bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of tislelizumab combined with lenvatinib and FOLFOX4-HAIC in conversion therapy of middle-advanced stage hepatocellular carcinoma (HCC): A real-world retrospective study.
Authors: Tan Kai , He Xiaojun , Zhang Hu , Zhao Shoujie , Gong Chenyu , Zhao Yaoyao , Nan Haiyan , Zang Li , Luo Zhonghua , Yin Jikai , Du Xilin 
Published: June 2023

e16137 Background: Conversion therapy achieve tumor downstaging and provide middle-advanced stage HCC patients with opportunities for radical resection. Lenvatinib combined with immune checkpoint inhibitors (ICIs) and FOLFOX-HAIC has shown high conversion success rates. This study aimed to evaluate the efficacy and safety of tislelizumab combined with lenvatinib and FOLFOX4-HAIC as first-line conversion therapy in this population. Methods: Between April, 2021, and April, 2022, we retrospectively analyzed clinical data of HCC patients with BCLC stage B or C who underwent tislelizumab combined with lenvatinib and FOLFOX4-HAIC. The primary outcome included objective response rate (ORR), disease control rate (DCR), conversion resection rate (CRR) and treatment-related adverse events (TRAEs). Data were expressed as median(range). Results: A total of 18 patients (17 male, 1 female) completed conversion therapy assessment until the last follow-up time (December 27, 2022). The patients were characterized with a median age of 55.5 years (37-72), body mass index 24.9(19.8-33.9), 1 patient with BCLC stage B, 16 patients with BCLC stage C, and 1 patient with HCC postoperative recurrence with intrahepatic metastasis. According to mRECIST criteria, tumor shrinkage was observed in all patients, with an ORR of 94.4% (17/18, including 61.1% [11/18] complete response), DCR of 94.4% (17/18), and median time to response(mTTR) of 1.4 months (0.7-3.0). Successful conversion was observed in 11 (61.1%) of 18 patients per mRECIST. As of cut-off date, the actual CRR and pathological complete response(pCR) were 38.9% (7/18) and 57.1% (4/7), respectively. No surgical deaths occurred, and at the last follow-up review, there was disease free survival in all patients after operation. With a follow-up time of 20.7 months, median progression-free survival (PFS) and overall survival (OS) were not reached, with a 3- and 6-month progression-free survival rate of 94.4% and 83.3%. During the follow-up period, 6 patients developed disease progression with a median time to progression (mTTP) of 5.4 months (1-6.7), of whom 3 died due to disease progression. Most common TRAE was aspartate aminotransferase (AST) increased (16 patients, 88.9%). Grades ≥3 TRAEs occurred in 12 patients (66.7%), with only one grade 4 TRAE (AST increased). All TRAEs were tolerable and manageable. Conclusions: Tislelizumab combined with lenvatinib and FOLFOX4-HAIC showed high conversion rate and acceptable toxicity in the treatment of middle-advanced stage HCC, suggesting that this combination could be considered as a new conversion strategy in this population.
OS analysis of patients with different short-term response and progression patterns of donafenib versus sorafenib as first-line therapy for advanced hepatocellular carcinoma: An exploratory subgroup analysis of ZGDH3.
Authors: Qin Shukui , Bi Feng , Xu Jianming , Du Chengyou , Fan Qingxia , Zhang Longzhen , Tao Min , Jiang Da , Wang Senming , Chen Yongping , Sheng Jifang , Zhuang Xuelong , Wu Jun 
Published: June 2023

e16143 Background: Donafenib, a deuterated derivative of sorafenib, significantly prolonged overall survival (OS) in patients with advanced hepatocellular carcinoma in an open, randomized, parallel-controlled phase II/III trial (ZGDH3) compared with sorafenib. The purpose of this study was to explore and analyse the OS benefits of donafenib and sorafenib treatment in patients with different short-term response and progression patterns. Methods: This analysis was based on the ITT population of ZGDH3 study (defined as all randomized patients). The median OS of donafenib and sorafenib was assessed by the Kaplan-Meier method and was compared according to different short-term response (SD, others) and progression patterns (intrahepatic lesion growth, intrahepatic new lesion, extrahepatic lesion growth, extrahepatic new lesion). The stratified Cox proportional hazard model was used to calculate the hazard ratio and its 95% confidence interval. Results: 668 patients were included in the analysis (334 in each group). Donafenib was associated with a trend of improved OS benefit when compared with sorafenib in most subgroups (HR < 1), including best short-term response of SD or others, confirmed short-term response of SD or others, intrahepatic lesion growth or not, intrahepatic new lesion or not, extrahepatic new lesion or not, no extrahepatic lesion growth. The benefit was statistically significant in the following subgroups: in patients with response of SD, the mOS of donafenib and sorafenib were 19.3 and 15.5 months, respectively (HR 0.714, 95%CI 0.550-0.928). Among patients with confirmed response of SD, the mOS was 29.0 and 22.8 months, respectively (HR 0.641, 95% CI 0.418-0.983). Among patients without extrahepatic lesion growth (defined as lesion growth ≥20% from baseline), the mOS was 12.6 months and 10.0 months, respectively (HR 0.783, 95% CI 0.648-0.945). Among patients without new extrahepatic lesions, the mOS was 13.1 months and 11.0 months (HR 0.816, 95% CI 0.677-0.998), respectively. Conclusions: Donafenib exhibited better survival benefit than sorafenib in most subgroups, especially in patients with the best response and confirmed best response of SD, which further confirmed the excellent efficacy of donafenib in first-line treatment of advanced HCC. Clinical trial information: NCT02645981 . [Table: see text]
Transarterial chemoembolization combined with camrelizumab and apatinib in the treatment of advanced hepatocellular carcinoma: Preoperative or postoperative combination? A prospective clinical study.
Authors: Xie Hui , Yang Yuqing , Liu Yane , Wen Zhenyu , Wang Junxiao 
Published: June 2023

e16150 Background: The timing of the combination of an antiangiogenic agent (apatinib) and an immune checkpoint inhibition inhibitor (camrelizumab) in patients with advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is unclear. Therefore, this study aims to evaluate the efficacy and safety of TACE combined with camrelizumab and apatinib for advanced hepatocellular carcinoma (HCC), and to explore the timing of the combination therapy. Methods: The institutional Review Board approved our study and registered it in the Chinese Clinical Trial Registry (ChiCTR2000034155). Between June 2020 and January 2022, we prospectively recruited patients with unresectable HCC not receiving systemic therapy and randomly divided them into preoperative and postoperative medication groups according to the timing of drug administration. Patients in the preoperative medication group received camrelizumab 200 mg per 2 weeks intravenously and oral apatinib 250 mg/day orally prior to TACE. Patients in the postoperative medication group received the same dose of camrelizumab and apatinib after recovery of liver function following TACE. The primary endpoint of the study was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events. Results: A total of 33 patients were enrolled in this study. There were 15 patients in the preoperative medication group and 18 patients in the postoperative medication group. Median OS was significantly longer in the postoperative medication group than in the preoperative medication group (20 months vs. 12 months; P = 0.034). Patients in the postoperative medication group achieved a higher DCR than that in the preoperative medication group [17 cases (94.4%) vs. 10 cases (66.7%), P = 0.039] Multivariate Cox regression analysis showed that post-TACE combination of apatinib and camrelizumab provided better OS than pre-TACE combination drug therapy (HR = 0.353, 95% CI:0.131-0.953, P = 0.040). No serious adverse events were observed in the two groups. Conclusions: TACE combined with apatinib and camrelizumab treatment in the patients with advanced HCC showed promising efficacy and a manageable safety profile. Compared to pre-TACE with apatinib plus camrelizumab, post-TACE with apatinib plus camrelizumab significantly improved OS and DCR in patients with advanced HCC. Clinical trial information: ChiCTR2000034155 . [Table: see text]
A study of cadonilimab combined with regorafenib as second-line or later therapy in patients with advanced hepatocellular carcinoma (aHCC).
Authors: Qi Qi , Liu Yang , Li Rentao , Liu Yayue , Zhang Xihao , Lu Wei , Li Huikai 
Published: June 2023

e16154 Background: Current second-line treatment options for aHCC patients (pts), including single TKI or anti-PD-1+anti-CTLA4, result in limited survival benefits, objective responses or increasing concerns regarding adverse effects. An exploration of safer and more effective second-line or later therapies for aHCC is paramount. Cadonilimab is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in HCC. Previous data indicated that cadonilimab possesses an improved safety profile and an encouraging anti-tumour activity compared to combined administration of anti-PD-1 plus anti-CTLA-4 antibodies. Regorafenib was the first TKI that approved globally as a second-line treatment of aHCC. Here, we evaluated the safety of cadonilimab plus regorafenib as second-line or later therapy in pts with aHCC. Methods: The study population derived from prospectively collected retrospectively analyzed data (10/2022-02/2023) of pts treated with cadonilimab plus regorafenib as second-line or later therapy for aHCC at Tianjin Cancer Hospital Airport Hospital. The primary endpoint was safety. Results: We identified 29 pts with aHCC who received cadonilimab plus regorafenib. The median age was 59 years; 86.2% were male; 72% were ECOG PS 0; 72% had a Child-Pugh score of A at diagnosis. High risk factors for HCC included MVI (3pts), ≥3 tumour lesions (10pts), tumour diameter ≥5cm (5pts), AFP≥400ng/mL (5pts). Six pts (21%) received cadonilimab plus regorafenib in the second-line while the rest of pts (79%) received it as third-line or later. All pts previously received at least one line of immunotherapy combined with anti-angiogenic target agents. Seven pts received triple combination regimens (ICIs+TKIs/Bev+HAIC) before. At time of data extraction, no pts were assessed for efficacy due to the COVID-19 pandemic (especially the outbreak in early December 2022) and short follow-up time, we focused on the safety and tolerability in this report. Any grade treatment related adverse events (TRAEs) occurred in 24pts (83%). The most common TRAEs of any grade were hypoalbuminemia (24%), lymphocyte count decreased (21%), rash (14%), nausea (14%) and infusion reaction (14%). Only four (14%) patients experienced grade 3 TRAEs including infusion reaction (2pts), lymphocyte count decreased (1pt) and gastrointestinal hemorrhage (1pt, regorafenib related). No grade 4-5 TRAEs were observed. Conclusions: The combination of cadonilimab plus regorafenib was generally well tolerated. The prospective trail of cadonilimab combined with regorafenib as second-line or later therapy for aHCC is ongoing (NCT05644379). Although it needs to be reconfirmed, the treatment responses of some patients are encouraging (including sharp decrease in AFP level and/or reduced tumor size). Related data will be reported in the future.
Phase II study of fruquintinib as second or further-line therapy for patients with advanced biliary tract cancer.
Authors: Zhang Pengfei , Yang Yu , Gou Hongfeng , Li Qiu 
Published: June 2023

e16161 Background: Biliary tract cancer (BTC) is a rare but aggressive disease, and most patients present with unresectable or metastatic disease. Gemcitabine combined with cisplatin (GP) has been established as the standard first-line treatment in patients with unresectable BTC. Nevertheless, no standard second or further-line treatment regimen has been approved in this disease. Fruquintinib is an oral multi-kinase inhibitor targeting vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2 and VEGFR3. In this single arm phase II study, we explored the efficacy and safety of fruquintinib as a novel second or further-line therapy in advanced or metastatic BTC. Methods: BTC patients with ECOG PS 0-1 and adequate liver, kidney and bone marrow function were given fruquintinib (5 mg, PO, D1-21, Q4W) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The exploratory endpoint was the correlation of clinical outcomes with biomarkers. Results: 20 patients were enrolled in the study. 9(45.0%) were men, and the median age was 57.5(36-78) years. 18 patients were diagnosed with ICC, 1 with ECC, and 1 with GBC. 6 (30%) patients were refractory to second-line treatment, and 5 (25%) patients were refractory to third-line treatment. 18 patients were assessable for response. The median PFS was 4.6 months (95%CI: 2.1-7.1 months). ORR was 5.6%, and DCR was 66.7%. The incidence of treatment-related grade 1-2 adverse events (TRAEs) was 83.3%, and the most common grade 1-2 AEs were hand-foot syndrome (66.6%), fatigue (61.1%), stomatitis (44.4%), and hypertension (38.9%). Conclusions: Fruquintinib showed promising efficacy and acceptable toxicity as second or further-line therapy in advanced or metastatic BTC. Clinical trial information: NCT04156958 .
Chemoembolization plus hepatic arterial infusion chemotherapy combined with donafenib, anti-PD-1 antibody for unresectable hepatocellular carcinoma (uHCC): A retrospective analysis.
Authors: Yin Linan , Liu Ruibao , Li Shijie , Hou Xunbo 
Published: June 2023

e16163 Background: Chemoembolization plus hepatic arterial infusion chemotherapy significantly improved ORR and PFS over chemoembolization alone in patients with uHCC in previous study. And donafenib showed the survival benefit and better safety compared with sorafenib in a Phase III trial. In consideration of synergism, we evaluated the safety and efficacy of TACE plus hepatic arterial infusion chemotherapy combined with donafenib, anti-PD-1 antibody in patients with uHCC. Methods: We retrospectively analyzed the patients who were diagnosed as unresectable hepatocellular carcinoma and received the treatment of TACE plus HAIC combined with donafenib, anti-PD-1 antibody as first-line therapy from Nov 2021 to Nov 2022 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), time to response (TTR) and safety. Results: Of 36 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 (range, 44-80). The study population was predominantly male (75%), and 89% were HBV-positive. Patients were classified as BCLC stage A (8.3%), stage B (8.3%) and stage C (83.4%). The rates of patients with portal vein tumor thrombus and extrahepatic metastasis were 69% and 11% respectively. 30.6% patients received interventional therapy before the combination treatment. By Feb 2023, 23 patients had received at least one imaging evaluation, 19(82.6%) of them achieved partial response, ORR and DCR were 82.6% and 100% per modified RECIST criteria respectively. And the median TTR was 1.1 months. With 3.8 months of median follow-up time, the 6-month PFS rate was 51.2%. The median PFS and OS were not reached. All 36 patients had at least one treatment-related AE (TRAE), and treatment-related deaths did not occur in this study. Grade 3 TRAEs occurred in 8 (22.2%) patients, and no grades 4 or 5 were reported. The most common TRAEs included alanine aminotransferase increased (77.8%), alkaline phosphatase increased (77.8%), platelet count decreased (69.4%) and blood bilirubin increased (63.9%). Conclusions: Chemoembolization plus hepatic arterial infusion chemotherapy combined with donafenib, anti-PD-1 antibody are effective and tolerable for uHCC patients.
Atezolizumab and bevacizumab in advanced hepatocellular carcinoma: Real-world data.
Authors: Bezalel Nomi , Davidov Yana , Likhter Mariya , Cohen Ezra Oranit , Inbar Yael , Halpern Naama , Boursi Ben , Beller Tamar , Pery Ron , Shmueli Einat S , Nachmany Ido , Ben Ari Ziv , Margalit Ofer 
Published: June 2023

e16167 Background: Treatment of advanced unresectable hepatocellular carcinoma (HCC) has advanced substantially in the past few years with the use of immunotherapy. The IMbrave 150 phase III study assessed the combined treatment of atezolizumab plus bevacizumab (atezobev) and has demonstrated better overall and progression-free survival compared with sorafenib. We aimed to assess the efficacy and toxicity of atezobev in real-world data. Methods: We reviewed the medical records of patients with a diagnosis of advanced HCC treated at the Sheba Medical Center between January 2020 and February 2023. Eligible patients were those treated with atezobev as first line systemic therapy. Adverse events were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response assessment was performed according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Results: We identified 37 patients that were treated with atezobev, mean age of the study population was 70 (IQR 60-72), 19% were females (n = 7), median ECOG performance status was 1 (IQR 0-1.5) and HCC etiology was non-viral in 35% (n = 13) and viral (HBV/HCV) in 65% of patients (n = 24). Overall response rate (ORR) was 29.7% (n = 11), stable disease was noted in 27.0% (n = 10) and progressive disease in 43.2% (n = 16) of patients. In comparison, the ORR reported in the IMbrave 150 study was 27%. There was no difference in response rate according to previous local treatment or HCC etiology. Grade 3/4 adverse events included grade 3 hepatitis (10.8%, n = 4), grade 3 diarrhea (2.7%, n = 1), and grade 4 infusion-related reaction (2.7%, n = 1). In comparison, the IMbrave 150 study reported grade 3/4 hepatitis, diarrhea, and infusion-related reaction in 7.0%, 1.8% and 2.4% of patients, respectively. Conclusions: In this cohort of advanced HCC patients treated in a large tertiary medical center, the efficacy and toxicity profile of atezobev was similar to that reported in the IMbrave 150 phase III study.
Genomic profiling of biliary tract carcinomas by their location.
Authors: Gatalica Zoran , Edwards David K. , Flannery Cynthia A. , Hall David W. , Hoag Jess R , Therala Nishitha , LoBello Janine R. , Thakkar Snehal Govind , Basu Gargi D. , Abdelrahim Maen 
Published: June 2023

e16175 Background: Historically, biliary tract cancers have had a poor prognosis. Genomic profiling allows identification of alterations in genes with FDA-approved matched therapies either in these cancers ( FGFR2/3 fusions, certain IDH1 missense mutations), in all solid tumors (e.g. BRAF V600E mutations), or in other cancers (e.g. BRCA1/2 loss-of-function mutations) that could inform treatment. Here we examine the frequency of matched therapies in biliary tract carcinomas and the association with tumor location. Methods: All biliary tract carcinoma patient samples receiving the OncoExTra assay between April 2018 and November 2022 were included. The assay uses tumor-normal, whole-exome, whole-transcriptome sequencing to identify genomic alterations. Alterations in genes with FDA-approved matched therapies in any cancer, with matched clinical trials, or with evidence in cancer guidelines or the literature for possible matched therapies were recorded. Results: A total of 155 patient samples were processed: 92 intrahepatic CCA, 34 gall bladder carcinomas, 9 extrahepatic CCA, and 20 ampulla of Vater carcinomas. Targetable alterations were found in 153 (98.7%) samples; 31 (20.3%) had FDA-approved matched therapies, including 5 (3.3%) with microsatellite unstable and/or tumor mutational burden-high (eligible for immunotherapy) and 7 (4.6%) homologous recombinational repair deficient. Alterations of several genes showed a significant association with tumor type (Table). Cancers in the ampulla of Vater were enriched for KRAS, APC and ARID2 alterations; TP53 alterations were less frequent in biliary tract/intrahepatic cancers. Among the 15 FGFR1/2/3 alterations, there were 3 amplifications (1 FGFR1, 1 FGFR2, 1 FGFR3), 3 missense FGFR2 mutations, and 9 FGFR2 fusions. Conclusions: Comprehensive genomic profiling of biliary tract cancers identifies numerous targetable alterations. The distribution of altered genes varies, suggesting that appropriate therapies may differ by location, reflecting different lineage types. [Table: see text]
Changing survival of intrahepatic cholangiocarcinoma based on Surveillance, Epidemiology, and End Results Database (2000–2018).
Authors: Wang Yating , Reap Leo Edward , Chang Kevin Wei-Lun , Terebelo Howard R. , Lyons Susan Elizabeth , Yu Zhiyong , Yu Qian 
Published: June 2023

e16182 Background: Intrahepatic cholangiocarcinoma (iCCA) is a primary hepatic malignancy arising from peripheral intrahepatic bile ducts with poor survival and increasing incidence. Treatment regimen has changed in the last two decades, whereas new molecular targeted therapies have emerged. The present study aims to characterize changes in treatment outcomes of iCCA using a national representative database. Methods: Data were retrieved from the Surveillance, Epidemiology and End Results (SEER) 18 Research Plus Database. Overall survival (OS) was analyzed based on age, gender, race, histological grade, stage, and treatment. Predictors of OS were evaluated by Cox regression models. Statistical analysis was performed with Stata 15.1 (STATA Corp., College Station, TX, USA). Results: The overall observed OS from 2000 to 2018 at 12, 36, and 60 months were 42.6%, 16.4%, and 10.2%, respectively. The median survival time (MST) increased from 6 to 11 months from 2000-2004 time period to 2015-2018 (p < 0.0001). Such an improved trend was observed in all stage groups (p < 0.0001). Among patients diagnosed after 2015, the 12, 24, and 36 month OS were 45.9%, 26.4% and 17.4 %, respectively; the MST were 25, 13, and 6 months for patients with localized (12-month OS: 72.7%; 36-month OS: 37.5% ), regional (12-month OS: 51.4%; 36-month OS: 18.9%), and distant diseases(12-month OS: 28.2%; 36-month OS: 4.5%), respectively (p < 0.0001). On multivariable analysis, older age, female, grade, stage, whether surgery, chemotherapy or radiotherapy was performed were statistically significant predictors of OS (p < 0.001). Conclusions: Survival outcomes of iCCA improved in the last twenty years in all cancer stages. Age, gender, grade, stage, and whether interventions were performed were prognostic factors.