bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donafenib combined with hepatic artery infusion chemotherapy (HAIC) and sintilimab for unresectable hepatocellular carcinoma (uHCC): A prospective, single-arm phase II trial (DoHAICs study).
Authors: Zhang Wei , Gao Wei , Liu Chen , Li Guangtao , Zhang Qin 
Published: June 2023

e16165 Background: The combination of anti-angiogenesis and immune checkpoint inhibitors has been proved to improve clinical outcomes of uHCC, but efficacy still does not meet clinical needs. In Phase III study (ZGDH3), donafenib showed the survival benefit and better safety compared with sorafenib. HAIC significantly improved treatment responses over TACE in patients with large uHCC in a Phase III trial. Considering the different mechanisms, this study aimed to investigate the safety and efficacy of HAIC combined with donafenib and sintilimab in patients with uHCC. Methods: This is a prospective, single-arm phase II study (NCT05166772). Patients with histologically diagnosed uHCC, no previous systemic treatment, Child-Pugh A5-B7, ECOG performance status (PS) of 0 or 1 were eligible for inclusion. Enrolled patients received donafenib (200 mg, bid), sintilimab (200 mg, q3w) and HAIC (oxaliplatin 85 mg/m2 2h, leucovorin 400 mg/m2 2h, fluorouracil bolus 400 mg/m2 in the first 10 minutes, and fluorouracil infusion 1200 mg/m2 for 23 hours, q3w) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Results: From December 2021 to December 2022, 24 patients (19 men and 5 women; median age, 58 years) were enrolled: BCLC stage A/B/C: 2/9/13; Child-Pugh class A/B: 23/1; ECOG PS 0/1: 23/1. There were 19 (79.2%) pts with hepatitis B. The median tumor size was 7.9 cm (range, 1.7-16.3), 45.8% pts presented macro vascular invasion, the invasion rates of Vp3, Vp4 and inferior vena cava were 25.0%, 4.2% and 8.3% respectively, 16.7% had extrahepatic metastasis. As of February 10, 2023, the median follow-up time was 107 days, the median number of HAIC was 3 times (range, 1-8). Based on mRECIST, the ORR was 78.3% (95% CI, 56.3%-92.5%) with 3 (13.0%) complete responses (CR) and 15 (65.2%) partial responses (PR). The disease control rate (DCR) was 95.7% (95% CI, 78.1%-99.9%). Of 23 pts evaluable for response, the conversion success rate was 65.2% (15/23), 10 of them (43.5%) received hepatectomy, 3 cases (30.0%) achieved complete pathological response and 5 cases (50.0%) achieved major pathological response. The median time to response (TTR) was 1.9 months (range, 1.2-5.2). The median progression-free survival (PFS) was 10.2 months (95% CI, NR) and 6 months PFS rate was 89.1%. The median duration of response (DoR) was not reached. Any grade treatment-emergent adverse events (TEAEs) occurred in 95.8% of pts. The most common TEAEs were thrombocytopenia (66.7%), neutropenia (45.8%), rash (41.7%). Grade 3-4 TEAEs occurred in 37.5% of pts. No grade 5 TEAEs were observed. Conclusions: Preliminary analysis showed that donafenib combined with HAIC and sintilimab showed promising clinical benefits and acceptable toxic effects in patients with uHCC. The enrollment and follow-up are continuing. Clinical trial information: NCT05166772 .
Efficacy and safety of regorafenib alone or in combinations in the second-line setting for advanced hepatocellular carcinoma: A multicenter real-world study.
Authors: Zhang Wei , Zhao Yanrong , Ma Guixiang , Zhang Yu , Guo Yuan , Chen Zhong 
Published: June 2023

e16172 Background: Due to drug resistance or intolerable adverse events, most hepatocellular carcinoma (HCC) patients tend to experience TKI-based first-line therapy failure. However, there is no unified choice of second-line treatment after this. Different authors have demonstrated that the combination of regorafenib and PD-1 inhibitors or TACE depicts synergistic effect. Therefore, the major goal of this research is to explore the efficacy and safety of regorafenib alone or in combinations as second-line therapy for advanced HCC in a real-world setting. Methods: In this study 94 advanced HCC patients (84 male and 10 females, average age of 59.8 years) were included from 3 Chinese centers between September 2018 and August 2022. It includes pathologically or clinically diagnosed advanced HCC patients who received regorafenib alone or in combinations in the second-line setting for at least 28 consecutive days. The primary endpoints were objective response rate (ORR, mRECIST criteria), and progression-free survival (PFS), however, the secondary endpoints included overall survival (OS) rate at 12-month, disease control rate (DCR) and treatment-related adverse events (TRAEs). Statistical analysis was performed with Kaplan-Meier method by using log-rank test. Results: 32 (34.0%) patients had BCLC stage B (others had BCLC stage C) and 72 (76.6%) patients were of Child-Pugh A (others were of Child-Pugh B). Half of the patients received regorafenib 160mg once daily during weeks 1–3 of each 4-week cycle. The proportions of patients received single drug regorafenib therapy (REGO) and combination therapies (COM) were 26.6% and 73.4%, respectively. The combination treatment regimens included regorafenib plus PD-1 inhibitors (36.2%), regorafenib combined with TACE (11.7%), and triple therapy (regorafenib, PD-1 inhibitors, TACE) (25.5%). The ORR and DCR were 28.7% and 72.3% with a median PFS of 8.4 months (range 6.33-10.47) and 12-month OS rate was 92.6%. The median PFS of COM group was 8.7 months ranging from 7.09-10.32, which was significantly longer compared to REGO group (4.2 months, range 0.45-7.95) (P = 0.031). Moreover, 66 (70.2%) recipients had TRAEs and most frequent TEAEs (≥5%) included hand-foot syndrome (31.9%), diarrhea (20.2%), rash (13.8%), fatigue (7.4%), oral mucositis (7.4%) and arthralgia (5.3%). 12 (12.8%) recipients had grade 3 TRAEs, including hand-foot syndrome (8.5%), hypertension (2.1%), diarrhea (1.1%) and rash (1.1%). No Grade 4 TRAE and new safety signal were identified. Conclusions: In the second-line treatment of advanced HCC, regorafenib alone or in combinations is effective and well-tolerated. The combination therapy showed a longer survival than regorafenib alone.
Efficacy and safety in unresectable hepatocellular carcinoma using atezolizumab plus bevacizumab in later-line: A retrospective analysis of real-world evidence.
Authors: Cheng Jiamin , Chen Bowen , Zhang Xinfeng , Su Guodong , Peng Caiyun , Zhou Lin , Lei Jin , Li Yinyin , Lu Yinying 
Published: June 2023

e16173 Background: As far, no data has been published about later-line application of atezolizumab plus bevacizumab (T+A) in patients with unresectable hepatocellular carcinoma (uHCC). Methods: We retrospectively recruited uHCC patients who treated with later-line T+A. Efficacy endpoints included overall survival (OS) and progression free survival (PFS), in accordance with RECIST v1.1. Safety was evaluated with CTCAE v5.0. We also continually enrolled uHCC patients who received later-line regorafenib plus PD-1 inhibitors (Reg+PD-1) as a comparison. Results: Total 33 patients were continually included, 12 used T+A and 21 chose Reg+PD-1. Baseline performance status, liver function and BCLC tumor stage were similar between two cohorts. At data cut-off at February 2023, following median following-up at 18.9 months, median OS in cohort T+A and Reg+PD-1 were 8.2 (95%CI: 5.8-10.6) vs 15.6 (95%CI: 7.6-23.6) (p = 0.237). Median PFS in cohort T+A and Reg+PD-1were 5.1 (95%CI: 1.1-9.1) vs 3.5 (95%CI: 2.1-4.9) (p = 0.575). OS rate and PFS rate are listed. None of efficacy endpoints reached statistical difference. All patients suffered from AEs. No AEs-related death occurred. Conclusions: Efficacy and safety of later-line T+A in uHCC patients was similar with those who used regorafenib plus PD-1 inhibitors, which needed to be further confirmed. [Table: see text]
Comparison of Child-Turcotte-Pugh score and albumin bilirubin index score for advanced hepatocellular carcinoma at an LMIC tertiary cancer facility.
Authors: Sinha Nishant , Porwal Jasmine , Sehrawat Amit , Mitra Ruchi , Gargy Sumedha 
Published: June 2023

e16174 Background: Liver cancer, most commonly HCC, ranks third in cancer-related deaths. Hepatic dysfunction is a key factor in management. BCLC Staging uses CTP Score with objective biosynthetic and subjective parameters as ascites and encephalopathy. Albumin-bilirubin Index (ALBI) grade is an objective method of assessing hepatic dysfunction. Many studies have validated its predictive accuracy. The present study is an attempt to study the clinical profile, risk factor and to compare ALBI with CTP Score as a predictive marker of hepatic function in HCC. Methods: This is a prospective observational study from Feb 2022-Jan 2023. Patients with suspected HCC had physical examination and relevant lab investigations. Diagnosis is established with either appropriate imaging with raised AFP or by Histopathology. ECOG PS, CTP score, ALBI Grade, and BCLC Stage of HCC were assigned. Patients were treated accordingly and are being actively followed. The data was analysed using SPSS with appropriate statistical tests to study their clinical profile and the correlation between the two prognostic scores. Results: There were 54 new patients of HCC with 78.6% being males. Mean age of presentation was 60.88±10.6 yr, with majority had abdominal pain and distension. 78% were diagnosed on imaging with raised AFP. 31 had viral hepatitis with 19 having hepatitis B, and 12 Hepatitis C. 2 were HIV+ with Hepatitis B. 50% were alcoholic. 4 patients had active autoimmune conditions with 2 having RA, 1 had AIH and 1 having AS. 75% had cirrhosis with the majority having>50% liver involvement,61% having portal vein and bile duct invasion. 10,28, and 11 patients belonged to CTP class A,B and C respectively. 57% fell to BCLC Stage 3. 5,21,28 patients belonged to ALBI Grade 1,2 and 3 respectively. The higher ALBI Index had poorer biochemical, radiological profiles and BCLC Stages, signifying the similarity in prognostic severity. Positive correlation found between the CTP score and the ALBI grade (r=0.339; P Value=0.012). Conclusions: The above study concluded ALBI Index as a good prognostic tool for HCC management in low and middle-income countries. It has only 2 biochemical parameters, can easily be done on a single visit and as it correlates significantly with CTP Score.[Table: see text]
A retrospective study on the efficacy and safety of regorafenib alone or in combination in advanced hepatocellular carcinoma.
Authors: Fu Shouzhong , Chen Cong , Zhao Suming , Dai Feng , Yuan Hongxin , Gu Weiwei , Gu Zhuxin , Shi Rongfeng , Jia Pengfei , Lu Xiaohua , Chen Kang , He Ning , Zhao Hui 
Published: June 2023

e16176 Background: The earlier randomized phase III RESORCE trial and several real-world studies demonstrate that regorafenib improves overall survival (OS) in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of regorafenib alone or in combinations in advanced HCC. Methods: 60 Patients with pathologically or clinically diagnosed advanced HCC were enrolled. We retrospectively analyzed the efficacy and safety of patients who received at least one cycle of regorafenib between March 7, 2019 and December 25, 2022 in the Affiliated Hospital of Nantong University and Nantong Third People's Hospital. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). The secondary endpoints were overall survival (OS), disease control rate (DCR), and safety. The safety and efficacy were assessed by investigators per CTCAE v5.0 and mRECIST v1.1, respectively. Data on survival rates were calculated using the Kaplan-Meier method. Results: The average age was 62.63 years, and 95% were male. Most patients had a Child-Pugh A score (73.3%), and the proportion of patients with BCLC stage B and C classes were 41.7% and 58.3%, respectively. 3 (5%) patients received single-drug regorafenib therapy, and the remaining patients (95%) received different combination therapies, including regorafenib plus immune checkpoint inhibitors (ICIs) (10%), regorafenib combined with TACE (40%), and triple therapy (TKI, ICI, TACE) (45%). The ORR and DCR were 40% and 92%, respectively. With a median follow-up of 16.10 months (95%CI, 11.067-21.133), the median PFS was 8.4 months (95% CI, 5.597-11.203), and the median OS has not been reached. Most patients tolerated 120mg or 160mg once daily during weeks 1–3 of each 4-week cycle. 23 patients (38.33%) experienced adverse events (AEs). The most frequent AE (≥5%) included hand-foot syndrome (23.33%), diarrhea (11.67%), and fatigue (6.77%). The incidence of grade 3 AE was 3%. No grade 4 AE and new safety signals were identified. Conclusions: Regorafenib alone or in combination had a manageable safety profile and promising efficacy in advanced HCC patients.
Cholangiocarcinoma: A nationwide trend analysis from 2016 to 2020.
Authors: Ishaya Michelle , Litvin Rafaella , Pan Chun-Wei , Ibrahim Muhammad Bilal , Shah Mihir 
Published: June 2023

e16177 Background: Cholangiocarcinomas (CCAs) are epithelial malignancies arising from the biliary ductal system, occurring with an incidence of 1/100,000 people per year in the US. Most patients present with advanced-stage disease and prognosis is very poor, with five-year mortality rates ranging from 2-24% depending on stage and subtype. This study was designed to determine the trends and adverse outcomes of CCA. Methods: This retrospective trend study analyzes data from the Nationwide Inpatient Sample (NIS) for the years 2016-2020 to identify adult hospitalizations with a diagnosis of cholangiocarcinoma and to highlight epidemiological trends. Inpatient mortality, mean length of stay (LOS), mean total hospital charge (THC), and rates of procedures and complications were estimated. Multivariate regression trend analysis was used to assess statistical significance and adjust for confounders. Results: There was an increase in the number of CCA hospitalizations per total hospitalizations from 8.49/100,000 in 2016 to 11.0/100,000 in 2020 (p < 0.01). Mean age remained around 67 years old, and male predominance remained constant throughout this period (52.7%). White patients made up the majority of the study population (65.6%). Inpatient mortality ranged from 6.8% to 7.1%, with no statistically significant trend. However, there was an increase in mean THC (P-trend <0.05) with no significant change in mean LOS (P-trend 0.76). We found a decrease in endoscopic retrograde cholangiopancreatographies (ERCPs) performed (1.6% to 1.2%, p=0.05), biliary duct stents placed (1.2% to 0.6%, p=0.003), and percutaneous biliary tract drains placed (4.2% to 3.4%, p=0.002) from 2016 to 2020. An increase was seen in rates of acute kidney injury (AKI) (22.9% to 28.6%, P<0.05), stent-related complications (2.0% to 2.6%, P=0.01), and peritoneal metastasis (7.7% to 9.3%, P<0.05). Biliary duct obstruction, stent-related infection, and palliative care utilization did not show any statistically significant change during this time. Conclusions: CCA hospitalizations increased from 2016 to 2020. Demographics remained unchanged, with a stable inpatient mortality rate but increased THC. The use of ERCPs, biliary duct stents, and percutaneous biliary tract drainage devices decreased, but rates of AKI, stent-related complications, and peritoneal metastasis increased. It is unclear what factors led to decreased procedure rates and increased complication rates. No significant changes were observed in biliary duct obstruction, stent-related infections, or palliative care utilization.[Table: see text]
A survey on the detection of hepatitis B virus (HBV) in blood samples of patients with hepatocellular carcinoma (HCC) in China.
Authors: Gao Biwei , Xu Ruilian , Hu Bo 
Published: June 2023

e16178 Background: China is the country with the highest occurrence of HCC, accounting for about 45.3% of the new cases in the world. HBV can cause chronic infection and potentially leads to the occurrence of HCC. Generally, HBV genomic segments are able to be integrated into the host’s genome, then affect the expression of host genes, form carcinogenic proteins and cause chromosomal aberrations in host cells. HCC tumor tissue samples have more integration sites of HBV on the genome compared with para-cancerous tissues. It suggests that HBV is likely to be continuously enriched and integrated in the host genome during the development of HCC, and promotes the occurrence of HCC. There is plenty of tumor molecular information in the blood plasma of patients. Features of virus integration patterns and relatively quantitative level of virus DNA in the blood plasma should be intriguing to study. Methods: 216 blood samples of 178 HCC Chinese patients were collected. Circulating cell-free DNA (cfDNA) was processed by hybridization-based target enrichment and sequenced by next-generation sequencing (NGS) technique using Haplox HapOnco 680 panel. Results: In the blood of 178 HCC patients, the cfDNA of a total of 58 patients was detected with HBV genome fragments integration. These HBV genome fragments mainly belong to two subtypes, HBV-B and HBV-C, of which single HBV-B type was detected in 18 cases, accounting for 31% of HBV integrated infections, single HBV-C type was detected in 39 cases, accounting for 67.2% of HBV integrated infections. Additionally, HBV-B and HBV-C were co-integrated in 1 case. In the integrated host genome, the average number of breakpoints produced by HBV-B infection was 3.158, and the most frequent integration site was ANKRD26P1 (6 times). The average number of breakpoints produced by HBV-C integration was 3.65, and the most frequent integration site was TERT (15 times). There was no significant difference in the number of breakpoints produced between HBV-B and HBV-C groups (p=0.49). In the total of 58 HBV-B datasets and 64 HBV-C datasets, the average abundance of integrated HBV-B reads was 5.6e-05, and the average abundance of HBV-C was 5.04e-0.5, and there was no significant difference between them (p = 0.71). Conclusions: Approximately one third of the 178 HCC patients were detected positive for HBV integrationin their blood samples, with the ratio of subtypes HBV-B and HBV-C roughly 1:2. HBV-B is slightly lower than HBV-C in the number of average breakpoint, but the difference is not significant. Similarly, the overall abundance of HBV-B and HBV-C of integrated reads in blood is also quite similar. However, the hotspot integration sites of HBV-B and HBV-C on the host genome are quite different.
Trends in hepatocellular carcinoma rates by age, region, race, and ethnicity: A SEER database population study 2000-2019.
Authors: Schodowski Eve , Alkrekshi Akram , Al Zubaidi Anas , Al Armashi Abdul Rahman 
Published: June 2023

e16179 Background: Liver cancer (LC) incidence has tripled over the past four decades, with hepatocellular carcinoma (HCC) being the most common type (72%). Further, LC mortality often coincides with incidence, as the disease is often fatal. To illustrate, the five-year survival rate (2012-2018) for LC is 21% at all stages, compared to lung cancer at 23% and colon cancer at 65%. While incidence and death rates of LC have stabilized in the past 5 years, troubling disparities have been identified when rates are stratified by region, age, race, and ethnicity. For example, HCC incidence in rural areas has increased by 5.7% annually, with rates approaching that of urban ones, despite a historically lower incidence. Consequently, as several inequalities in HCC have been established, the study herein aims to identify whether recognition of these disparities has helped to reduce their growth. Methods: We identified incidence rates of HCC from the Surveillance, Epidemiology and End Results Program database at 4-year time intervals from 2000-2019, stratified by age above (>) and below (<) 60, metropolitan (M) vs nonmetropolitan (NM) counties, race, and ethnicity. Next, we calculated percent change and percent difference in HCC rates across time intervals and groups to evaluate trends. Results: Percent change in rates of HCC has increased since 2000 in those >60 in both M and NM areas with larger growth observed in NM counties. Conversely, between 2010 and 2019 HCC rates have declined in those <60, with a steeper decline observed in M (-18.2%) vs NM (-10.0%) counties. Alarmingly, when 2015-2019 HCC rates are stratified by race/ethnicity, each minority group studied exhibited considerably higher rates of HCC when compared to whites and non-Latinos of the same age group and region (percent difference = >60 M; >60 NM; <60 M; <60 NM): Black (50.3%; 37.2%; 24.1%; 26.6%), American Indian (21.2%; 85.8%; 7.6%; 77.5%), Asian (17.3%; 17.8%; 21.1%; 28.1%), and Latino (39.0%; 45.6%; 40.0%; 36.1%). [Reference: white rates = 35.4; 31.7; 5.1; 4.9 and non-Latino rates = 36.5; 33; 2.4; 2.5, respectively, per 100,000 and age adjusted to the 2000 US Standard Population]. Conclusions: Recent data describes a stabilization in LC incidence and death rates over the past 5 years. However, when HCC incidence is stratified by age, region, race, and ethnicity, disconcerting trends continue to be revealed. As such, interventions should be targeted at those >60, living in NM areas, and in the minority groups studied to combat these disparities. [Table: see text]