bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single-arm, prospective study on the efficacy and safety of TACE-HAIC combined with lenvatinib and tislelizumab in the treatment of unresectable hepatocellular carcinoma.
Authors: Zhu Jun , Feng Xu , Duan Jintao , Fu Yu , Liang Jie , Peng Mi , Zhu Zimo 
Published: July 2024

e16143 Background: Hepatocellular carcinoma is one of the common tumors in China. In recent years, innovative drugs such as molecular targeted drugs and immune preparations have begun to be used clinically and have achieved good results. Interventional therapy combined with targeted immunotherapy has become a hot topic in HCC treatment research. However, the matching mode, application timing, efficacy and safety of various combination treatment options are still unclear. Therefore, a study of TACE-HAIC combined with lenvatinib and tislelizumab in the treatment of unresectable hepatocellular carcinoma is conducted to evaluate the efficacy and safety. Methods: According to the inclusion and exclusion criteria, 15 patients with unresectable hepatocellular carcinoma were included, all of whom received TACE-HAIC combined with lenvatinib and tislelizumab. The mRECIST criteria is used to evaluate the objective response rate (ORR) and disease control rate (DCR).The CTCAE version 5.0 is used to grade treatment-related adverse events of TACE-HAIC combined with lenvatinib and tislelizumab. Results: Among the 15 patients included in the study, 14 are male and 1 is female. All patients were treated with TACE-HAIC combined with lenvatinib and tislelizumab as planned, and the treatment was well tolerated. The total number of patients for optimal efficacy evaluation is 15, including 5 patients with CR, 8 patients with PR, and 2 patients with SD. The ORR is 86.7%, and DCR is 100% in best efficacy. In the safety analysis set (n = 15), none TEAEs is ≥ grade 3. In the treatment-related adverse events, abdominal pain(8/15, 53.3%), fever(4/15, 26.7%), vomiting(4/15, 26.7%), weight loss(4/15, 26.7%), nausea(2/15, 13.3%), neutropenia(2/15, 13.3%) and liver function damage(1/15, 6.7%) are all ≤ grade 2. Conclusions: TACE-HAIC combined with lenvatinib and tislelizumab has definite efficacy in the treatment of patients with unresectable hepatocellular carcinoma, with high objective response rate, good treatment tolerance, and controllable treatment-related adverse events. This therapy may be a treatment option for patients with unresectable hepatocellular carcinoma. Clinical trial information: ChiCTR2300067362. [Table: see text]
Transarterial chemoembolization (TACE) combined with donafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): A real-world clinical study.
Authors: Zhang Weihong , Zhu Bowen , Tang Yiyang , Xue Miao , Wu Yanqin , Zhao Yue , Fan Wenzhe 
Published: July 2024

e16145 Background: To evaluate the efficacy and safety of TACE combined with Donafenib, which is as a new tyrosine kinase inhibitors therapy recommended by the China liver cancer staging (CNLC) system for the treatment of unresectable hepatocellular carcinoma (uHCC). Methods: We conducted a single-center, retrospective study on patients diagnosed with uHCC treated by TACE plus Donafenib as the first-line therapy between May 2021 and September 2023 at The First Affiliated Hospital of Sun Yat-sen University. The primary outcomes evaluated in this study were progression-free survival (PFS) and overall survival (OS). Local response, one-year survival rate, safety and tolerability were the secondary outcomes. Results: All of 48 eligible patients by August, 2023, with the median age of 59 years. The clinical characteristics were as follows: BCLC stage A:2 (4.2%), B:16 (33.3%), and C:30 (62.5%); Child-Pugh class A:33 (68.8%) and B:15 (31.2%); ECOG PS 0: 27 (56.2%) and 1: 21 (43.7%). In this study, 10 (20.8%) patients had huge intrahepatic lesions, 15 (31.2%) subjects exhibited extrahepatic metastases at multiple sites, 19 (42.2%) patients presented with portal vein tumor thrombus, and 4 patients were diffuse-type HCC.107 TACE sessions were performed. Three patients had liver transplantation as frequent therapy, and histopathological examination of tissue from these subjects revealed complete necrotic foci. The median PFS was 12.8 months (95% CI: 8.66–NA) , mOS was not reached and the one-year OS rate was 87.5% (95% CI: 77%-97%) in the survival results. The tumor objective response rate was 58.3% with 14.5% complete response and 43.7% partial response based on mRECIST assessment. The disease control rate of the study group was 81.3%. The most common treatment-related adverse events (TRAEs) observed were elevated aspartate aminotransferase (AST) levels (75.0%), increase in bilirubin level (72.9%), elevated alanine aminotransferase (ALT) levels (54.2%), hand-foot syndrome (53.1%), diarrhea (29.1%), rashes (22.9%), hair loss (18.4%) and hypertension (12.5%). Twenty-three (46.9%) patients presented with grade 3 or 4 TRAEs including elevated AST levels (22.4%), elevated ALT levels (16.3%), increase in bilirubin level (4%), diarrhea (4%) and hypertension (2%). No Grade 5 TRAEs were observed. Conclusions: The combination of TACE and Donafenib presented good efficacy and tolerability, which could be potentially used as the first-line treatment of Chinese uHCC patients.
A multi-center retrospective study on the efficacy and safety of regorafenib plus immune checkpoint inhibitors with or without TACE as a second-line treatment for advanced hepatocellular carcinoma.
Authors: Li Jinpeng , Song Jinlong 
Published: July 2024

e16147 Background: At present, there are no definitive optimal treatment options for patients with hepatocellular carcinoma (HCC) following first-line treatment failure. To maximize the survival benefit of patients, we compared the efficacy and safety of regorafenib plus immune checkpoint inhibitors (ICIs) with transarterial chemoem bolization (R+ICIs+TACE) versus regorafenib plus ICIs (R+ICIs) as a second-line treatment for patients with advanced HCC. Methods: This retrospective study included patients with advanced HCC from our multicenter who received R+ICIs+TACE or R+ICIs as a later-line therapy from June 2020 to August 2022.Objective response rate (ORR), disease control rate (DCR), median progression-free survival (m-PFS), and safety were evaluated according to the modified Response Evaluation Criteria in Solid Tumors(m-RECIST). Factors affecting PFS and OS were analyzed using a Cox proportional-hazards regression model. Results: A total of 78 patients were included in the study (regardless of first-line treatment), including 48 who received R+ICIs+TACE and 30 who received R+ICIs. The R+ICIs+TACE group had a significantly higher ORR (31.6% vs. 9.8%, P = 0.021), higher DCR (73.8%vs. 45.7%, P = 0.008), longer PFS (median 8.5 vs.3.6 months, P < 0.0001) and and a longer OS (14.6 vs 8.5 months, P = 0.024) than those who received R+ICIs group. Child-Pugh class A6 and B7, R+ICIs and extrahepatic metastasis were found as independent prognostic factors for poor PFS. R+ICIs, a-fetoprotein > 400 ng/mL and Child-Pugh class were noted as independent prognostic factors for poor OS.There was no notable difference in the total incidence of treatment-related adverse effects (TRAEs) (76.8% vs. 71.3%, P = 0.41) and the incidence of grade 3/4 serious adverse effects (6.2% vs. 16.1%, P = 0.21) between the two group. Conclusions: Regorafenib plus ICIs with TACE showed a promising efficacy with favorable safety in HCC patients with PD-1 inhibitor resistance, especially in the standard second line patients.
A real-world experience of hepatic arterial infusion chemotherapy combined with tislelizumab and lenvatinib for unresectable hepatocellular carcinoma with type IV portal vein tumor thrombus.
Authors: Li Xiaowei , Cao Kunkun , Fu Zhigang , Zhong Jiaming , Liu Li , Chen Xiaoxia , Ding Ning , Zhang Xiaoli , Qu Zengqiang , Zhai Jian 
Published: July 2024

e16154 Background: Clinical improvement of interventional therapy with PD-(L)1 inhibitors plus molecular targeted therapies in have been confirmed by several studies, such as EMERALD-1, CHANCE001 etc. Limited data of this treatment in unresectable hepatocellular carcinoma (uHCC) patients (pts) with type IV portal vein tumor thrombus (PVTT) is available. This study aims to describe the efficacy and safety in uHCC pts with type IV PVTT (Vp4) who received HAIC combined with tislelizumab and lenvatinib (HAIC+Tisle+Len) in the real-world setting. Methods: This was a single-center, retrospective analysis of Vp4 uHCC pts treated with HAIC+Tisle+Len as first line systemic therapy between Apr 2020 and Dec 2022. Patient characteristics, treatment information, adverse events and survival data were collected. Pts received HAIC of modified FOLFOX (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; 5-fluorouracil bolus, 400 mg/m2 on day 1; 5-fluorouracil infusion, 2400 mg/m2 for 46 h), lenvatinib (8 or 12 mg once daily for body weight, 60 or ≥60 kg), and tislelizumab (200 mg q3w). HAIC was allowed to repeat on demands. Outcomes evaluated included overall survival (OS), progression free survival (PFS), overall response rate (ORR), overall disease control rate (DCR), and treatment-related adverse events (TRAEs). Results: A cohort of 54 pts was identified with a median age of 55 years (range 49-59). Pts characteristics were as follows: male (90.7%), hepatitis B (79.6%), BCLC C stage (100%), Child-Pugh A (88.9%), tumor number [ = 1 (50%), = 2 (7.4%), ≥3 (42.6%)], tumor diameter ≥10 cm (42.6%), extrahepatic metastasis (7.4%), beyond up to steven status (90.7%). As of Dec 20, 2023, the median follow-up duration was 21.3 mo (95% CI, 16.1-26.0), and the median number of HAIC was 3 (range 2-4). The median PFS was 8.1 months (95% CI, 6.8-12.3), while the median OS reached 16.8 months (95% CI:13.1-NR). ORR was 53.7% (3 CR, 26 PR) per RECIST 1.1; ORR was 66.7% (12 CR, 24 PR) per mRECIST. DCR was 96.3% per either RECIST 1.1 or mRECIST. Two pts received surgical treatment after conversion, one of whom underwent liver transplantation and remains tumor-free. The post-PD therapies after first-line treatment were as follows: Tisle+Len (24.1%), TACE+Tisle+Len (18.5%), Tisle+Len+Radiotherapy (7.4%), HAIC+Tisle+Regorafenib (5.6%), others (18.5%). The most common grade 3-4 TRAEs were hypertension (14.8%), decrease in albumin (11.1%), anorexia (9.3%), leukopenia (9.3%), abdominal pain (7.4%) and AST/ALT elevation (7.4%). Conclusions: The combination of HAIC with tislelizumab and lenvatinib represents a promising efficacy and manageable safety for uHCC pts with Vp4, which supplements the trial data for Vp4-HCC with real world outcomes.
Safety and efficacy of camrelizumab and apatinib in combination with IMRT in unresectable hepatocellular carcinoma: A non-randomised phase 2 study.
Authors: Wang Wei-Hu , Xing Baocai , Wang Hongzhi , Zhu Xianggao , Wang Kun , Zheng Xuan , Dong Dezuo 
Published: July 2024

e16157 Background: This study aimed to assess the efficacy and safety of combining Camrelizumab (an anti-programmed death 1 antibody) and Apatinib (a tyrosine kinase inhibitor) with intensity-modulated radiotherapy (IMRT) in patients with unresectable hepatocellular carcinoma (HCC). Methods: This non-randomized phase 2 study enrolled patients with unresectable HCC who were either systemic treatment-naïve or refractory/intolerant to first-line targeted therapy. The enrolled patients received IMRT at a dose of 50-60 Gy in 25-30 fractions, with the target volume encompassing all visible lesions. Patients were administered Camrelizumab intravenously at a dose of 200 mg every 3 weeks and Apatinib orally a dose of 250 mg once daily during IMRT, continuing for 2 years or until unacceptable toxicity or disease progression. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), local control (LC) rate, overall survival (OS) and adverse events. Results: From October 2020 to January 2024, 33 patients were included in the preliminary analysis (31 men and 2 women; median age, 57 years [range, 39-77 years]). Among them, 30 patients were diagnosed with BCLC stage C (90.9%). The median number of lesions was one (range, 1-5), with a median tumor diameter of 6.0 cm (range, 2.6-16.0 cm). Tumor thrombus was observed in 22 cases (66.7%), and lymph node metastases was found in 6 cases (18.2%). The ORR based on RECIST 1.1 and modified RECIST criteria were 78.8% and 90.9%, respectively, with a complete response (CR) rate of 12.1% and 54.5%, respectively. The median follow-up time was 20.0 months (range, 3.3-38.6 months). The LC rate at 2 years was 88.3% (95% CI, 68.1-96.1%). The median PFS was 17.5 months (95% CI, 12.6-NA), and the PFS rate at 2 years was 43.9% (95% CI, 26.1-73.8%). The median OS was 25.9 months (95% CI, 14.0-NA), and OS rate at 2 years was 58.5% (95% CI, 41.9-81.6%). According to CTCAE 5.0, grade 3-4 treatment-related adverse events were observed in 27 patients (81.8%), with the most common being thrombocytopenia (42.5%), leukopenia (33.3%) and hypertension (39.4%). No treatment-related deaths occurred. Conclusions: The combination of systematic therapies involving Camrelizumab and Apatinib with local-regional treatment of IMRT showed promising outcomes and manageable toxicities in patients with unresectable HCC. These findings warrant to be confirmed in phase 3 prospective studies. Clinical trial information: ChiCTR2000035052.
Efficacy and safety of lenvatinib plus durvalumab combined with hepatic arterial infusion chemotherapy for unresectable intrahepatic cholangiocarcinoma.
Authors: Zhao Rongce , Zhou Jing , Li Shaohua , Wei Wei , Guo Rongping 
Published: July 2024

e16184 Background: The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) is effective in patients with unresectable ICC. In this study, we determined the preliminary clinical efficacy and safety of lenvatinib plus durvalumab combined with FOLFOX-HAIC in patients with untreated, unresectable ICC. Methods: Between July 2021 and July 2023, patients with unresectable ICC who initially received lenvatinib plus durvalumab combined with FOLFOX-HAIC at the Sun Yat-Sen University Cancer Center (SYSUCC) were retrospectively reviewed for eligibility. Efficacy was evaluated by tumor response rate and survival, and safety was assessed by the frequency of key adverse events (AEs). Results: A total of 28 eligible patients were enrolled. The objective response rates (ORRs) based on mRECIST and RECIST 1.1 criteria were 65.2% and 39.1%, respectively. The median OS was 17.9 months (95% CI, 5.7–30.1) and the median PFS was 11.9 months (95% CI, 6.7–17.1). Most patients (92.9%) experienced adverse events (AEs), whereas 46.5% (13/28) experienced grade 3 or 4 AEs. Conclusions: Lenvatinib plus durvalumab combined with FOLFOX-HAIC showed promising antitumor activity and manageable AEs in patients with treatment-naive unresectable ICC. This regimen may be suitable as a novel first-line treatment option for this patient population.
Envafolimab combined with lenvatinib and gemcitabine plus cisplatin in advanced biliary tract cancer as first-line treatment: A single-arm, open-label, phase II study (ENLIGHTEN study).
Authors: Kuang Ming , Xu Lixia , Zhang Mengping , Zheng Gaomin , Zhang Chuankai , Zhang Ying , Su Tianhong , Wang Jifei , Wang Fang , Wang Fengjie , Chen Huanwei 
Published: July 2024

e16188 Background: The prognosis of advanced biliary tract cancer (BTC) remains unsatisfactory despite first-line treatment with PD-1/PD-L1 inhibitors in combination with gemcitabine and cisplatin. Lenvatinib (LEN), an anti-angiogenic multi-kinase inhibitor, has recently demonstrated promising antitumor activity in various tumors. This study aimed to determine the efficacy and safety of envafolimab (PD-L1 inhibitor) and LEN in combination with gemcitabine and cisplatin as first-line treatment in advanced BTCs. Methods: This prospective, open-label, single-arm, Simon’s two-stage, phase II study in patients with advanced BTC is ongoing at two centers. All patients received subcutaneous envafolimab (400mg, Q3W) and LEN (8 mg/day, orally once daily) combined with gemcitabine (1000mg/m2, IV, days 1, 8, Q3W) plus cisplatin (25mg/m2, IV, days 1, 8, Q3W) up for 6-8 cycles, followed by maintenance envafolimab and LEN until disease progression (PD) or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). A Simon’s two-stage phase II optimal design was used with following statistical assumptions: If 4 or more patients had partial response (PR) in 10 patients in stage 1, the cohort would expand to a total of 39 patients, and the outcomes would be positive if 15 or more patients achieved PR. The secondary endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and safety. Results: Between October 2022 and October 2023, 20 patients were enrolled, and included for efficacy and safety analysis. All patients received at least two doses of study medication. Of the first 10 patients enrolled, confirmed responses were noted in 4 patients, and the trial continued to accrual. The ORR and DCR were 45% and 80%, respectively. Nine patients (9/20, 45%) exhibited PR, seven patients (7/20, 35%) showed stable disease (SD), and four patients (4/20, 20%) experienced PD. The most common grade 3/4 treatment-related adverse events (TRAEs) were GGT increased (n = 3, 15%) and platelet decreased (n = 2, 10%). No unacceptable toxicity or treatment-related deaths occurred. Conclusions: Envafolimab and LEN in combination with gemcitabine and cisplatin seems to be an effective and tolerable treatment option in advanced BTC. Survival data is immature and will be updated in the future. Clinical trial information: NCT05410197 .
Outcomes of patients with intrahepatic cholangiocarcinoma with a focus on the interaction between tumor stage and age on mortality over the past decade.
Authors: Bangolo Ayrton , Nagesh Vignesh , Dey Shraboni , Tran Hadrian , Elias Daniel , Mansour Charlene , Aguilar Izage Kianifar , Siddiqui Aman , Wadhwani Nikita , Weissman Simcha , Fwelo Pierre 
Published: July 2024

e16201 Background: Intrahepatic cholangiocarcinoma(iCCA) is the second most prevalent liver tumor and originates from the epithelial cells of the bile duct . The purpose of this study is to assess to the extent independent prognostic factors influence mortality in iCCA. We also investigated the clinical characteristics and survival outcomes of patients with iCCA between 2010 and 2017. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database provided information on 5083 iCCA patients in the USA, between 2010 and 2017. Demographics, clinical features, overall mortality (OM), cancer-specific mortality (CSM), and the interaction between age and tumor stage were analyzed. Variables with p < 0.1 in univariate Cox regression were included in the multivariate model, with a hazard ratio (HR) > 1 indicating adverse prognostic factors. Results: Multivariate Cox proportional hazard regression analyses showed higher OM in males (HR = 1.19), metropolitan counties with 250,000 population (HR = 1.15), and lower in the age groups 40-59 (HR = 0.58) and 60-79 (HR = 0.65). Patients who underwent radiation therapy (HR = 0.78), chemotherapy (HR = 0.54), and surgery (HR = 0.29) had lower OM. Similarly, CSM was higher in males (HR = 1.17) and metropolitan counties (HR = 1.18), but lower in age groups 40-59 (HR = 0.52) and 60-79 (HR = 0.57). Interaction analysis revealed higher OM in stage III tumors with lymph node involvement aged 40-59 (HR = 2.30). CSM was higher in ages 40-59 with stage III iCCA (HR = 2.60) and stage IV (HR = 2.81), as well as in 60-79 with stage III (HR = 2.24) and stage IV tumors (HR = 2.93). OM and CSM were higher in all age groups > 40 compared to the younger population. Conclusions: In this large retrospective study using the SEER database, we unfolded an aspect of iCCA mortality that has not been previously studied. We found a significant interaction between two independent prognostic factors that enhance mortality. This data may assist treating oncologists in selecting patients that would benefit from early aggressive treatment modalities which proved to be beneficial as seen in our study. This study paves the way for future prospective randomized clinical trials to further understand the impact of such interactions in patients with iCCA, especially in the era of precision oncology.
Survival outcomes in patients with advanced intrahepatic cholangiocarcinoma in United States: A nationwide analysis.
Authors: Jayram Diya , Aziz Nouman , Naeem Hamza , Ahmad Shahzaib , Chaudhary Muhammad Ahsan Hanif , Bellur Shreyas S. , Ganiyani Mohammad Arfat , Ayoobkhan Fathima Shehnaz , Ahluwalia Manmeet Singh 
Published: July 2024

e16211 Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy after hepatocellular carcinoma. Anecdotal evidence shows that chemotherapy and radiotherapy after surgical resection confer better survival outcomes in patients with advanced disease. This study aims to demonstrate outcomes of different therapeutic options in patients with stage 4 ICC. Methods: We queried the National Cancer Database from 2004 to 2020 to identify patients with stage 4 ICC. The study compared median overall survival (mOS) using Kaplan-Meier methodology and pair-wise log-rank test among different therapeutic groups, including surgery (Sx) alone, chemotherapy (CT) alone, radiotherapy (RT) alone, surgery + chemotherapy (Sx+CT), surgery + chemoradiation (Sx+CRT), and chemoradiation (CRT). The results of the study were reported in concordance with STROBE guidelines. Results: Among 13,735 patients with stage 4 ICC, the median age was 64 years (range: 17-90+ years), 51.0% were male, 83.6% were White, 9.1% Black and 4.0 % Asian. 342 (2.5%) underwent Sx, 10061 (73.3%) CT alone, 427 (3.1%) underwent RT alone, 744 (5.4%) Sx+CT, 314 (2.3%) Sx+CRT, and 1847 (13.5%) underwent CRT. Patients who underwent Sx+CRT had better mOS (23.8 months, 95% CI 20.5-24.1) than all other modalities, including Sx (11.1 months, 95% CI 8.2-13.4), CT (8.6 months, 95% CI 8.4-8.9), RT (4.7 months, 95% CI 3.8-5.2), Sx+CT (21.9 months, 95% CI 20.0-24.1) and CRT (11.7 months, 95% CI 11.1-12.3) p < 0.01. Conclusions: Unlike other gastrointestinal malignancies, multimodal therapy i.e., chemoradiation after surgical resection of primary tumor improves survival in advanced ICC. However, prospective studies affirming these findings are warranted.[Table: see text]