bluuebunny/crossref_metadata_2025_split huggingface dataset:
A real-world study of TACE combined with regorafenib as a second-line treatment for advanced hepatocellular carcinoma.
Authors: Liu Shaoxing , Gao Song , Guo Jianhai , Kou Fuxin , Zhang Xin , Liu Baojiang , Feng Aiwei , Wang Xiaodong , Chen Hui , Zhu Xu 
Published: June 2023

e16144 Background: Regorafenib is a guideline-recommended second-line systemic drug, and its combination with transarterial chemoembolization (TACE) for the treatment of advanced liver cancer after first-line therapy has been gradually recognized by clinicians. We investigated the efficacy and safety of TACE combined with regorafenib with or without anti-PD-1 immunotherapy as a second line choice for advanced hepatocellular carcinoma (HCC). Methods: In this retrospective study, we retrieved patients with advanced liver cancer who had failed first-line therapy in our center from January 2019 to December 2021, and screened out patients who received TACE combined with regorafenib as second-line therapy. The data of objective response rate (ORR), progression-free survival (PFS) and adverse reactions (ARs) of treatment in these patients were analyzed and summarized. Subgroup analysis of patients with and without PD-1 inhibitors was also performed. Results: A total of 43 eligible patients were screened and treated with TACE in combination with regorafenib in second-line therapy, including 29 patients treated with PD-1 inhibitors. In all patients, one patient had complete response (CR) and 11 patients had partial response (PR), with ORR of 27.91% (12/43) and 24 patients had stable disease (SD), with disease control rate (DCR) of 83.72% (36/43). The median PFS was 10.0 months for all patients in survival follow-up, with PFS rates of 77.65% and 37.17% at 6 and 12 months follow-ups, respectively. Overall survival (OS) rates were 90.49%, 67.03%, and 58.65% at 12, 18, and 24 months, respectively. In subgroup analysis, there was no statistical difference in median PFS between the groups with or without PD-1 inhibitors (11.0 months vs 8.0 months, p=0.229), but there was a trend toward survival benefit in the combined group (hazard ratio/HR 0.62). The incidence of treatment-related ARs in all treated patients was 81.40% (35/43), all grade 1-2. Among ARs, hand-foot syndrome (27.91%), loss of appetite (20.93%), and elevated transaminases (16.28%) were predominant. Conclusions: This study verified the efficacy and safety of TACE combined with regorafenib as second-line therapy for the treatment of advanced HCC after failure of first-line therapy, and the results need to be further justified in future prospective studies with larger sample sizes. [Table: see text]
Hepatic arterial infusion chemotherapy (HAIC) combined with tislelizumab and lenvatinib for advanced hepatocellular carcinoma (aHCC) with Vp3-4 portal vein tumor thrombosis (PVTT): A single-arm, phase II study.
Authors: Xu Yongkang , Fu Shumin , Mao Ye , Huang Shenglan , Li Dan , Wu Jianbing 
Published: June 2023

e16145 Background: aHCC patients (pts) with Vp3-4 PVTT have a poor prognosis. HAIC combined with immune checkpoint inhibitors and targeted therapies has shown local control and survival benefits in aHCC. However, the optimal combination in aHCC pts with Vp3-4 PVTT remains unclear. Here, we reported the preliminary efficacy and safety of HAIC combined with tislelizumab and lenvatinib in this population. Methods: In this ongoing, single-site, prospective, single-arm, phase II study, eligible pts were aged ≥18 years, histologically confirmed aHCC, ECOG PS ≤1, Child-Pugh A/B, and had at least 1 measurable lesion per RECIST 1.1. Pts received HAIC with modified FOLFOX (oxaliplatin, 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1; and 5-fluorouracil infusion 2400 mg/m2 for 46 h), combined with lenvatinib (8 or 12 mg QD for body weight <60 or ≥60 kg) and tislelizumab (200mg Q3W). HAIC was conducted repeatedly on demand. The primary endpoint was the objective response rate (ORR) per RECIST 1.1. Secondary endpoints included the ORR per mRECIST, disease control rate (DCR), surgical conversion rate, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Results: From June 2021 to January 2023, 27 aHCC pts with Vp3-4 PVTT were enrolled; of these, 22 pts were valuable for efficacy and safety analyses. The 22 pts were characterized with a median age of 52.5 years (range 33-72), 40.9% ECOG PS 0, 90.9%Child-Pugh A, and 45.5% extrahepatic metastasis. Till data cut-off (January 20, 2023), median follow-up was 11.3 months (95% CI, 6.0-13.1), 17 pts were alive and 14 pts remained on treatment. The ORR was 45.5% (95% CI, 25.1%-67.3%) with all partial responses per RECIST 1.1. Notably, 17 of 22 pts (77.3%; 95% CI, 54.2%-91.3%) achieved objective response as per mRECIST, with 6 (27.3%) complete responses and 11 (50%) partial responses. The DCR was 90.9% (95% CI, 69.4%-98.4%) either by RECIST 1.1 or mRECIST. Surgical conversion was achieved in 22.7% (5/22; 95% CI, 8.7%-45.8%) pts. Median PFS was not reached, with a 6- and 12-month PFS rate of 50% and 27.3%. OS data was not mature by the cut-off date. TRAEs were reported in 18 of 22 pts (81.8%). Most common TRAEs of any grade were hypertension (11/22, 50%), neutropenia (10/22, 45.5%), and aspartate aminotransferase (AST) increased (7/22, 31.8%). Grades ≥3 TRAEs occurred in 6 pts (27.3%), including 3 neutropenia (13.6%), 2 abdominal pain (9.1%), and 1 AST increased (4.6%). Conclusions: HAIC combined with tislelizumab and lenvatinib showed encouraging clinical activity and acceptable toxicity in aHCC pts with Vp3-4 PVTT, suggesting that this combination could be considered in this population. Study enrollment is ongoing, more mature data will be presented later. Clinical trial information: ChiCTR2200064384 .
Comparative efficacy and safety of anti-PD-1/L1 antibody plus anti-VEGF antibody and anti-PD-1/L1 antibody plus VEGFR-targeted tyrosine kinase inhibitor as first-line therapy for unresectable hepatocellular carcinoma (uHCC): A systematic review and network meta-analysis.
Authors: Jieer Ying , Zhuo Yiwen , Li Jingjing , Lu Beibei , Zheng Yuxi 
Published: June 2023

e16148 Background: Anti-PD-1/L1 antibody combined with anti-VEGF antibody and anti-PD-1/L1 antibody combined with VEGFR-targeted tyrosine kinase inhibitor are both effective first-line therapies for uHCC in clinical practice widely. However, direct comparisons across the two regimens are not available. We conducted a network meta-analysis of them in terms of overall survival (OS), progression free survival (PFS), objective response rate (ORR) and incidence of treatment-related adverse events (TRAEs). Methods: After a literature research performed in PubMed, MEDLINE, Embase, the Cochrane library and several major scientific societies from January 1 2007 to November 6 2022, 3,279 records were obtained. 6 phase III trials has been identified for the final analysis: REFLECT, IMbrave150, ORIENT-32, COSMIC-312, Qin 2022 and LEAP-002. The experiments were broadly classified into three groups: anti-PD-1/L1 antibody + anti-VEGF antibody (IMbrave150 and ORIENT-32), anti-PD-1/L1 antibody + VEGFR-targeted tyrosine kinase inhibitor (COSMIC-312, Qin 2022 and LEAP-002) and intermediate reference group (lenvatinib vs sorafenib, REFLECT). We derived hazard ratios (HR) with 95% confidence intervals (95%CI) for OS and PFS, odds ratio (OR) for ORR and relative risks (RR) for all grade and grade ≥3 TRAEs. With fixed effect models to estimate the indirect pooled HRs, ORs, RRs and 95%CI, a frequentist network meta-analysis was conducted using sorafenib as intermediate reference. Results: 4,012 patients were included in the analysis overall, among them, 1815 patients were treated with anti-PD-1/L1 antibody+VEGF-antibody (A+A), 1,099 patients were treated with anti-PD-1/L1 antibody+VEGFR-TKI (A+T), 877 patients were treated with lenvatinib (LEN) and 1,320 patients were treated with sorafenib (SOR). With a p-score of 98%, the combination of A+A provided the greatest reduction in the risk of death, was not significantly different from A+T (HR=0.84, 95%CI: 0.66-1.06). Besides, A+T were associated with the greatest effect in prolonging PFS and improving ORR with 91% for p-score, but there are no statistical differences with A+A (HR=1.06, 95%CI: 0.87-1.30, OR=0.82, 95%CI: 0.47-1.46). Considering the risk of TRAEs, A+A were significantly safer than A+T (RR=0.91, 95%CI: 0.84-0.98) in all grade of TRAEs and ≥3 grade (RR=0.91, 95%CI: 0.84-0.98). Conclusions: The combination of anti-PD-1/L1 antibody and anti-VEGF antibodies has the greatest probability of delivering the longest OS, while anti-PD-1/L1 antibody plus VEGFR-targeted tyrosine kinase inhibitor is correlated with larger PFS benefit at the cost of a lower safety rate.
Efficacy and safety of regorafenib and PD-1 combined with cryoablation in the treatment of advanced hepatocellular carcinoma after second-line targeted therapy.
Authors: Chen Yan , Kong Huifang , Wang Sihao , Zhang Wei , Chang Xiujuan , Huang Jiagan , Dong Zheng , Gao Xudong , Yang Bin , Zhang Huixin , Zhang Bailong , Yang Yongping , Zeng Zhen 
Published: June 2023

e16151 Background: Targeted therapy is the most effective therapeutic approach for middle and late-stage hepatocellular carcinoma (HCC). Regorafenib or PD-1 as a second-line treatment of patients with advanced HCC has achieved good results. Argon-helium cryoablation is one commonly used method for local ablation of liver cancer. Whether systemic therapy combined with local therapy can benefit patients with advanced liver cancer is a hot topic. This study is aimed to investigate the efficacy and safety of regorafenib and PD-1 combined with cryoablation in the treatment of patients with advanced HCC after the failure of second-line targeted treatment. Methods: In this retrospective study, unresectable HCC patients received regorafenib and PD-1combined with cryoablation after the failure of second-line targeted treatment from January 2019 to December 2021 were enrolled. Depending on whether combining local therapy, patients were grouped as RP (regorafenib and PD-1), or RPC groups (regorafenib and PD-1 combined with cryoablation). Objective response rate (ORR), disease control regorafenib rate (DCR), progression free survival (PFS), and safety were recorded. The PFS was defined as the time from the first dose of RP, or from the time of using RPC until disease progression or death. Results: A total of 50 patients were reviewed, including 21 patients in RP group and 29 patients in RCP group. One patient was classified as Barcelona Clinic Liver Cancer (BCLC) stage B and 20 patients were at BCLC stage C in RP group, while one patient was at BCLC stage B and 28 patients were at BCLC stage C in RPC group. The ORR and DCR were 4.8% and 23.8% in PR group respectively, and 31.0% and 69.0% in RPC group respectively. The 6-month PFS rate of RP group and RPC group was 14.3% and 53.6% respectively. Thirteen (61.9%) and eighteen (62.1%) patients experienced adverse events (AEs) in two groups respectively. Two (9.5%) and three (10.7%) patients experienced grade 3 AEs that occurred in RP group and RPC group respectively. The most frequency AE was hand-foot-skin reaction in both groups (58.0% and 50.0%, respectively). No patient discontinued regorafenib and PD-1 due to AE in these two groups. Conclusions: Regorafenib and PD-1 combined with cryoablation showed potential anti-tumor effect and tolerance on unresectable HCC after the failure of second-line targeted treatment. [Table: see text]
Landscape of FGFR2/3 alterations in hepatobiliary malignancies.
Authors: Liu Hongyan , Liu Huanhuan , Qin Jiayue , Cao Shanbo 
Published: June 2023

e16152 Background: Genomic aberrations (GAs) in FGFRs are involved in the pathogenesis of Hepatobiliary Malignancies, and clinical trials have shown efficacy of FGFR inhibitors in treating hepatobiliary malignancies patients with FGFR GAs. However, the molecular profile of FGFR2/3 in hepatobiliary malignancies is still lacking. Here, we focused on mutational landscape of FGFR2/3 GAs in hepatobiliary malignancies. Methods: We prospectively sequenced 876 tumors and matched blood DNA from Chinese and TCGA patients with hepatobiliary malignancies using next-generation sequencing techniques. Comprehensive molecular characterization was analyzed. Results: 13.2% (116/876) hepatobiliary malignancies carried FGFR2/3 GAs, including somatic mutation (56, 6.4%), CNV (41, 4.7%), and fusion (23, 2.62%). In FGFR2/3 mutation cohorts, the five most frequently somatic mutated genes were TP53 (46%), NCOR2 (26%), LRP1B (18%), KMT2C (17%), and FAT1 (16%), except for FGFR2 and FGFR3 gene. For FGFR2/3 wildtype cohorts, the five most frequently mutated genes were TP53 (46%), NCOR2 (13%), CTNNB1 (12%), LRP1B (12%), and ARID1A (10%). 77 mutated genes were significant difference between FGFR2/3 mutation and FGFR2/3 wildtype cohorts, such as NCOR2, KMT2C, FAT1, ROS1 and KMT2B, excluding the FGFR2 and FGFR3 gene. In addition, patients with FGFR2/3 GAs harbored a significantly higher TMB than those in patients without FGFR2/3 GAs (12.6 vs 9.0, p=0.003). There was no significant difference in genomic instability between the FGFR3 mutant group and the wild group (p>0.05), including ploidy, wGII, and ITH. Conclusions: FGFR2/3 GAs are frequently altered in hepatobiliary malignancies. Comprehensive genomic profiling of FGFR2/3 GAs highlights the clinical and therapeutic implication. There were characterized the genomic differences and similarities, stratified by the FGFR2/3 status, which may reflect the hepatobiliary malignancies patients with FGFR2/3 GAs harbored specific molecular mechanism.
Efficacy and safety in unresectable hepatocellular carcinoma with VP4 tumor embolus using sinilimab plus bevacizumab: A retrospective analysis of real-world evidence.
Authors: Cheng Jiamin , Chen Bowen , Zhang Xinfeng , Su Guodong , Peng Caiyun , Lei Jin , Yu Lingxiang , Li Yinyin , Lu Yinying 
Published: June 2023

e16156 Background: Recently, sinilimab plus bevacizumab has shown promising effects on unresectable hepatocellular carcinoma (uHCC) in ORIENT-32. However, its efficacy and safety in uHCC patients with VP4 cancer embolus remained unclear. Methods: In this retrospective study, uHCC patients with VP4 tumor embolus who received first-line sinilimab plus bevacizumab were consecutively enrolled. We also included similar patients who were treated with first-line sorafenib as comparison. Main efficacy endpoint was overall survival (OS), following progression free survival (PFS), objective response rate (ORR) and disease control rate (DCR) to be secondary endpoints, evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: Total 43 eligible patients were enrolled, with 15 in sinilimab plus bevacizumab arm (arm 1) and the other 28 in sorafenib arm (arm 2). No statistical differences were found in etiology, liver function and performance status. At data cut-off at February 2023, median PFS in arm 1 and arm 2 were 3.7 (95%CI: 1.2-6.2) and 3.8 (95%CI:3.1-4.5) months, following ORR and DCR were 6.7% & 46.7% and 7.1% & 35.7%. OS in arm 1 was not matured and in arm 2 was 16.1 (11.1-21.1). Not any difference was detected among all efficacy endpoints. AEs happened among almost all patients. But nobody died of AEs. Conclusions: Efficacy and safety of sinilimab plus bevacizumab in uHCC patients with VP4 tumor embolus was similar with sorafenib, which needs to be further confirmed. [Table: see text]
Combined immune checkpoint inhibition with durvalumab and tremelimumab with and without radiofrequency ablation in patients with advanced biliary tract carcinoma.
Authors: Monge B. M. Cecilia , Coffman Kelley Lauren , Hrones Donna M. , Steinberg Seth M. , Redd Bernadette , Wood Bradford , Xie Changqing , Greten Tim F. 
Published: June 2023

e16158 Background: The prognosis of advanced bile tract cancer (BTC) is unfavorable with a 5-year overall survival (OS) rate of less than 10%. Durvalumab has been approved in the first line setting in combination with chemotherapy (gemcitabine with cisplatin) for advanced BTC. Monotherapy with immune checkpoint inhibitors (ICI) in BTC in the second line is suboptimal with ORR reported in the 5-15% range. The purpose of this study was to explore the efficacy of an anti-PD-L1 (durvalumab) agent in combination with an anti-CTLA4 (tremelimumab) agent with and without radio frequency ablations (RFA) in advanced BTC. Methods: Eligible patients with advanced BTC who had received or refused at least one prior line of systemic therapy were treated with tremelimumab 75 mg intravenously (IV) and durvalumab 1500 mg (IV) for 4 combined doses followed by monthly durvalumab 1500 mg IV alone until progression of disease or unacceptable toxicity. Objective response was assessed through CT or MRI by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 8 weeks. Adverse events (AEs) were recorded and managed. The primary endpoint was 6-month progression free survival (PFS). All patients underwent a pretreatment and on treatment biopsy. Results: 22 patients with advanced BTC were enrolled in this study; 10 patients were treated with durvalumab and tremelimumab (Durva/ Treme -Arm A) and 12 patients were treated with the combination of durvalumab and tremelimumab and an ablative procedure (Durva/ Treme/ RFA -Arm B). A total of 18 patients were evaluable (10 in Arm A and 8 in Arm B). The best clinical response in Arm A were as follows: PR (n=8), SD (n=1), PD (n=1) and in Arm B: SD (n=3), PD (n=5). The median progression free survival (PFS) in the Durva/ Treme Arm A was 3.3 months (95% CI: 1.9-3.9) and Durva/ Treme/ RFA Arm was 2 months (95% CI: 1.3-2.5)). The median overall survival (OS) in the Durva/ Treme Arm A was 6.1 months (95% CI: 3.5-7.4) and Durva/ Treme/ RFA Arm was 5.7 months (95% CI: 2.9-7.6). The most common study hematologic related Grade 3-4 adverse events (AEs) were lymphopenia (n=6) and anemia (n=3) and the most common non hematologic AEs included increased AST (n=9), increased alk phos (n=7) and increased total bilirubin (n=6). Conclusions: Combined ICI with Durva/ Treme with and without RFA is well tolerated; Durva/ Treme alone showed promising activity in this small early-stage study, with an ORR of 80%, in patients with advanced BTC. Clinical trial information: NCT02821754 .
Efficacy and safety of regorafenib + PD-1 inhibitor combined with local therapy as second-line treatment in patients with advanced hepatocellular carcinoma: A multicenter retrospective real-world study.
Authors: Fu Xiaobo , Mu Maoyuan , Qi Han , Jiang Weiwei , Chen Zixiong , Gao Fei 
Published: June 2023

e16159 Background: Regorafenib and PD-1 inhibitor both are recommended as the standard second-line treatment for advanced hepatocellular carcinoma (HCC) in currently authorized guidelines. Local interventional therapies showed significant benefits in the treatment of HCC. We aimed to evaluate to investigate the efficacy and safety of regorafenib + PD-1 inhibitor combined with intervention therapy as the second-line treatment option for advanced HCC. Methods: From October 2019 to February 2022, 31 patients with advanced HCC treated with regorafenib+PD-1 were retrospectively included. All patients were divided into two groups: group A (n = 17, patients received regorafenib +PD-1 combined with local therapy), and group B (n = 14, patients received regorafenib+PD-1). The inclusion criteria are as follows: the first-line treatment was sorafenib or lenvatinib; advanced HCC (BCLC-C); ECOG score was 0-1; Child-Pugh score was 5-7; at least one measurable lesion; expected survival time ≥ 3 months. The treatment efficacy was evaluated by modified-RECIST. Objective response rate (ORR) and disease control rate (DCR) were evaluated in two groups. Major complications referred to those that result in death or serious adverse effects including sepsis, uncontrollable bleeding, and acute renal failure; others were considered minor complications. Results: The median follow-up time was 12.9 months. The median PFS was 8.3 months vs. 7.5 months (p = 0.814). The median TTP (Time to Progression) time was 8.3 months vs. 7.5 months (p = 0.973). In group A, eleven patients received TACE, 2 received thermal ablation, and 4 received HAIC. In group A: four patients reached PR (Partial response), and 7 patients stayed SD (Stable disease), while six patients suffered tumor progression (PD, Progression disease); In group B, only one patient reached PR, and 7 patients stayed SD, 6 patients suffered tumor progression. The ORR was 23.5% (group A) vs. 7.1% (group B), respectively. The DCR was 64.7% (group A) vs 57.1% (group B), respectively. The daily dose of Regorafenib was 80mg (58.8%), 120mg (29.4%), and 160mg (11.8%), respectively in group A. The daily dose of Regorafenib was 80mg (57.1%), 120mg (28.5%), and 160mg (14.3%), respectively in group B. The dose for the PD-1 inhibitor was 200mg (every three weeks). Adverse events of systemic drugs in group A and group B were 58.8% (10/17), and 35.7% (5/14), respectively. Hand–foot skin reaction was the most common adverse event in both groups (47.1% (8/17) vs 35.7% (4/140), respectively). No major complications of local therapies were observed in both groups. Conclusions: Regorafenib+PD-1 combined with local therapy as the second-line treatment option for advanced HCC may be effective and safe and provides better benefits than regorafenib+PD-1 alone.
Effect on in-hospital outcomes of patients with hepatocellular carcinoma on aspirin.
Authors: Dhaliwal Armaan , Sohal Aalam , Chaudhry Hunza , Singh Ishandeep , Sharma Raghav , Dukovic Dino , Kalra Shivam , Arora Kirti , Bains Kanwal , Somasundar Ponnandai Sadasivan 
Published: June 2023

e16162 Background: Despite the use of new immunotherapies, hepatocellular carcinoma (HCC) has a poor survival rate. Through multiple molecular mechanisms, aspirin (ASA) has demonstrated a reduced incidence of HCC, however, the impact of long-term aspirin use on in-hospital outcomes has not been studied. Methods: We queried the National Inpatient Sample (NIS) database from 2016 to 2020 to identify patients with HCC. Patients were stratified into two groups, based on long-term aspirin use. Information was collected regarding patient demographics, Elixhauser comorbidities, interventions, etiology and decompensations of the liver disease. Outcomes studied included sepsis, shock, acute kidney injury, ICU admission, and in-hospital mortality. The association between long-term aspirin use and outcomes was studied using multivariate analysis. Results: 224,735 patients were included in the study. Of them, 18,835 (8.4%) patients were on long-term aspirin. The majority of the patients with ASA use were White (61.3%), men (78.2%), and aged > 65 years old (68.8%). Patients in the ASA group had a higher incidence of NASH and decreased rates of hepatic decompensation than those not on ASA. Patients with aspirin use had lower incidence of sepsis (2.76% vs 3.54%), shock (4.86% vs 8.23%), AKI (30.9% vs 33.4%), ICU admission (3.88% vs 7.4%) and in-hospital mortality (5.18% vs 9.87%). After adjusting for confounding factors, ASA use was associated with a 30% lower risk of in-hospital mortality (aOR-0.70, 95% CI-0.60-0.82, p<0.001). ASA users also had a 21% lower odds of developing shock (aOR-0.79, 95% CI-0.67-0.94, p-0.007) and 31% lower odds of requiring ICU admission (aOR-0.69, 95% CI-0.54-0.78, p<0.001). No statistically significant difference was noted in the risk of sepsis and AKI between the two groups. Conclusions: Our study noted that patients on long-term aspirin use had better in-hospital outcomes such as mortality, shock and ICU admissions compared to non-aspirin users. These findings are of interest, and further randomized clinical trials confirming the benefits of aspirin in improving outcomes in HCC patients need to be conducted. [Table: see text]