bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective study on the efficacy and safety of donafenib combined with transarterial chemoembolization (TACE) and with/without immunotherapy in intermediate-advanced hepatocellular carcinoma (HCC).
Authors: Chen Cong , Fu Shouzhong , Zhao Suming , Yuan Hongxin , Dai Feng , Gu Weiwei , Gu Zhuxin , Shi Rongfeng , Yang Xiaohu , Lu Xiaohua , Jia Pengfei , Si Luyi , Zhao Hui 
Published: July 2024

e16171 Background: Recent phase III clinical trial ZGDH3 and several real-world studies have demonstrated the potential of Donafenib in improving overall survival (OS) in advanced HCC. This study aims to evaluate the efficacy and safety of Donafenib combined with TACE and with/without immunotherapy as first-line treatment in intermediate-advanced HCC. By retrospectively analyzing data from previous clinical trials, we will further explore the potential of Donafenib in enhancing the survival rate of patients with intermediate-advanced HCC and its safety profile. Methods: Thirty-eight patients diagnosed with intermediate-advanced HCC through pathology or clinical assessment were included in the study. We conducted a retrospective analysis of the efficacy and safety of patients treated with at least one cycle of Donafenib between September 2021 and December 2023, at the Affiliated Hospital of Nantong University and the Third People's Hospital of Nantong City. The primary endpoints were Objective Response Rate (ORR) and Progression-Free Survival (PFS). Secondary endpoints included Disease Control Rate (DCR), overall survival (OS) and safety. Safety and efficacy were assessed according to CTCAE v5.0 and mRECIST, respectively. Survival data were calculated using the Kaplan-Meier method. Results: The median age was 67 years old, and 76.3% were male. 39.5% of patients had Child-Pugh score A, 39.5% had BCLC stage B, and 60.5% had stage C. 17 patients (44.7%) received Donafenib combined with TACE treatment, while the remaining patients (55.3%) received Donafenib combined with TACE and immunotherapy. The median duration of therapy (mDOT) was 7.18 months (range, 2.14 -21.75). The ORR and DCR were 57.89% (22/38) and 89.47% (34/38), respectively. The median follow-up time was 9.17 months (range, 2.99-27.93), and the 6-month PFS rate was 81.1% (95% CI: 67.1%-98.0%). The 12-month PFS rate was 73.7% (95% CI: 56.5%-96.2%). The 6-month OS rate was 94.0% (95% CI: 86.2%-100.0%), and the 12-month OS rate was 88.1% (95% CI: 75.6%-100.0%), with the median PFS and OS not reached yet. Most patients took Donafenib 200mg twice a day. A total of 6 patients (15.79%) experienced grade 3 adverse events (AEs). The common grade 3 AEs included hand-foot syndrome (7.89%), diarrhea (2.63%), rash (2.63%), and hypertension fatigue (2.63%). No grade 4 or 5 AEs or new safety signals were found. Conclusions: Donafenib combined with TACE and with/without immunotherapy showed manageable safety and promising efficacy in intermediate-advanced HCC patients.
TACE-HAIC combined with donafenib and immunotherapy for hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT): A retrospective analysis.
Authors: Yin Linan , Liu Ruibao , Hou Xunbo , Lu Junrong 
Published: July 2024

e16174 Background: The probability of Chinese hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) is relatively large and the long-term survival of this part of patients is poor. Systemic therapy, transcatheter arterial chemoembolization (TACE), and hepatic artery infusion chemotherapy are widely used in HCC patients with PVTT. We want to explore the efficacy and safety of TACE plus hepatic arterial infusion chemotherapy combined with Donafenib, anti-PD-1 antibody in uHCC patients with PVTT. Methods: We retrospectively analyzed the patients who were diagnosed as uHCC with PVTT and received the treatment of TACE plus HAIC combined with Donafenib, anti-PD-1 antibody as first-line therapy from Dec 2021 to Jun 2023 in Harbin Medical University Cancer Hospital. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progress free survival (PFS), overall survival (OS) and safety. Results: Of 106 patients included in the analysis, all of them received first-line treatment of TACE (embolization of pirarubicin hydrochloride 40mg, iodized oil 10-20ml with or without gelatin sponge) plus HAIC (oxaliplatin 85 mg/m2 2h, leucovorin 400 mg/m2 1h, fluorouracil bolus 400 mg/m2 in the first 10 minutes, and fluorouracil infusion 2400 mg/m2 for 46h) combined with donafenib 200mg bid, anti-PD-1 antibody Q3W. The median age was 58 years (IQR, 52-64). The study population was predominantly male (79.2%), and 79.2% were HBV-positive. All HCC patients are accompanied by PVTT, most of which are VP3(72.6%).The rate of patients with extrahepatic metastasis were 16.0%. All patients were classified as BCLC stage C and 84.0% were classified as CNLC stage IIIa. As of December 2023, 106 patients had received at least one imaging evaluation, 11 (10.4%), 60 (56.6%) and 28 (26.4%) of them achieved complete response, partial response and stable disease, and the overall objective response rate and disease control rate was 67.0% and 93.4% per modified RECIST criteria respectively. With 16.3 months of median follow-up time, the 12-month PFS rate was 81.3% and the 12-month OS rate was 90.1%. The median PFS and OS were not reached. 103 of all patients had at least one treatment-related AE (TRAE), and treatment-related deaths did not occur in this study. Grade 3 TRAEs occurred in 33 (31.1%) patients, and no grades 4 or 5 were reported. The most common Grade 3 TRAEs included aspartate transaminase increased (18.9%), platelet count decreased (14.2%) and blood bilirubin increased (8.5%). Conclusions: TACE-HAIC combined with Donafenib and immunotherapy are effective and tolerable for uHCC patients with PVTT.
The safety and efficacy of adebelimumab combined apatinib and hepatic artery infusion chemotherapy in the treatment of unresectable hepatocellular carcinoma: A retrospective study.
Authors: Chen Bin , Lin Run , Huang Yonghui , Dai Haitao , Tang Keyu , Zhang Guiyuan 
Published: July 2024

e16175 Background: The combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) used for hepatic arterial infusion chemotherapy (HAIC) has shown promise for advanced hepatocellular carcinoma (HCC) patients. The combined therapy of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) is now an approved first-line approach for unresectable HCC. This study evaluated the safety and the effect of combining Adebelimumab (a PD-L1 inhibitors) and Apatinib (a tyrosinase kinase inhibitor) with HAIC-FOLFOX for unresectable HCC patients. Methods: The records of patients with unresectable HCC treated with HAIC from March 2023 to November 2023 at our center were retrospectively reviewed. Eligible patients were given a maximum of four cycles of FOLFOX-HAIC, along with Adebelimumab and Apatinib, until either disease progression or intolerable toxicities emerged. The primary outcome measured was the safety and the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modify RECIST of combined therapy. Results: Twenty patients were enrolled in the study. The most frequent grade ≥3 or above treatment-related adverse events included elevation of AST (50%) and diminished PLT count (15%). There was no treatment related death. Based on RECIST v1.1 and mRECIST criteria, the confirmed ORR stood at 35% and 70%, with a disease control rate of 85% both. Conclusions: The combination of Adebelimumab, apatinib, and FOLFOX-HAIC demonstrated manageable safety and encouraging results for unresectable HCC.
The efficacy and safety of donafenib combined with transcatheter arterial chemoembolization and anti-PD-1 antibodies as first-line therapy for hepatocellular carcinoma: A retrospective study.
Authors: Song Danjun , Hao Weiyuan , Cao Fei , Luo Jun , Guo Liwen , Zhang Zhewei , Zheng Jiaping 
Published: July 2024

e16178 Background: In Phase III study (ZGDH3), donafenib showed the survival benefit and better safety compared with sorafenib as the first-line treatment for uHCC. Recently, combination therapies have shown favorable results in patients with HCC. Some studies have shown that molecular targeted drugs combined with anti-PD1 antibodies and TACE exhibit improved anti-tumor efficacy compared with monotherapy. This study aimed to evaluate the efficacy and safety of the combination therapy of donafenib,anti-PD-1 antibodies and TACE as first-line treatments for HCC patients in the real world. Methods: This single-center retrospective study involved patients with histopathologically/cytologically or clinically confirmed HCC at Zhejiang Cancer Hospital between July 2021 and June 2023. Eligible patients were treated with donafenib (100 mg po bid) combined with TACE and anti-PD-1 antibodies until the point of disease progression, death, or intolerable toxicity. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) datas of patients were collected and analyzed according to the mRECIST, and the incidence of adverse events (AEs) was evaluated using CTCAE 5.0. Results: There were 34 patients in this study (Table). The median age was 64 years (IQR: 57, 69) at the data cut-off in January 2024, with 94.1% of the population being male and 82.4% having HBV infection. Of these patients, 5(14.7%) were classed as BCLC stage A, 11(32.3%) were classed as BCLC stage B, and 18 (52.9%) were BCLC stage C. The median PFS was 7.9 months (95%CI, 5.6–NA), and median OS was not reached, respectively, the 12-month PFS and OS rates were 46.9% (95%CI: 16.8%-72.5%) and 96.9% (95%CI: 79.8%-99.6%). The ORR and DCR for all patients were 73.5% and 97.1%, respectively, based on both mRECIST (CR 3 [8.8%], PR 22 [64.7%], SD 8 [23.5%]). The surgical conversion rate was 26.5%. Treatment-related adverse events (TRAE) of any grade were observed by 18 patients (52.9%), of which 4 patients (11.8%) had grade 3 TRAE. No grade 4 or 5 TRAE was observed. Conclusions: The study indicated that donafenib combined with TACE and anti PD-1 antibodies exhibited encouraging efficacy and favorable safety profile in patients with HCC. [Table: see text]
Effect of BCL9/BCL9L inhibition–derived Th1 cells on dendritic cells–mediated antigen presentation in hepatocellular carcinoma and on the efficacy of CAR-T immunotherapy.
Authors: Zhu Yuanyuan , Feng Mei , Wang Feng , Zhu Andrew X. , Zhu Di , Zhao Enfeng 
Published: July 2024

e16180 Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy with limited treatment options. The emerging field of tumor immunotherapy, primarily focusing on CD8+ T cells and the tumor microenvironment (TME), has garnered substantial attention. CD4+ T cells, on the other hand, play a crucial role in maintaining immune equilibrium and orchestrating immune responses through interactions with various cell types. As crucial participants and coordinators in innate and adaptive immune responses, the role of CD4+ T cells in tumor development remain further exploration. Conventional dendritic cells (cDCs) are thought to perform antigen presentation to prime CD4+ T cells or CD8+ T cells. However, the reverse regulatory impact of CD4+ T cells on cDCs remains poorly understood. Methods: Initially, we examined the role of CD4+ T cell subsets in HCC development using TCGA database. Subsequently, we established Cd4-Cre Bcl9fl/fl Bcl9lfl/fl mice to explore the impact of T cell-specific Bcl9/Bcl9l deficiency on HCC development. We further investigate the impact of Bcl9/Bcl9l deficiency in CD4+ T cells on the therapeutic efficacy of mouse CAR-T treatment. Moreover, using single-cell RNA sequencing (scRNA-seq) databases from Bcl9/Bcl9l KO tumor-bearing mice and HCC patients, we investigated the regulatory role of CD4+ T cells on the function of cDCs. Finally, we validated the mechanism by which CD4+ T cells regulate cDCs function in a mouse HCC model and explored their influence on tumor-specific CD8+ T cells response. Results: We found elevated Th1 cell infiltration in various cancers including liver hepatocellular carcinoma (LIHC). High Th1 infiltration is associated with a favorable prognosis in LIHC, but there is a significant negative correlation between the expression of B-cell lymphoma 9/B-cell lymphoma 9-like (BCL9/BCL9L) and the infiltration of Th1 cells. We found that blocking T cell-intrinsic BCL9/BCL9L increased frequencies of Th1 cells, thereby suppressing HCC tumor growth. The enrichment of Th1 cells inversely regulates innate immune response to augment cDCs activation. BCL9/BCL9L inhibition amplifies CD4+ T cell and cDCs crosstalk and promotes cDCs antigen presentation. The reinforced cross-presentation of tumor antigens by cDCs promotes activation and proliferation of CD8+ T cells. Moreover, genetic editing of BCL9/BCL9L in CD4+ T cells can enhance the anti-tumor immunity by promoting CAR-T cell toxicity. Conclusions: Thus, BCL9/BCL9L inhibition orchestrate an adaptive immune to innate immune circuit wherein Th1 cells triggers cDCs antigen presentation in turn activate tumor-specific CD8+ T cells response to promote cancer immunity.
Efficacy and safety of arterial FOLFOX chemotherapy plus anti-PD-(L)1 immunotherapy as first-line treatment for unresectable intrahepatic cholangiocarcinoma: A propensity score matched analysis.
Authors: Hu Yue , Lyu Ning , Zhao Ming 
Published: July 2024

e16189 Background: This study aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus anti-programmed death (ligand)-1 [PD-(L)1] immunotherapy compared to systemic chemotherapy (SCT) plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with unresectable intrahepatic cholangiocarcinoma (uICC). Methods: In this retrospective study, unresectable treatment-naive ICC patients who were treated with HAIC plus anti-PD-(L)1 immunotherapy [HAIC+αPD-(L)1] or SCT plus anti-PD-(L)1 immunotherapy [SCT+αPD-(L)1] were included. The clinical characteristics, therapeutic outcomes and adverse events (AEs) of patients between the two groups were compared. The propensity score matching (PSM) was performed to minimize biases between groups. Results: From January 2019 to January 2023, a total of 182 patients were enrolled, including 147 patients in HAIC+αPD-(L)1 group and 35 patients in SCT+αPD-(L)1 group. After PSM, 61 and 26 patients were included in the HAIC+αPD-(L)1 and SCT+αPD-(L)1 groups, respectively. The HAIC+αPD-(L)1 group showed longer median overall survival (OS) and progression free survival (PFS) than the SCT+αPD-(L)1 group (OS: 14.5 vs 10.5 months, P = 0.019; PFS: 6.4 vs 10.1 months, P = 0.020). The disease control rate of HAIC+αPD-(L)1 group were higher than those of SCT+αPD-(L)1 group (91.8% vs 69.2%, P = 0.007). The overall incidence of adverse events (AEs) was comparable between the two groups, but the HAIC+αPD-(L)1 group showed a lower incidence of grade 3~4 AEs related to anemia, weight loss and fatigue. Conclusions: HAIC plus anti-PD-(L)1 immunotherapy had acceptable toxic effects and might improve outcomes compared to SCT plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with uICC.
The efficacy of atezolizumab plus bevacizumab in the treatment of unresectable hepatocellular carcinoma in cirrhotic and non-cirrhotic patients.
Authors: Aranda-Gutierrez Alejandro , Conde-Flores Emilio , Meraz-Brenez Andres , Escorza Salvador , Meneses-Medina Mónica I. Isabel , Huitzil-Melendez Fidel David , de la Mora-Molina Héctor , Rosas Camargo Vanessa 
Published: July 2024

e16214 Background: The IMbrave150 trial established that the combination of atezolizumab plus bevacizumab (AB) confers a significant progression-free survival (PFS) benefit when compared with sorafenib in patients with unresectable hepatocellular carcinoma (HCC). However, the nuanced impact of cirrhotic status on treatment response was not established by the study, leaving a critical aspect of patient stratification and outcomes yet to be fully understood. Methods: We conducted a retrospective single-center study of patients with HCC treated with AB between 2020 and 2023. Eligible patients were those who underwent at least one cycle of AB and had a follow-up period of at least three months post-AB initiation. Independent samples T-test and X2 and Fisher’s exact tests were used to evaluate associations between variables. PFS was calculated using the Kaplan-Meier method and compared according to cirrhotic status using the log-rank test. A Cox regression analysis was performed to estimate survival hazard ratios (HR). Results: Among 28 patients, the mean age at diagnosis was 64 years (SD 11), 18 (64%) were male, 26 (93%) had Child-Pugh (CP) class A liver function, and 18 (64%) were cirrhotic. Most patients presented with Barcelona Clinic Liver Cancer stage C disease (61%) and received AB in the first-line setting (93%). Clinicopathological features according to cirrhotic status are detailed in Table 1. With a median follow-up of 14 months (95% CI 8-20) since AB initiation, 16 progression events were recorded, resulting in a median PFS of 12 months (95%CI 6-18) for the entire cohort. Univariate analysis revealed an inferior median PFS in patients with cirrhotic HCC (7 months [95%CI 5-9] vs. not reached [p = 0.038]). However, in a multivariate Cox analysis, only obesity emerged as a significant predictor of an inferior PFS (HR 4.6; 95% CI 1.3 - 16.0, p = 0.018). Conclusions: In our study, cirrhosis was not associated with an inferior PFS. Notably, the majority of cirrhotic patients in this cohort exhibited CP A liver function, so uncertainties persist regarding the impact of cirrhosis on cancer progression in patients with CP B and C liver function. Further investigation is warranted to comprehensively evaluate whether cirrhotic, non-cirrhotic, and obese subgroups respond differently to AB therapy. [Table: see text]
Nivolumab monotherapy and associations in the treatment of advanced unresectable biliary tract cancer (BTC): A systematic review and meta-analysis.
Authors: Filogonio Victor , Maia Yara Rafaela , Maia Lucas Henrique , Beck Mauren Carbonar , Beck Theodoro 
Published: July 2024

e16216 Background: Patients with advanced unresectable BTC have a poor prognosis, and treatment options are limited and with variable response rates. Nivolumab (NIVO), a PD-1 inhibitor, has shown its effectiveness against multiple cancer types and has been tested as a therapeutic option in diverse settings and associations. Methods: We performed a systematic review and single arm meta-analysis of clinical trials of NIVO monotherapy or combined therapy in advanced unresectable BTC. PubMed, Embase, and Cochrane database were searched for clinical trials published up to May 1, 2023. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. The primary endpoints of interest were objective response rate (ORR = CR+PR) and disease control (DC = SD or better response) per RECIST v1.1, at any period of the trial. Results: Out of 80 database results, 6 clinical trials and 358 patients were included, all were using some form of NIVO therapy. Overall, NIVO and associations present an ORR = 13% (95% CI 0.08-0.16, I² = 23%, p = 0.26) and DC = 39% (95% CI 0.27-0.51, I² = 69%, p < 0.05). NIVO monotherapy present an ORR = 6% (95% CI 0.02-0.10, I² = 36%, p = 0.19) and DC = 28% (95% CI 0.04-0.51, I² = 87%, p < 0.001) while NIVO + ipilimumab association show an ORR = 11% (95% CI 0.004-0.22, I² = 76%, p < 0.05) and DC = 37% (95% CI 0.24-0.49, I² = 28%, p = 0.23). NIVO + gencitabine + cisplatin association trials reported an ORR within 13-18% and DC around 32%. This data suggests that associations of NIVO present higher efficacy in the treatment of BTC and should be considered among the first choices of therapy, however drug adverse effects tolerability might play an important part in the individualized patient care. Conclusions: There are marked limitations to the applicability of these findings in clinical practice, therefore a cautionary approach to this data is recommended, given their overall low statistical power, heterogenous study design, and tolerability to adverse effects. New trials of NIVO + associations with better standardized outcomes and comparative arms for different associations and populations will help to better clarify the effects of NIVO in the treatment of advanced unresectable BTC. [Table: see text]
Clinicopathologic and treatment characteristics of mixed hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC).
Authors: Ozer Muhammet , Goksu Suleyman Yasin , Sahin Ilyas 
Published: July 2024

e16218 Background: Mixed hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC) represents a rare subtype of primary hepatic malignancy demonstrating morphological and biological features characteristic of both Hepatocellular Carcinoma (HCC) and Intrahepatic Cholangiocarcinoma (ICC). In this study, we describe the clinical and tumor characteristics of survival in HCC-ICC by using a large cohort. Methods: We selected patients diagnosed with HCC‐ICC, HCC, or ICC between 2011 and 2018 and were identified from the National Cancer Data Base (NCDB) using the International Classification of Diseases for Oncology codes. Baseline characteristics were delineated using percentages. Median overall survival (OS) was calculated using the Kaplan-Meier method. Demographic variables (age at diagnosis, gender, race, insurance status), comorbidity score, and treatment features were included. Short‐ and long‐term outcomes were evaluated through univariate analysis. Results: Out of 124,723 patients, 84.6% were diagnosed with HCC, 14.5% with ICC, and 1% with HCC‐ICC. Median survival was significantly better in HCC compared to HCC-ICC and ICC patients (16.2 months, 10.8 months, and 9.4 months, respectively, p < 0.001). Surgical intervention was used by 26.3% of HCC-ICC cases, 19.2% of ICC cases, and 9% of HCC cases. Multiagent chemotherapy was notably more utilized in ICC compared to HCC-ICC and HCC (42.6%, 22.8%, and 5.4%, respectively, p < 0.001). Meanwhile, single-agent chemotherapy was more commonly administered in HCC than in HCC-ICC and ICC (32.3%, 16.5%, and 11.4%, respectively, p < 0.001). Conclusions: HCC-ICC is an aggressive primary liver malignancy with a worse prognosis than HCC and ICC. The primary treatment approach for operable cases continues to be major hepatectomy combined with resection of hilar lymph nodes. Further research is urgently needed to better understand the exact role of the systemic therapies in managing HCC-ICC.