bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic artery infusion chemotherapy (HAIC) plus sintilimab and bevacizumab biosimilar (IBI305) in initial unresectable hepatocellular carcinoma (HCC): A retrospective study.
Authors: Zhang Xihao , Liu Yang , Fu Linlin , Liu Yayue , Qi Qi , Li Rentao , Cui Yunlong , Lu Wei , Li Huikai 
Published: July 2024

e16185 Background: Combining sintilimab with IBI305 has shown significant survival benefits over sorafenib in first-line HCC treatment. Our prior study has indicated improved outcomes with sintilimab and bevacizumab biosimilar (IBI305) in combination with HAIC for HCC (Clinical trial: NCT05029973). This study aims to evaluate combining HAIC with sintilimab and IBI305 for initial unresectable HCC in real word. Methods: Eligible patients (pts) had histologically or cytologically diagnosed or clinically confirmed HCC, with China liver cancer staging (CNLC) stage Ib-IIIb, no prior systemic treatment, Child-Pugh A or B, and ECOG 0 or 1. Patients were administered FOLOFOX-HAIC, combined with intravenous Sintilimab (200 mg, Q3W) and intravenous IBI305 (7.5 mg/kg, Q3W). Primary endpoints included objective response rate (ORR) and disease control rate (DCR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Secondary endpoints included surgical conversion rate, R0 resection rate, and pathological complete response (pCR) rate. Results: Data were collected from 106 patients (from Apr, 2021 to Jul, 2023), median age 61, with the majority being male (91, 85.9%), ECOG 0 (106, 100%), and classified as Child-Pugh A (82, 77.4%). CNLC staging: Ib (19), IIa (2), IIb (20), IIIa (42), IIIb (23). HBV infection: 84 (79.3%), HCV: 3 (2.8%). AFP levels were > 400ng/ml in 53 patients (50.0%), with tumor diameters > 10 cm in 47 patients (44.3%). Single tumors were noted in 35 patients (33.0%), vascular invasion in 60 patients (56.6%), and extrahepatic metastasis in 26 patients (24.5%). Among the 106 patients evaluable for response, ORR was 39.6% with 42 patients demonstrating partial responses (PR); DCR was 96.2% (102/106), comprising 42 PR, 60 stable disease (SD). The surgical conversion rate was 40.56% (43/106), achieving R0 resection in all 43 patients and complete pathological response (pCR) in 9/43(20.9%) patients and major pathological response (MPR) in 12/43 (27.9%). The 1-year progression-free survival (PFS) and overall survival (OS) rates were 54.5% and 74%, respectively. The 2-year PFS and OS rates were 41.4% and 58.6%, respectively. No new safety signals were observed, and no treatment-related adverse events (TRAEs) led to death. Conclusions: Combining HAIC with Sintilimab and IBI305 as conversion therapy for unresectable HCC shows promising benefits with manageable safety.
Body mass index (BMI) as a prelude to hepatocellular carcinoma (HCC) and metabolic dysfunction–associated steatohepatitis (MASH) risk factors in patients with no identified risk factor for developing hepatocellular carcinoma (HCC).
Authors: Al Mahmasani Layal , Capanu Marinela , Srivastava Amitabh , Chou Joanne F. , Shia Jinru , El Dika Imane H. , Yaqubie Amin , Harding James J. , O'Reilly Eileen M. , Abou-Alfa Ghassan K. 
Published: July 2024

e16193 Background: Common risk factors for hepatocellular carcinoma (HCC) include viral hepatitis (hepatitis B and hepatitis C), alcoholic liver disease, and metabolic dysfunction-associated steatohepatitis (MASH). Non-risk factored HCC has been suggested where patients who do not have common risk factors develop HCC (Journal of Clinical Oncology Volume 35, Number 15_suppl, May 2017). This is described more commonly among young, females more than males. Is this a misdiagnosis or a truly non-factored risk? Methods: Patients diagnosed with histology confirmed HCC between years 2014 and 2017 with none of the known HCC risk factors, were assessed part of our previous effort add to more recent gathered data at Memorial Sloan Kettering (MSK). In an institutional IRB approved retrospective study, demographic and treatment data in addition to DNA sequencing were compiled and evaluated. Detailed clinical and genomic information was abstracted from the medical record. Pathology data was reviewed (AS). Results: A total of 428 patients diagnosed with HCC were identified, of whom 18 (4.2%) patients had no identifiable HCC risk factors. Fourteen patients were females (78%), and four were males (22%). Median age at diagnosis was 59 years (range 18-77 years). All 18 patients did not meet any of the clinical and/or radiologic alleged criteria for a diagnosis of MASH. The average body mass index (BMI) was 27.9 kg/m2 (16.7-54.4). Six patients (33%) had BMI greater than 30 kg/m2, and five (28%) patients had BMI ranging from 25 to 29.9 kg/m2. Three patients had diabetes mellitus. With the lack of non-tumorous liver cancer surrounding tissue, only three patients had mild steatosis documented on pathology. At the molecular level, few somatic mutations were detected including TERT and CTNNB1 in 37% of cases. No germline mutations were identified in 4 tested patients. Conclusions: Among 18 patients diagnosed with HCC with presumed no or unknown risk factors we previously reported, average BMI was 27.9 kg/m2. This is in the absence of any clinical and/or radiologic alleged criteria for a diagnosis of MASH. In the presence of subtle clinical and/or radiologic findings suggestive of MASH, evaluating patient’s BMI may be considered as an added variable for evaluation of patients with HCC. We clinicians need to be aware of increased BMI as a possible prelude for MASH and HCC. This is added to an invitation for acquired biopsies to include tumor and normal tissue to assess liver cirrhosis or fibrosis.
Factors associated with the receipt of palliative care in Native American patients with hepatocellular carcinoma: A retrospective analysis.
Authors: Dentinger Lauren , Kolluru Sowmya Prathika , Bine Christopher Reese , Silberstein Peter T. 
Published: July 2024

e16202 Background: Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related deaths in the United States. This primary liver malignancy often has a poor prognosis and commonly metastasizes to the lungs, lymph nodes, bones, and adrenal glands. HCC has a high burden of disease with many patients suffering from discomfort and pain related to the disease and its treatment. Palliative care is a unique form of specialized care that provides relief, increasing comfort, and quality of life to patients suffering from illness. Many studies note its effectiveness in helping patients at any point in their illness. Furthermore, recent studies have shown that Native Americans face barriers to receiving palliative and end of life care. Thus, this study aims to examine the factors associated with receipt of palliative care within Native American HCC patients. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with Hepatocellular Carcinoma from 2004 to 2019 using the histology code 8170 and race code 03 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 28 and statistical significance was set at α = 0.05. Results: Out of 1536 Native American patients with HCC, 92 (5.9%) received palliative care. Patients who received palliative care experienced shorter mean survival than those who did not receive palliative care (15 vs 42 months; p < 0.001). After controlling for age, year of diagnosis, surgical status and adjuvant therapies, not receiving palliative care was associated with an independent decrease in hazard (HR = 0.625, p < 0.05). Palliative care patients were more likely to present with stage III and IV HCC, experience a longer delay in receiving treatment (69 vs 48 days) and have bone and lung metastasis when compared to those who did not receive palliative care (p < 0.05). Patients who did not receive palliative care were more likely to have Medicare or Medicaid for insurance (p < 0.05). There were no significant differences in the age, income bracket, facility type, tumor size or time to surgery between the patients who received palliative care and those who did not. Conclusions: This study found that patients with HCC are more likely to utilize palliative care if they have severe disease that metastasized to other organ systems. There is a higher mortality among patients who receive palliative care most likely because they had more severe disease. This research demonstrates the common trend of HCC patients underutilizing palliative care in the early stages of disease. Exploring the impacts early palliative care can have on HCC patients’ survival and quality of life would be valuable future areas of research.
Primary and secondary resistance to immune checkpoint inhibitors in hepatocellular carcinoma.
Authors: Cui Xiaowen , Ruan Minghao , Li Yao , Yang Cheng , Zhou Liuyu , Zhang Jin , Jin Riming , Wu Dong , Wang Ruoyu 
Published: July 2024

e16209 Background: Immunotherapy have revolutionized the therapeutic landscape of hepatocellular carcinoma (HCC). However, clinical features affecting immune resistance remain largely unknown. This retrospective cohort study aims to investigate the outcomes and characteristics of pts with resistance to immunotherapy in HCC. Methods: Pts with HCC who received immune checkpoint inhibitors (ICIs) of PD-1/PD-L1 antibodies at Eastern Hepatobiliary Surgery Hospital between 2016 and 2021 were retrospectively enrolled and screened for eligibility. Recommended by the Society for Immunotherapy of Cancer (SITC), primary resistance was defined as when pts were exposed to ICIs therapy for at least 6 weeks and with the best overall response (BOR) of PD or SD for less than 6 months. Secondary resistance was defined as pts having disease progression after the initial objective response (CR/PR) or SD for more than 6 months. The durable response group consists of pts with the durable response (CR, PR, or SD) for more than 6 months without progression at data cutoff. Time to progression (TTP), overall survival (OS) and clinicopathological features of HCC pts were compared between groups. Subsequent management after resistance and post-progression survival (PPS) were also analyzed. Results: Of 496 pts included, 229 (46.2%) and 141 (28.4%) pts developed primary resistance and secondary resistance, and 126 (25.4%) pts achieved a durable response. The median follow-up was 22.8 months. For pts with primary resistance, secondary resistance, and durable response, the median TTP was 2.83 [2.56-3.09] months, 11.93 [10.45-13.40] months, and not reached, respectively. Whereas the median OS was 12.83 [10.36-15.30] months, 31.53 [28.09-34.97] months and not reached, respectively. Multivariate logistic regression revealed that the Child-Pugh score (Child-Pugh B versus A, OR 3.28 [1.51-7.13], p= 0.003), BCLC stage (BCLC B versus A, OR 3.55 [1.70-7.43], p= 0.001; BCLC C versus A, OR 2.88 [1.47-5.65], p= 0.002), and combinational therapies (ICIs+bevacizumab versus monotherapy, OR 0.14 [0.04-0.51], p= 0.003; ICIs plus lenvatinib+monotherapy, OR 0.43 [0.26-0.72], p= 0.001) were independently associated with primary resistance, and only the combination of ICIs plus bevacizumab (ICIs+bevacizumab versus monotherapy, OR 0.10 [0.01-0.52], p= 0.007) was independently associated with secondary resistance. AFP levels and post-progression therapies were independently associated with PPS in pts with primary resistance, while post-progression therapies were independently associated with PPS in pts with secondary resistance. Conclusions: Risk for resistance was significantly lower among pts who received ICIs plus bevacizumab.High AFP levels independently predict the survival of pts after primary resistance to immunotherapy. ICI-based maintenance therapy after resistance may provide a significant survival advantage for HCC pts.
Fibrolamellar hepatocellular carcinoma (FL-HCC) epidemiology, survival characteristics, and outcomes: Surveillance, epidemiology, and end results database (SEER) study.
Authors: Alnabulsi Zaid , Batra Nitya , Khosla Atulya Aman , Attia Abdelrahman M. , Kiryakoza Morgan , Deb Novonil , Ezekwudo Daniel 
Published: July 2024

e16213 Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare and distinctive form of liver cancer that primarily affects adolescents and young adults without underlying liver disease. Unlike conventional HCC, it exhibits unique clinical and histological features and poses a diagnostic and therapeutic challenge. Using a national registry, we sought to evaluate the incidence, demographics, survival, and treatment characteristics of FL-HCC. Methods: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with microscopically confirmed FL-HCC between 2000-2020 using ICD-O-3 site code C22.0 and an 8171/3 histology code. The epidemiological characteristics included were age, gender, ethnicity, American Joint Committee on Cancer [AJCC] staging, annual income, and treatment modalities. The Kaplan-Meier survival curve was used to compare survival. Survival was stratified according to age, gender, race, stage, income, and treatment modalities. Multivariate analysis was done with Cox regression analysis on R programming language version 3.6.3. Results: We identified a total of 362 patients with fibrolamellar hepatocellular carcinoma with median age at diagnosis 27(8-84) years. It was found to be more common in males (62.2%) and among whites (78.2%). There was a striking increment in incidence with 1.9% in 2005 compared to 5.8% in 2020. The majority of the patients had stage IV disease (26.4%). Alpha-fetoprotein was noted to be positive only in 15.8% of patients. The majority of the patients received surgery (50.3%) and chemotherapy (48.1%) with a median time from diagnosis to treatment of 1.00 month (IQR: 0.00–1.00). A total of 11% of patients received radiation, and 25% received multiple treatments. Survival analysis revealed a median overall survival of 24.50 months (IQR: 7.00, 63.00), with a majority experiencing death attributable to the cancer diagnosis (60.2%). Median overall and cause-specific survival for stage I disease was 92 months, and stage IV disease was 21 months (p < 0.05). Patients below the age of 20 had a median survival of 85 months (95% CI: 41 to NA) compared to those aged between 20 and 59, i.e., 30 months (95% CI: 22 to 41 months). The higher-income categories, $55,000−59,999 (HR = 0.29, p = 0.05) and $60,000−64,999 (HR = 0.24, p = 0.03), demonstrated significantly lower hazards compared to < $35,000. We concluded that sex, location, and race did not influence the survival of FL-HCC. Conclusions: Our comprehensive analysis of FL-HCC revealed that diagnosis at a younger age, stage I disease, and higher annual income improved survival, whereas gender and race did not affect outcomes. Further collaborative efforts are warranted to advance our understanding of FL-HCC pathogenesis, optimize treatment strategies, and improve outcomes for affected individuals.
Prognostic significance of real-world (RW) recurrence patterns after resection or ablation of early-stage hepatocellular carcinoma (HCC): Insights from the US Medicare population.
Authors: Maithel Shishir K. , Wang Rongrong , Harton Joanna , Yopp Adam C. , Shah Shimul , Rocha Flavio G. , Hernandez Sairy , Cheng Spencer , Ogale Sarika , Tan Amie 
Published: July 2024

e16241 Background: The prognosis after curative-intent resection or ablation of early-stage HCC remains poor, largely due to high rates of recurrence. We aimed to characterize real-world recurrence patterns and determine whether the timing of recurrence was associated with overall survival (OS). Methods: Patients (pts) with early-stage HCC who underwent resection and/or ablation were identified from the SEER-Medicare database (2010-2019). Pts who received liver transplant were excluded. A proxy for recurrence was defined as the receipt of new HCC treatments (surgery, locoregional therapy, systemic therapy) or a secondary malignant neoplasm claim (excluding liver). Pseudo-recurrence dates were assigned to pts without recurrence to match the distribution of time between initial resection/ablation and recurrence in the recurrence cohort, to avoid immortal time bias. Early vs late recurrence was defined as occurring within 1 year vs after 1 year of initial resection/ablation. Primary outcome was OS as measured both from the time of recurrence/pseudo-recurrence and initial resection/ablation. Results: 1,146 eligible pts with early-stage HCC were identified. 63% were male, mean age was 74 yrs, and initial therapy was resection (39%), ablation (50%), or both (11%). 736 (64%) experienced recurrence. Among them, 53% received ablation, 37% surgery, and 11% received both. Median OS from recurrence or pseudo-recurrence was 22 months (mo) vs 67 mo (p < 0.001) for pts with vs without recurrence, respectively. When measured from resection/ablation date, median OS was 39 mo vs 83 mo (p < 0.001). After adjusting for relevant demographic and clinico-pathologic factors, including type of index therapy, in a multivariable Cox regression model, recurrence remained significantly associated with an increased risk of death (hazard ratio [HR]: 2.24; 95% CI: 1.85-2.71; p < 0.001). Among pts who recurred, 380 (52%) had early recurrence and 356 (48%) had late recurrence. Median OS from recurrence was 17 mo vs 30 mo (p < 0.001) for early vs late recurrence, respectively, and 23 mo vs 63 mo when measured from resection/ablation The adjusted HR for the risk of death associated with early recurrence was 1.39 (95% CI: 1.14-1.68; p < 0.001) compared to late recurrence. Other significant prognostic factors associated with reduced OS included larger tumor size ( > = 5cm), greater extent of disease, and poor differentiation (grade III and above). Conclusions: In this study among US Medicare pts, early recurrence within one year after curative-intent treatment of early-stage HCC was significantly associated with decreased OS compared to pts who recur later or without recurrence. This highlights the need for developing and utilizing effective adjuvant therapy regimens to delay or avoid recurrence.
The efficacy and safety of donafenib-containing regimens as first-line therapy for hepatocellular carcinoma (HCC): A multicenter retrospective study.
Authors: Zhang Qingqiao , Yin Guowen , Xu Qingyu , Xiao Jinchang , Shen Bin , Chen Guofeng , Zhang Genshan , Feng Wei , Yang Yong , Hu Jianping , Wang Chenghu 
Published: July 2024

e16243 Background: HCC is a common malignant tumor worldwide, safer and more potent treatments are desperately needed to increase the survival rates of HCC patients. Some studies have shown that transcatheter arterial chemoembolization/hepatic arterial infusion chemotherapy (TACE/HAIC) combined with systemic therapies shows potential synergistic effects in patients with HCC, the ZGDH3-III RCT's findings showed that donafenib(D) is highly safe and effective as first-line treatment for uHCC. This study aimed to evaluate the efficacy and safety of donafenib-containing regimens (D+TACE/HAIC, D+TACE/HAIC+ICI, D+ICI, D) as first-line systemic treatments for HCC patients in the real world. Methods: We retrospectively analyzed patient data from January 2022 to December 2023 in seven Chinese institutions with first-line therapeutic regimens based on donafenib. Donafenib-based treatments were administered to eligible patients until the point of disease progression, death, or intolerable toxicity. We examined the progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) per the modified Response Evaluation Criteria in Solid Tumors, and safety (CTCAE5.0). Results: There were 102 patients in this study (Table). The median age was 60 years (IQR: 52, 68) at the data cut-off in January 2024, with 87.3% of the population being male and 78.4% having HBV infection. Most patients received D+TACE/HAIC therapy (59.8%), D+TACE/HAIC+ICI therapy (35.3%), or other treatments. Median PFS and OS not yet been achieved, respectively, the 12-month PFS and OS rates were 87.0% (95%CI: 79.7%-95.0%) and 91.4% (95%CI: 84.9%-98.4%). The ORR was 68.6% and DCR was 88.2%, with complete response in 14 patients, partial response in 56 patients, stable disease in 20 patients, and progressive disease in 12 patients. Among the population, 51 patients (50.0%) had treatment-related adverse events (TRAE) of any grade, and the incidence of grade 3 TRAE was 13.7% (14/102), none of the patients experienced grade 4 or 5 TRAE. Conclusions: These results preliminarily showed that donafenib-containing treatment regimens exhibited encouraging efficacy and favorable safety profile in patients with HCC. [Table: see text]
Adjuvant tislelizumab combined with capecitabine for patients with biliary tract cancer with high risk of postoperative relapse (ACTIVE): Primary analysis from a prospective cohort study.
Authors: Yang Luyu , Lu Lu , Wang Xiangyu , Sun Haoting , Zhu Ying , Xu Da , Yang Jimeng , Yin Baobing , Yang Xin , Zhu Wenwei , Jia Huliang , Chen Jinhong , Qin Lunxiu 
Published: July 2024

e16248 Background: Only 20% of biliary tract cancer (BTC) patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. This rate is even lower in patients with high-risk features. Capecitabine as an adjuvant therapy in biliary tract cancer has been verified to improve overall survival, however, the efficacy still remains limited. PD-1/L1 antibody combined with chemotherapy have been demonstrated to improve survival in advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of adjuvant tislelizumab and capecitabine following surgery for biliary tract cancer with high risk of recurrence. Methods: This was a single-center, prospective cohort phase II study. BTC patients (pts) underwent R0/R1 resection with high postoperative recurrence risk were eligible. The high-risk factors included positive resection margins, positive lymph nodes, positive perineural invasion, and tumor > 5cm in diameter. The patients were divided into two groups, the tislelizumab (TIS 200 mg Q3W for 1 year )+capecitabine (CAP D1-14, 1500mg/m2 for eight 3-weekly cycles) group and the capecitabine group. The primary endpoint was DFS (disease free survival). The second endpoints was OS (overall survival) and adverse event (AE). Results: A total of 37 pts were enrolled into the study, while 22 pts in the TIS+CAP group and 15 in CAP group, 23 males and 14 females with a median age of 66 years. According to the location of the tumor, 37.8% pts were intrahepatic cholangiocarcinoma, 21.6% were gallbladder cancer, 5.4% were distal cholangiocarcinoma and 35.1% were hilar cholangiocarcinoma. The median DFS was 16.2 months (95% CI, 8.1-26.2) in the TIS+CAP group, which was longer than CAP group (11.4 months, 95% CI 4.2-27.1). 12-month RFS rates were 56.5% and 36.6% , respectively. The most common adverse events (AEs, any grade) were rash (18.2%), vomiting (13.6%), neutropenia (13.6%) and anorexia (13.6%) in the TIS+CAP group. Conclusions: Tislelizumab in combination with capecitabine were effective and safe as adjuvant therapy, which can prolong the DFS of BTC patients with high recurrence risk after resection. Clinical trial information: NCT04782804 .