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This study aimed to assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with modified FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as an alternative treatment option in advanced hepatocellular carcinoma (HCC) patients with failed or unsuitability for transarterial chemoembolization (TACE). MATERIALS AND METHODS: From September 2018 to January 2020, 87 advanced HCC patients who progressed on TACE or were not eligible for TACE received HAIC treatment with modified FOLFOX. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1, and adverse events graded according to CTCAE 5.0. Based on prognostic factors determined by multivariate analysis, a nomogram was developed to predict patient survival.The median OS and PFS were 9.0 months (95%CI 7.6-10.4) and 3.7 months (95%CI 3.1-4.3), respectively. The objective response rate was 13.8%, with a disease control rate of 48.3%. Grade 3 adverse events were observed, such as infection (9.2%), thrombocytopenia (5.7%), hyperbilirubinemia (3.4%), abdominal pain (2.3%) and alanine aminotransferase increase (2.3%). Albumin, AST, and extrahepatic metastasis were incorporated to construct a new nomogram that could stratify patients into three prognostic subgroups, including low-, intermediate-, and high-risk groups, with significant differences in 9-month OS rates (71%, 42% and 6%, respectively; p0.001). The nomogram was better than the Okuda, AJCC, and CLIP staging systems for OS prediction.These findings support the feasibility of HAIC with modified FOLFOX as an alternative treatment strategy for advanced HCC when TACE is ineffective or unsuitable.

Background We evaluated organ-specific response rates (OSRRs) to first-line lenvatinib plus anti-PD-1 antibodies in patients with advanced hepatocellular carcinoma (HCC). Methods This retrospective analysis included Chinese patients with unresectable/advanced HCC who received first-line lenvatinib (8 mg/day) plus ≥3 infusions of anti-PD-1 antibodies between October 2018 and May 2020. Tumor and macrovascular tumor thrombi (MVTT) treatment responses were evaluated every 2 months using RECIST v1.1. The overall response rate (ORR)/OSRR was defined as the percentage of patients with a best overall response of complete or partial response (CR or PR). Results In total, 60 patients were included in the analysis; 96.7% had measurable intrahepatic lesions, 55% had MVTT and 26.7% had extrahepatic disease. In all 60 patients, the ORR was 33.3%, median progression-free survival was 7.0 months (95% CI, 1.7–12.3) and median overall survival was not reached. The OSRR for MVTT (54.5%) was higher versus intrahepatic tumors (32.8%), extrahepatic lung metastases (37.5%) and lymph node metastases (33.3%). Among 33 patients with intrahepatic tumors and MVTT, 18 had differential responses in each site, including 13 with a better response in MVTT versus intrahepatic lesions. Among 18 patients whose MVTT achieved a radiographic CR or PR, six underwent surgical resection: 4/6 achieved a pathological CR in MVTT and 2/6 in the intrahepatic tumor. Conclusions First-line lenvatinib plus anti-PD-1 antibodies resulted in better tumor responses in MVTT versus intrahepatic lesions. Complete MVTT necrosis may allow downstaging and subsequent eligibility for surgical resection in a proportion of patients with advanced HCC.

Background: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. Methods: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. Results: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4–8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8–15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. Conclusions: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

Background Combined treatment with tyrosine kinase inhibitors (TKI) plus anti-PD-1 antibodies showed high anti-tumor efficacy and made conversion resection possible for patients with unresectable hepatocellular carcinoma (HCC). However, long-term survival has not been reported. Methods A cohort of consecutive patients who received combined TKI/anti-PD-1 antibodies as first-line treatment for initially unresectable HCC at the authors’ hospital between August 2018 and September 2020 was eligible for this study. Patients who were responding to systemic therapy and met the criteria for hepatectomy underwent liver resection with curative intention. The study also investigated the association of clinical factors with successful conversion resection and postoperative recurrence. Results The study enrolled 101 patients including 24 patients (23.8 %) who underwent R0 resection a median of 3.9 months (interquartile range: 2.5–5.9 months) after initiation of systemic therapy. Patients with an Eastern cooperative oncology group performance status of 0, fewer intrahepatic tumors, or a radiographic response to systemic therapy were more likely to be able to receive curative resection. After a median follow-up period of 21.5 months, hepatectomy was independently associated with a favorable overall survival (hazard ratio [HR], 0.050; 95 % confidence interval [CI], 0.007–0.365; P = 0.003). For the 24 patients who underwent surgery, the 12-month recurrence-free survival and overall survival rates were respectively 75% and 95.8%. Achieving a pathologic complete response (n = 10) to systemic therapy was associated with a favorable recurrence-free survival after resection, with a trend toward significance (HR, 0.345; 95% CI, 0.067–1.785; P = 0.187). Conclusions Selected patients with initially unresectable HCC can undergo hepatectomy after systemic therapy with combined TKI/anti-PD-1 antibodies. In this study, conversion resection was associated with a favorable prognosis.

Purpose: The prognosis of patients with intermediate-stage hepatocellular carcinoma (HCC) treated by conventional TACE (cTACE) is greatly heterogeneous. This study aimed to develop a new survival prediction model to help select patients who would benefit better from cTACE treatment. Methods: We collected data of 848 treatment-naive patients with BCLC B HCC who received cTACE as first-line therapy. The prognostic model's variables were derived from univariate and multivariate Cox regression analyses. The concordance index (C-statistic) calculated through cross-validation and bootstrap resampling was used for the model selection. The calibration of our final prediction model was also assessed. Results: The model showed a better discrimination ability than Bolondi's BCLC B1-B4 subclassification to predict the prognosis of BCLC B patients (C-statistic, 0.66 vs. 0.60; difference, 0.05, 95% CI, 0.03-0.07). In cross-validation, bootstrap resampling demonstrated that the model maintained sufficiently discriminant (an average of C-statistic, 0.66; 95% CI, 0.65-0.68). The model calibration was accurate in predicting survival of patients matched well with the observed outcomes. On the basis of the improved survival of 18 months or more as the responding patient, the observations of patients in each response category (responder and non-responder) were fair-moderately matched with those predicted by the model (κ=0.40, P

4094 Background: The outcome of advanced intrahepatic cholangiocarcinoma (ICC) remains poor with current gemcitabine-based chemotherapy. This study is to evaluate the safety and efficacy of anti-PD1 agent toripalimab, lenvatinib in combination with oxaliplatin and gemcitabine (Gemox) chemotherapy. Methods: Locally advanced or metastatic ICC patients (pts) were given 240 mg toripalimab Q3W via intravenous (IV) infusion, 8 mg lenvatinib QD orally, and 1g/m² gemcitabine on Day 1 and Day 8, and 85 mg/m² oxaliplatin Q3W by IV for 6 cycles. The primary outcome was objective response rate (ORR), which was evaluated according to RECIST v1.1. Secondary outcomes included safety, progression-free survival (PFS) and overall survival (OS). Treatment would be terminated by confirmed disease progression, unacceptable toxicity, or voluntary withdrawal. Whole exome sequencing was performed on available tumor tissues and PD-L1 expression was determined by immunohistochemistry staining. Results: From May 2019 to Oct 2019, 30 pathologically-confirmed advanced ICC pts with a mean age of 56.5 (range, 25-73) years, including 11 women (37%), were enrolled at Zhongshan Hospital, Fudan University (one pt withdrawn). At the end of last follow-up (February 1, 2021), the ORR was 80% (24/30; 95% CI: 61.4%-92.3%), and disease control rate (DCR) was 93.3% (28/30; 95% CI:77.9%-99.2%). Median follow-up was 16.6 months. One pt achieved complete response (CR). Three pts with locally advanced disease were down-staged and then underwent resection. They remained disease-free survival at the end of last follow-up. 23 pts experienced disease progression and 12 pts (including one pt withdrawn) have died. The median PFS was 10.0 months and median duration of response (DOR) was 9.8 months. The median OS have not been reached. 12-months OS rate was 73.3% (95% CI: 57.5%-89.2%). No grade 5 adverse event (AE) was observed in present study. Grade 3 or 4 neutropenia and thrombocytopenia observed in 3 (10%) and 1 (3.3%) patient, respectively. Non-hematological toxic effects were jaundice (10 %), rash (6.7 %), proteinuria (6.7 %), increased AST level (3.3%), vomiting (3.3%), upper gastrointestinal hemorrhage (3.3%), sepsis (3.3%), gastrointestinal fistula (3.3%), adrenocortical insufficiency (3.3%), interstitial pneumonia (3.3%), and hyponatremia (3.3%). High ORR was significantly associated with positive PD-L1 expression ( p= 0.048) and DNA damage repair (DDR)-related mutations ( p= 0.022) in tumor samples. Conclusions: Gemox chemotherapy in combination with Anti-PD1 antibody Toripalimab and Lenvatinib provided remarkable efficacy with reasonable tolerability in advanced ICC patients. These findings warrant further validation in a large randomized clinical trial. Clinical trial information: NCT03951597.

4099 Background: Lenvatinib monotherapy and lenvatinib plus PD-1 antibody have shown some clinical benefit for advanced intrahepatic cholangiocarcinoma (ICC) in the second-line setting. Our study assesses the role of lenvatinib plus toripalimab (PD-1 antibody) for advanced ICC patients as the first line therapy. Methods: Patients (pts) with locally advanced or metastatic ICC received 12 mg/day (Body Weight ≥60 kg) or 8 mg/day (Body Weight

e16163 Background: The prognosis of advanced intrahepatic cholangiocarcinoma (ICC) remains dismal with gemcitabine-based first-line chemotherapy. This study is to evaluate the safety and efficacy of lenvatinib in combination with gemcitabine and oxaliplatin (Gemox) chemotherapy in the advanced ICC. Methods: Locally advanced or metastatic ICC patients (pts) were given lenvatinib 12 mg/day (body weight ≥60 kg) or 8 mg/day (body weight

e16144 Background: Pathological complete response (CR) and major pathological response (MPR) are associated with long-term survival after neoadjuvant/conversion surgery of HCC. The relationship between imaging and histopathological evaluations of response to combined TKI plus anti-PD-1 antibody treatment is unclear. Methods: This retrospective analysis included 23 patients with an initial diagnosis of unresectable HCC who underwent resection after combined TKI/anti-PD-1 antibody treatment between March 2019 and December 2020 at Zhongshan Hospital of Fudan University. MRI was performed before and after treatment and objective response rate (ORR; CR or partial response [PR]) was evaluated using RECIST 1.1 and mRECIST by investigator assessment (INV) and independent imaging review (IIR). Histopathological response was evaluated in resected tumor tissue using residual viable tumor (RVT; RVT area/total tumor bed surface area under 100X microscopy). MPR was defined as

304 Background: Combination therapy with anti-angiogenic agents plus anti-PD-1 antibodies has shown high anti-tumor activity in uHCC. However, predicting the efficacy of this combination therapy remains a challenge. Methods: This study included consecutive patients with uHCC who received lenvatinib (8 mg/d regardless of body weight) and an anti-PD-1 antibody as first-line systemic therapy between Sep 2018 and July 2020, and had at least one imaging evaluation. Tumor response was assessed every 2 months (± 2 week) by the investigators using modified RECIST criteria. Patients were evaluated as having a radiological response (complete or partial response) or non-radiological response (stable disease or progressive disease) at the best overall response evaluation. Serum tumor markers for HCC, including alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), were evaluated at baseline and 2-3 weeks after therapy was initiated and their association with radiological response were assessed. Patients with baseline AFP or PIVKA-II between the upper limit of normal and the maximum measuring range of the kit were evaluable for AFP decrease or PIVKA-II decrease. Results: A total of 76 patients were eligible for this study. Baseline AFP ≥400 ng/mL or PIVKA-II ≥400 mAU/mL was not associated with radiological response (P = 0.167 and P = 0.916, respectively). At 2-3 weeks after the initiation of therapy, 51 patients were evaluable for AFP decrease; 78.4% experienced a > 20% AFP decrease and 51.0% experienced a > 50% AFP decrease. Patients with a > 50% AFP decrease had a higher rate of radiological response than those with AFP increase or a ≤50% AFP decrease (73.1% vs 32.0%, P = 0.003). In 57 patients evaluable for PIVKA-II decrease, 50.9% and 35.1% experienced a > 20% and > 50% PIVKA-II decrease, respectively. Patients with a > 50% PIVKA-II decrease had a higher rate of radiological response than those with PIVKA-II increase or a ≤50% PIVKA-II decrease (85.0% vs 29.7%, P < 0.001). Both AFP decrease > 50% and PIVKA-II decrease > 50% predicted radiological response, with an area under receiver operating characteristic curve of 0.706 (95% CI, 0.560-0.852, P = 0.012) and 0.752 (95% CI, 0.621-0.883, P = 0.001), respectively. Furthermore, patients with a > 20% AFP or PIVKA-II increase from baseline had a lower rate of radiological response (0% vs 57.4%, P = 0.043; and 21.7% vs 69.7%, P < 0.001, respectively). Conclusions: A tumor marker decrease was seen in most patients as early as 2-3 weeks after the initiation of the combination therapy. Early on-treatment AFP or PIVKA-II decrease may serve as a predictor for objective response for patients with uHCC receiving combination anti-angiogenic and immune therapy.

281 Background: TACE and lenvatinib has each shown to prolong overall survival in patients with unresectable HCC, combination of which may also improve clinical outcomes and have been widely used in the real world accordingly. However, the optimal timing of adding on lenvatinb to TACE remains unclear. We are aiming to evaluate the efficacy and safety between two combination strategies. Methods: From Nov 2018 to Jun 2020, 79 consecutive patients had received a combination treatment of lenvatinib and TACE. Patients followed up for more than 2 months were included in this analysis. They were classified as early-combination group(add on lenvatinib before or after the first TACE ) and late-combination group(add on lenvatinib after at least two procedures of TACE ). Tumor response and progression-free survival (PFS,time from the first day of prescribing lenvatinib to progression or death) were assessed according to RECIST1.1 criteria. Liver function were also evaluated at baseline and every 2 months later. AEs were recorded during the combination treatment period according to CTCAE 5.0. Results: A total of 48 u-HCC patients was finally enrolled. Median follow-up in all patients was 9.3(5.3-14.3)months. Patients’ baseline characteristics were similar in two groups. For early-combination group(n=22)and late-combination group(n=26), the mean age was 65±9.7 and 61±11.6years(p=0.2);BCLC stage C HCC was 59% and 54%(p=0.89);and Child-Pugh A proportion was 81.8% and 77%(p=0.73) respectively. The objective response rate(ORR) was 22.9% in total 48 cases. There was no significant difference in response rate (18.2% vs 26.9%, P=0.51) or disease control rate (90.9% vs 92.3%, P=1.00). Median PFS was significantly longer in the early-combination group than that in late-combination group (14.5 vs 8.9 months; p=0.048). The safety profile was similar between two groups. Grade 3/4 adverse events were 3 (13.6%) and 2 cases(7.7%) respectively (P=0.65). Conclusions: This is to date the first real-world data of the combination timing of lenvatinib with TACE in u-HCC patients. Early-combination strategy may be a better option for the u-HCC patients with a longer mPFS.

280 Background: Lenvatinib has become available as first-line therapy in patients with unresectable hepatocellular carcinoma (u-HCC). Although 8mg or 12mg/day is the standard starting dose according to weight, the high rate of adverse events (AEs) leading to dose reduction often limits its application. Various dosing schedules are used clinically to alleviate toxicities in practice. This study evaluated the safety and antitumor activity of two dosing strategies for lenvatinib administrations. Methods: Patients administered lenvatinib for u-HCC between April 2018 and July 2019 were enrolled. The dose-escalation strategy was conducted as follow, starting dose 4mg/day orally with biweekly escalation (As common AE always occurred within 2 weeks after administered), per 4 mg increment, to 8 or 12mg finally per body weight if no significant drug-related (no more than G2) adverse events occurred. Patients with a standard-dose strategy (8/12mg/day orally per body weight) were also included for comparison.Objective response rate(ORR) and progression-free survival (PFS) were assessed according to RECIST1.1 criteria. Dose-reduction rate was recorded and treatment-related adverse events (TRAE) was evaluated according to the CTCAE 5.0. Results: Totally 56 patients were included (37 in dose-escalation group and 19 in standard-dose group). The mean weight was 64.79±1.66 kg in dose-escalation group and 58.76±2.45 kg in standard-dose group, BCLC stage C proportion was 51.4% and 63.2%, Child-pugh B proportion was 16.2% and 5.3% respectively. Baseline demographic parameters were comparable between two groups (P>0.05). There was no significant difference in response rate (32.43% vs 42.1%, P=0.335), disease control rate (86.4% vs 84.2%, P=0.686) and PFS (P=0.631). The proportion of patients who reached the full dose (per weight) was also similar (48.6% vs 63.2%, p=0.399). Dose reduction rate was significantly higher in standard-dose group than dose-escalation group (36.8%vs 13.5%,p=0.044). Although, no difference in grade 3/4 adverse events was found between two groups (P=0.083), patients in standard-dose group(36.8%,7/19) have a higher incidence trend of G3/4 AEs than those of dose-escalation group(16.2%,6/37). Conclusions: The dose-escalation strategy may be an alternative approach to prolong lenvatinib treatment period, with comparable efficacy and more tolerance. More data are needed to confirm the long-term efficacy and safety of the dose-escalation strategy.

AIM Accumulating evidence suggests platelets play critical roles in tumor metastasis. Moreover, the role of platelets in metastasis is partially correlated with inflammation. However, evidence regarding the contribution of platelets to hepatocellular carcinoma (HCC) metastasis is lacking. This study investigated the association between platelets and metastatic risk in HCC. METHODS We used huge HCC (diameter over 10 cm), a tumor subgroup with a strong inflammatory background, as a model to evaluate the potential predictive role of platelets and platelet-related biomarkers for metastasis in HCC patients undergoing transarterial chemoembolization. A logistic regression model was used to analyze risk factors for metastasis. RESULTS Patients with huge HCC (n = 178) were enrolled, and 24.7% (44/178) of patients had remote metastases after treatment. Univariate analyses showed high platelet counts (P = 0.012), pretreatment platelet-to-lymphocyte ratios (pre-PLR) of 100 or more (P = 0.018) and post-PLR of 100 or more (P = 0.013) were potential risk factors for metastasis. Furthermore, multivariate analyses showed high platelet counts (odds ratio, 2.18; 95% confidence interval, 1.074-4.443; P = 0.031) and platelet-related biomarkers were independent risk factors for HCC metastasis. Particularly, the risk of metastasis in patients with high post-PLR values was significantly greater than patients with low post-PLR values. For tumor response and survival, patients with high platelet counts had faster disease progression (P = 0.002) and worse survival (P

e16654 Background: Lenvatinib (LEN) has been used in clinical practice because of its high response rate since administrated in China. However, no recommendation is available as second-line agents after LEN treatment. The combination therapy of anti-programmed death-1(PD1) antibodies with LEN have demonstrated promising clinical efficacy in advanced HCC. Some patients were used this combination treatment after progressed on LEN in real world settings in China. Preclinical studies also showed the immune-moderate effects of LEN. This study was retrospectively analyzed the efficacy and safety of 26 unresectable HCC patients treated with LEN and anti-PD1 antibody after progressed on LEN. Methods: Unresectable HCC (uHCC) patients who treated with the combination of LEN with anti-PD1 antibody after progressed on LEN were enrolled. Patients who combine other loco-treatment and systemic therapy during the LEN combination with PD-1 antibody treatment period were excluded. The efficacy of LEN and anti-PD1 antibody was evaluated by mRECIST criteria after 2 cycles of combination treatment. AE data were recorded during the combination treatment period. Results: From October 2018 to October 2019, 26 patients were finally enrolled. As of January 10, 2020, median follow-up was 6.7±3.19 months. Median age was 56.15±11.9 years old, 80.77% (21/26) was Child-pugh(CP) A while 19.23% (5/26) was CPB7 and 88.5% (23/26) was BCLC stage C. Before combination therapy, 11 patients (42.31%) used LEN only and the other 15 patients (57.69%) were experienced sorafenib/chemotherapy before LEN. Drugs of PD1 antibodies were Keytruda and Toripalimab. The median duration of combination treatment was 6.7±3.15months. The ORR was 26.9% in total 26 cases. 2 cases of them were complete response, and the disease control rate (DCR) was 88.5% (23/26). The most common adverse events (AEs) of combination treatment were hypertension (42.31%), diarrhea (38.46%), hypothyroidism (38.46%) and anorexia (34.62%). Grade 3 or higher AEs occurred in 6 (23.08%) patients. Conclusions: This was the first real-world data of sequential therapy of LEN combination with anti-PD1 followed LEN in uHCC patients. For advanced patients who have progressed after LEN treatment, the results were promising, showing high DCR and well tolerated. 2 cases even achieve complete response. Sequential therapy may be an option for these patients. The efficacy of combination treatment needs random clinical trial to be further studied.

e16690 Background: Combination of tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody showed a high tumor response for advanced hepatocellular carcinoma (HCC). We are aiming to study the effect of combination therapy followed by resection in pts with initially unresectable HCC. Methods: 60 consecutive pts with unresectable or advanced HCC were treated with combination therapy as first-line treatment, including 2 in BCLC-A (China Liver Cancer stage [CNLC]-Ib), and 13 in BCLC-B (CNLC-IIa and IIb), 26 in BCLC-C (vascular invasion, CNLC-IIIa) and 19 in BCLC-C (extrahepatic metastasis, CNLC-IIIb). Tumor response and resectability were evaluated by imaging every 2 months (± 1 week). The criteria of resectability included: (1) R0 resection can be achieved; (2) remnant liver volume ≥ 40%; (3) Child-Pugh score is 5; (4) no contra-indications for hepatectomy. Results: Conversion to resectable HCC was identified in 11 (18.3%) pts after combination therapy. Of them, 2 pts are still under treatment for immune-related adverse events, and 9 underwent hepatectomy as of January 2020. Of the 9 pts, the initial tumor was unresectable because of macro-vascular invasion (n = 6, 1 Vp3, 3 Vp4, 1 hepatic vein, 1 inferior vena cava), extrahepatic metastasis (n = 1, right adrenal gland), tumor nodules ≥ 4 (n = 1) and recurrent HCC within 2 months after first resection (n = 1). The TKIs used were lenvatinib (n = 6) and apatinib (n = 3); anti-PD-1 antibodies used were pembrolizumab (n = 4), sintilimab (n = 3), camrelizumab (n = 1) and nivolumab (n = 1). The median interval between start of combination therapy and resection was 99 days (range, 73–251). The median post-operative hospital stay was 14 days (range, 11–68). The prevalence of post-hepatectomy liver dysfunction (the criteria by ISGLS) is 5 (55.6%) pts, and the post-operative complications (by Clavien–Dindo classification) occurred in 4 (44.4%) pts, including grade I in 1, grade IIIa in 2, and grade V in 1 (died from immune-related adverse events). Tumor response (RECIST v1.1) evaluated before surgery were PR (n = 5), SD (n = 3), and PD (n = 1). Pathological CR (pCR) was found in 5 (55.6%) cases. After a median follow up of 72 days (range, 11–184), tumor recurrence were diagnosed in 1 patient, and mortality without tumor recurrence in 1 patient, the other 7 cases remained tumor-free. Conclusions: This is to date the largest cohort of pts underwent R0 resection after combination therapy for initially un-resectable HCC. The combination of a TKI and anti-PD-1 antibody is feasible as a conversion therapy.

e16610 Background: Combination therapy of anti-angiogenic therapy and anti-PD-1 antibody had shown promising anti-tumor effects for advanced hepatocellular carcinoma (HCC) in clinical trials. Here we report the effectiveness and safety of the combination therapy of lenvatinib and anti-PD-1 antibodies in a cohort of unresectable or advanced HCC pts. Methods: From Sep 2018 to Jan 2020, 77 consecutive pts received a combination treatment of lenvatinib and an anti-PD-1 antibody. Lenvatinib was given 8 mg/d regardless of patient body weight and anti-PD-1 antibody was used either q2wk (nivolumab or camrelizumab) or q3wk (pembrolizumab, sintilimab or toripalimab). pts who completed at least one efficacy and safety assessment were eligible for this study. Tumor response were evaluated with abdominal contrast-enhanced MRI/CT and/or chest CT every 2 mo (± 1 wk). Laboratory tests were monitored every 2-3 wk. Results: 59 pts were eligible for this study. Of them, 1 (1.7%) were BCLC stage A, 10 (16.9%) were BCLC stage B, 48 (81.4%) were BCLC stage C (including 20 pts in China Liver Cancer [CNLC] stage IIIa and 28 in CNLC stage IIIb). 43 (72.9%) pts were treated as first-line therapy. The table below shows efficacy results. R0 resection was performed in 6 (10.2%) pts due to tumor regression. By the data cut-off date, 13 pts died, and mOS was not mature. Overall, the combination treatment was well tolerated. 28 (47.5%) pts had at least one ≥ grade 3 treatment-emergent adverse event. 3 (5.1%) pts died from immune-related adverse events, 2 of them died from immune-related adverse events after hepatectomy. Conclusions: The combination of lenvatinib + anti-PD-1 antibody is effective and well-tolerated in pts with HCC as first-line or second-line treatment. It is also noted that initially unresectable HCC may be converted to resectable HCC following this combination treatment. [Table: see text]

Inflammation plays a critical role in tumor metastasis. However, few inflammation-related biomarkers are currently available to predict the risk of metastasis for advanced hepatocellular carcinoma (HCC). Using huge tumors (diameter >10 cm) as a model, we evaluated the potential risk of pre- and post-treatment inflammatory responses in the development of metastasis of HCC patients undergoing transarterial chemoembolization (TACE). A logistic regression model was used to analyze the risk factors. One hundred and sixty-five patients with huge HCC were enrolled in the study. Metastases were identified in 25.5 % (42/165) patients by imaging evaluation post-TACE. Neutrophils increased, whereas lymphocytes decreased significantly post-TACE. Univariate analysis showed that high post-treatment neutrophil-to-lymphocyte ratio (NLR; p = 0.003), low post-treatment lymphocyte count (p = 0.047), and high baseline NLR (p = 0.100) were potential risk factors for metastasis. Further, multivariate analysis showed that high post-treatment NLR, but not pre-treatment NLR, was an independent risk factor for metastasis; this was confirmed by receiver operating characteristic curve analysis. Post-treatment NLR, however, had no correlation to tumor response and overall survival of patients. In conclusion, post-treatment NLR but not pre-treatment NLR independently increases the risk of metastasis in huge HCC. Our findings suggest the potential contribution of treatment-related inflammation to metastasis in advanced HCC.

Gender disparity is well known in hepatocellular carcinoma (HCC). SRY is a critical sex-determination gene involved in embryonic development. The potential relevance of SRY to HCC progression was evaluated. SRY expression in HCC cell lines and tissues was evaluated. Invasion and wound healing assays were used to evaluate the role of SRY in HCC cell migration. The prognostic value of SRY for HCC patient survival was evaluated. SRY was highly expressed in HCC cell lines and tumor tissues. Downregulation of SRY expression decreased migration and invasion potential of HCC cells. High SRY levels correlated with poor HCC patient survival. Additionally, neither spatial position nor expression intensity of SRY was correlated with HCC gender disparity. High levels of SRY expression correlated with cancer progression and poor HCC patient survival. However, high SRY levels are not significantly correlated with HCC sex bias.

Serum γ-glutamyltranspeptidase (GGT) level, which is often elevated in hepatocellular carcinoma (HCC), has now been found to be an oxidative stress marker which correlates with inflammation in the extracellular hepatic microenvironment. The aim of this study was to investigate the prognostic significance of GGT serum levels in patients undergoing radiofrequency ablation (RFA) therapy for the treatment of HCC. This retrospective study included 254 patients with small liver cancer (tumor of ≤5 cm in diameter and nodule of ≤3 cm) who had been treated with RFA. Baseline serum GGT was examined before therapy, and overall survival (OS) and recurrence-free survival were evaluated by the Kaplan–Meier method. Univariate and multivariate analyses were used to analyze the significance of GGT and other serum markers as prognostic factors. After a median follow-up of 27 months, 51 patients had died and 123 had hepatic recurrence. After treatment with RFA, HCC patients with elevated GGT had a shorter OS versus those with normal GGT level (p = 0.001); they also had higher recurrence (p = 0.001). On multivariate analysis, albumin (p = 0.003), GGT (p = 0.035), and tumor size (p = 0.027) were independent risk factors for survival, and GGT (p = 0.010) and tumor size (p = 0.026) were significant risk factors for recurrence. Serum GGT is a convenient prognostic biomarker related to OS and recurrence in HCC patients undergoing RFA treatment.

To evaluate whether elastic (stiffness) characteristics of tumours were associated with treatment responses and survival of patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolisation (TACE).A retrospective cohort study of 59 HCC patients with unresectable HCC who underwent TACE was undertaken. Acoustic radiation force impulse imaging (ARFI) was used to measure tissue stiffness of the index tumours and non-tumoural liver before TACE treatment. The correlation between the parameters of tumour stiffness and treatment response to TACE was assessed using mRECIST criteria as well as according to patient survival.Tumour stiffness and its stiffness difference between tumour and non-tumoural liver were significantly associated with tumour response to TACE (p=0.019 and 0.010, respectively). Patients with tumour stiffness of2 m/s or stiffness difference between tumour and non-tumoural liver of0.5 were more likely to have treatment response to TACE. Univariate analysis showed that the difference in stiffness between tumour and non-tumoural livers (p=0.039) was one of the significant predictors of overall survival (OS). In multivariate analysis, alpha-fetoprotein (AFP) (p=0.006) and Barcelona Clinic Liver Cancer (BCLC) stage (p=0.017) were identified as independent predictors of survival.Tumour stiffness characteristics might be an added predictive marker of treatment response to TACE in patients with HCC.

Accumulating evidence suggests platelets play critical roles in tumor metastasis. Moreover, the role of platelets in metastasis is partially correlated with inflammation. However, evidence regarding the contribution of platelets to hepatocellular carcinoma (HCC) metastasis is lacking. This study investigated the association between platelets and metastatic risk in HCC.We used huge HCC (diameter over 10 cm), a tumor subgroup with a strong inflammatory background, as a model to evaluate the potential predictive role of platelets and platelet-related biomarkers for metastasis in HCC patients undergoing transarterial chemoembolization. A logistic regression model was used to analyze risk factors for metastasis.Patients with huge HCC (n = 178) were enrolled, and 24.7% (44/178) of patients had remote metastases after treatment. Univariate analyses showed high platelet counts (P = 0.012), pretreatment platelet-to-lymphocyte ratios (pre-PLR) of 100 or more (P = 0.018) and post-PLR of 100 or more (P = 0.013) were potential risk factors for metastasis. Furthermore, multivariate analyses showed high platelet counts (odds ratio, 2.18; 95% confidence interval, 1.074-4.443; P = 0.031) and platelet-related biomarkers were independent risk factors for HCC metastasis. Particularly, the risk of metastasis in patients with high post-PLR values was significantly greater than patients with low post-PLR values. For tumor response and survival, patients with high platelet counts had faster disease progression (P = 0.002) and worse survival (P 0.0001).High platelet counts increase the extrahepatic metastasis risk of huge HCC undergoing chemoembolization, which supply clinical verification of the association between high platelet counts and HCC metastasis.

Patients with huge hepatocellular carcinoma >10 cm in diameter represent a special subgroup for treatment. To date, there are few data and little consensus on treatment strategies for huge hepatocellular carcinoma. In this study, we summarized the effects and safety of transarterial chemoembolization for huge hepatocellular carcinoma. A retrospective study was performed based on a large cohort of patients (n = 511) with huge hepatocellular carcinoma who underwent serial transarterial chemoembolization between January 2008 to December 2011 and were followed up until March 2013. We found median survival time was 6.5 months. On multivariate analysis, Child-Pugh class (A versus B) (p < 0.0001), alpha-fetoprotein (≤400 µg/L) (p = 0.002), Barcelona Clinic Liver Cancer stage (B versus C) (p = 0.013), and other treatments after transarterial chemoembolization such as surgical resection (p = 0.008), radiation (p = 0.018), and local radiofrequency ablation (p = 0.002) were factors significantly associated with better overall patient survival after chemoembolization. Twenty-nine percent of these patients showed a tumor response after serial transarterial chemoembolization. Severe complications were few (4.9%), including oncolytic syndrome (n = 3), tumor rupture (n = 3), gastrointestinal bleeding (n = 4), deep venous thrombosis (n = 3), acute cholecystitis (n = 4), femoral artery pseudoaneurysm (n = 1), acute pancreatitis (n = 1), and acute hepatic failure (n = 6). In conclusion, transarterial chemoembolization is a safe and effective treatment for selected patients with huge hepatocellular carcinoma and is recommended as a component of combination therapy. In addition, patients with good liver function and low alpha-fetoprotein levels may acquire greater survival benefits from transarterial chemoembolization.

Radiofrequency ablation (RFA) is a first-line option for the treatment of small liver cancers, but the recurrence remains a problem affecting long-term survival. Hepatitis B virus (HBV) activity is associated with the prognosis of hepatocellular carcinoma (HCC). We investigated the significance of hepatitis B surface antigen (HBsAg) in HCC recurrence after curative RFA treatment in HBV-related small HCC. We enrolled 404 HBV-related patients with small HCC (≤3 cm) who underwent curative RFA. We used univariate and multivariate analyses to investigate the baseline levels of HBsAg, in addition to other known risk factors for HCC recurrence, for association with HCC tumor recurrence after curative RFA. The overall 1-, 2-, and 3-year recurrence-free survival (RFS) rates were 75%, 50%, and 34%, respectively. The median recurrence-free time was 25 months. The level of HBsAg was an independent risk factor for recurrence in patients with lower HBV-DNA levels. In hepatitis Be antigen (HBeAg)-negative patients, the 1-, 2-, and 3-year RFS rates were 79%, 64%, and 44%, respectively, for that with low HBsAg levels, compared with 73%, 50%, and 37%, respectively, for that with high HBsAg levels (P = .039). HBsAg might serve as a valuable marker to evaluate the risk of HCC recurrence in HBeAg-negative patients with low HBV viral load.

Inflammation is particularly strong in huge hepatocellular carcinoma (HCC). However, it is unclear whether the platelet-to-lymphocyte ratio (PLR), as an inflammatory-related marker, can predict survival of patients with huge HCC. In this study, we enrolled 291 patients with huge HCC (diameter over 10 cm) who were undergoing repeated transarterial chemoembolization (TACE) at our institute. The baseline PLR was calculated from complete serum blood counts before the first chemoembolization. We found that a baseline PLR cutoff value over 150 best predicted huge HCC survival. The 12, 24, and 36 months survival rates in the high PLR group (22.6, 8.1, and 4.1 %, respectively) were significantly lower than in the low PLR group (35.6, 22.4, and 14 %, respectively). Thus, a significant difference was found in overall survival (log–rank test, p

The homeobox gene, goosecoid (GSC), is a transcription factor that participates in cell migration during embryonic development. Because cell migration during development has characteristics similar to cell invasion during metastasis, we evaluated the potential role of GSC in the metastasis of hepatocellular carcinoma (HCC). GSC expression in HCC cell lines and tissues was evaluated, and its effects on the migration potential of HCC cells were determined by GSC knock-down and overexpression methods. In addition, the prognostic role of GSC expression in the metastasis of cancer cells in HCC patients was determined. Our data showed that GSC was highly expressed in several HCC cell lines, particularly in a highly metastatic HCC cell line. Overexpression of GSC promoted cell migration and invasion of HCC cells in vitro. Gain-of-function induced the epithelial-mesenchymal transition but not collective cell migration, whereas loss-of-function induced the reverse change. High-level expression of GSC correlated closely with poor survival and lung metastasis in HCC patients; lung metastases showed more upregulated GSC expression than the primary tumor. We conclude that GSC promotes metastasis of HCC potentially through initiating the epithelial-mesenchymal transition. GSC is also a prognostic factor for poor survival and metastasis of HCC, which suggests its potential as a therapeutic target for metastatic HCC.

The aim of this study was to evaluate the therapeutic efficacy and to determine the prognostic factors of TACE in patients with colorectal liver metastases (CRLM).The clinical data of 183 patients with unresectable CRLM treated with TACE from Jan. 2002 to Dec. 2008 were retrospectively reviewed. Log-rank method was used for univariate analysis and Cox proportional hazard model was used for multivariate analysis of the prognostic factors.The median survival time was 22 months, and the 0.5-, 1-, 2-, 3-, 5-year survival rates were 93.9%, 81.1%, 39.8%, 18.2%, and 3.9%, respectively. Multivariate analysis showed that tumor involved more than one lobe of the liver, and elevated CEA and CA19-9 levels were independent risk factors for the overall survival (P0.01). Females, more times of TACE, combination with regional therapy and received phase II resection were related with a good survival (P0.01) in CRLM patients after TACE treatment.Transcatheter arterial chemoembolization is an effective therapy for unresectable colorectal liver metastases. Patients with tumor spread more than one lobe of the liver, high CEA and CA19-9 levels are independent poor prognostic factors. Females, patients received more times of TACE, combined with regional therapy and received phase II resection may have a good survival.

Alpha-fetoprotein (AFP) has been used as a diagnostic biomarker for hepatocellular carcinoma (HCC), but its prognostic significance is not well defined. This study was performed to classify the prognostic significance of AFP status in HCC patients after transarterial chemoembolization (TACE).Four hundred forty-one HCC patients from a prospective maintained database with pathologic confirmation including 139 with normal AFP levels and 302 with elevated AFP levels were retrospectively studied for prognostic significance of AFP in treatment response and survival after TACE. Univariate and multivariate analyses were used to identify the prognostic factors.There were significant differences in overall survival (OS) after TACE between AFP-negative and AFP-positive HCC patients when the AFP cutoff value was defined as 20 ng/ml (P0.0001). Among the AFP-positive patients, different AFP levels had no significantly prognostic effects on OS after TACE (P = 0.093). Multivariate analysis revealed that AFP status for AFP-negative or positive was an independent prognostic factor for HCC patients after TACE (P = 0.001), along with γ-glutamyltransferase (GGT) level (P = 0.004) and tumor diameter (P0.0001). In addition, there were significant differences in clinicopathologic features between AFP-positive and AFP-negative patients with regard to age, gender, alanine transferase level, GGT level, tumor diameter, and Barcelona Clinic Liver Cancer stage.Compared with AFP-positive HCC patients, patients with AFP-negative status have a better treatment response and prognosis after TACE.

Systemic chemotherapy would suppress the immune system and cause reactivation of hepatitis B virus (HBV) in the tumor patients with HBV infection, which seriously affect the prognosis. Our study was to investigate the effect of transcatheter arterial chemoembolization (TACE) on HBV DNA level in primary liver cancer patients, and explore related factors.Clinical data of 162 patients with primary liver cancer who underwent TACE from December 2004 to July 2008 were analyzed. All patients' HBV DNA level, alpha-fetoprotein (AFP) and liver function before and after TACE were evaluated. Correlation of HBV DNA alteration to AFP was analyzed.The positive rate of HBV DNA was decreased significantly after TACE (55.6% vs. 71.6%, P0.01). HBV DNA level was inclined to decrease after TACE in the patients with HBV DNA ofor =1 x 10(5)/mL (odds ratio = 2.7, P0.01). The decrease of HBV DNA was also related with the decrease of AFP level (odds ratio = 2.6,P0.05).TACE can decrease HBV DNA level in primary liver cancer patients, especially for those with preoperative HBV DNA level ofor =1 x 10(5)/mL and those with postoperative AFP decline.

To evaluate the efficacy of radiofrequency ablation for the treatment of postoperative recurrence of hepatocellular carcinoma and whether radiofrequency ablation can be used as first line treatment for recurrent hepatocellular carcinoma.There were 213 patients with small recurrent hepatocellular carcinoma (tumor size of 3 cm or less and no more than 3 nodules) who treated in Liver Cancer Institute, Fudan University from January 2000 to December 2005. Among these patients 68 were treated with radiofrequency ablation and 145 were treated with repeated surgical resection. Kaplan-Meier method was used to evaluate the overall survival or disease free survival. Log-rank used to determine the survival difference between groups and COX proportional hazard was used for multivariate analysis to evaluate the risk factors for prognosis. The overall survival or disease free survival was calculated from the time treated with radiofrequency or repeated surgical resection.The 1-, 3-, 5-years overall survival rates were 94.7%, 65.1%, 37.3% and 88.1%, 62.6%, 41.0% in radiofrequency ablation group and surgical repeated resection group, respectively. There was no significant difference between two groups (P = 0.693). However, the disease free survival was better in repeated surgical resection than in radiofrequency ablation, which were 79.4%, 48.1%, 34.4% and 58.0%, 27.8%, 12.4% in repeated surgical resection and radiofrequency ablation, respectively (P = 0.001). The interval between recurrence and initial hepatectomy with more than 2 years was independent factor favor to good prognosis.Radiofrequency ablation seems to be as effective as repeated surgical resection owing to comparable overall survival and can be considered as alternative therapy for surgical resection treatment of small recurrent hepatocellular carcinoma.

AIM: To investigate transarterial chemoembolization (TACE) with hepatic infusion of oxaliplatin and 5-fluorouracil and Lipiodol chemoembolization in large hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 132 patients with unresectable HCCs larger than 10 cm were treated with hepatic infusion of oxaliplatin and 5-fluorouracil followed by Lipiodol chemoembolization. The primary endpoint was overall survival (OS). Sixteen-week disease-control rate, time to progression (TTP), and major complications were also studied. Univariate and multivariate analyses were performed to identify prognostic factors affecting OS and TTP. RESULTS: A total of 319 procedures were performed in the 132 patients. Eleven (8.3%) patients received radical resection following TACE treatment (median time to initial TACE 4.3 ± 2.3 mo). The median OS and TTP were 10.3 and 3.0 mo respectively, with a 50.0% 16-wk disease-control rate. Major complications were encountered in 6.0% (8/132) of patients following TACE and included serious jaundice in 1.5% (2/132) patients, aleukia in 1.5% (2/132), and hepatic failure in 3.0% (4/132). One patient died within one month due to serious hepatic failure and severe sepsis after receiving the second TACE. The risk factor associated with TTP was baseline alpha-fetoprotein level, and vascular invasion was an independent factor related to OS. CONCLUSION: Hepatic infusion of oxaliplatin and 5-fluorouracil followed by lipiodolized-chemoembolization is a safe and promising treatment for patients with HCCs larger than 10 cm in diameter.

To investigate the effect of transcatheter hepatic arterial chemoembolization (TACE) therapy on the survival and prognosis of recurrent hepatocellular carcinoma (HCC) after surgical resection.The data of 130 surgically resected but recurrent HCC patients treated by TACE were reviewed retrospectively. The survival and influencing factors on the prognosis were analyzed.The overall 1-, 3-, 5-year survival rates of these 130 patients were 83.0%, 45.5% and 17.6% respectively (median survival time 2.4 years). Ninty-four of the series were treated with TACE alone, which gave the 1-, 3- year survival rates of 76.4% and 37.1%, respectively (median survival time 2.1 years). Thirty-six out of 130 patients treated with TACE plus percutaneous ethanol injection (PEI), the 1-, 3-year survival rates were 100.0% and 66.5% respectively with a median survival time (MST) of 3.5 years. The survival of TACE plus PEI group was significantly better, and the mortality risk was significantly lower than that of TACE alone group (P0.05). The mortality risk of those with5 cm diameter recurrent tumor or with distant metastasis was significantly higher than those withor = 5 cm diameter tumor or without metastasis (P0.05).TACE combined with PEI may improve the survival of recurrent HCC patients.

To study the clinical safety and effect on local recurrence in unresectable small hepatocellular carcinoma treated by radiofrequency ablation (RFA) with and without chemotherapy through a prospective randomized trial.Thirty-eight unresectable small hepatocellular carcinoma patients with diameter/= 3 cm were selected, of which 27 patients have been followed up for 1 year. Through a prospective randomized trial, 12 patients were in the RFA group and 15 patients in the RFA combined with systemic chemotherapy group. RFA was given image-guided. The regimen of systemic chemotherapy: EADM 50 mg on day 1, 3; CDDP 40 mg on day 1, 3 and FUDR 500 mg on day 1, 2, 3. After RFA treatment, liver function, WBC count and complications were observed on day 1, 4, 7; CT scan was performed in 1, 6, 12 months. The safety and local recurrence were analyzed.There was no local recurrence of the tumor in the two groups 1 month after RFA treatment. The 6- and 12-month local recurrence rates were significantly lower in the combined group than that in RFA group alone (P0.01). There were no severe complications in the two groups, and nor was there any significant difference in liver function and WBC count.RFA combined with systemic chemotherapy is safe, and it can reduce the local recurrence of unresectable small hepatocellular carcinoma/= 3 cm in diameter.

As a new technique of local therapy for liver cancer, radiofrequency ablation (RFA) was widely used these years in China. This study was to evaluate the treatment efficacy of RFA on primary liver cancer (PLC), identify the risk factors of recurrence, and determine the indications of RFA for PLC.Records of 94 primary small liver cancer patients underwent a single session of percutaneous RFA in Liver Cancer Institute/Zhongshan Hospital from Jan. 2001 to Dec. 2003 were reviewed retrospectively. Data analyses were performed using SPSS for windows Ver. 11.5 software.With a median follow-up of 16 months affer RFA treatment, the cumulative survival rate of 94 patients was 85.5% at 1 year, and 75.6% at 2 years. The cumulative recurrence-free survival rate was 31.3% at 1 year, and 10.4% at 2 years. The total recurrence rate was 66.0% (62/94). Log-rank test revealed that tumor with diameter of3 cm (P0.05), proximity to intrahepatic vessels (P0.01), and subcapsular location (P0.05) were related to tumor recurrence,while gender, Child-pugh class, alpha fetoprotein (AFP) concentration, and combination therapy with percutaneous ethanol injection were not related to tumor recurrence. Cox regression analysis indicated that tumor proximity to intrahepatic vessels (95%CI, 2.102-7.899; P=0.000), and subcapsular location (95%CI, 1.672-6.289; P=0.001)were associated independently with recurrence after RFA treatment. Severe complications occurred in 2 cases (2.1%), including 1 case of bile duct hemorrhage, 1 case of sub-diaphragm effusion. No RFA related death and other severe complications occurred.RFA appears to be a safe treatment for liver cancer. Patients with tumor diameter ofor= 3 cm, no proximity to intrahepatic vessels, and subcapsular location may be the most suitable candidates for RFA.

The neutrophil-to-lymphocyte ratio (NLR) is a useful biomarker that reflects systemic inflammation responses. However, the prognostic value of the NLR in patients with primary liver cancer (PLC) remains controversial. We performed a meta-analysis of 26 studies (comprising 4,461 patients) to evaluate the association between the pre-treatment NLR and clinical outcomes of overall survival (OS) and disease-free survival (DFS) in patients with PLC. The correlation between NLR and tumor characteristics or other inflammation-related parameters was also assessed. Data were synthesized using the random-effects model of DerSimonian and Laird, and the hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was used to estimate effect size. Our analysis indicated that a high NLR predicted poor OS (HR, 2.102; 95% CI: 1.741-2.538) and DFS (HR, 2.474; 95% CI: 1.855-3.300) for PLC. A high NLR was associated with the presence of tumor vascular invasion (OR: 1.889, 95% CI: 1.487-2.400; p

AIM: To study the immunoprotective effect of liver cancer vaccine with co-transfected IL-2 and B7-1 genes on hepatocarcinogenesis in mice. METHODS: The murine liver cancer cell line Hepal-6 was transfected with IL-2 and/or B7-1 gene via recombinant adenoviral vectors and the liver cancer vaccines were prepared. C57BL/6 mice were immunized with these vaccines and challenged with the parental Hepal-6 cells afterwards. The immunoprotection was investigated and the reactive T cell line was assayed. RESULTS: The immunoprotection of the tumor vaccine was demonstrated. The effect of IL-2 and B7-1 genes co-transfected Hepal-6 liver cancer vaccine (Hep6-IL2/B7 vaccine) on the onset of tumor formation was the strongest. When attacked with wild Hepal-6 cells, the median survival period of the mice immunized with Hep6-IL2/B7 vaccine was the longest (68 d, χ2 = 7.70-11.69, P < 0.05) and the implanted tumor was the smallest (z = 3.20-44.10, P < 0.05). The effect of single IL-2 or B7-1 gene-transfected vaccine was next to the IL2/B7 gene co-transfected group, and the mean survival periods were 59 and 54 d, respectively. The mean survival periods of wild or enhanced green fluorescence protein gene modified vaccine immunized group were 51 and 48 d, respectively. The mice in control group all died within 38 d and the implanted tumor was the largest (z = 3.20-40.21, P < 0.05). The cellular immunofunction test and cytotoxicity study showed that the natural killer (NK) cell, lymphokine activated killer (LAK) cell and cytotoxic T lymphocyte (CTL) activities were significantly increased in mice immunized with the Hep6-IL2/B7 vaccine, (29.5% ± 2.5%, 65.0% ± 2.9%, 83.1% ± 1.5% respectively, compared with other groups, P < 0.05). CONCLUSION: The Hep6-IL2/B7 liver cancer vaccines can induce the mice to produce activated and specific CTL against the parental tumor cells, and demonstrate stronger effect on the hepatocarcinogenesis than single gene modified or the regular tumor vaccine. Therefore, the vaccines may become a novel potential therapy for recurrence and metastasis of HCC.