Transarterial chemoembolization versus hepatic arterial infusion chemotherapy as initial treatment for stage CNLC Ⅲa hepatocellular carcinoma

Transarterial chemoembolization versus hepatic arterial infusion chemotherapy as initial treatment for stage CNLC Ⅲa hepatocellular carcinoma | 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 Transarterial chemoembolization versus hepatic arterial infusion chemotherapy as initial treatment for stage CNLC Ⅲa hepatocellular carcinoma Benyi He, Min Deng, Shaohua Li, Jie Mei, Lianghe Lu, Chengyou Yu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3416587/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The Chinese Liver Cancer (CNLC) staging recommends transarterial chemoembolization (TACE) as the standard treatment for hepatocellular carcinoma (HCC) patients with macrovascular invasion and without extrahepatic metastasis (CNLC IIIa). As a recently emerging approach, the efficacy of hepatic arterial infusion chemotherapy (HAIC) compared to TACE in this group of patients is unclear. Methods From December 2016 to June 2020, patients diagnosed with CNLC IIIa stage HCC who underwent TACE (n = 91) or HAIC (n = 190) as their initial treatment were included. Propensity score matching (PSM) was used to reduce selection bias and other imbalances. Objective response rates (ORR), overall survival (OS), progression-free survival (PFS), rate of subsequent resection, and safety were compared in these two groups. Results After PSM, 77 pairs of patients were matched. The ORR was higher in HAIC group than that of TACE group (29.9% vs. 9.1%, P = 0.013). Median progression-free survival of the HAIC group was longer than that of TACE group (4.7 vs. 1.4 months, P = 0.002), but there was no significant difference in the median OS between the HAIC and TACE groups (19.6 vs. 18.1 months, P = 0.122). The HAIC group also showed a better safety profile than the TACE group. Conclusions HAIC is an effective and safe option in the treatment of HCC patients with CNLC IIIa stage compared with TACE. Hepatocellular carcinoma Hepatic arterial infusion chemotherapy Liver Transarterial chemoembolization Figures Figure 1 Figure 2 Introduction Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. It is also the second leading cause of cancer-related deaths in China [ 1 , 2 ]. For intermediate stage HCC, transarterial chemoembolization (TACE) was recommended as standard treatment in Barcelona Clinic Liver Cancer (BCLC) staging and the National Comprehensive Cancer Network (NCCN) guideline[ 3 , 4 ]. In the Guidelines for diagnosis and treatment of primary liver cancer in China (2022 edition), TACE can be applied for HCC patients with stage Ib (single tumor larger than 5 cm) to IIIb (with extrahepatic metastases)[ 5 ]. The serious adverse events cause by TACE, such as ectopic embolization, post-embolization syndrome, and abnormal liver and renal function are mainly related to the effect of embolization agents. The presence of macrovascular invasion (CNLC IIIa) might increase the impairment of liver function and further reduce the patient's tolerance to TACE. In a retrospective study, hepatic arterial infusion chemotherapy with modified oxaliplatin, fluorouracil, and leucovorin (FOLFOX-HAIC) could improve both progression free and overall survival in patients with advanced hepatocellular carcinoma against Sorafenib [ 6 ]. When combined with sorafenib, FOLFOX-HAIC can significantly prolong survival and has a higher tumor response rate (40.8% vs. 2.46%) compared to sorafenib alone, with acceptable adverse events rate in patients with HCC and portal vein invasion[ 7 ]. In a recent prospective randomized study, HAIC has also shown significantly superior antitumor efficacy and lower toxicity compared to TACE, in patients with unresectable large hepatocellular carcinoma[ 8 ]. However, to date, no study has compared the efficacy and safety of TACE and FOLFOX-HAIC in HCC patients with macrovascular invasion and without extrahepatic metastasis (CNLC IIIa stage). Therefore, the aim of this study was to explore the safety and efficacy of FOLFOX-HAIC and TACE as the initiate therapy in this group of patients, and to provide the basis for the potential prospective study. Methods Study Design This was a retrospective study conducted at the Sun Yat-sen University Cancer Center. The trial protocol was approved by the Institutional Review Board (IRB) and Institutional Ethics Committee (IEC) of Sun Yat-sen University Cancer Center (No. B2018-126-01), and complied with the Declaration of Helsinki. All patients provided written informed consent to participate in this study. The primary endpoint was OS of patients with macrovascular invasion and without extrahepatic metastasis following TACE or HAIC, while secondary endpoints were ORR, PFS, rate of subsequent resection, and safety in those patients. Eligibility Criteria The eligibility criteria for inclusion were as follows: (1) aged ≥ 18 to ≤ 75 years; (2) no previous treatments for HCC; (3) meet the non-invasive diagnosis criteria of European Association for the Study of Liver[ 9 ] and the American Association for the Study of Liver Diseases[ 10 ]; (4) Eastern Cooperative Oncology Group Performance Score (ECOG PS) ≤ 2; (5) Child-Pugh score of A or B; (6) The presence of macrovascular invasion on the image without extrahepatic metastasis. The exclusion criteria were as follows: (1) previous treatments for HCC before TACE or HAIC; (2) HCC combined with other cancers; (3) the imaging data of pretreatment or follow-up was missing; (4) combined with other anti-tumor treatments. The detailed process of patient screening is shown in Fig. 1 . Treatment Procedures Transarterial Chemoembolization TACE was performed using the techniques we have described previously[ 11 ]. In brief, the catheter was placed into celiac trunk or superior mesenteric artery for arteriography through the femoral artery using the Seldinger technique, then 50 mg of lobaplatin, and 50 mg of epirubicin mixed with iodized oil were injected slowly through the catheter into the feeding arteries of the tumor. If necessary, polyvinyl alcohol(PVA)particles was also used to enhance the embolic effect. TACE was repeated every 4 weeks until tumor progression or intolerable adverse events were observed. The subsequent treatment was determined by the patient's tumor response and the opinion of the multidisciplinary team discussions. Hepatic Arterial Infusion Chemotherapy After successful percutaneous hepatic artery puncture and catheterization, superior mesenteric and hepatic arteriography were performed. Then the main feeding artery of the tumor was intubated to the predetermined position and patients with indwelling catheter would be sent back to the ward. The catheter was connected to the injection pump and the following chemotherapeutic drugs were continuously pumped: oxaliplatin, 130mg/m 2 , from hour 0 to 3 on day 1, leucovorin, 400 mg/m 2 , from hour 3 to 4.5 on day 1, fluorouracil, 400mg/m 2 , from 4.5 to 6.5 on day 1, and fluorouracil, 2400mg/m 2 , over 46 hours from day 1 to day 3. After the completion of chemotherapy, the catheter was removed and pressure bandaged to stop bleeding. The patient could be discharged after 12 hours. HAIC was repeated for every 4 to 6 weeks according to the condition of the patients. After every two cycles of HAIC, patients would be assessed for tumor response. The subsequent treatment was determined according to the opinion of the multidisciplinary team. Follow-up and Assessment All patients were followed up at an interval of 2–3 months. At each scheduled follow-up visit, physical examination, blood test (serum tumor markers and liver function), enhanced abdominal computed tomography or magnetic resonance imaging scan were performed. The study was censored on July 2022. Tumor response was assessed according to the modified response evaluation criteria in solid tumors (mRECIST) [ 12 ], including complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The objective response rate (ORR) was defined as the ratio of patients with CR and PR. And the disease control rate (DCR) was defined as ORR plus SD. Statistics Analysis The primary end point was overall survival (OS) which was defined as the time from the initial treatment to the date of death or last follow-up. The secondary end points included progress-free survival (PFS) which was defined as the time from the initial treatment to the date of tumor progression, death, or last follow-up. TACE or HAIC associated adverse events (AEs) were recorded from registration to the subsequent treatments or the last follow-up. Toxicity was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0)[ 13 ]. Survival curve were estimated using the Kaplan-Meier method and compared using the log-rank test. The median survival with 95% confidence interval (CI) was calculated. Cox proportional analyses were performed to estimate HRs with 95% CIs. The t-test was used for comparisons between groups for continuous variables when they were normally distributed and the Wilcoxon rank-sum test was used when they were not normally distributed. We used propensity score matching (PSM) between the TACE and HAIC groups to reduce the effects of selection bias and potential confounding variables that are vital to clinical outcomes. The PSM model included age, sex, Child-Pugh class, cirrhosis, tumor size, number of tumors, Cheng 's classification of PVTT (portal vein tumor thrombus)[ 14 ], and TBIL. The matched pairs between the TACE and HAIC groups were reduced by 1:1 nearest-neighbor match with a caliper of 0.2. P values of < 0.05 were termed as significant. All statistical analyses were performed using R (version 4.2.1) and graphs were generated using GraphPad Prism 8. Results Patient Characteristics Between December 2016 and July 2020, 3875 patients with liver tumors received TACE or HAIC at our center. Those patients who did not meet the inclusion criteria were excluded, including non CNLC IIIa stage (n = 2940), with previous treatment (n = 4), the imaging data of pretreatment or follow-up was missing (n = 126), other treatments were applied except TACE or HAIC (n = 59), and non-hepatocellular carcinoma (n = 465), Finally, 281 eligible patients were enrolled in the analysis. There were 91 patients received TACE and 190 patients received HAIC (Fig. 1 ). The baseline characteristics of patients in the TACE and HAIC groups are shown in Table 1 . Table 1 Baseline characteristics of patients in TACE group and HAIC group. Characteristics Before PSM After PSM TACE (n = 91) HAIC (n = 190) P TACE (n = 77) HAIC (n = 77) P Age(y), mean ± SD 54.41 ± 12.62 52.45 ± 11.25 0.192 55.22 ± 12.88 53.91 ± 11.75 0.510 Sex Male 77 (84.6) 176 (92.6) 0.059 67 (87.0) 70 (90.9) 0.607 Female 14 (15.4) 14 (7.4) 10 (13.0) 7 (9.1) Child-Pugh class A 87 (95.6) 188 (98.9) 0.170 76 (98.7) 76 (98.7) 1 B 4 (4.4) 2 (1.1) 1 (1.3) 1 (1.3) Hepatitis virus Absence 17 (18.7) 29 (15.3) 0.613 16 (20.8) 13 (16.9) 0.680 HBV 74 (81.3) 160 (84.2) 61 (79.2) 64 (83.1) HCV NA 1(0.5) NA NA AFP (ng/ml) <400 38 (41.8) 60 (31.6) 0.123 30 (39.0) 29 (37.7) 1.000 ≥ 400 53 (58.2) 130 (68.4) 47 (61.0) 48 (62.3) PIVKAⅡ (mAU/ml) <40 3 (3.3) 6 (3.2) 1.000 2 (2.6) 0 (0) 0.497 ≥ 40 88 (96.7) 184 (96.8) 75 (97.4) 77 (100.0) Cirrhosis Absence 70 (76.9) 168 (88.4) 0.020 65 (84.4) 62 (80.5) 0.672 Presence 21 (23.1) 22 (11.6) 12 (15.6) 15 (19.5) Size of tumor (mm), mean ± SD 83.08 ± 33.79 94.74 ± 37.38 0.012 87.32 ± 31.00 86.55 ± 35.40 0.885 Number of tumors Multiple 57 (62.6) 110 (57.9) 0.530 47 (61.0) 46 (59.7) 1 Single 34 (37.4) 80 (42.1) 30 (39.0) 31 (40.3) Cheng’s classification TypeⅠ 9 (9.9) 24 (12.6) 0.537 6 (7.8) 8 (10.4) 0.325 TypeⅡ 65 (71.4) 125 (65.8) 57 (74.0) 53 (68.8) TypeⅢ 17 (18.7) 38 (20.0) 14 (18.2) 13 (16.9) TypeⅣ 0 (0.0) 3 (1.6) 0 (0.0) 3 (3.9) Subsequent resection 5 (5.5) 27 (14.2) 0.081 5 (6.5) 10 (13.0) 0.336 Median HGB (g/L) 140.59 (22.92) 145.26 (19.09) 0.074 143.43 (20.48) 144.43 (19.24) 0.755 Median PLT (10^9/L) 204.31 (94.75) 215.93 (102.46) 0.363 215.75 (89.99) 216.96 (113.19) 0.942 Median ALB (g/L) 40.75 (4.18) 41.03 (4.20) 0.598 41.16 (3.84) 41.13 (3.76) 0.954 Median ALP (U/L) 136.34 (74.88) 151.83 (109.31) 0.223 135.90 (70.08) 137.86 (89.48) 0.880 Median ALT (U/L) 56.27 (42.42) 60.85 (60.16) 0.514 54.75 (40.07) 58.16 (60.96) 0.682 Median TBIL (umol/L) 20.64 (21.90) 16.41 (6.71) 0.015 16.73 (7.41) 16.78 (7.00) 0.961 Median CRE (umol/L) 73.08 (15.72) 72.59 (18.36) 0.828 74.12 (16.50) 74.70 (20.61) 0.849 Data were compared by using the Chi square test. PSM, propensity score match; TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy; SD, standard deviation; ALBI, albumin-bilirubin; AFP, Alpha-fetoprotein; PIVKAⅡ, Protein Induced by Vitamin K Absence or Antagonist-II; HGB, hemoglobin; PLT, platelet; ALB, albumin; ALP, alkaline phosphatase; ALT, alanine aminotransferase; TBIL, total bilirubin; CRE, creatinine. Cut-off of AFP is 400ng/ml. Cut-off of PIVKAⅡ is 40mAU/ml. Before PSM, the HAIC group differed from the TACE group in terms of cirrhosis ( P = 0.020) (defined by radiological assessments), tumor size ( P = 0.012), and total bilirubin (TBIL) ( P = 0.015). After 1:1 PSM, we obtained matched cohorts of 77 patients per group with well-balanced variables without significant difference. Radiological And Clinical Response Rate The tumor response of patients in the two groups were summarized in Table 2 . Before PSM, the PR, ORR, and DCR in the HAIC group were 35.3%, 35.3% and 80.6%, respectively, which were significantly higher than those in the TACE group (8.8%, 8.8% and 51.7%, respectively). After PSM, the rates of PR, ORR, and DCR in the HAIC group were 29.9%, 29.9% and 84.4%, respectively, which were still significantly higher than those in the TACE group (9.1%, 9.1% and 48.1%, respectively). Table 2 Tumor responds between TACE and HAIC group. mRECIST Non-PSM PSM TACE(n = 91) HAIC(n = 190) P TACE(n = 77) HAIC(n = 77) P CR 0(0) 0(0) 1.000 0(0) 0(0) 1.000 PR 8(8.8) 67(35.3) * < 0.001 7(9.1) 23(29.9) * 0.013 SD 39(42.9) 86(45.3) 0.904 30(39.0) 42(54.5) 0.305 PD 44(48.4) * 37(19.5) 0.001 40(51.9) * 12(15.6) 0.001 ORR 8(8.8) 67(35.3) * < 0.001 7(9.1) 23(29.9) * 0.013 DCR 47(51.7) 153(80.6) * 0.043 37(48.1) 65(84.4) * 0.042 mRECIST, modified Response Evaluation Criteria In Solid Tumors; PSM, propensity score matching; TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR; disease control rate. Subsequent resection rate The patients who received subsequent resection in the two groups were summarized in Table 3 . For patients with PVTT of type I-II (according to the Cheng’s classification), the subsequent resection rate in the HAIC group was 17.4%, which was significantly higher than that in the TACE group (5.4%, P = 0.045). For patients with PVTT of type Ⅲ-Ⅳ, there was one patient from each of the two groups underwent subsequent resection ( P = 0.514). After PSM, there was no significant difference between the TACE and HAIC groups in the subsequent resection rate for patients with PVTT of type I-II ( P = 0.195) and type Ⅲ-Ⅳ ( P = 1.000). Table 3 | Number of patients who received Resection in TACE or HAIC group Type Type I - II Type III - IV Treatment TACE (n=91) HAIC (n=190) TACE (n=91) HAIC (n=190) n(%) n(%) P n(%) n(%) P Total 74(81.3) 149(78.4) 17(18.7) 41(21.6) Resection 4(5.4) 26(17.4) 0.045 1(5.9) 1(2.4) 0.514 Number of patients who received Resection in TACE or HAIC group（PSM） Type Type I - II Type III - IV Treatment TACE (n=77) HAIC (n=77) TACE (n=77) HAIC (n=77) n(%) n(%) P n(%) n(%) P Total 63(81.8) 61(79.2) 14(18.2) 16(20.8) Resection 4(5.4) 10(16.4) 0.195 1(7.1) 0(0.0) 1.000 Type Ⅰ, Ⅱ, Ⅲ, Ⅳ are defined by Cheng’s classification of thrombus. Data in parentheses are percentages. Data were compared by using Chi square test or the Fisher’s exact test. PSM, propensity score match; TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy. OS and PFS Analysis The follow-up ended in July 2022. The incidence of death was 45.1% (41/91) in the TACE group and 46.3% (88/190) in the HAIC group. Patients in the HAIC group had a median overall survival of 26.5 months compared to 16.9 months in the TACE group (Fig. 2 A, P = 0.041). The PFS in the HAIC group was also significantly longer than that in the TACE group (Fig. 2 C, 4 .1 vs. 1.4 months, P < 0.001). After PSM, there was no significant difference in overall survival between the HAIC and TACE groups (Fig. 2 B, 19 .6 vs. 18.1 months, P = 0.116). However, the PFS in the HAIC group was still significantly longer than that in the TACE group (Fig. 2 D, 4 .7 vs. 1.4 months, P < 0.001). Adverse Events Treatment-related adverse events in the two groups after PSM are summarized in Table 4 . Overall, the adverse reactions were similar and mostly mild in both groups. Compared to the HAIC group, gastrointestinal events such as abdominal pain (19.5% vs. 5.2%, P = 0.032) and anorexia (18.2% vs. 3.9%, P = 0.023) were more frequent in the TACE group. In addition, one patient in the HAIC group developed flushing, one patient developed ascites, and two patients developed typhlitis. No treatment-related deaths occurred in either of the groups. Total treatment-related adverse events in the two groups are summarized in Supplementary Table 3 . Table 4 Adverse events appeared in TACE and HAIC group after PSM Event, n(%) TACE (n = 77) HAIC (n = 77) P value Any grade Grade 1/2 Grade 3/4 Any grade Grade 1/2 Grade 3/4 Any grade Blood/bone marrow suppression Leukopenia 4 (5.2) 4 (5.2) 0 (0) 10 (13.0) 9 (11.7) 1 (1.3) 0.209 Neutropenia 6 (7.8) 6 (7.8) 0 (0) 12 (15.6) 10 (13.0) 2 (2.6) 0.276 Reduced hemoglobin level 20 (26.0) 19 (24.7) 1 (1.3) 12 (15.6) 12 (15.6) 0 (0) 0.274 Thrombocytopenia 13 (16.9) 12 (15.6) 1 (1.3) 22 (28.6) 17 (22.1) 5 (6.5) 0.235 Constitutional symptom Fever 6 (7.8) 6 (7.8) 0 (0) 1 (1.3) 1 (1.3) 0 (0) 0.118 Dermatology/Skin Flushing 0 (0) 0 (0) 0 (0) 1 (1.3) 1 (1.3) 0 (0) NA Gastrointestinal events Abdominal pain 15 (19.5) 14 (18.2) 1 (1.3) 4 (5.2) 3 (3.9) 1 (1.3) 0.032 Abdominal distension 8 (10.4) 8 (10.4) 0 (0) 13 (16.9) 13 (16.9) 0 (0) 0.429 Anorexia 14 (18.2) 14 (18.2) 0 (0) 3 (3.9) 3 (3.9) 0 (0) 0.023 Ascites 0 (0) 0 (0) 0 (0) 1 (1.3) 1 (1.3) 0 (0) NA Typhlitis 0 (0) 0 (0) 0 (0) 1 (1.3) 1 (1.3) 0 (0) NA Nausea 3 (3.9) 3 (3.9) 0 (0) 2 (2.6) 2 (2.6) 0 (0) 1.000 Vomiting 3 (3.9) 2 (2.6) 1 (1.3) 1 (1.3) 1 (1.3) 0 (0) 0.620 Hepatic funtion Elevated ALP 34 (44.2) 34 (44.2) 0 (0) 42 (52.6) 41 (52.1) 1 (0.5) 0.541 Elevated ALT 37 (48.1) 31 (40.3) 6 (7.8) 38 (46.8) 36 (44.7) 2 (2.1) 1.000 Elevated TBIL 27 (35.1) 24 (31.2) 3 (3.9) 26 (26.3) 21 (23.2) 4 (3.2) 1.000 Hypoalbuminemia 44 (57.1) 44 (57.1) 0 (0) 49 (63.2) 49 (63.2) 0 (0) 0.781 Renal/Genitourinary Elevated CRE 16 (20.8) 16 (20.8) 0 (0) 15 (16.8) 13 (15.8) 2 (1.1) 1.000 Data in parentheses are percentages. Data were compared by using Chi square test or the Fisher’s exact test. ALP, alkaline phosphatase; ALT, alanine aminotransferase; TBIL, total bilirubin; CRE, creatinine. TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy; Discussion In this retrospective cohort study, we compared the efficacy and safety of FOLFOX-HAIC versus TACE in propensity score-matched HCC patients with the CNLC IIIa stage. The results showed that FOLFOX-HAIC can significantly improve the response rate and PFS, and compared to TACE, FOLFOX-HAIC had fewer serious AEs. Although there was no significant improvement in OS and conversion rates for patients in the FOLFOX-HAIC group, prospective studies with the combination of FOLFOX-HAIC and other approaches are still worthy of conduction. There is still controversy over the optimal treatment modalities for patients with CNLC stage IIIa (corresponding to BCLC stage C and UICC/NCCN stage IIIB). The 2022 BCLC and NCCN recommends systemic antitumor drugs such as Atezolizumab-Bevacizumab, lenvatinib and sorafenib as first-line drugs for patients with vascular tumor thrombus without hepatic function deterioration and poor performance status [ 15 ]. However, tyrosine kinase inhibitors cannot be widely used in China because of their low tumor response rate, modest survival advantages, economic factors, and individual differences [ 16 – 19 ]. Recently, arterially directed therapies in highly selected patients have been shown to be safe in the presence of limited tumor invasion of the portal vein. Several studies have reported that TACE and HAIC, as the main locoregional therapies of HCC, show encouraging survival benefits and are recommended as standard therapies in the Chinese guidelines for the diagnosis and treatment of HCC. However, which therapeutic approach is more appropriate for those HCC patients with macrovascular invasion remains unclear. In this study, we found that the ORR and DCR of the HAIC group were significantly higher than those of the TACE group (29.9% and 84.4% vs. 9.1% and 48.1%, respectively) according to the mRECIST criteria after PSM. Similar findings are also observed in a meta-analysis in patients with Vp3-Vp4 PVTT[ 20 ]. The better local antitumor effect of HAIC compared with TACE may be partly because the following reasons. First, HAIC continuously infuses the therapeutic drug into the target artery, resulting in a higher concentration of the drug accumulating in the lesions. Second, the efficacy of TACE is limited due to incomplete deposition of iodide, especially in condition of existence of arterial portal fistula, lack blood supply in large tumors, and reduced use of iodide on account of liver dysfunction. Third, in this study, TACE was performed every 4–8 weeks, while HAIC was performed every 3 weeks as a more proactive strategy with the tolerable AEs. In this study, a higher proportion of patients in the TACE group had hepatic dysfunction and abdominal pain. A possible cause was that these patients already had a portal vein tumor thrombus. When embolization was added to the feeding artery, the liver had an insufficient blood supply, which might have caused abnormal liver function. In particular, embolism-specific adverse events, such as hyperbilirubinemia, were significantly more frequent in the TACE group compared to the HAIC group. A minority of patients in the HAIC group had specific constitutional symptoms, such as flushing and drug-associated typhlitis, due to more radical locoregional chemotherapy regimens. The lower incidence of liver dysfunction allowed patients to receive more treatment sessions and obtain better curative effects. This has been confirmed in previous studies [ 21 ]. Considering that during patients’ treatment against liver cancer, subsequent therapies would be selected after initial treatment, which might affect the OS and PFS. As is summarized in Supplementary Table 2 , more than a half of patients in both TACE group and HAIC group underwent subsequent treatment. The subsequent therapies analysis showed that patients in the two groups received the similar second-line treatments. To note, after PSM, more patients received subsequent ablation after initial TACE compared with those after HAIC ( P = 0.010). The difference may be attributed to efficacy of initial treatment. It partly suggests that ablation is an optional replacement therapy after TACE failure or tumor recurrence. A number of patients in both TACE group and HAIC group underwent subsequent treatment crossover. In clinical practice, the two treatments have complementary effects, selective use of subsequent TACE or HAIC will remain necessary for patients with tumors that remain unsuitable for surgical resection. After PSM processing, it was observed that the median OS of the HAIC group was higher than that of the TACE group, but there was no significant difference (OS, 19.6 vs. 18.1 months; P = 0.116), while the PFS was significantly higher in the HAIC group than in the TACE group (4.7 vs. 1.4 months, P < 0.001). The overall survival in our results was higher than that in an earlier study comparing mFOLFOX-HAIC versus TACE in advanced HCC (OS, 13.9 vs. 6.0 months; P < 0.001) [ 22 ]. Our study did not include patients with EHM. Previous studies have shown that the efficacy of HAIC in patients with EHM is relatively poor [ 23 ]. Moreover, the efficacy of HAIC in reducing serum tumor markers (AFP and PIVKAⅡ) of hepatocellular carcinoma was significantly better than that of TACE. Mechanically, oxaliplatin infusion can reform the immune microenvironment of liver cancer and affects inflammation levels in the body [ 24 ]. An analysis of the level of inflammation indicated significant differences in the TACE group after treatment, showing an increase in CRP and NLR and a decrease in PNI levels. Patients in the HAIC group showed decreased PLR, SII, and PNI values ( Supplementary Table 1 ). PNI and NLR scores are prognostic factors for OS in patients with HCC [ 25 ]. Thus, low-grade inflammation results in a better survival benefit for HAIC. Our study has several limitations. First, this was a retrospective single-center study, which might have led to a selection bias in patient enrollment. PSM was implemented to reduce the effect of selection bias and confounding factors, but the smaller sample size after PSM might still affected the results. Second, a majority of included patients were with hepatitis-B-related HCC. The results need to be validated in external institutions with different disease backgrounds. Third, with the rapid development of targeted drugs and immunotherapy, studies on TACE or HAIC-mFOLFOX combined with targeted and immunotherapeutic drugs are needed to determine the effect of locoregional therapy. Conclusions The results suggested that FOLFOX-HAIC might be the better option, as the initiative therapy, for this group of patients with macrovascular invasion and without extrahepatic metastasis. Abbreviations AEs: Adverse events AFP: Alpha-fetoprotein ALB: Albumin ALBI: albumin-bilirubin ALP: Alkaline phosphatase ALT: Alanine aminotransferase BCLC: Barcelona Clinic Liver Cancer CNLC: Chinese Liver Cancer CR: Complete response CRE: Creatinine CRP: C-reactive protein DCR: Disease control rate DSA: Digital subtraction angiography EHM: Extrahepatic metastasis HAIC: Hepatic arterial infusion chemotherapy HCC: Hepatocellular carcinoma HGB: Hemoglobin mFOLFOX: Modified oxaliplatin, fluorouracil and leucovorin mRECIST: Modified Response Evaluation Criteria In Solid Tumors MVI: Macrovascular invasion NLR: Neutrophil-to-lymphocyte ratio ORR: Objective response rate OS: Overall survival PD: Progressive disease PFS: Progression-free survival PIVKA II: Protein induced by vitamin K absence or antagonist-II PLR: Platelet-to-lymphocyte ratio PLT: Platelet PNI: Prognostic nutritional index PR: Partial response PSM: Propensity score match PVTT: Portal vein tumor thrombus SD: Stable disease SII: Systemic immune-inflammatory index TACE: Transarterial chemoembolization TBIL: Total bilirubin Declarations Ethics approval and consent to participate: The study was a retrospective review of medical records. The study protocol was approved by the Clinical Research Ethics Committee of SYSUCC. Consent for publication: No individual patient data are presented in this paper, and consent for publication was not required. Availability of data and materials: The data that support the findings of this study are available from the corresponding author. Competing interests: The authors declare no conflicts of interest. Funding: This study was supported by the National Natural Science Foundation of China (No. 82172579, No.82303879, No.82303875, No.82203111); Science and Technology Planning Project of Guangzhou (No. 2023A04J1777, No. 2023A04J1781); China Postdoctoral Science Foundation（2023M734035）; Clinical Trials Project (5010 Project) of Sun Yat-sen University (No. 5010-2017009, No. 5010-2023001). Author contributions Benyi He : Conceptualization; Formal analysis; Investigation; Methodology; Project administration; Visualization; Writing – original draft; Writing – review & editing. Min Deng : Conceptualization; Formal analysis; Investigation; Methodology; Project administration; Visualization; Writing – original draft; Writing – review & editing. Shaohua Li : Investigation; Writing – review & editing. Jie Mei : Methodology; Writing – review & editing. Lianghe Lu : Methodology; Writing – review & editing. Chengyou Yu : Conceptualization; Writing – review & editing. Zhijun Zuo : Conceptualization; Writing – review & editing. Rongping Guo : Conceptualization; Writing – original draft; Writing – review & editing. Wei Wei : Conceptualization; Writing – original draft; Writing – review & editing. Acknowledgments The authors acknowledge and express their deepest gratitude to the participants of this research. References Sung, H., et al., Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca-a Cancer Journal for Clinicians, 2021. 71 (3): p. 209-249. Chen, W., et al., Cancer statistics in China, 2015. CA Cancer J Clin, 2016. 66 (2): p. 115-32. Forner, A., M. Reig, and J. Bruix, Hepatocellular carcinoma. Lancet, 2018. 391 (10127): p. 1301-1314. Benson, A.B., et al., Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2021. 19 (5): p. 541-565. Bureau of Medical Administration, N.H.C.o.t.P.s.R.o.C., [Standardization for diagnosis and treatment of hepatocellular carcinoma (2022 edition)]. Zhonghua Gan Zang Bing Za Zhi, 2022. 30 (4): p. 367-388. Lyu, N., et al., Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol, 2018. 69 (1): p. 60-69. He, M., et al., Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial. JAMA Oncol, 2019. 5 (7): p. 953-960. Li, Q.J., et al., Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Transarterial Chemoembolization for Large Hepatocellular Carcinoma: A Randomized Phase III Trial. J Clin Oncol, 2022. 40 (2): p. 150-160. European Association for the Study of the Liver. Electronic address, e.e.e. and L. European Association for the Study of the, EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol, 2018. 69 (1): p. 182-236. Heimbach, J.K., et al., AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology, 2018. 67 (1): p. 358-380. Wei, W., et al., Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety. Cancer Commun (Lond), 2018. 38 (1): p. 61. Lencioni, R. and J.M. Llovet, Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis, 2010. 30 (1): p. 52-60. Shepshelovich, D., et al., Feasibility Assessment of Using the Complete Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item Library. Oncologist, 2019. 24 (4): p. e146-e148. Shi, J., et al., A new classification for hepatocellular carcinoma with portal vein tumor thrombus. J Hepatobiliary Pancreat Sci, 2011. 18 (1): p. 74-80. Villanueva, A., Hepatocellular Carcinoma. N Engl J Med, 2019. 380 (15): p. 1450-1462. Cheng, A.L., et al., Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol, 2009. 10 (1): p. 25-34. Llovet, J.M., et al., Sorafenib in advanced hepatocellular carcinoma. New England Journal of Medicine, 2008. 359 (4): p. 378-390. Qin, S.K., et al., Cost-effectiveness analysis of FOLFOX4 and sorafenib for the treatment of advanced hepatocellular carcinoma in China. Cost Effectiveness and Resource Allocation, 2018. 16 . Chen, J., et al., Potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma. Cancer Lett, 2015. 367 (1): p. 1-11. Si, T., et al., Hepatic arterial infusion chemotherapy versus transarterial chemoembolization for unresectable hepatocellular carcinoma: A systematic review with meta-analysis. Front Bioeng Biotechnol, 2022. 10 : p. 1010824. Li, S.H., et al., Transarterial infusion chemotherapy with FOLFOX for advanced hepatocellular carcinoma: a multi-center propensity score matched analysis of real-world practice. Hepatobiliary Surgery and Nutrition, 2021. 10 (5): p. 631-+. Li, S., et al., Hepatic Artery Infusion Chemotherapy Using Fluorouracil, Leucovorin, and Oxaliplatin versus Transarterial Chemoembolization as Initial Treatment for Locally Advanced Hepatocellular Carcinoma: A Propensity Score-Matching Analysis. J Vasc Interv Radiol, 2021. 32 (9): p. 1267-1276.e1. Ueshima, K., et al., Hepatic Arterial Infusion Chemotherapy versus Sorafenib in Patients with Advanced Hepatocellular Carcinoma. Liver Cancer, 2020. 9 (5): p. 583-595. Pol, J., et al., Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy. Oncoimmunology, 2015. 4 (4): p. e1008866. Liu, C., et al., Neutrophil-lymphocyte Ratio Plus Prognostic Nutritional Index Predicts the Outcomes of Patients with Unresectable Hepatocellular Carcinoma After Transarterial Chemoembolization. Scientific Reports, 2017. 7 . Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable1.pdf SupplementaryTable2.pdf SupplementaryTable3.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3416587","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":239651702,"identity":"056b01d2-6165-4d77-981c-e3918397065b","order_by":0,"name":"Benyi He","email":"","orcid":"","institution":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer，Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Benyi","middleName":"","lastName":"He","suffix":""},{"id":239651703,"identity":"083794e7-7f3f-420e-981c-aa170fe921c6","order_by":1,"name":"Min Deng","email":"","orcid":"","institution":"The Seventh Affiliated Hospital of Sun Yat-sen University, China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Min","middleName":"","lastName":"Deng","suffix":""},{"id":239651704,"identity":"1924c286-5e12-4aa4-9e65-afa25bac9e53","order_by":2,"name":"Shaohua Li","email":"","orcid":"","institution":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer，Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shaohua","middleName":"","lastName":"Li","suffix":""},{"id":239651705,"identity":"995fc467-eace-4518-a7b5-2fd2fb414dc6","order_by":3,"name":"Jie Mei","email":"","orcid":"","institution":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer，Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Mei","suffix":""},{"id":239651706,"identity":"67e9c54a-4a70-434b-9c39-93755bae5685","order_by":4,"name":"Lianghe Lu","email":"","orcid":"","institution":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer，Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lianghe","middleName":"","lastName":"Lu","suffix":""},{"id":239651707,"identity":"a0e320f6-e228-43a1-9b84-776fb946c3fb","order_by":5,"name":"Chengyou Yu","email":"","orcid":"","institution":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer，Sun Yat-sen University Cancer 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Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rongping","middleName":"","lastName":"Guo","suffix":""},{"id":239651710,"identity":"82cab439-9d1c-4685-bbd0-82af1d4adfdd","order_by":8,"name":"Wei Wei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYFACxgYGBgMb0rWkkW7VYRLUGhxvbpP4UHDe3uD8GcMPPxhs8uUdmJ89wKvlzME2yRkGtxM33MgxluxhSLPceIDN3ACfFrMbiW23eQxuJxjc4DFjBrrQwLCBh00Cr5b7D9tu/zE4B3IYsVpuMLbdZjA4wLjhQA5EizwDAS32ZxLbf/YYJCfOvJFWLNljkGZgwMxmhleLZPvxxwY//tjZ850/vPHDjwobA/n25md4tcCBwgEQCQwqA6LjSL4BnTEKRsEoGAWjAAoAzgBHPNu3RKgAAAAASUVORK5CYII=","orcid":"","institution":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer，Sun Yat-sen University Cancer Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2023-10-06 14:29:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3416587/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3416587/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":44741071,"identity":"2cf3a663-56ce-4d31-840e-20029e1ef087","added_by":"auto","created_at":"2023-10-16 23:23:03","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":348446,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patients selected in the study. HAIC, hepatic artery infusion chemotherapy; TACE, transarterial chemoembolization; HCC, hepatocellular carcinoma; CNLC, China liver cancer staging.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3416587/v1/9176f7e6454867ac91c4668b.jpg"},{"id":44741072,"identity":"78fa10ae-07c8-4ac5-9926-d621f65e00da","added_by":"auto","created_at":"2023-10-16 23:23:04","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":435898,"visible":true,"origin":"","legend":"\u003cp\u003eBefore (A,B) \u0026amp; after (C,D) propensity score matching (PSM) of Kaplan-Meier analyses about overall survival (OS) and progression-free survival (PFS). TACE group \u0026amp; HAIC group, period of CNLCⅢa HCC patients treated with TACE or HAIC-mFOLFOX as their first treatment. TACE, transarterial chemoembolization; HAIC-mFOLFOX, hepatic arterial infusion chemotherapy of modified fluorouracil, leucovorin and oxaliplatin.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3416587/v1/7af203a12397be17ad258c1e.jpg"},{"id":57477027,"identity":"56117534-c118-4b3c-bb3a-b473fe2fb22f","added_by":"auto","created_at":"2024-05-31 08:24:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1937015,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3416587/v1/6de17c6f-1e44-42ba-9ebb-e6667cfd693a.pdf"},{"id":44741074,"identity":"72fafbfa-d337-46bf-bcd6-513779d15a84","added_by":"auto","created_at":"2023-10-16 23:23:04","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":112281,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3416587/v1/73ec0aecf9f41abcc3035453.pdf"},{"id":44741076,"identity":"5954546f-ab73-4bfd-b3bd-3a1f6d65b5ac","added_by":"auto","created_at":"2023-10-16 23:23:04","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":107750,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3416587/v1/87af3257a094cd7eb4ffae64.pdf"},{"id":44741075,"identity":"9c7068ca-0196-4fd9-9e56-f2b968f8036d","added_by":"auto","created_at":"2023-10-16 23:23:04","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":111427,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3416587/v1/d518309cdb294f4fba2a6b51.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Transarterial chemoembolization versus hepatic arterial infusion chemotherapy as initial treatment for stage CNLC Ⅲa hepatocellular carcinoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. It is also the second leading cause of cancer-related deaths in China [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. For intermediate stage HCC, transarterial chemoembolization (TACE) was recommended as standard treatment in Barcelona Clinic Liver Cancer (BCLC) staging and the National Comprehensive Cancer Network (NCCN) guideline[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In the Guidelines for diagnosis and treatment of primary liver cancer in China (2022 edition), TACE can be applied for HCC patients with stage Ib (single tumor larger than 5 cm) to IIIb (with extrahepatic metastases)[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The serious adverse events cause by TACE, such as ectopic embolization, post-embolization syndrome, and abnormal liver and renal function are mainly related to the effect of embolization agents. The presence of macrovascular invasion (CNLC IIIa) might increase the impairment of liver function and further reduce the patient's tolerance to TACE.\u003c/p\u003e \u003cp\u003eIn a retrospective study, hepatic arterial infusion chemotherapy with modified oxaliplatin, fluorouracil, and leucovorin (FOLFOX-HAIC) could improve both progression free and overall survival in patients with advanced hepatocellular carcinoma against Sorafenib [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. When combined with sorafenib, FOLFOX-HAIC can significantly prolong survival and has a higher tumor response rate (40.8% vs. 2.46%) compared to sorafenib alone, with acceptable adverse events rate in patients with HCC and portal vein invasion[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In a recent prospective randomized study, HAIC has also shown significantly superior antitumor efficacy and lower toxicity compared to TACE, in patients with unresectable large hepatocellular carcinoma[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, to date, no study has compared the efficacy and safety of TACE and FOLFOX-HAIC in HCC patients with macrovascular invasion and without extrahepatic metastasis (CNLC IIIa stage). Therefore, the aim of this study was to explore the safety and efficacy of FOLFOX-HAIC and TACE as the initiate therapy in this group of patients, and to provide the basis for the potential prospective study.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis was a retrospective study conducted at the Sun Yat-sen University Cancer Center. The trial protocol was approved by the Institutional Review Board (IRB) and Institutional Ethics Committee (IEC) of Sun Yat-sen University Cancer Center (No. B2018-126-01), and complied with the Declaration of Helsinki. All patients provided written informed consent to participate in this study. The primary endpoint was OS of patients with macrovascular invasion and without extrahepatic metastasis following TACE or HAIC, while secondary endpoints were ORR, PFS, rate of subsequent resection, and safety in those patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEligibility Criteria\u003c/h2\u003e \u003cp\u003eThe eligibility criteria for inclusion were as follows: (1) aged\u0026thinsp;\u0026ge;\u0026thinsp;18 to \u0026le;\u0026thinsp;75 years; (2) no previous treatments for HCC; (3) meet the non-invasive diagnosis criteria of European Association for the Study of Liver[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and the American Association for the Study of Liver Diseases[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]; (4) Eastern Cooperative Oncology Group Performance Score (ECOG PS)\u0026thinsp;\u0026le;\u0026thinsp;2; (5) Child-Pugh score of A or B; (6) The presence of macrovascular invasion on the image without extrahepatic metastasis.\u003c/p\u003e \u003cp\u003eThe exclusion criteria were as follows: (1) previous treatments for HCC before TACE or HAIC; (2) HCC combined with other cancers; (3) the imaging data of pretreatment or follow-up was missing; (4) combined with other anti-tumor treatments.\u003c/p\u003e \u003cp\u003eThe detailed process of patient screening is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eTreatment Procedures\u003c/h2\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003eTransarterial Chemoembolization\u003c/h2\u003e \u003cp\u003eTACE was performed using the techniques we have described previously[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In brief, the catheter was placed into celiac trunk or superior mesenteric artery for arteriography through the femoral artery using the Seldinger technique, then 50 mg of lobaplatin, and 50 mg of epirubicin mixed with iodized oil were injected slowly through the catheter into the feeding arteries of the tumor. If necessary, polyvinyl alcohol(PVA)particles was also used to enhance the embolic effect. TACE was repeated every 4 weeks until tumor progression or intolerable adverse events were observed. The subsequent treatment was determined by the patient's tumor response and the opinion of the multidisciplinary team discussions.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eHepatic Arterial Infusion Chemotherapy\u003c/h2\u003e \u003cp\u003eAfter successful percutaneous hepatic artery puncture and catheterization, superior mesenteric and hepatic arteriography were performed. Then the main feeding artery of the tumor was intubated to the predetermined position and patients with indwelling catheter would be sent back to the ward. The catheter was connected to the injection pump and the following chemotherapeutic drugs were continuously pumped: oxaliplatin, 130mg/m\u003csup\u003e2\u003c/sup\u003e, from hour 0 to 3 on day 1, leucovorin, 400 mg/m\u003csup\u003e2\u003c/sup\u003e, from hour 3 to 4.5 on day 1, fluorouracil, 400mg/m\u003csup\u003e2\u003c/sup\u003e, from 4.5 to 6.5 on day 1, and fluorouracil, 2400mg/m\u003csup\u003e2\u003c/sup\u003e, over 46 hours from day 1 to day 3. After the completion of chemotherapy, the catheter was removed and pressure bandaged to stop bleeding. The patient could be discharged after 12 hours. HAIC was repeated for every 4 to 6 weeks according to the condition of the patients. After every two cycles of HAIC, patients would be assessed for tumor response. The subsequent treatment was determined according to the opinion of the multidisciplinary team.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up and Assessment\u003c/h2\u003e \u003cp\u003eAll patients were followed up at an interval of 2\u0026ndash;3 months. At each scheduled follow-up visit, physical examination, blood test (serum tumor markers and liver function), enhanced abdominal computed tomography or magnetic resonance imaging scan were performed. The study was censored on July 2022. Tumor response was assessed according to the modified response evaluation criteria in solid tumors (mRECIST) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], including complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The objective response rate (ORR) was defined as the ratio of patients with CR and PR. And the disease control rate (DCR) was defined as ORR plus SD.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistics Analysis\u003c/h2\u003e \u003cp\u003eThe primary end point was overall survival (OS) which was defined as the time from the initial treatment to the date of death or last follow-up. The secondary end points included progress-free survival (PFS) which was defined as the time from the initial treatment to the date of tumor progression, death, or last follow-up. TACE or HAIC associated adverse events (AEs) were recorded from registration to the subsequent treatments or the last follow-up. Toxicity was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0)[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSurvival curve were estimated using the Kaplan-Meier method and compared using the log-rank test. The median survival with 95% confidence interval (CI) was calculated. Cox proportional analyses were performed to estimate HRs with 95% CIs. The t-test was used for comparisons between groups for continuous variables when they were normally distributed and the Wilcoxon rank-sum test was used when they were not normally distributed.\u003c/p\u003e \u003cp\u003eWe used propensity score matching (PSM) between the TACE and HAIC groups to reduce the effects of selection bias and potential confounding variables that are vital to clinical outcomes. The PSM model included age, sex, Child-Pugh class, cirrhosis, tumor size, number of tumors, Cheng 's classification of PVTT (portal vein tumor thrombus)[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and TBIL. The matched pairs between the TACE and HAIC groups were reduced by 1:1 nearest-neighbor match with a caliper of 0.2. P values of \u0026lt;\u0026thinsp;0.05 were termed as significant. All statistical analyses were performed using R (version 4.2.1) and graphs were generated using GraphPad Prism 8.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics\u003c/h2\u003e \u003cp\u003eBetween December 2016 and July 2020, 3875 patients with liver tumors received TACE or HAIC at our center. Those patients who did not meet the inclusion criteria were excluded, including non CNLC IIIa stage (n\u0026thinsp;=\u0026thinsp;2940), with previous treatment (n\u0026thinsp;=\u0026thinsp;4), the imaging data of pretreatment or follow-up was missing (n\u0026thinsp;=\u0026thinsp;126), other treatments were applied except TACE or HAIC (n\u0026thinsp;=\u0026thinsp;59), and non-hepatocellular carcinoma (n\u0026thinsp;=\u0026thinsp;465), Finally, 281 eligible patients were enrolled in the analysis. There were 91 patients received TACE and 190 patients received HAIC (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The baseline characteristics of patients in the TACE and HAIC groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of patients in TACE group and HAIC group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAfter PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTACE (n\u0026thinsp;=\u0026thinsp;91)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHAIC (n\u0026thinsp;=\u0026thinsp;190)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTACE (n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHAIC\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge(y), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.41\u0026thinsp;\u0026plusmn;\u0026thinsp;12.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.45\u0026thinsp;\u0026plusmn;\u0026thinsp;11.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.192\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55.22\u0026thinsp;\u0026plusmn;\u0026thinsp;12.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e53.91\u0026thinsp;\u0026plusmn;\u0026thinsp;11.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.510\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\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 \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\u003e77 (84.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e176 (92.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.059\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67 (87.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e70 (90.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.607\u003c/p\u003e \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\u003e14 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChild-Pugh class\u003c/b\u003e\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 \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\u003e87 (95.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e188 (98.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76 (98.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e76 (98.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\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\u003e4 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHepatitis virus\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (18.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.613\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 (20.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.680\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\u003e74 (81.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e160 (84.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61 (79.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e64 (83.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAFP (ng/ml)\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003c400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 (39.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29 (37.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \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\u003e53 (58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130 (68.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47 (61.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e48 (62.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePIVKAⅡ (mAU/ml)\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.497\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88 (96.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e184 (96.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75 (97.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e77 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCirrhosis\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (76.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e168 (88.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65 (84.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62 (80.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.672\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15 (19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSize of tumor (mm), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83.08\u0026thinsp;\u0026plusmn;\u0026thinsp;33.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94.74\u0026thinsp;\u0026plusmn;\u0026thinsp;37.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e87.32\u0026thinsp;\u0026plusmn;\u0026thinsp;31.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e86.55\u0026thinsp;\u0026plusmn;\u0026thinsp;35.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.885\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of tumors\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (62.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110 (57.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.530\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47 (61.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46 (59.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (37.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (42.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 (39.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 (40.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCheng\u0026rsquo;s classification\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTypeⅠ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.537\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.325\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTypeⅡ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e125 (65.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e57 (74.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e53 (68.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTypeⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (18.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTypeⅣ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSubsequent resection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.336\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian HGB (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e140.59 (22.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e145.26 (19.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e143.43 (20.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e144.43 (19.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.755\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian PLT (10^9/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e204.31 (94.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e215.93 (102.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.363\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e215.75 (89.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e216.96 (113.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.942\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian ALB (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.75 (4.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.03 (4.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.598\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.16 (3.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41.13 (3.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.954\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian ALP (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136.34 (74.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e151.83 (109.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e135.90 (70.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e137.86 (89.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.880\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian ALT (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.27 (42.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.85 (60.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.514\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54.75 (40.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e58.16 (60.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.682\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian TBIL (umol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.64 (21.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.41 (6.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.73 (7.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.78 (7.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.961\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian CRE (umol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73.08 (15.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.59 (18.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.828\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e74.12 (16.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e74.70 (20.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.849\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eData were compared by using the Chi square test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003ePSM, propensity score match; TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy; SD, standard deviation; ALBI, albumin-bilirubin; AFP, Alpha-fetoprotein; PIVKAⅡ, Protein Induced by Vitamin K Absence or Antagonist-II; HGB, hemoglobin; PLT, platelet; ALB, albumin; ALP, alkaline phosphatase; ALT, alanine aminotransferase; TBIL, total bilirubin; CRE, creatinine.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eCut-off of AFP is 400ng/ml. Cut-off of PIVKAⅡ is 40mAU/ml.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBefore PSM, the HAIC group differed from the TACE group in terms of cirrhosis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020) (defined by radiological assessments), tumor size (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012), and total bilirubin (TBIL) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015). After 1:1 PSM, we obtained matched cohorts of 77 patients per group with well-balanced variables without significant difference.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eRadiological And Clinical Response Rate\u003c/h2\u003e \u003cp\u003eThe tumor response of patients in the two groups were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Before PSM, the PR, ORR, and DCR in the HAIC group were 35.3%, 35.3% and 80.6%, respectively, which were significantly higher than those in the TACE group (8.8%, 8.8% and 51.7%, respectively). After PSM, the rates of PR, ORR, and DCR in the HAIC group were 29.9%, 29.9% and 84.4%, respectively, which were still significantly higher than those in the TACE group (9.1%, 9.1% and 48.1%, respectively).\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\u003eTumor responds between TACE and HAIC group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRECIST\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTACE(n\u0026thinsp;=\u0026thinsp;91)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHAIC(n\u0026thinsp;=\u0026thinsp;190)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTACE(n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHAIC(n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67(35.3) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7(9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23(29.9) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39(42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86(45.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.904\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30(39.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e42(54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.305\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(48.4) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37(19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40(51.9) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12(15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eORR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67(35.3) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7(9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23(29.9) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47(51.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e153(80.6) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37(48.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e65(84.4) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003emRECIST, modified Response Evaluation Criteria In Solid Tumors; PSM, propensity score matching; TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR; disease control rate.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSubsequent resection rate\u003c/h2\u003e \u003cp\u003eThe patients who received subsequent resection in the two groups were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. For patients with PVTT of type I-II (according to the Cheng\u0026rsquo;s classification), the subsequent resection rate in the HAIC group was 17.4%, which was significantly higher than that in the TACE group (5.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045). For patients with PVTT of type Ⅲ-Ⅳ, there was one patient from each of the two groups underwent subsequent resection (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.514). After PSM, there was no significant difference between the TACE and HAIC groups in the subsequent resection rate for patients with PVTT of type I-II (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.195) and type Ⅲ-Ⅳ (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.000).\u003c/p\u003e \n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e | Number of patients who received Resection in TACE or HAIC group\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType I - II\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.10204081632653%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType III - IV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTACE (n=91)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHAIC (n=190)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTACE (n=91)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHAIC (n=190)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e74(81.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\" valign=\"top\"\u003e\n \u003cp\u003e149(78.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e17(18.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e41(21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eResection\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e4(5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\" valign=\"top\"\u003e\n \u003cp\u003e26(17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e1(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e1(2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e0.514\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNumber of patients who received Resection in TACE or HAIC group（PSM）\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.26530612244898%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType I - II\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.10204081632653%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType III - IV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTACE (n=77)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHAIC (n=77)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTACE (n=77)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHAIC (n=77)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e63(81.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\" valign=\"top\"\u003e\n \u003cp\u003e61(79.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e14(18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e16(20.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eResection\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e4(5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\" valign=\"top\"\u003e\n \u003cp\u003e10(16.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e0.195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e1(7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.631578947368421%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eType Ⅰ, Ⅱ, Ⅲ, Ⅳ are defined by Cheng\u0026rsquo;s classification of thrombus.\u003c/p\u003e\n\u003cp\u003eData in parentheses are percentages. Data were compared by using Chi square test or the Fisher\u0026rsquo;s exact test.\u003c/p\u003e\n\u003cp\u003ePSM, propensity score match; TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy.\u003c/p\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eOS and PFS Analysis\u003c/h2\u003e \u003cp\u003eThe follow-up ended in July 2022. The incidence of death was 45.1% (41/91) in the TACE group and 46.3% (88/190) in the HAIC group. Patients in the HAIC group had a median overall survival of 26.5 months compared to 16.9 months in the TACE group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, P\u0026thinsp;=\u0026thinsp;0.041). The PFS in the HAIC group was also significantly longer than that in the TACE group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC, \u003cb\u003e4\u003c/b\u003e.1 vs. 1.4 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After PSM, there was no significant difference in overall survival between the HAIC and TACE groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB, \u003cb\u003e19\u003c/b\u003e.6 vs. 18.1 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.116). However, the PFS in the HAIC group was still significantly longer than that in the TACE group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD, \u003cb\u003e4\u003c/b\u003e.7 vs. 1.4 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eAdverse Events\u003c/h2\u003e \u003cp\u003eTreatment-related adverse events in the two groups after PSM are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Overall, the adverse reactions were similar and mostly mild in both groups. Compared to the HAIC group, gastrointestinal events such as abdominal pain (19.5% vs. 5.2%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032) and anorexia (18.2% vs. 3.9%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023) were more frequent in the TACE group. In addition, one patient in the HAIC group developed flushing, one patient developed ascites, and two patients developed typhlitis. No treatment-related deaths occurred in either of the groups. Total treatment-related adverse events in the two groups are summarized in \u003cb\u003eSupplementary Table\u0026nbsp;3\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdverse events appeared in TACE and HAIC group 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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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\u003eEvent, n(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTACE (n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHAIC (n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP\u003c/p\u003e \u003cp\u003evalue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAny grade\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGrade\u003c/p\u003e \u003cp\u003e1/2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGrade\u003c/p\u003e \u003cp\u003e3/4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAny\u003c/p\u003e \u003cp\u003egrade\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGrade\u003c/p\u003e \u003cp\u003e1/2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGrade\u003c/p\u003e \u003cp\u003e3/4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAny\u003c/p\u003e \u003cp\u003egrade\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood/bone marrow suppression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10 (13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e9 (11.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.209\u003c/p\u003e \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\u003e6 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e10 (13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReduced hemoglobin level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (26.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (24.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e12 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.274\u003c/p\u003e \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\" colname=\"c2\"\u003e \u003cp\u003e13 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e22 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e17 (22.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.235\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eConstitutional symptom\u003c/b\u003e\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\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.118\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDermatology/Skin\u003c/b\u003e\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\u003eFlushing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGastrointestinal events\u003c/b\u003e\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\u003eAbdominal pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal distension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e13 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.429\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnorexia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAscites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTyphlitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.620\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHepatic funtion\u003c/b\u003e\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\u003eElevated ALP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (44.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (44.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e42 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e41 (52.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.541\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated ALT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (48.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (40.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e38 (46.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e36 (44.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated TBIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (35.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e21 (23.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.000\u003c/p\u003e \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\u003e44 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e49 (63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e49 (63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.781\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRenal/Genitourinary\u003c/b\u003e\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\u003eElevated CRE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (20.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (20.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15 (16.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e13 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eData in parentheses are percentages. Data were compared by using Chi square test or the Fisher\u0026rsquo;s exact test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eALP, alkaline phosphatase; ALT, alanine aminotransferase; TBIL, total bilirubin; CRE, creatinine. TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy;\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\u003eIn this retrospective cohort study, we compared the efficacy and safety of FOLFOX-HAIC versus TACE in propensity score-matched HCC patients with the CNLC IIIa stage. The results showed that FOLFOX-HAIC can significantly improve the response rate and PFS, and compared to TACE, FOLFOX-HAIC had fewer serious AEs. Although there was no significant improvement in OS and conversion rates for patients in the FOLFOX-HAIC group, prospective studies with the combination of FOLFOX-HAIC and other approaches are still worthy of conduction.\u003c/p\u003e \u003cp\u003eThere is still controversy over the optimal treatment modalities for patients with CNLC stage IIIa (corresponding to BCLC stage C and UICC/NCCN stage IIIB). The 2022 BCLC and NCCN recommends systemic antitumor drugs such as Atezolizumab-Bevacizumab, lenvatinib and sorafenib as first-line drugs for patients with vascular tumor thrombus without hepatic function deterioration and poor performance status [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, tyrosine kinase inhibitors cannot be widely used in China because of their low tumor response rate, modest survival advantages, economic factors, and individual differences [\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Recently, arterially directed therapies in highly selected patients have been shown to be safe in the presence of limited tumor invasion of the portal vein. Several studies have reported that TACE and HAIC, as the main locoregional therapies of HCC, show encouraging survival benefits and are recommended as standard therapies in the Chinese guidelines for the diagnosis and treatment of HCC. However, which therapeutic approach is more appropriate for those HCC patients with macrovascular invasion remains unclear.\u003c/p\u003e \u003cp\u003eIn this study, we found that the ORR and DCR of the HAIC group were significantly higher than those of the TACE group (29.9% and 84.4% vs. 9.1% and 48.1%, respectively) according to the mRECIST criteria after PSM. Similar findings are also observed in a meta-analysis in patients with Vp3-Vp4 PVTT[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The better local antitumor effect of HAIC compared with TACE may be partly because the following reasons. First, HAIC continuously infuses the therapeutic drug into the target artery, resulting in a higher concentration of the drug accumulating in the lesions. Second, the efficacy of TACE is limited due to incomplete deposition of iodide, especially in condition of existence of arterial portal fistula, lack blood supply in large tumors, and reduced use of iodide on account of liver dysfunction. Third, in this study, TACE was performed every 4\u0026ndash;8 weeks, while HAIC was performed every 3 weeks as a more proactive strategy with the tolerable AEs.\u003c/p\u003e \u003cp\u003eIn this study, a higher proportion of patients in the TACE group had hepatic dysfunction and abdominal pain. A possible cause was that these patients already had a portal vein tumor thrombus. When embolization was added to the feeding artery, the liver had an insufficient blood supply, which might have caused abnormal liver function. In particular, embolism-specific adverse events, such as hyperbilirubinemia, were significantly more frequent in the TACE group compared to the HAIC group. A minority of patients in the HAIC group had specific constitutional symptoms, such as flushing and drug-associated typhlitis, due to more radical locoregional chemotherapy regimens. The lower incidence of liver dysfunction allowed patients to receive more treatment sessions and obtain better curative effects. This has been confirmed in previous studies [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConsidering that during patients\u0026rsquo; treatment against liver cancer, subsequent therapies would be selected after initial treatment, which might affect the OS and PFS. As is summarized in \u003cb\u003eSupplementary Table\u0026nbsp;2\u003c/b\u003e, more than a half of patients in both TACE group and HAIC group underwent subsequent treatment. The subsequent therapies analysis showed that patients in the two groups received the similar second-line treatments. To note, after PSM, more patients received subsequent ablation after initial TACE compared with those after HAIC (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010). The difference may be attributed to efficacy of initial treatment. It partly suggests that ablation is an optional replacement therapy after TACE failure or tumor recurrence. A number of patients in both TACE group and HAIC group underwent subsequent treatment crossover. In clinical practice, the two treatments have complementary effects, selective use of subsequent TACE or HAIC will remain necessary for patients with tumors that remain unsuitable for surgical resection.\u003c/p\u003e \u003cp\u003eAfter PSM processing, it was observed that the median OS of the HAIC group was higher than that of the TACE group, but there was no significant difference (OS, 19.6 vs. 18.1 months; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.116), while the PFS was significantly higher in the HAIC group than in the TACE group (4.7 vs. 1.4 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The overall survival in our results was higher than that in an earlier study comparing mFOLFOX-HAIC versus TACE in advanced HCC (OS, 13.9 vs. 6.0 months; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Our study did not include patients with EHM. Previous studies have shown that the efficacy of HAIC in patients with EHM is relatively poor [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Moreover, the efficacy of HAIC in reducing serum tumor markers (AFP and PIVKAⅡ) of hepatocellular carcinoma was significantly better than that of TACE. Mechanically, oxaliplatin infusion can reform the immune microenvironment of liver cancer and affects inflammation levels in the body [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. An analysis of the level of inflammation indicated significant differences in the TACE group after treatment, showing an increase in CRP and NLR and a decrease in PNI levels. Patients in the HAIC group showed decreased PLR, SII, and PNI values (\u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e). PNI and NLR scores are prognostic factors for OS in patients with HCC [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Thus, low-grade inflammation results in a better survival benefit for HAIC.\u003c/p\u003e \u003cp\u003eOur study has several limitations. First, this was a retrospective single-center study, which might have led to a selection bias in patient enrollment. PSM was implemented to reduce the effect of selection bias and confounding factors, but the smaller sample size after PSM might still affected the results. Second, a majority of included patients were with hepatitis-B-related HCC. The results need to be validated in external institutions with different disease backgrounds. Third, with the rapid development of targeted drugs and immunotherapy, studies on TACE or HAIC-mFOLFOX combined with targeted and immunotherapeutic drugs are needed to determine the effect of locoregional therapy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe results suggested that FOLFOX-HAIC might be the better option, as the initiative therapy, for this group of patients with macrovascular invasion and without extrahepatic metastasis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAEs: Adverse events\u003c/p\u003e\n\u003cp\u003eAFP: Alpha-fetoprotein\u003c/p\u003e\n\u003cp\u003eALB: Albumin\u003c/p\u003e\n\u003cp\u003eALBI: albumin-bilirubin\u003c/p\u003e\n\u003cp\u003eALP: Alkaline phosphatase\u003c/p\u003e\n\u003cp\u003eALT: Alanine aminotransferase\u003c/p\u003e\n\u003cp\u003eBCLC: Barcelona Clinic Liver Cancer\u003c/p\u003e\n\u003cp\u003eCNLC: Chinese Liver Cancer\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCR: Complete response\u003c/p\u003e\n\u003cp\u003eCRE: Creatinine\u003c/p\u003e\n\u003cp\u003eCRP: C-reactive protein\u003c/p\u003e\n\u003cp\u003eDCR: Disease control rate\u003c/p\u003e\n\u003cp\u003eDSA: Digital subtraction angiography\u003c/p\u003e\n\u003cp\u003eEHM: Extrahepatic metastasis\u003c/p\u003e\n\u003cp\u003eHAIC: Hepatic arterial infusion chemotherapy\u003c/p\u003e\n\u003cp\u003eHCC: Hepatocellular carcinoma\u003c/p\u003e\n\u003cp\u003eHGB: Hemoglobin\u003c/p\u003e\n\u003cp\u003emFOLFOX: Modified oxaliplatin, fluorouracil and leucovorin\u003c/p\u003e\n\u003cp\u003emRECIST: Modified Response Evaluation Criteria In Solid Tumors\u003c/p\u003e\n\u003cp\u003eMVI: Macrovascular invasion\u003c/p\u003e\n\u003cp\u003eNLR: Neutrophil-to-lymphocyte ratio\u003c/p\u003e\n\u003cp\u003eORR: Objective response rate\u003c/p\u003e\n\u003cp\u003eOS: Overall survival\u003c/p\u003e\n\u003cp\u003ePD: Progressive disease\u003c/p\u003e\n\u003cp\u003ePFS: Progression-free survival\u003c/p\u003e\n\u003cp\u003ePIVKA II: Protein induced by vitamin K absence or antagonist-II\u003c/p\u003e\n\u003cp\u003ePLR: Platelet-to-lymphocyte ratio\u003c/p\u003e\n\u003cp\u003ePLT: Platelet\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePNI: Prognostic nutritional index\u003c/p\u003e\n\u003cp\u003ePR: Partial response\u003c/p\u003e\n\u003cp\u003ePSM: Propensity score match\u003c/p\u003e\n\u003cp\u003ePVTT: Portal vein tumor thrombus\u003c/p\u003e\n\u003cp\u003eSD: Stable disease\u003c/p\u003e\n\u003cp\u003eSII: Systemic immune-inflammatory index\u003c/p\u003e\n\u003cp\u003eTACE: Transarterial chemoembolization\u003c/p\u003e\n\u003cp\u003eTBIL: Total bilirubin\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study was a retrospective review of medical records. The study protocol was approved by the Clinical Research Ethics Committee of SYSUCC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e No individual patient data are presented in this paper, and consent for publication was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe data that support the findings of this study are available from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study was supported by the National Natural Science Foundation of China (No. 82172579, No.82303879, No.82303875, No.82203111); Science and Technology Planning Project of Guangzhou (No. 2023A04J1777, No. 2023A04J1781); China Postdoctoral Science Foundation（2023M734035）; Clinical Trials Project (5010 Project) of Sun Yat-sen University (No. 5010-2017009, No. 5010-2023001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBenyi He\u003c/strong\u003e: Conceptualization; Formal analysis; Investigation; Methodology; Project administration; Visualization; Writing \u0026ndash; original draft; Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMin Deng\u003c/strong\u003e: Conceptualization; Formal analysis; Investigation; Methodology; Project administration; Visualization; Writing \u0026ndash; original draft; Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eShaohua Li\u003c/strong\u003e: Investigation; Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eJie Mei\u003c/strong\u003e: Methodology; Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLianghe Lu\u003c/strong\u003e: Methodology; Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eChengyou Yu\u003c/strong\u003e: Conceptualization; Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eZhijun Zuo\u003c/strong\u003e: Conceptualization; Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRongping Guo\u003c/strong\u003e: Conceptualization; Writing \u0026ndash; original draft; Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWei Wei\u003c/strong\u003e: Conceptualization; Writing \u0026ndash; original draft; Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge and express their deepest gratitude to the participants of this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSung, H., et al., \u003cem\u003eGlobal cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.\u003c/em\u003e Ca-a Cancer Journal for Clinicians, 2021. \u003cstrong\u003e71\u003c/strong\u003e(3): p. 209-249.\u003c/li\u003e\n\u003cli\u003eChen, W., et al., \u003cem\u003eCancer statistics in China, 2015.\u003c/em\u003e CA Cancer J Clin, 2016. \u003cstrong\u003e66\u003c/strong\u003e(2): p. 115-32.\u003c/li\u003e\n\u003cli\u003eForner, A., M. 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Electronic address, e.e.e. and L. European Association for the Study of the, \u003cem\u003eEASL Clinical Practice Guidelines: Management of hepatocellular carcinoma.\u003c/em\u003e J Hepatol, 2018. \u003cstrong\u003e69\u003c/strong\u003e(1): p. 182-236.\u003c/li\u003e\n\u003cli\u003eHeimbach, J.K., et al., \u003cem\u003eAASLD guidelines for the treatment of hepatocellular carcinoma.\u003c/em\u003e Hepatology, 2018. \u003cstrong\u003e67\u003c/strong\u003e(1): p. 358-380.\u003c/li\u003e\n\u003cli\u003eWei, W., et al., \u003cem\u003eAdjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety.\u003c/em\u003e Cancer Commun (Lond), 2018. \u003cstrong\u003e38\u003c/strong\u003e(1): p. 61.\u003c/li\u003e\n\u003cli\u003eLencioni, R. and J.M. Llovet, \u003cem\u003eModified RECIST (mRECIST) assessment for hepatocellular carcinoma.\u003c/em\u003e Semin Liver Dis, 2010. \u003cstrong\u003e30\u003c/strong\u003e(1): p. 52-60.\u003c/li\u003e\n\u003cli\u003eShepshelovich, D., et al., \u003cem\u003eFeasibility Assessment of Using the Complete Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item Library.\u003c/em\u003e Oncologist, 2019. \u003cstrong\u003e24\u003c/strong\u003e(4): p. e146-e148.\u003c/li\u003e\n\u003cli\u003eShi, J., et al., \u003cem\u003eA new classification for hepatocellular carcinoma with portal vein tumor thrombus.\u003c/em\u003e J Hepatobiliary Pancreat Sci, 2011. \u003cstrong\u003e18\u003c/strong\u003e(1): p. 74-80.\u003c/li\u003e\n\u003cli\u003eVillanueva, A., \u003cem\u003eHepatocellular Carcinoma.\u003c/em\u003e N Engl J Med, 2019. \u003cstrong\u003e380\u003c/strong\u003e(15): p. 1450-1462.\u003c/li\u003e\n\u003cli\u003eCheng, A.L., et al., \u003cem\u003eEfficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial.\u003c/em\u003e Lancet Oncol, 2009. \u003cstrong\u003e10\u003c/strong\u003e(1): p. 25-34.\u003c/li\u003e\n\u003cli\u003eLlovet, J.M., et al., \u003cem\u003eSorafenib in advanced hepatocellular carcinoma.\u003c/em\u003e New England Journal of Medicine, 2008. \u003cstrong\u003e359\u003c/strong\u003e(4): p. 378-390.\u003c/li\u003e\n\u003cli\u003eQin, S.K., et al., \u003cem\u003eCost-effectiveness analysis of FOLFOX4 and sorafenib for the treatment of advanced hepatocellular carcinoma in China.\u003c/em\u003e Cost Effectiveness and Resource Allocation, 2018. \u003cstrong\u003e16\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eChen, J., et al., \u003cem\u003ePotential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma.\u003c/em\u003e Cancer Lett, 2015. \u003cstrong\u003e367\u003c/strong\u003e(1): p. 1-11.\u003c/li\u003e\n\u003cli\u003eSi, T., et al., \u003cem\u003eHepatic arterial infusion chemotherapy versus transarterial chemoembolization for unresectable hepatocellular carcinoma: A systematic review with meta-analysis.\u003c/em\u003e Front Bioeng Biotechnol, 2022. \u003cstrong\u003e10\u003c/strong\u003e: p. 1010824.\u003c/li\u003e\n\u003cli\u003eLi, S.H., et al., \u003cem\u003eTransarterial infusion chemotherapy with FOLFOX for advanced hepatocellular carcinoma: a multi-center propensity score matched analysis of real-world practice.\u003c/em\u003e Hepatobiliary Surgery and Nutrition, 2021. \u003cstrong\u003e10\u003c/strong\u003e(5): p. 631-+.\u003c/li\u003e\n\u003cli\u003eLi, S., et al., \u003cem\u003eHepatic Artery Infusion Chemotherapy Using Fluorouracil, Leucovorin, and Oxaliplatin versus Transarterial Chemoembolization as Initial Treatment for Locally Advanced Hepatocellular Carcinoma: A Propensity Score-Matching Analysis.\u003c/em\u003e J Vasc Interv Radiol, 2021. \u003cstrong\u003e32\u003c/strong\u003e(9): p. 1267-1276.e1.\u003c/li\u003e\n\u003cli\u003eUeshima, K., et al., \u003cem\u003eHepatic Arterial Infusion Chemotherapy versus Sorafenib in Patients with Advanced Hepatocellular Carcinoma.\u003c/em\u003e Liver Cancer, 2020. \u003cstrong\u003e9\u003c/strong\u003e(5): p. 583-595.\u003c/li\u003e\n\u003cli\u003ePol, J., et al., \u003cem\u003eTrial Watch: Immunogenic cell death inducers for anticancer chemotherapy.\u003c/em\u003e Oncoimmunology, 2015. \u003cstrong\u003e4\u003c/strong\u003e(4): p. e1008866.\u003c/li\u003e\n\u003cli\u003eLiu, C., et al., \u003cem\u003eNeutrophil-lymphocyte Ratio Plus Prognostic Nutritional Index Predicts the Outcomes of Patients with Unresectable Hepatocellular Carcinoma After Transarterial Chemoembolization.\u003c/em\u003e Scientific Reports, 2017. \u003cstrong\u003e7\u003c/strong\u003e.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hepatocellular carcinoma, Hepatic arterial infusion chemotherapy, Liver, Transarterial chemoembolization","lastPublishedDoi":"10.21203/rs.3.rs-3416587/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3416587/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe Chinese Liver Cancer (CNLC) staging recommends transarterial chemoembolization (TACE) as the standard treatment for hepatocellular carcinoma (HCC) patients with macrovascular invasion and without extrahepatic metastasis (CNLC IIIa). As a recently emerging approach, the efficacy of hepatic arterial infusion chemotherapy (HAIC) compared to TACE in this group of patients is unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFrom December 2016 to June 2020, patients diagnosed with CNLC IIIa stage HCC who underwent TACE (n\u0026thinsp;=\u0026thinsp;91) or HAIC (n\u0026thinsp;=\u0026thinsp;190) as their initial treatment were included. Propensity score matching (PSM) was used to reduce selection bias and other imbalances. Objective response rates (ORR), overall survival (OS), progression-free survival (PFS), rate of subsequent resection, and safety were compared in these two groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAfter PSM, 77 pairs of patients were matched. The ORR was higher in HAIC group than that of TACE group (29.9% vs. 9.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013). Median progression-free survival of the HAIC group was longer than that of TACE group (4.7 vs. 1.4 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), but there was no significant difference in the median OS between the HAIC and TACE groups (19.6 vs. 18.1 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.122). The HAIC group also showed a better safety profile than the TACE group.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eHAIC is an effective and safe option in the treatment of HCC patients with CNLC IIIa stage compared with TACE.\u003c/p\u003e","manuscriptTitle":"Transarterial chemoembolization versus hepatic arterial infusion chemotherapy as initial treatment for stage CNLC Ⅲa hepatocellular carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-16 23:22:59","doi":"10.21203/rs.3.rs-3416587/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8fc51bbb-e8eb-4595-9464-66d33751d3c4","owner":[],"postedDate":"October 16th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-31T08:16:12+00:00","versionOfRecord":[],"versionCreatedAt":"2023-10-16 23:22:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3416587","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3416587","identity":"rs-3416587","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}