorDoi":"10.1007/s12072-026-11052-0","vorDoiUrl":"https://doi.org/10.1007/s12072-026-11052-0","workflowStages":[]},"version":"v1","identity":"rs-8029505","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8029505","identity":"rs-8029505","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}