bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of donafenib combined with anti-PD-1 antibodies for initially unresectable hepatocellular carcinoma (HCC): A retrospective real-world study.
Authors: Liu Sulai , Zhou Shuyi , Song Yinghui , Liu Jianming , Guo Chao , Yang Pingzhou , Li Ou , Yi Weimin , Peng Chuang 
Published: July 2024

e16131 Background: Given its clear efficacy and high safety demonstrated in the phase 3 ZGDH3 study, donafenib has been recommended by the Chinese guidelines for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). Recently, combination therapies have shown favorable results. However, the clinical experience of donafenib combined with anti-PD-1 therapy for uHCC has not yet been investigated. Thus, we aimed to investigate the efficacy and safety of donafenib combined with anti-PD-1 antibody in the treatment of uHCC. Methods: A single-center, retrospective study was performed based on the medical records of consecutive patients diagnosed with HCC who were not suitable for curative surgery at Hunan Provincial People's Hospital from July 2021 to September 2023. Patient with ≥18 years, no prior systemic therapy, having at least one measurable lesion (per mRECIST) were enrolled. Patients were treated with donafenib and anti-PD-1 antibodies until disease progression or unacceptable toxicity, local treatment such as TACE, HAIC or ablation were allowed. The primary endpoint was progression-free survival (PFS) by mRecist criteria, and secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by mRecist criteria, and safety. The last follow-up time was December 15, 2023. Results: In total, 48 patients were enrolled: 87.5% males, median age 59.5 years (range, 32.0-78.0), 95.8% ECOG of 0, 68.8% HBV positive, 14.6% BCLC stage B, 75.0% BCLC stage C, 47.9% baseline AFP≥400 ng/mL, 70.8% with macrovascular invasion. Among them, 9 patients (18.8%) received donafenib combined with anti-PD-1 antibody as first-line treatment, 37 (77.1%) with concurrent TACE(n = 25) or HAIC(n = 6) or both as treatment(n = 6), 2 (4.2%) received ablation treatment. At the time of data cut-off, the median follow-up time was 10.0 months (95% CI, 6.37-12.2). Considering efficacy, 9 pts (18.7%) achieved complete response, 20 (41.7%) achieved partial response, 17 (35.4%) had stable disease, and 2(4.2%) had progressive disease. The ORR and DCR were 60.4% and 95.8% by mRecist, respectively. Median progression-free survival was 15.8 months (95% CI, 8.9-NA). Median overall survival was not reached, 12-month OS rate were 90.7% (95% CI:73.7%-96.9%). In terms of safety, 44 pts (91.7%) had TRAEs. The incidence of ≥grade 3 TRAEs was 33.3% (16/48). Common TRAEs included elevated AST(45.8%), hand-foot syndrome (39.6%), decreased platelet count(35.4%),elevated ALT(31.2%), rash (25.0%) and decreased white blood cell count (14.6%). Grade 3/4 TRAEs included elevated AST(10.4%), elevated ALT(8.3%), rash(8.3%) and hand-foot syndrome (8.3%). No grade 5 TRAEs were observed. Conclusions: Donafenib combined with anti-PD-1 antibodies shows promising efficacy and manageable toxicity in patients with initially uHCC.
Hepatocellular carcinoma etiology drives survival outcomes: A population-based analysis.
Authors: Cranford Hannah M. , Jones Patricia Denise , Liu Qinran , Koru-Sengul Tulay , Reis Isildinha M. , Pinheiro Paulo S. 
Published: July 2024

e16142 Background: Previous studies on survival differences according to etiology of hepatocellular carcinoma (HCC) (5-year observed survival of 23%) are limited to hospital-based series and restricted cohorts. We performed a population-based survival analysis by major HCC etiologies, inclusive of hepatitis-C virus (HCV), hepatitis-B virus (HBV), alcohol-related liver disease (ALD), and non-alcoholic fatty liver disease (NAFLD) as singular causes, in addition to unexplored dual etiological groups, (HCV&HBV, HCV&ALD, and HBV&ALD), and accounting for age at diagnosis, tumor characteristics, and socio-demographics. Methods: All 19,956 cases of HCC diagnosed in Florida during 2005–2018 from the Florida cancer registry were linked for HCC etiology using Agency for Healthcare Administration and Florida Department of Health viral hepatitis data. Survival analysis was performed for the 15,759 linked HCC cases, comparing HCC etiologic groups (4 single and 3 dual). Results included age-adjusted 5-year survival, Kaplan-Meier curves, and adjusted hazard ratios from Cox regression models. Results: The leading single etiology was ‘HCV only’ (n=4,983; 31.6%); the leading dual etiology was ‘HCV&ALD’ (n=2,694; 17.1%). The age-adjusted 5-year survival was low (<22%) across all HCC etiologies; however, non-ALD causes showed higher survival [‘HCV only’ (21.5%; 95%CI:20.2%–22.8%), ‘HBV only’ (20.2%; 95%CI:16.6%–23.9%), ‘NAFLD only’ (19.9%; 95%CI:18.7%–21.2%)] than ALD-related etiologies [‘ALD only’ (14.4%; 95%CI:12.7%–16.0%), ‘HCV&ALD’ (10.4%; 95%CI:9.0%–11.9%), ‘HBV&ALD’ (8.1%; 95%CI:2.2%–14.1%)]. Compared to the reference category ‘HCV only,’ age-adjusted hazard ratios were 1.69 (95%CI: 1.41–2.03; p-value<0.0001) for ‘HBV&ALD,’ 1.33 (95%CI:1.26–1.40; p-value<0.0001) for ‘HCV&ALD,’ and 1.35 (95%CI:1.28–1.43; p-value<0.0001) for ‘ALD only.’ Multivariable analysis including additional factors showed minimal variation from these results. Conclusions: Significant differences in survival based on HCC etiology are important for prevention, surveillance, and targeted treatments based on etiologic-specific biomarkers. Specific pathophysiological mechanisms for ALD in addition to viral hepatitis could be responsible for poorer outcomes for dual etiologies involving alcohol use, compared to viral etiology alone. To increase overall survival, improved screening is needed for patients with multiple HCC risk factors. [Table: see text]
Comparing the efficacy and safety of TACE combined with donafenib or lenvatinib in the treatment of unresectable hepatocellular carcinoma.
Authors: Wei Ning , Lu Dong , Zhou Chunze , Cheng Delei , Zhang Zhengfeng , Zhang Xingming , Xiao Jingkun , Lv Weifu 
Published: July 2024

e16153 Background: For unresectable Intermediate/Advanced-Stage Hepatocellular Carcinoma (uHCC), the efficacy of TACE monotherapy has been unsatisfactory. Studies have shown that TACE combined with molecular targeted drugs exhibits potential synergistic effects, which can prolong the overall survival (OS) of uHCC patients (pts). Donafenib and lenvatinib are small molecule targeted drugs approved as first-line treatments for HCC. The aim of this study is to evaluate the efficacy and safety of TACE combined with donafenib or lenvatinib in the treatment of uHCC. Methods: A retrospective analysis was conducted on the clinical data of uHCC pts treated with donafenib combined with TACE (Dona-TACE) or lenvatinib combined with TACE (Lenva-TACE) at The First Affiliated Hospital of USTC from January 2018 to October 2022. The OS, progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR) of two groups of pts were evaluated according to the mRECIST, and the incidence of adverse events (AEs) was evaluated using CTCAE 5.0. Pts with complete baseline information and at least one follow-up evaluation were incorporated in the final analysis. Results: A total of 105 pts treated with donafenib and 59 pts treated with lenvatinib met the study criteria. After matching with a 1:1 propensity score, 35 pts in the Dona-TACE group and 35 pts in the Lenva-TACE group were included in this study. The baseline characteristics of the two groups are similar (males, 85.7% vs. 85.7%; ECOG PS of 1, 74.3% vs. 71.4%; Exceeding up-to-seven criteria, 74.3% vs. 62.9%; BCLC stage C, 42.9% vs. 40.0%; Combination immunotherapy, 62.9% vs. 54.3%). There was no significant difference in median OS (29.0 vs. 27.3m, P = 0.748) and median PFS (10.5 vs. 10.3m, P = 0.869) in the Dona-TACE and Lenva-TACE groups. The ORR (85.7% vs. 74.3%, P = 0.969) and DCR (94.3% vs. 97.1%, P = 0.280) of the Dona-TACE and Lenva-TACE group were equivalent. Compared with the Lenva-TACE group, pts in the Dona-TACE group had a lower incidence of grade 3-4 adverse events (any grade, 94.3% vs. 91.4%; grade 3 or 4, 34.3% vs. 57.1%, P < 0.05). Among them, pts in the Dona-TACE group had a lower incidence of proteinuria (any grade, 22.9% vs 42.9%; grade 3 or 4, 0 vs17.1%, P < 0.05) and hypertension (any grade, 42.9% vs 71.4%; grade 3 or 4, 2.9% vs 25.7%, P < 0.05) than those in the Lenva-TACE group. Multivariate analysis showed that ECOG PS score, up-to-seven criteria, and tumor blood supply were independent prognostic factors affecting OS (HR, 3.470, 3.619, 3.067; P < 0.05). Conclusions: The efficacy of donafenib and lenvatinib combined with TACE in the treatment of uHCC is equivalent. Furthermore, compared to lenvatinib combined with TACE, donafenib combined with TACE has higher safety.
Changing treatment patterns for hepatocellular carcinoma: A SEER-Medicare study.
Authors: Iheanacho Franklin , Tramontano Angela , Abrams Thomas Adam , Manz Christopher 
Published: July 2024

e16166 Background: Sorafenib was the first systemic therapy approved in 2005 for hepatocellular carcinoma (HCC), then 9 new therapies were approved between 2017-2022. No studies have evaluated treatment patterns of systemic therapy since these therapies became available. Methods: This retrospective cohort study used SEER-Medicare data to identify patients with a new diagnosis of HCC between 2014-2019 and associated comorbidity and treatment claims through 2020. Patients had continuous coverage with Medicare Parts A/B/D from 3 months before diagnosis to the earlier of 3 years, death or censoring. We excluded deaths reported by death certificate or autopsy. We used claims to identify receipt of local therapies (ablation, transplant, resection, transarterial bland/chemo/radioembolization, external/stereotactic radiation, brachytherapy) and all FDA-approved systemic therapies for HCC. We described cohort characteristics, treatment patterns, and overall survival (OS) and used Chi-squared statistics to compare treatment patterns and OS for patients diagnosed between 2014-17 vs 2018-19. Results: 11,799 patients were included (69.2% male, 76.9% White, median age: 71 years, 36.2% NAFLD, 44.1% Hepatitis C, 10.6% Hepatitis B, 28.1% alcoholic liver disease). Within one year of diagnosis, 76.3% of all patients received any local or systemic treatment, which did not change over time (2014-17: 76.1%, 2018-19: 76.6%, p=0.60). Receipt of local therapy within 1 year was unchanged (2014-17: 73%, 2018-19: 73.2%, p=0.77) and there were no clinically significant changes in treatment rates for specific local therapies. Receipt of systemic therapy in the first year decreased slightly (2014-17: 16.97%, 2018-19: 15.2%, p=0.012). First line systemic treatment changed drastically: 83.7% of patients diagnosed in 2014-17 received first-line sorafenib vs only 40.1% of those diagnosed 2018-19 (Table). Median overall survival for patients receiving no treatment, systemic therapies first or local therapies first was 1.9, 11 and 16.3 months, respectively. Among patients receiving systemic therapy first, survival from initiation of first line treatment increased from 9.1 to 11.2 months for patients diagnosed in 2014-17 vs 2018-19 (p= <.0001). Conclusions: While overall local and systemic treatment rates have not changed substantially, more recent patients with HCC are more likely to receive first-line novel therapies over first-line sorafenib and associated survival has modestly increased. [Table: see text]
The safety of atezolizumab plus bevacizumab (atezo/bev) treatment in Chinese patients (pts) with hepatocellular carcinoma (HCC) with active hepatitis B virus (HBV) infection: Results from the TALENTop study.
Authors: Zhu Xiao-Dong , Sun Hui-Chuan , Shen Feng , Bai Xueli , Chen Minshan , Huang Zhiyong , Song Tianqiang , Zeng Yongyi , Kuang Ming , Xiang Bangde , Liu Lianxin , Li Deyu , Wen Tianfu , Chen Yongjun , Peng Tao , Li Xiangcheng , Zhou Jian , Fan Jia 
Published: July 2024

e16168 Background: HCC pts with active HBV infection were excluded from most clinical trials involving immune checkpoint inhibitors because of safety concerns. We are aiming to evaluate the treatment safety of atezo/bev treatment in the TALENTop study (NCT04649489) which enrolled a large number of pts with active HBV infection. Methods: The TALENTop study is to clarify whether liver resection may provide additional benefits in Chinese HCC pts with macrovascular invasion who responded to conversion therapy with atezo/bev. After two versions of protocol modification, pts with active HBV infection were allowed. This study is ongoing, and the primary analysis is expected later. The current analysis is to evaluate treatment safety in pts with active HBV infection in the induction phase when pts received 3 cycles of atezo/bev and 1 cycle of atezo monotherapy. We compared the adverse events (AEs) between pts with active (baseline serum HBV-DNA ≥500 IU/mL) or inactive HBV infection (HBV-DNA < 500 IU/mL). All pts with detectable HBV-DNA or positive hepatitis B surface antigen received oral antiviral therapy throughout the study. Results: From Apr 2021 to Sep 2023, 296 pts were enrolled and completed induction phase therapy of atezo/bev. 274 pts (92.6%) had HBV-related HCC, and 133 pts (44.9%) had active HBV infection. The baseline characteristics were mainly balanced between groups, except pts with active HBV infection were younger (52 vs 56 years, P = 0.024), had larger tumor size (the diameter of target lesion 88.3 vs 78.1 mm, P = 0.007), and had higher album-bilirubin score (-2.62 vs -2.80, P < 0.001). In the induction phase, the AEs of any grade were higher in pts with active HBV infection (88.0% vs 73.6%, P = 0.002). However, the grade ≥3 AEs (20.3% vs 17.8%, P = 0.584), grade ≥3 treatment-related AEs (12.0% vs 12.3%, P = 0.950) and serious AEs (15.0% vs 13.5%, P = 0.706) were comparable between pts with active and inactive HBV infection. Additionally, the incidence of liver-related AEs was also comparable, including increased AST (17.3% vs 16.0%), increased ALT (17.3% vs 14.7%), and increased bilirubin (10.5% vs 12.9%). AEs leading to treatment withdrawal were also comparable (6.0% vs 6.1%, P = 0.966). In pts with active HBV infection, 20.8% remained serum HBV-DNA ≥500 IU/mL at the end of cycle 4. Conclusions: Active HBV infection did not compromise the safety of atezo/bev therapy. These findings could support that, with concurrent use of oral antiviral therapy, pts with active HBV infection should be not excluded from clinical trials or delayed for immunotherapy. Clinical trial information: NCT04649489 .
The treatment outcomes of patients who failed to be randomly assigned after atezo/bev induction therapy in the Chinese TALENTop study.
Authors: Chen Yiwen , Sun Huichuan , Shen Feng , Chen Minshan , Huang Zhiyong , Song Tianqiang , Zeng Yongyi , Kuang Ming , Xiang Bangde , Liu Lianxin , Li Deyu , Wen Tianfu , Chen Yongjun , Peng Tao , Li Xiangcheng , Zhu Xiaodong , Zhou Jian , Fan Jia , Bai Xueli , Liang Tingbo 
Published: July 2024

e16183 Background: Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) are considered to be at an advanced stage of disease with limited treatment options. The combination therapy of atezolizumab (atezo) plus bevacizumab (bev) has become a global standard of care for those patients and made conversion resection possible. The Chinese TALENTop study (NCT04649489) is aiming to clarify whether hepatic resection may provide additional benefit in HCC patients with MVI responding to atezo/bev. For patients without opportunity to receive hepatic resection, subsequent treatment outcomes will be reported. Methods: Potentially resectable HCC patients with MVI and without extrahepatic metastasis are eligible for this study. Eligible patients receive 3 cycles of atezo/bev and 1 cycle of atezo as primary systemic therapy (induction phase). Patients assessed as partial response (PR) or stable disease (SD) per RECIST v1.1 and considered suitable for R0 hepatic resection are randomized in a 1:1 ratio to either Arm A, hepatic resection followed by atezo/bev for 1 year, or Arm B, continuing atezo/bev therapy. The primary endpoint is the time to treatment failure. Patients failed to be randomized will enter the survival follow-up phase. After 296 patients entered induction phase, the patient profile, subsequent treatments per local standard of care and survival of patients who failed to be randomized were analyzed. Results: From Apr 2021 to Jun 2023, 296 patients were enrolled and entered induction phase and 175 patients failed to be randomized and were followed up until Sept 2023. The main reasons for failure to be randomized were disease progression (64.6%), investigator assessment of unsuitability for R0 hepatic resection (14.3%), and others. The 175 patients were characterized with a median age of 52 (26-76), and 166 (95%) had HBV infection. Among them, 165 (94%) had combined PVTT, 24 (14%) had combined HVTT and 5 (3%) had combined IVCTT. At a median follow-up time of 10.9 months (9.7-13.1), the median overall survival (mOS) is 13.8 months (8.9-15.8), 6- and 12-month survival rate were 71% and 53%, respectively. As the result of best response during induction phase, 3 patients (1.7%) achieved PR, 92 patients (52.6%) achieved SD and 65 patients (37.1%) were PD. 123 patients (70%) received subsequent therapy. The mOS of patients received different subsequent therapies was showed below. Conclusions: This study provides data on HCC patients with MVI after receiving atezo/bev. The result shows favorable survival even in patients failed to randomization to receive conversion resection, and subsequent treatment strategy may differ survival outcomes. Clinical trial information: NCT04649489 . [Table: see text]
Association between somatic mutation pathways and treatment response in patients with biliary tract cancers (BTCs).
Authors: Birda Vaibhav , Osataphan Soravis Alm , Lyon James , Paredes Rodrigo , Rattani Ahmed Anwer Ali , Peters Mary Linton Bounetheau 
Published: July 2024

e16196 Background: Comprehensive somatic genomic profiling has become the standard of care for patients with BTCs, serving to identify targetable mutations and aiding in prognostication. While previous studies have identified individual somatic mutations such as TP53, CDKN1A, and KRAS as negative prognostic markers, little is known about their role as predictive biomarkers. This study aimed to investigate the predictive potential of somatic mutations and pathways using commercially available next-generation sequencing. Methods: We conducted a retrospective cohort study at Beth Israel Deaconess Medical Center (BIDMC) from January 2016 to January 2023, with data censoring in January 2024. Patient characteristics, including age, gender, race, stage, site of metastasis, performance status, and survival status, were collected. Somatic genomic alterations data were extracted from FoundationOneCDx, a commercially available NGS platform designed to capture 324 genetic alterations validated for therapy targets or unambiguous drivers of oncogenesis. Genetic alterations were classified into 14 oncogenic pathways constructed based on the TCGA and Reactome databases. Multivariate Cox proportional hazards regression analysis was performed between pathway alterations, progression-free survival and overall survival, accounting for selected covariates with p < 0.05 or potential known confounders. Results: Among 97 BTCs, 90 were successfully sequenced. Among these, 40 patients received gemcitabine and cisplatin, and 28 received fluorouracil and oxaliplatin (FOLFOX) therapy. Intrahepatic cholangiocarcinoma was present in 70% of cases, perihilar or distal cholangiocarcinoma in 27%, and gallbladder carcinoma in 3%. At presentation, 18% had stage I disease, and 44% had stage IV. The median follow-up time was 15 months. A total of 339 genomic alterations were identified, with 8% of samples harboring FGFR fusion or mutation, 9% IDH1 mutation, 6 % HER2 amplification, 30% KRAS mutation, and 32% with TP53 mutation. The most affected pathways were the cell cycle (66%) and DNA repair (50%). In multivariate regression analysis accounting for age, ECOG, and anatomical location, TP53 mutation was associated with shorter progression-free survival on gemcitabine and cisplatin treatment (n = 11, 2 vs. 6 months, HR 4.19, 95% CI 1.51 – 11.7, p < 0.01), whereas cell cycle pathway mutation was associated with longer progression-free survival (n = 14, 6 vs. 5 months, HR = 0.43, 95% CI 0.19-0.96, p < 0.05). No association was found between oncogenic pathways and treatment response to FOLFOX therapy. Conclusions: TP53 mutation is associated with a worse response, whereas cell cycle pathway mutations are associated with an improved response to gemcitabine and cisplatin therapy in patients with BTCs. Further research is needed to understand the mechanisms contributing to these observed effects.
Magnesium microspheres to enhance lipiodol-mediated transarterial chemo-embolization (TACE) of hepatocellular carcinoma: From bench to a pilot clinical study.
Authors: Zheng Liyun , Ji Jiansong 
Published: July 2024

e16204 Background: Transarterial chemoembolization (TACE) has been extensively used in clinic to treat unresectable hepatocellular carcinoma (HCC). However, arterial embolization would worsen the hostile physicochemical features in the tumor microenvironment (TME) by further reducing its pH and increasing hypoxia, leading to immunosuppressive TME and drug resistance. Methods: Magnesium microspheres (Mg MSs), acting as H2 donors and pH modulators, were prepared via gas atomization pulverization. Characterization included inverted optical microscopy, SEM, and XRD analysis. Their H2 generation and acid neutralization capabilities were confirmed. The Lip-Mg dispersion (Mg MSs dispersed in lipiodol) was tested for therapeutic efficacy in H22 murine liver tumor-bearing mice, 4T1, and CT26 subcutaneous tumor models, as well as in vivo interventional TAE therapy for rabbit orthotopic liver tumors. The modulated capacities of Lip-Mg in H2 gas generation, acid neutralization, and promotion of antitumor immune response were investigated in vivo. Finally, a single-center, single-arm, open-label trial (ChiCTR2200064999) evaluated the safety and efficacy of TACE treatment with Lip-Mg (M-TACE) in Chinese HCC patients. Results: Inverted optical microscopy and SEM images confirmed uniform, smooth Mg microspheres (~60 μm) with a grayish-white color. In acidic buffer (pH 6.4), Mg microspheres rapidly increased pH, as measured by pH meter or fluorescent probe. Lip-Mg treatment significantly inhibited tumor growth compared to controls, prolonging mouse survival by ~2-fold, validated in 4T1 and CT26 models. Ultrasonic and multispectral fluorescence imaging demonstrated Lip-Mg's ability to release H2 and neutralize pH in vivo, reversing the immunosuppressive tumor microenvironment. Clinical study showed manageable treatment-related adverse events, with no unexpected toxicities and negligible impact on serum magnesium levels, confirming the safety of Mg microspheres for M-TACE. According to mRECIST, M-TACE exhibited high CR (61.5%), PR (38.5%), and ORR (100%) rates, with an overall response rate and CR rate of 90% and 60%, respectively. Conclusions: Metallic Mg microspheres (~60 μm) were developed to enhance lipiodol-mediated TAE/TACE for HCC. When combined with lipiodol and injected, they neutralized the acidic TME, triggered hydrogen therapy, and reversed immunosuppression, effectively inhibiting tumor growth. Lip-Mg showed superior outcomes to lipiodol alone for TAE therapy, with M-TACE treatment exhibiting higher ORR and CR rates than cTACE. Post-M-TACE, adverse events were managed well without treatment discontinuations. Our study introduces Mg microspheres as a promising embolic device for M-TACE therapy, potentially improving TACE benefits. Clinical trial information: ChiCTR2100050327.