bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular profiling of Chinese patients with advanced hepatocellular carcinoma using circulating tumor DNA.
Authors: Zhu Jianjiao , Li Mingwei , Ma Xiaoxue , Qin Jiayue , Cao Shanbo 
Published: June 2023

e16186 Background: Hepatocellular carcinoma (HCC) has limited treatment options. Molecular analysis of its mutational landscape may enable the identification of novel therapies. Noninvasive strategies are critical to HCC given the challenge of obtaining liver tissue biopsies. Recent studies show that circulating tumor DNA (ctDNA) can reflect tumor genomic profiles. Thus, we aimed to analyze the molecular characteristics of HCC using ctDNA. Methods: A total of 308 plasma samples and 32 matched tumor tissues from Chinese patients with hepatocellular carcinoma (n = 308) were analyzed by Acornmed panel with 808 cancer-related genes. Results: A total of 4984 somatic variations were identified in 96.1% (296/308) ctDNA, including 4202 single nucleotide variants, 772 copy number variations and 10 fusions, and the median blood tumor mutation burden (bTMB) was 4.36 mut/Mb. Alterations in TP53 (152/308, 49.4%) were the most prominent variation, followed by those in TERT (48/308, 15.6%), ARID1A (37/308, 12.0%), CTNNB1 (34/308, 11.0%), NF1 (16/308, 7.7%), BRAF (16/308, 7.7%), PTEN (22/308, 7.1%) and EGFR (19/308, 6.2%). Interestingly, in MET and MYC, amplifications occurred more frequently than mutations. Moreover, we systematically evaluated clinically actionable mutations and totals of 587 potential drug-related targets from 211 patients (68.5%) were identified. In addition, in 32 patients with matched tumor tissues and plasma samples, sequencing detected alterations in 96.9% (31/32) tumor tissue DNA (tDNA) and 100% (32/32) ctDNA, respectively. Further analysis found that 25.4% of mutations of tissues were founded in ctDNA and 32.5% of mutations of ctDNA were detected in tissues. Among them, 68.8% (22/32) patients had at least one overlapping variant called by tDNA and ctDNA. The most common shared mutation was TP53 (8/32, 25.0%), followed by PTEN (2/32, 6.3%) and ARID1A (2/32, 6.3%). Meanwhile, two shared copy number variants were detected in two patients (6.3%), respectively. Conclusions: This study contributes to the understanding of the molecular characteristics of HCC using ctDNA and suggests potential clinical utility for this technology. Furthermore, it can more comprehensively reflect the molecular mutation status of patients by combining tissue and ctDNA detection.
Real-world experience with atezolizumab plus bevacizumab in the management of non-resectable hepatocellular carcinoma refractory to first-line systemic therapy: Review of literature.
Authors: Devarkonda Vishal , Byreddi Laxman Yashwant , Balmuri Shravya , Gudi Thulasi , Gaddam Shiva Jashwanth , Keerty Dinesh 
Published: June 2023

e16189 Background: Hepatocellular carcinoma is the fifth most common cancer worldwide and the third leading cause of cancer-associated deaths. In 2020, the positive results of the IMbrave 150 trial and FDA (Food and Drug Administration) approval subsequently revolutionized the management of non-resectable hepatocellular carcinoma as the first-line treatment. However, their role as second-line therapy in people refractory to systemic therapy needs to be better studied. We perform a comprehensive literature review evaluating outcomes of atezolizumab plus bevacizumab in patients refractory to first-line systemic therapy. Methods: We performed a comprehensive literature search of PubMed, Embase, and Cochrane, evaluating the outcomes of atezolizumab plus bevacizumab in patients refractory to first-line systemic therapy. Results: Conclusions: Atezolizumab plus Bevacizumab is Safe and effective in the patient’s refractory to prior systemic therapy. However, when used as a second-line therapy, patients tend to have lower Median Odds of survival and Median progression-free survival. The outcome also changes with the type of prior systemic chemotherapy, with initial hyper-progression reported with prior therapy with lenvatinib. The AFP response at six weeks could be a predictive indicator of disease progression. [Table: see text]
Donafenib combined with camrelizumab and transarterial chemoembolization (TACE) as conversion therapy for unresectable hepatocellular carcinoma (uHCC): A prospective, single-arm, phase II study.
Authors: Cao Yajuan , Zhang Xuebin , Yue Yang , Peng Jin , Li Binghua , Shi Jiong , Tang Min , Chen Chaobo , Su Ke , Zhang Laizhu , Cheng Chunxiao , Yu Decai 
Published: June 2023

e16203 Background: Approximately 64% of Chinese patients with HCC were evaluated as China Liver Cancer Stage (CNLC) II/III tumors, equivalent to Barcelona Liver Cancer Stage (BCLC) B or C. The conversion of an initially unresectable HCC (uHCC) to a resectable HCC may be an optimal approach to achieve better outcomes. Although donafenib, camrelizumab and transarterial chemoembolization (TACE) were recommended for uHCC in Chinese guidelines, the effect of these agents in the pre-operative setting was unclear. The present study was to assess the feasibility and safety of donafenib plus camrelizumab with TACE as conversion therapy in patients with uHCC. Methods: Patients were enrolled if they were aged 18 to 70 with primary CNLC stage IIb/IIIa uHCC, Child-Pugh classification A or B (≤7 points) and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. The patients received donafenib (100 mg po Bid), camrelizumab (200 mg iv Q3W) and TACE for up to 4 cycles (usually 2 cycles, increased to 3 or 4 cycles if necessary), followed by investigator assessment. The primary endpoint was the rate of major pathologic response (MPR), defined as ≤10% residual viable tumor in postoperative specimens. The secondary endpoints were the R0 resection rate, event-free survival (EFS), objective response rate (ORR) and disease control rate (DCR) by mRECIST criteria, and safety. Results: Sixteen patients, 11 men (68.8%) and five women (31.2%), of median age 58 years (range 49-70 years) were enrolled from May 2021 to July 2022. At the data cut-off (November 2022), one patient was still awaiting surgery, whereas 12 (80.0%) of the remaining 15 patients were successfully converted to resectable. Of the 12 patients who underwent successful hepatectomy (R0 resection), 6 (50%) achieved MPR. Based on mRECIST criteria, the ORR was 81.3%, and the DCR was 93.8%. Median EFS was 9.0 months (95%CI 7.1-10.9 months). Most treatment-related adverse events (TRAEs) were grade 1-2. Grade 3 TRAEs occurred in 4 patients. No patient experienced a Grade 4 or 5 TRAE. Conclusions: These preliminary results suggested that conversion therapy with donafenib, camrelizumab and TACE was safe and effective for uHCC. Clinical trial information: ChiCTR2100043462 .[Table: see text]
A prospective, single-arm, phase II clinical study of tislelizumab in combination with lenvatinib for perioperative treatment of resectable primary hepatocellular carcinoma with high risk of recurrence.
Authors: Song Tianqiang 
Published: June 2023

e16218 Background: Surgery is the main radical treatment for hepatocellular carcinoma (HCC), but the high postoperative recurrence rate makes the survival benefit of patients limited. Neoadjuvant therapy mainly reduces postoperative recurrence by controlling micrometastasis and reducing preoperative tumor load and other high recurrence risk factors, but there are limited data on its application in liver cancer. Tislelizumab, a PD-1 monoclonal antibody, has shown promising efficacy with acceptable safety profile in combination with lenvatinib in the first-line treatment of advanced HCC. This study aims to explore the safety and feasibility of tislelizumab combined with lenvatinib in the neoadjuvant therapy and adjuvant therapy of resectable HCC. Methods: This prospective, single-center, single-arm phase II study (NCT04834986) enrolled patients with histologically confirmed resectable HCC who were at high risk of recurrence, as assessed by the investigators before surgery. Patients did not have any medical treatment in the past, with ECOG of 0-1, and had adequate organ and bone marrow function. Eligible patients received 4 cycles with tislelizumab (200mg, d1, Q3W) combined with Lenvatinib (8mg/kg, PO, qd) and surgery was performed within 4 weeks after treatment. At 4-8 weeks after surgery, adjuvant therapy was started with tislelizumab (200mg, d1, Q3W) and lenvatinib (8mg/kg, PO, qd) for at least half a year or until disease progression or intolerance of adverse reactions. Primary endpoints were safety and feasibility; secondary endpoints were ORR, 1 and 2-years DFS%, pCR, and DFS. Results: From Sep 7,2021 to Nov 9,2022, 24 patients (median age, 57.5 years) were enrolled, with most patients were males (95.8%) and 22 patients (91.7%) had HBV infection. All patients had Child-Pugh grade A and ECOG PS 0. The median treatment period was 4 cycles. In 24 patients, 17 patients (70.8%) underwent R0 resection, 3 patients (3/17, 17.6%) achieved complete pathological response (PCR), and 6 patients (6/17, 35.3%) achieved major pathological response rate (MPR, necrosis > 70%). 3 patients (12.5%) had significant tumor shrinkage and refused surgery. 1 patient (4.2%) is waiting surgery. 3 patients (12.5%) developed disease progression. According to RECIST1.1, ORR was 54.2% (13/24, CR 1, PR 12), DCR was 87.5%. According to mRECIST, ORR was 75.0% (18/24, CR 6, PR 12), DCR was 87.5%. No grade 3 or above adverse events were observed during neoadjuvant treatment period. The most common adverse events of any grade were rash (14/24,58.3%), hypertension (5/24,20.8%) and diarrhea (4/24,16.7%). Conclusions: Tislelizumab in combination with lenvatinib was well tolerated and showed promising efficacy as a neoadjuvant therapy for resectable HCC with high risk of recurrence. Clinical trial information: NCT04834986 .
Adjuvant therapy in localized vs regional biliary tract cancers: A SEER analysis.
Authors: Wei John X , Wang Christina , Pintova Sofya 
Published: June 2023

e16221 Background: Biliary Tract Cancers (BTC) are aggressive malignancies. Treatment of early-stage disease involves surgical resection, but whether adjuvant therapy offers a clear survival benefit remains inconclusive. This study aims to explore the impact of demographic factors and adjuvant therapy on survival outcomes at a population level through the lens of the latest SEER (Surveillance, Epidemiology, and End Results) registries. Methods: Cases were filtered by the following criteria: histologic type (adenocarcinoma), anatomic location (gallbladder, intrahepatic, extrahepatic), stage (local and regional), microscopically confirmed diagnosis, and confirmed surgical resection. Cases with incomplete entries were excluded. A Cox proportional hazard model was used to analyze survival in the context of race, gender, income, and type of adjuvant therapy (none, chemotherapy (AC), chemo-radiotherapy (CRT), and radiation (RT)). Data analysis was performed in RStudio. Results: Between 2005 and 2019, 3565 patients were identified. Patients with regional BTC demonstrated improved median survival with AC (27 vs 23 months, HR 0.72, CI 0.63-0.82, p ≤.05) and CRT (28 vs 23 months, HR 0.63, CI 0.56-0.72, p ≤.05). Median survival in localized BTC was 52 months. Adjuvant therapy of any type did not impact survival for localized BTC. Analysis of race as a covariate in localized BTC showed that all minority groups had improved survival compared to non-Hispanic whites (Asian, HR 0.33; Black, HR 0.50; Hispanic, HR 0.38, p≤.05). In regional gallbladder BTC, this survival benefit was limited to Asians only (HR 0.52, p≤.05). Conclusions: Our data show that AC and CRT may improve survival in patients with regional BTC across all anatomic subtypes. In our cohort, adjuvant therapy had no impact on survival in localized BTC. Differences in outcomes may exist among racial groups for different subtypes of BTC. Future adjuvant clinical trials for BTC should consider stratifying for regional and localized disease. [Table: see text]
Ultra-sensitive baseline-informed MRD assay to predict prognosis outcomes in patients with resectable hepatocellular carcinoma.
Authors: Hu Jie , Tang Haoran , Xie Feng , Zhang Yue , Jia Shidong , Zhou Jian 
Published: June 2023

e16228 Background: The detection of minimal residual disease (MRD) has been shown to be a potential biomarker for the prognosis and post-surgery treatment of resectable hepatocellular carcinoma (HCC). However, the application of MRD in HCC has been limited by the traditional requirement of carrying out MRD over 30 days post-surgery, which is often incompatible with the time window for adjuvant treatment decisions. Additionally, MRD results may be impacted by post-surgery imbalances if assayed too soon after surgery. Methods: This retrospective study enrolled 255 early-stage HCC patients who received surgical resections and had complete information on relapse and survival. Matched tumor and normal tissue samples were collected at the time of surgery and plasma samples were collected as early as 7 days post-surgery. An ultra-sensitive, baseline-informed MRD assay (PredicineBEACON) was used to evaluate the correlation between peri-surgical MRD status and prognosis outcomes. Somatic mutations were identified through PredicineWES+ whole exon sequencing, and up to 50 somatic mutations were selected for the design of a patient-specific capture panel, in addition to a fixed panel of 500 actionable variants. Results: The study has completed MRD tests for 58 patients, of which 8 were called MRD positive with ≥0.005% tumor fractions. The tumor fraction proportion of MRD-positive patients ranged from 0.008% to 5.653% (median 0.315%). The relapse-free survival (RFS) and overall survival (OS) were correlated with MRD status: the median RFS of MRD-positive patients was 13.9 months compared to not reached after 44.4 months for MRD-negative patients (p = 0.1), and the median OS of MRD-positive patients was 27.2 months compared to not reached after 55.5 months for MRD-negative patients (p = 0.03). Conclusions: Our results demonstrate the feasibility of using an ultra-sensitive, baseline-informed MRD assay to detect strong correlations between MRD status and prognosis outcomes in peri-surgical plasma samples collected as early as 7 days post-surgery in resectable HCC patients. This study highlights the clinical utility of MRD testing in peri-surgical settings.
Effect of UBR7 deficiency on glycolysis and PDAC resistance to gemcitabine by promoting PRMT5 stability.
Authors: Bi Lei , Zhao Miaoqing , Ru Kun , Tang Bo , Wang Yunshan 
Published: June 2023

e16265 Background: Pancreatic ductal adenocarcinoma (PDAC) is a common malignant tumor of the digestive tract. Although gemcitabine and other therapeutic agents are effective in patients with advanced and metastatic pancreatic cancer, drug resistance has severely limited their use. However, the mechanisms of gemcitabine resistance in pancreatic cancer are poorly understood. Methods: In this study, ATAC-seq, ChIP-seq, and RNA-seq were performed to compare chromatin accessibility and gene expression in a patient-derived tumor xenograft (PDX) model of pancreatic cancer with or without gemcitabine resistance. Results: Analyzing these sequencing data, we found a dramatic change in chromatin accessibility in the PDX model of gemcitabine-resistant tissues and identified a key gene, UBR7, which plays an important role in mediating gemcitabine resistance. Further research found that depletion of UBR7 significantly increased pancreatic carcinogenesis and the immunosuppressive microenvironment. Mechanistically, depleted UBR7 increased the stability of PRMT5, thereby promoting glycolysis in pancreatic cancer cells. Finally, an inhibitor that blocks PRMT5 (DS-437) significantly reduced gemcitabine resistance in pancreatic cancer caused by UBR7 depletion. Conclusions: In conclusion, our results indicated that the UBR7-PRMT5 axis is a key metabolic regulator of PDAC and a promising target for the clinical treatment of gemcitabine resistance in PDAC.
Soluble urokinase-type plasminogen activator receptor, suPAR, as a prognostic biomarker in advanced pancreatic cancer.
Authors: Eefsen Rikke Løvendahl , Christensen Ib Jarle , Calatyud Dan , Johansen Astrid Zedlitz , Chen Inna Markovna , Rasmussen Louise Skau , Pfeiffer Per , Hollander Niels Henrik , Andersen Fahimeh , Johansen Julia S. , Hoyer-Hansen Gunilla 
Published: June 2023

e16277 Background: High levels of intact and cleaved forms of the urokinase-type Plasminogen Activator Receptor (uPAR) in tissue and blood are associated with a poor prognosis in several types of cancer, including lung, colon, bladder, and cholangiocarcinoma. The soluble forms of uPAR (suPAR) have not been investigated in patients with pancreatic ductal adenocarcinoma (PDAC). The aim was to determine if circulating levels of intact and cleaved suPAR were associated with overall survival (OS) in patients with advanced PDAC. Methods: Patients with PDAC stage 3 or 4 were consecutively included in the BIOPAC study (ClinicalTrials.gov ID: NCT03311776) in a training cohort (n = 230, age 45-89 years, 56% females) from Herlev Hospital and a validation cohort (n = 115, age 40-82 years, 59% females) from four other Danish hospitals between 2008 to 2014. A total of 95% of the patients in the training cohort and 93% in the validation cohort received first-line palliative chemotherapy. One patient was alive at the time of analysis at 8 years follow-up. Serum samples were collected prior to palliative chemotherapy. Different suPAR forms were determined using time-resolved fluorescence immunoassays (TR-FIA). The Cox proportional hazards model was used for uni- and multivariate analyses. Age, performance status, stage (4 vs 3), gender, Charlson age-adjusted comorbidity index, and CA19-9 were included in the multivariate analysis for OS. Results: In the training cohort, high level of suPAR domain I was an independent biomarker of short OS (HR, 1.37, 95% CI 1.15-1.63, p = 0.0004). High CA19-9 (HR, 1.08, 95% CI 1.04-1.12, p < 0.0001), PS, and stage were also independent prognostic parameters in the training cohort. In the validation cohort, high level of suPAR domain I (HR, 1.91, 95% CI 1.36-2.69, p = 0.0002) and CA 19-9 (HR, 1.09, 95% CI 1.01-1.17, p = 0.02) were confirmed as independent prognostic biomarkers for short OS. No correlation was observed between suPAR domain 1 and CA19-9 (r = 0.059, p = 0.21). Conclusions: A high pretreatment circulating level of suPAR domain I is associated with a short OS in patients with advanced PDAC, and the biomarker is independent of CA19-9. The results warrant further investigation of suPAR domain 1 as a biomarker in patients with PDAC.
Utilization of germline testing in patients with early-onset pancreatic cancer (EOPC).
Authors: Ehsan Hamid , Symanowski James Thomas , Athens Aly , Wilson Katherine , Tobik Katie , Elrefai Sara , Salem Mohamed E. , Hwang Jimmy J. , Kadakia Kunal C. 
Published: June 2023

e16300 Background: EOPC is associated with significant life years lost. Approximately 5%-10% of pancreatic adenocarcinoma (PAC) have an underlying genetic predisposition and national guidelines recommend testing in all patients with PAC. Certain germline mutations such as BRCA2 and PALB2 predict response to specific treatments including platinum and targeted therapies. It is currently unknown to what extent patients with EOPC pursue recommended germline testing. We examined the utilization of germline testing in patients with EOPC who were referred to genetics. Methods: A retrospective review of patients with EOPC at the Levine Cancer Institute (LCI), defined as ≤60 years of age at time of diagnosis, who were referred and seen by genetics between January 2019 and December 2021 was performed. Germline testing was performed using multi-gene cancer panels. Positive germline testing was considered as any known pathogenic or likely pathogenic variant not including variants of unknown significance (VUS). Results: We identified 69 patients with EOPC who were evaluated by genetics. The median age was 55 years (range 25-60) with 36 (52%) male, 33 (48%) female, 48 (70%) white, 16 (23%) Black, 61 (89%) with ECOG 0-1, 36 (52%) current or prior smoking history, and 28 (42%) presenting with metastatic disease. As shown, out of 69 patients, 10 (14%) declined testing or had unknown results, 30 (43%) had negative germline testing, 29 (42%) had genetic testing that revealed 19 (65%) had VUS, and 10 (34%) had pathogenic variants. The most frequently seen pathogenic variants were ATM (30%), BRCA1 (30%), BRCA2 (10%), MLH1 (10%), RAD51C+ (10%) and CFTR (10%). Conclusions: Our data suggest that most patients with EOPC who are evaluated undertake germline testing. Given the predictive nature of certain pathogenic mutations on PAC treatment options, characteristics of patients with EOPC who decline testing should be further explored. There is need for larger studies to confirm the high incidence of pathogenic variants observed in our cohort of EOPC patients. [Table: see text][Table: see text]
Prognostic impact of hyponatremia in patients with pancreatic cancer: A nationwide analysis.
Authors: Kumar Vikash , Kumar Naresh , Vachhani Bhavyakumar , Singh Surbhi , Naz Sidra , Shulimovich Max 
Published: June 2023

e16304 Background: Hyponatremia has historically been reported to increase mortality and length of stay in hospitalized patients with solid tumors. There are sparse reports of hyponatremia linked to Pancreatic cancer in the published literature. Therefore, we evaluated mortality, morbidity, and resource utilization in Pancreatic cancer patients secondary to hyponatremia. Methods: A retrospective analysis was performed by utilizing the National Inpatient Sample database 2019 and the ICD- 10 codes to identify the patients > 18 years old with the principal diagnosis of Pancreatic cancer. Effect of hyponatremia was studied on mortality, morbidity, and resource utilization. Categorical variables were compared using the chi-square test, and continuous variables were compared using the t- test. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. Confounding variables were adjusted using multivariate logistic and linear regression analyses. These included: gender, race, Charlson Comorbidity Index, chronic kidney disease, congestive heart failure, cirrhosis, nephrotic syndrome, hypothyroidism, alcohol use disorder, and various patient and hospital characteristics. Results: We identified a total of 110,980 patients with primary diagnosis of pancreatic cancer in 2019, Of whom 18.1% (5,845) had hyponatremia on presentation. Patients with hyponatremia had 9.48 % in-hospital mortality, while 6.68% for patients without hyponatremia. After adjusting for confounders, hyponatremia imparted higher odds of mortality (Adjusted odds ratio (aOR) for mortality 1.46, 95% confidence interval (CI): 1.28–1.67, P< 0.01). Pancreatic cancer patients with hyponatremia have higher odds of Sepsis (Odd ratio = 1.64), Acute kidney injury (Odd ratio = 2.03), Peritonitis (Odd ratio = 2.40), and ICU admission (Odd ratio = 3.82). Hyponatremia also resulted in higher resource utilization marked by the length of stay, and hospital charges, (higher mean LOS by 1.16 days, and higher mean total hospital charges by $ 12,320). Conclusions: Hyponatremia in Pancreatic cancer patients had a prevalence of 18.1% and resulted in increased in-hospital mortality. Whether time-efficient treatment of hyponatremia would help reduce mortality and improve outcomes remains to be determined in future studies. [Table: see text]