bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective cohort study on the improvement of disease-free progression survival in patients with hepatocellular carcinoma by combining Sophora japonica granules with targeted and immune checkpoint inhibitors.
Authors: Li Hui , Zhang Hongliang , Zhang Tong , He Wenting 
Published: July 2024

e16187 Background: To evaluate the clinical efficacy of combining Sophora japonica granules with targeted therapy and immune checkpoint inhibitors (ICIs) in patients with unresectable hepatocellular carcinoma (HCC) who had not undergone systemic treatment. Methods: A prospective cohort study design was adopted (ChiCTR2400079626), collecting HCC patients visited the Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from July 1, 2019, to July 1, 2023. All patients received targeted therapy and ICIs treatment. "Whether Sophora japonica granules were combined during treatment" was considered as the exposure factor. Patients who met this exposure factor were included in the exposure group (n = 48), and those who did not meet this factor were included in the non-exposure group (n = 44). The disease-free survival (PFS), six-month PFS rate, and subgroup analysis between two groups. Results: The PFS of the exposure group was 8.9 months (m), and that of the non-exposure group was 5m(P = 0.001 HR = 0.50, 95%CI (0.32~0.78)). The six-month PFS rates were 66.7% compared to 34.1%(P = 0.001). Subgroup analysis showed that in subgroups with hepatitis, cirrhosis, vascular invasion, extrahepatic metastasis, tumor maximum diameter ≥5cm, combined TKI, the exposure group had significantly longer PFS than the non-exposure group (respectively: 9m VS 5m, 10m VS 4m, 13m VS 3m, 8.3m VS 4m, 9m VS 4m, 9m VS 5m),(P < 0.05). In the subgroup with a history of alcohol consumption, the exposure group's PFS was extended by 9 m (14m VS 5m; P = 0.010); in the subgroup with baseline AFP ≥400ng/ml, PFS was extended by 6m (9m VS 3m; P = 0.017), and in the subgroup with baseline AFP < 400ng/ml, PFS was also extended by 2.9m (8.9m VS 6m; P = 0.024), with all differences being statistically significant. Multivariate analysis showed that extrahepatic metastasis was an independent prognostic factor, with a disease progression risk 1.77 times higher than that of patients without extrahepatic metastasis [HR = 1.77, 95%CI (1.11~2.81), P = 0.016]. Combining Sophora japonica granules was a protective factor [HR = 0.53, 95%CI (0.33~0.84), P = 0.006], reducing the risk of disease progression in HCC patients treated with targeted therapy and ICIs by 47%. Conclusions: Combining Sophora japonica granules can extend the progression-free survival of HCC patients treated with targeted therapy and ICIs, increase the six-month PFS rate, and significantly reduce the risk of disease progression. The survival benefit was more pronounced in subgroups with vascular invasion and a history of alcohol consumption, with PFS exceeding one year. After combining Sophora japonica granules, the survival benefit improved more in the ICIs + TKI subgroup compared to the ICIs + bevacizumab subgroup. Clinical trial information: ChiCTR2400079626.
A retrospective study of PD-1/PD-L1 combination therapy versus TKI monotherapy in elderly patients with uHCC.
Authors: Wang Nanya , Li Yu , Wang Ying , Liu Bo , Wang Shibo 
Published: July 2024

e16191 Background: The rising elderly population worldwide has led to an increase in cases of liver cancer among individuals aged ≥65 years. With the advancement of medical treatments, the management of unresectable hepatocellular carcinoma (uHCC) now predominantly involves immunotherapy combination therapy. However, existing data in elderly patients are limited. Therefore, we conducted a retrospective analysis on the efficacy and safety of immune combination therapy compared with TKI monotherapy in elderly uHCC patients. Methods: A retrospective analysis was conducted on uHCC patients aged ≥65 years at the First Hospital of Jilin University between March 2019 and July 2023. The targeted therapy used in this study included, but not limited to, sorafenib, lenvatinib. PD-1/PD-L1 inhibitors such as pembrolizumab and atezolizumab were also utilized. Follow-up was conducted until death, loss to follow-up, or December 2023. The primary endpoint was overall survival (OS), while the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs) and immune-related AEs (irAEs). Results: A total of 70 patients were included in this study, with 33 patients receiving monotherapy, and 37 patients receiving immune combination therapy. The median age was 68 years old, with 78.8% being male. The combination therapy group had a higher ORR (10.8% vs. 3.0%) DCR (48.5% vs. 45.9%) compared to the monotherapy group. However, there were no statistically significant differences in median PFS (7.0 vs. 12.0 months) and median OS (9.8 vs. 17.5 months) between the two groups. Among the subgroups, combination therapy showed better results except for patients with ascites. Immune combination therapy appeared to be superior to monotherapy in terms of both PFS (6.2 vs. 6.8 months, P = 0.888) and OS (6.8 vs. 10.2 months, P = 0.888). Multivariate analysis showed that elevated total bilirubin may be a risk factor for OS in patients ≥65 years old. Regarding safety, the adverse event (AE) rate was 39.3% in the monotherapy group. The most common AEs reported were abdominal distension (18.2%), fatigue (15.2%), and proteinuria (6.1%). In the combination therapy group, the AE rate was higher at 59.4%, with the most common AEs being thyroid function abnormalities (24.3%), fatigue(24.3%), decreased appetite(18.9%), and hypertension(18.9%). The rate of drug withdrawal due to adverse reactions was significantly higher in patients receiving combination therapy compared to those receiving monotherapy (40.5% vs. 12.1%, P = 0.008). Conclusions: In elderly uHCC patients (≥65 years old), immune combination therapy shows a higher ORR and potentially longer PFS and OS except patients with ascites. AEs and drug withdrawal rates are higher in the combination therapy group. Further discussions are needed to determine the optimal treatment strategy for elderly uHCC patients.
Role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in unresectable hepatocellular carcinoma (uHCC): Subgroup analysis of patients treated with camrelizumab (cam) + rivoceranib (rivo) in the CARES-310 trial.
Authors: Burgoyne Adam , Kaseb Ahmed Omar , Shi Wei , Alexander Laura , Meng Xianzhang , Ryan Kristin , Galloway Chris , Neubach Will , Vogel Arndt , Chan Stephen Lam 
Published: July 2024

e16197 Background: CARES-310 (NCT03764293) evaluated the combination of the PD-1 inhibitor, cam, and the VEGFR-2 tyrosine kinase inhibitor, rivo, compared to sorafenib (sor) for the treatment of 543 patients (pts) with uHCC. Cam + rivo significantly improved mOS (22.1 months [mo] [95% CI 19.1-27.2] vs 15.2 mo [13.0-18.5] HR 0.62 [95% CI 0.49-0.80]; one-sided p < 0.0001) and mPFS (5.6 mo [95% CI 5.5-6.3] vs 3.7 mo [2.8-3.7]; HR 0.54 [95% CI 0.44-0.67]; one-sided p < 0.0001) compared to sor. The most common (≥20%) grade ≥3 treatment-related adverse events (TRAEs) for cam + rivo were hypertension (37.5%) and increased AST (16.5%) vs palmar-plantar erythrodysesthesia syndrome (15.2%) for sor. An elevated level of inflammation, including NLR and PLR, have been associated with poor survival outcomes in pts with HCC (Lin S, et al. Trans Cancer Res. 2021). Here, we present a subgroup analysis of the CARES-310 trial evaluating the impact of baseline (BL) NLR and PLR status on pt outcomes. Methods: The subgroup of pts treated with cam+rivo and BL NLR < 5 or ≥5 and PLR < 300 or ≥300 were evaluated for mOS, mPFS, overall response rate (ORR), disease control rate (DCR), and safety. Results: Of 272 pts treated with cam+rivo, 64.3% of pts had extrahepatic spread, median AFP was 84.1 ng/mL, 86.8% were Child-Pugh (CP) class A5, 13.2% were CP class A6, 73.5% were ALBI grade 1, 26.5% were ALBI grade 2. Additionally, 249 pts had NLR < 5, 10 pts had NLR ≥5, 252 pts had PLR < 300, and 7 pts had PLR ≥300. Pts with BL NLR < 5 and PLR < 300 demonstrated improved outcomes in mOS, mPFS, ORR, and DCR vs pts with BL NLR ≥5 and PLR ≥300 (Table). Rates of any grade TRAEs and grade ≥ 3 TRAEs were comparable between pts with BL NLR < 5 and ≥5 and PLR < 300 and ≥300 (Table). Conclusions: These results suggest that NLR and PLR may serve as a prognostic marker in patients with uHCC, but larger studies are needed to validate these findings. Clinical trial information: NCT03764293 . [Table: see text]
Hepatic artery infusion of FOLFOX chemotherapy and camrelizumab combined with sorafenib for advanced stage hepatocellular carcinoma (Double-IA-001): A phase II trial.
Authors: Nuerhashi Gulijiayina , Shen Lujun , Fan Weijun 
Published: July 2024

e16199 Background: Hepatic arterial infusion chemotherapy (HAIC) using a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown excellent local control for hepatocellular carcinoma (HCC) patients classified under Barcelona Clinic Liver Cancer (BCLC) stage C. In China, both camrelizumab (a PD-1 inhibitor) and sorafenib were approved first-line approach for advanced stage HCC. This study (ChiCTR2100041874) aimed to the efficacy of combined hepatic artery infusion of FOLFOX chemotherapy and camrelizumab, together with sorafenib in BCLC stage C. Methods: Eligible patients were given a maximum of six cycles of hepatic artery infusion of HAIC-FOLFOX and camrelizumab, along with sorafenib, until either disease progression, intolerable toxicities emerged or disease downstaged and converted to received surgical resection. The primary outcome measured was the objective response rate (ORR) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: Twenty-five patients were enrolled. Based on mRECIST criteria, by the end of Feb 4, 2024, the confirmed ORR stood at 44.0%, with a disease control rate of 60.0%. The median progression-free survival was 3.33 months. Patient quality of life had a transient deterioration within four cycles of treatment, and generally recovered thereafter. A total of 28.0% of patients had grade ≥3 or above treatment-related adverse events, which could be alleviated after symptomatic treatment. Conclusions: The combination of double intrahepatic infusion of FOLFOX and camrelizumab with sorafenib demonstrated encouraging results and manageable safety concerns for BCLC stage C HCC. Clinical trial information: ChiCTR2100041874.
Impact of cholangiocarcinoma on the severity of acute cholangitis: A nationwide sample analysis.
Authors: Khan Shahryar , Amin Muhammad Kashif , Khan Muhammad Atif , Asif Samia , Khan Mashal Alam 
Published: July 2024

e16200 Background: Acute cholangitis (AC) is a clinical entity caused by bacterial infection of the hepatobiliary system, commonly secondary to obstruction of the bile duct or hepatic ducts. The outcomes are poor if not treated promptly. Cholangiocarcinoma (CC) is a group of heterogeneous cancers of the intrahepatic or extrahepatic bile ducts with a guarded prognosis. Our study aimed to evaluate the mortality and healthcare utilization of AC with and without CC in the United States. Methods: A retrospective cohort study of adult patients hospitalized in 2020 for AC in acute care hospitals across the USA. Patients were selected from the Nationwide Inpatient Sample (NIS) database. Our study population included all patients with a discharge diagnosis of AC with or without CC using the International Classification of Diseases (ICD-10). The primary outcome was in-hospital mortality, and secondary outcomes were the proportions of Endoscopic Retrograde Cholangiopancreatography (ERCP), early ERCP (within 24 hours), length of hospital stay (LOS), and total hospitalization charges. Analysis was performed using STATA version 18.0. Univariable logistic regression analysis was used to calculate the unadjusted odds ratio (ORs) for the primary and secondary outcomes. Multivariable logistic regression analysis was used to adjust for potential confounders. Results: Out of 32 million discharges included in the NIS database for 2020, our study included 38465 with AC including 2692 with CC and 35772 without CC. Comparing both cohorts, patients with AC, and CC were less likely to be female or white and had a higher Charlson comorbidity index. Furthermore, patients with AC and CC had lower adjusted in-hospital mortality (OR 0.66, 95% CI: 0.45-0.96), lower LOS(mean difference 1.102, CI: 0.31-1.88), lower total hospitalization charges $ (mean difference 22463, CI: 12115-32810). Patients with AC and CC had higher adjusted rate of in-hospital ERCP (OR 1.29, 95% CI: 1.07—1.56), and early ERCP within 24 hours (OR 1.29, 95% CI: 1.03-1.62). Total mortality in AC was found to be 6.8% (n = 2630, CI: 2374-2885), whereas mortality in CC from AC was 5.7%. Conclusions: Cholangiocarcinoma was observed to have an impact on the in-hospital mortality outcome of Acute cholangitis with increased utilization of resources, including ERCP. However, lower mortality from AC in CC is potentially contributed by early ERCP within 24 hours and a lower Charlson comorbidity index than AC without CC. [Table: see text] [Table: see text]
Survival of primary gallbladder cancer in the United States: SEER database analysis from 2000-2020.
Authors: Guragain Ashish , Inban Pugazhendi , Vaz Clint , Cheriyath Pramil , Nookala Vinod , Poudel Urusha , Kansakar Sajog , Shikhrakar Shreeja , Maroules Michael 
Published: July 2024

e16210 Background: Primary gallbladder cancer is a rare but aggressive cancer with poor outcomes. Our study aims to understand the survival trends of patients with Primary gallbladder cancer (PGC) and analyze the prognosis factors based on cases registered in the SEER database from 2000 to 2020. Methods: We usedSEER*Stat Version 8.4.3 software to extract primary gallbladder carcinoma cases from SEER 17 registries (2000-2020). 20,143 patients were included in the study. Those with unconfirmed histology were excluded. We analyzed overall mortality and primary gallbladder cancer-specific mortality (CSM) using a Cox proportional hazards model. The survival analysis was carried out using the Kaplan–Meier method and the log-rank test was used to compare survival curves. Results: There was an overall increase in gallbladder cancer cases by 23% in 2010-2020 compared to 2000-2010. There was no significant cancer-specific mortality difference identified between males and females (HR = 1.009; CI: 0.972-1.046). Non-Hispanic blacks had higher overall mortality (HR = 1.134; CI: 1.010-1.273) amongst different ethnicities. Crude analysis revealed overall mortality was higher among patients aged above 80 years (HR = 9.857; CI: 6.257-15.528). Crude analysis also revealed significantly higher cancer-specific mortality for cholangiocarcinoma (HR = 1.622; CI:1.509-1.744) amongst histological subtypes. Gallbladder cancer-specific mortality was high with regional disease (HR = 3.115; CI: 2.839-3.419) and increased significantly with distant metastases (HR = 7.169; CI 6.512-7.891). Treatment with surgery, chemotherapy, or radiation alone or in combination improved survival among patients. Conclusions: There is a significant increase in gallbladder carcinoma mortality even among patients with regional disease, and it was worse with metastatic disease. With limited early-stage diagnoses and poor overall survival rates, we recommend further research to develop effective screening methods, understand risk factors, and explore effective preventive and therapeutic strategies for primary gallbladder cancer.
Epidemiology, survival and new treatment modalities for intrahepatic cholangiocarcinoma (IHCC).
Authors: Wang Yating , Alsaraf Yasir , Bandaru Sai Samyuktha , Lyons Susan Elizabeth , Reap Leo Edward , Yu Zhiyong , Yu Qian 
Published: July 2024

e16217 Background: Intrahepatic cholangiocarcinoma (IHCC), a rare biliary tract cancer, has been rising in incidence and is associated with poor survival. With the advent of new treatment modalities and various ongoing research, population-based perspective can be helpful to reflect the progress in managing this deadly disease and provide updated outcome information as a reference for comparison during upcoming clinical studies. We would like to provide a 20-year update on incidence and survival with reference to landmark trials, with a focus on survival outcomes of the recent 5 years for future insights. Recent and ongoing clinical trials will be discussed. Methods: This study extracted population data from the Surveillance, Epidemiology, and End Results (SEER) database. Age-adjusted incidence rate (AAIRs) and survival rate (SR) trends were calculated from January 2000 to December 2020 using 22 registries for the US population. Incidence and survival rates were collected from the SEER database, reported per 100,000 population and age adjusted to the 2020 US standard population. The annual percent change (APC) was used to report long term trends. Results: In this analysis of 19,948 IHCC patients, the AAIR increased from 0.49 per 100,000 in 2000 to 1.38 in 2020 (APC 6.94, 95% CI 6.32 to 7.56), with a notable decline from 2019 to 2020. Incidence rates overall displayed an uptrend course across subgroups divided by sex, race, age, and disease stage. The age-adjusted mOS climbed from 5.28 months in 2000 to 9.3 months in 2013, maintaining between 8.0-9.0 months after 2013. Using 2010 as a cutoff, when the ABC-02 trial was published, the decade-based mOS increased from 6.55 in 2000-2010 to 9.06 in 2010-2020, which remained statistically significant at 1-year, 3-year, and 5-year OS. During 2015-2020, the overall mOS was 8.8 months, with mOS of 24.3 months, 12.1 months, and 5.4 months for local, regional, and distant stages, respectively. Conclusions: These results indicate a steady rise in IHCC incidence since 2000, consistent across all subgroups. Survival rates have improved since 2000 but stabilized after 2013, following the publication of the ABC-02 trial published in 2010, which used systemic gemcitabine and cisplatin for unresectable iHCC. Updated survival data from 2015 onwards will serve as a reference of comparison for forthcoming clinical trials.
Associations between radiomic phenotypes and genomic mechanisms in HBV-associated cholangiocarcinoma.
Authors: Jia Yunlu , Wan Mingyu , Shen Yifei , Ruan Jian 
Published: July 2024

e16249 Background: Despite the epidemiological association between cholangiocarcinoma (CCA) and HBV infection, little is known about the relevant oncogenic biomarkers for advancing cancer research and improving future patient therapy. Radiomics-based non-invasive biomarkers are promising to facilitate the translation of therapeutically related molecular subtypes for treatment allocation of patients with HBV-infected CCA. Methods: In this study, we included 55 CCA patients with whole-genome multi-omics data, proteomic data with matched magnetic resonance imaging (MRI) data from institute 1. A total of 431 patients with histopathological confirmed CCA (143 HBV-positive and 288 HBV-negative patients) were retrospectively enrolled from three institutes, and patients were allocated to the training (n = 302) and validation (n = 129) cohorts from different institutes or time period (7:3). Utilizing linear regression and gene set enrichment analysis, we identified statistically significant associations between radiomic imaging and various genomic features in HBV-positive or HBV-negative CCA patients. Additionally, we employed a random forest classifier based on radiomic features to predict the status of HBV infection, HBV-related gene mutations and protein expression profiling, and tested on an internal and an external CCA cohort (n = 53). Results: The analysis revealed significant and widespread associations between genomic features (somatic mutations, transcriptional activities and copy number variations) and radiomic features characterizing HBV infection status. Our results show that quantitative image features are capable of distinguishing several molecular phenotypes. We obtained significant predictive performance for HBV+ (AUC = 0.73), CA-199(AUC = 0.77) and NeuroInvasion (AUC = 0.71), activation of ESRP1(AUC = 0.79) and mutation of HNRNPUL2/MUC4 (AUC = 0.73). We externally validated the HBV prediction model (AUC = 0.76) on the internal and external cohort. The sensitivity, specificity, and accuracy were all > 70%. The radiomic signature succeeded to stratify patients into distinct survival outcomes according to HBV status, and remained an independent prognostic factor in multivariable analysis (DFS, P < 0.0001; OS, P = 0.029). Integrating the radiomic signature with clinicopathological-radiographic factors further improved prediction performance. A nomogram incorporating significant pathological predictors (HBV, CA-125, CA-199, Neuro invasion, peritoneal invasion, pT stage, pN stage, and differentiation, grade) and radiomics signatures displayed good prediction performance in estimating OS with AUC values of 0.895, 0.935, and 0.907 at 1, 3, and 5 years, respectively. Conclusions: This deep learning-driven combined radiomics model may provide as a useful tool to preoperatively predict HBV infection and improve therapeutic management of ICC patients.
Effect of malnutrition on cirrhotic patients with hepatocellular carcinoma: A nationwide study.
Authors: Obeidat Adham , Mansour Nour , Mahfouz Ratib , Aldiabat Mohammad 
Published: July 2024

e16250 Background: Liver cancer is the sixth most common cancer and the third leading cause of cancer mortality worldwide. There are two main types of primary liver cancers; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. HCC accounts for around 80% of primary liver cancer cases. Generally, HCC develops in genetically susceptible individuals with risk factors, especially in the presence of cirrhosis. Cirrhosis is a systemic disease, and malnutrition is a key feature as well as an important complication which can be associated with worse outcomes. In this study, we aim to characterize the potential effects of malnutrition on HCC patients with underlying cirrhosis. Methods: The United States Nationwide Inpatient Sample (NIS) was used to extract hospitalization data of patients admitted between 2016 to 2018. Using ICD10 revision codes, we identified adults with the diagnosis of cirrhosis who have HCC with concomitant malnutrition, including sarcopenia. The control group included cirrhotic HCC patients without malnutrition. The primary outcome was the in-hospital mortality. Secondary outcomes included encephalopathy, ascites, variceal bleed, hepatorenal syndrome (HRS) and length of stay (LOS). Multivariate logistic regression was used to adjust for relevant variables. Results: We identified 423,158 patients admitted with cirrhosis. 20,582 had HCC, and of those, 2560 patients had the diagnosis of malnutrition. In this group of patients, the mean age was 59.85 years. 30% were females and 62% were Caucasians. When adjusted to other relevant variables, malnutrition was associated with increased in-hospital mortality (OR 1.40; P-value 0.000). It was also associated with an increased chance of developing encephalopathy (OR 1.42; P-value 0.000), ascites (OR 1.62; P-value 0.000), and HRS (OR 1.33; P-value 0.000). Moreover, it was associated with increased LOS (OR 1.99; P-value 0.001). Other factors associated with increased in-hospital mortality in cirrhotic HCC patients are described in the table. Conclusions: Malnutrition is a common complication in patients with cirrhosis. If identified, it can be treated efficiently. In this study, cirrhotic HCC patients with malnutrition had an increased chance of mortality. Further, they were at increased risk for cirrhosis decompensation and other in-hospital complications, which in turn can lead to increased LOS and therefore increased financial burden. We recommend that clinicians pay attention to patients with malnutrition and to treat them in order to prevent these complications. [Table: see text]