bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunotherapy responses in viral hepatitis-induced hepatocellular carcinoma: A meta-analysis.
Authors: Anwar Junaid , Arslan Hafiz Muhammad , Sarfraz Zouina , Abdelhakeem Ahmed , Zafar Maha , Saeed Anwaar 
Published: July 2024

e16223 Background: The advent of immunotherapy has ushered in a paradigm shift in the management of advanced hepatocellular carcinoma (HCC). The distinctive etiological profiles of HCC, characterized by HBV predominance in Asia and HCV/nonviral prevalence in the West, may impart intricacies in the immunological milieu, thereby influencing treatment outcomes. This meta analysis delves into the immunotherapeutic outcomes in patients with hepatitis-induced HCC. Methods: A systematic search was conducted by applying the Boolean logic (and/or) in PubMed (MEDLINE), Embase and Cochrane Library until February 3, 2024. This study investigates the outcomes of patients with HCC complicated by hepatic infection, focusing on overall survival (OS) and progression-free survival (PFS). A meta-analysis was conducted, combining data from 6 studies for OS and 5 studies for PFS. Statistical analyses were conducted using R (v.4.3.2., Vienna). Results: A total of 6 clinical trials pooling in 2958 patients were included in this meta analysis. For OS, the random effects model estimated the cumulative survival across the studies to be 18.3950 months (95% CI [16.3869; 20.4032]). Quantifying heterogeneity revealed a tau-squared value of 5.1789 and Higgins I-squared of 72.7% [41.2%; 87.3%]. The test of heterogeneity indicated significant variability among the studies (Q = 21.99, df = 6, p = 0.0012). For PFS, the random effects model estimated the combined progression-free survival to be 5.9906 months (95% CI [4.2889; 7.6923]). Quantifying heterogeneity revealed a tau-squared value of 3.4995 and Higgins I-squared of 95.4% [91.9%; 97.4%]. The test of heterogeneity indicated significant variability among the studies (Q = 87.66, df = 4, p < 0.0001). Conclusions: The intricate relationship between HCC, hepatic infection, and treatment outcomes necessitates tailored therapeutic strategies for this patient population. Unveiling the heterogeneity in our analysis prompts a comprehensive exploration of potential factors, spanning both biological variances and clinical parameters. This inquiry fuels scientific discourse, urging an in-depth investigation into the immunological nuances influencing therapeutic responses in hepatitis-induced HCC. By addressing these complexities, we can optimize patient care and advance our understanding of effective treatment modalities for this challenging disease.
Differential IDH1 and IDH2 mutation-related landscape in intrahepatic cholangiocarcinoma.
Authors: Xu Shuaishuai , Qu Wenxin , Shen Yifei , Ruan Jian 
Published: July 2024

e16224 Background: Patients with intrahepatic cholangiocarcinoma (ICC) are prone to recurrence and poor survival. Targeted therapy related to isocitrate dehydrogenase (IDH) is an extremely important treatment. IDH1 and IDH2 mutations are generally thought to have similar effects on the tumor landscape. However, it is doubtful whether these two mutations have exactly the same effects on tumor cells and the tumor microenvironment. Methods: All collected tumor samples were subjected to simultaneous whole-exon sequencing and proteome sequencing. Results: IDH1 mutations accounted for 12.2%, and IDH2 mutations accounted for 5.5%, all missense mutations. Tumors with IDH mutations had lower proportions of KRAS and TP53 mutations. Mutated genes were obviously enriched in the kinase pathway in the tumors with IDH2 mutations. The signaling pathways were mainly enriched in the activation of cellular metabolic activities and an increase of inhibitory immune cells in the tumors with IDH mutations. Moreover, tumors had unique enrichment in DNA repair in IDH1 mutants and secretion of biological molecules in IDH2 mutants. Inhibitory immune cells might be more prominent in IDH2 mutants, and the expression of immune checkpoints PVR and HLA-DQB1 were more prominent in IDH1 mutants. IDH mutations were more related to metabolism-related and inflammation-immune response clusters, and some belonged to the DNA replication cluster. Conclusions: These results revealed the differential IDH1 and IDH2 mutation-related landscapes, and we have provided an important reference database to guide ICC treatment.
Postoperative adjuvant hepatic arterial infusion chemotherapy combined with donafenib in hepatocellular carcinoma with solitary large tumor and microvascular invasion: A multicenter, prospective, single-arm, phase II trial.
Authors: Long Yin , Huang Ziqi , He Xiaodong , Huang Jue , Liao Jianguo , Zeng Yongyi , Tang Yunqiang , Zhang Lei 
Published: July 2024

e16227 Background: Hepatocellular carcinoma (HCC) with solitary large tumor (≥ 5 cm) and microvascular invasion (MVI) was associated with high 5-year recurrence rate and poor survival prognosis. Postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) was found to improve the recurrence-free survival (RFS) with acceptable safety profiles in HCC patients with MVI. However, the prognosis of HCC who received adjuvant HAIC after hepatectomy still remain far from satisfactory. Several studies have shown that the combination of HAIC and tyrosine kinase inhibitors (TKIs) could exhibit a synergistic anticancer effect and improve the survival outcomes of advanced HCC. Thus, the present study was conducted to explore the efficacy and safety of adjuvant HAIC plus the novel multikinase inhibitor donafenib in HCC with solitary tumor ≥ 5 cm and MVI. Methods: This prospective, single-arm phase II study was conducted in three medical centers in China. HCC patients with both solitary tumor ≥ 5 cm and MVI, no evidence of recurrence at radiological follow-up at 4-8 weeks after hepatectomy, no previous treatment for HCC other than hepatectomy, Child-Pugh score A or B7 were enrolled. Eligible patients received one cycle of HAIC with oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX4), and followed by donafenib (200 mg orally twice daily) for up to 1 year until disease recurrence or unacceptable toxicity. The primary endpoint was 1-year recurrence-free survival rate (1-year RFS rate). Secondary endpoints included RFS, overall survival (OS) and safety. Results: A total of 18 patients were included for analysis. The median age was 59 years (range, 28–75), the median maximum tumor size was 7.0 cm (interquartile range [IQR], 6.2–7.8), 88.9% had low-risk MVI, 61.1% had Edmondson-Steiner grade III-IV and 44.4% had incomplete tumour capsule. As of November 27, 2023, 4 of 18 patients (22.2%) recurrenced and no deaths occurred with a median follow-up of 15.0 months (95% confidence interval [CI], 5.1–19.1). The 1-year RFS rate was 64.9% (95%CI, 39.2%–100%), and current immature median RFS was 14.3 months (95%CI, not available [NA], 11.2–NA). The most common treatment-related adverse events (TRAEs) were hand-foot skin reaction (72.2%), diarrhea (38.9%), decreased platelet count (22.2%), hypoalbuminemia (22.2%), and alopecia (22.2%). Grade 3 TRAEs occurred in 6 patients (33.3%), and no grade 4 or 5 TRAEs occurred. Conclusions: In this prospective study, the preliminary data indicated that HAIC combined with donafenib is an encouraging adjuvant therapy with well-tolerated safety profiles for HCC patients with solitary tumor ≥ 5 cm and MVI. Clinical trial information: NCT04962958 .
Comparing clinical outcomes between PD-1 and PD-L1 inhibitors plus bevacizumab combined with hepatic arterial interventional therapies in unresectable hepatocellular carcinoma: A single-center real-world study.
Authors: Pan Yangxun , Yuan Ze , Hu Dandan , Chen Minshan , Zhang Yaojun 
Published: July 2024

e16229 Background: Systemic therapies combined with locoregional therapies were considered a potent therapeutic strategy in treating patients with unresectable hepatocellular carcinoma (uHCC). Given the A+T strategy became the first-line treatment for advanced HCC patients, the roles of programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors in the combination therapies for treating patients with uHCC needed to be further discussed. The current study compared the clinical outcomes between PD-1 and PD-L1 inhibitors plus bevacizumab combined with hepatic arterial interventional therapies (HAIT) among patients with uHCC. Methods: From October 2019 to May 2023, 142 uHCC patients were retrospectively analyzed in Sun Yat-sen University Cancer Center, including 73 or 69 patients treated with either PD-1 (PD-1 group) or PD-L1 (PD-L1 group) inhibitors, respectively, combined with HAIT plus bevacizumab. The progression-free survival (PFS) and tumor responses were analyzed per mRECIST. Results: At the data cut-off, the median PFS was 5.5 months (95% CI 5.3-7.1 months) in the PD-1 group and 7.5 months (95% CI 7.0-9.6 months) in the PD-L1 group, respectively ( P=0.280; HR=0.74; 95%CI 0.43-1.28). The PD-L1 group showed a significantly better median intrahepatic PFS (8.1 months, 95%CI 7.6-10.2 months) than the PD-1 group (6.5 months, 95%CI 6.2-9.0 months; P=0.014; HR=0.35; 95%CI 0.16-0.81). The overall response rate (ORR; 49.3% vs. 66.7%, P=0.054), intrahepatic control rates (53.4% vs. 69.6%, P=0.070) and overall disease control rate (DCR; 68.5% vs. 78.3%, P=0.261) showed no significant difference in both groups, while the PD-L1 group demonstrated significantly higher intrahepatic disease control rate than the PD-1 group (76.7% vs. 92.6%, P=0.016). Conclusions: PD-1 and PD-L1 plus bevacizumab combined HAIT shared similar PFS, DCRs, and ORRs in treating uHCC patients. The PD-L1 plus bevacizumab combined with HAIT demonstrated a better intrahepatic control than those of PD-1, which needed further validation at a higher evidence level.
Intervention to improve care delivery and patient self-management for people with primary liver cancer who have socioeconomic disadvantages.
Authors: Weldon Christine B. , Mizrahi Jonathan , Therapondos George , Du Lingling , Palmer Carol , Medina Amanda , Sandow Tyler , Gimenez Juan , Cohen Ari , O'Brien Michelle , Ogale Sarika , Tan Amie , Trosman Julia R. 
Published: July 2024

e16232 Background: The 4R Oncology Model (4R = Right information/care/patient/time) supports patient self-management (Trosman, JCOOP 2021) and guideline-based care delivery (Liu, JCOOP 2022). 4R Care Sequence plans provide a care checklist and a graphical depiction of care timing and sequence. Here we report the impact of the 4R Care Sequence plans on care delivery and patient self-management among patients with primary liver cancer with socioeconomic disadvantages. Methods: 4R plans were provided to patients with liver cancer Jan – Dec ’23 (4R cohort). Patient-reported data were collected via surveys. Analyses compared the 4R cohort (N = 42) to a control cohort of patients who received care pre-4R, Jan - Dec ’22 (N = 52). Statistical analysis used Fisher’s exact and t-tests. Results: Survey response rates: control cohort 61% (52/85), 4R cohort 58% (42/73). Comparing control to 4R cohort respectively, patients exhibited the following characteristics: male (63%, 67%), White (67%, 74%), Black (25%, 19%), an average age (64.1, 63.9), and the majority had annual income less than $30,000 (62%, 67%). 4R significantly improved care delivery and patient self-management in all metrics vs control (Table). Patient rating of provider satisfaction on a 10-point scale was lower in the control cohort compared to the 4R cohort (8.4, 9.8, p < 0.0001), data not shown. The significant improvement across metrics was observed regardless of age, race, sex. Among patients who made < $30k annually, referral rates to a dentist before treatment increased significantly between control and 4R cohorts (19%,79%, p < 0.0001). Among patients who made > $30k annually, dental referral rates did not change between the control and 4R cohorts (70%, 71%, p = 1.00). Income was not a factor for other metrics. Conclusions: The 4R intervention using Care Sequence plans for patients with primary liver cancer facilitated improvements in care delivery and patient self-management regardless of age, race, sex or income. Our results indicate that 4R benefits all patients, including those with socioeconomic disadvantages. [Table: see text]
Durvalumab plus gemcitabine/cisplatin/nab-paclitaxel in resectable biliary tract cancer: A phase II, single-arm, open-label study (DurGAP).
Authors: Li Rentao , Liu Yang , Liu Yayue , Fu Linlin , Qi Qi , Zhang Xihao , Cui Yunlong , Lu Wei , Li Huikai 
Published: July 2024

e16260 Background: Biliary tract cancer (BTC) presents a formidable challenge, marked by its aggressive nature and dismal prognosis. While surgical resection remains the lone potentially curative option, 5-year survival rates have plateaued below 50%, largely due to high rates of recurrences and metastases. Given these sobering statistics, the imperative for neoadjuvant therapy to enhance outcomes is evident. Building upon the success of the TOPAZ-1 trial, which established durvalumab in combination with gemcitabine and cisplatin as a standard regimen for advanced BTC, this study seeks to assess the safety and efficacy of incorporating neoadjuvant durvalumab alongside gemcitabine, cisplatin, and Nab-paclitaxel for resectable BTC. Methods: Resectable, treatment-naïve BTC patients (pts) were enrolled and administered 3 cycles of neoadjuvant durvalumab (1000mg, iv, d1, q3w) + GAP (gemcitabine 1000mg/m2, cisplatin 25mg/m2, Nab-paclitaxel 100mg/m2, d1, d8, 21d cycle). Primary endpoints included assessing Adverse Events (AEs) and Objective Response Rate (ORR). Secondary endpoints comprised R0 resection rate, Recurrence-Free Survival (RFS), Overall Survival (OS). Results: Between Feb, 2023 to Jan, 2024, a total of 24 patients were enrolled, 12 (50.0%) were male, all with ECOG 0 and 18 (75.0%) presenting with N1 status. Median age: 65 years. Primary sites: intrahepatic (50.0%), extrahepatic (33.3%), gallbladder (16.7%). Median follow-up: 8.75 months; all pts received ≥2 neoadjuvant cycles. The ORR was 62.5%, with all 15 pts demonstrating partial responses (PR). The DCR was 87.5% with 15 PR and 6 stable disease (SD) responses. The most common treatment-related adverse events (TRAEs) were increased ALT/AST (28.6%), anemia (21.8%), hypoalbuminemia (16.0%). Grade ≥3 TRAEs occurred in 2 (8.3%) pts. 13 pts underwent resection, achieving R0 resection in 12 (92.3%) of cases, comprising 10 PR, 2 SD, and 1 pt deemed eligible for surgery post-assessment despite a PD response. 11 pts did not undergo resection, with reasons including patient refusal (4 PR, 1 SD), not meeting resection criteria (2 PD), lost to follow-up (1 PR, 1 SD), and still under active follow-up (2 SD). Conclusions: Neoadjuvant durvalumab combined with gemcitabine/cisplatin/Nab-paclitaxel demonstrated a promising ORR and DCR, with a tolerable safety profile, warranting further investigations in a larger cohort. Clinical trial information: NCT05640791 .
Preoperative BMI and long-term survival in NAFLD-associated hepatocellular carcinoma: A multicenter study revealing a paradox.
Authors: Zhang Wei , Li Zi-Qiang , Diao Yong-Kang , Liu Xing-Kai , Guo Hong-Wei , Wu Xiao-Chang , Wang Hong , Wang Si-Yuan , Zhou Ya-Hao , Lu Jun , Gu Wei-Min , Chen Ting-Hao , Li Jie , Liang Ying-Jian , Wang Ming-Da , Chen Zhong , Lv Guo-Yue , Yang Tian 
Published: July 2024

e16262 Background: As non-alcoholic fatty liver disease (NAFLD) emerges as a key factor in hepatocellular carcinoma (HCC) development, exacerbated by the global obesity epidemic, the prognostic role of body mass index (BMI) in NAFLD-HCC patients undergoing surgical resection remains unclear. This study aims to elucidate the impact of preoperative BMI on long-term outcomes after hepatectomy in patients with NAFLD-HCC, offering insights for more personalized treatment strategies. Methods: In this multicenter retrospective study, patients with early-stage (BCLC stage 0/A) NAFLD-HCC who underwent curative hepatectomy between 2009 and 2022 were analyzed. Based on preoperative BMI, patients were classified into lean ( < 23.0 kg/m2), overweight (23.0-27.4 kg/m2), and obese (≥ 27.5 kg/m2) categories. The primary endpoints, overall survival (OS) and recurrence-free survival (RFS), were compared across these BMI groups. Results: This large multicenter cohort comprised 309 early-stage NAFLD-HCC patients: 66 lean, 176 overweight, and 67 obese. Liver-, tumor-, and surgery-related characteristics were similar across groups. Lean patients exhibited significantly lower 5-year OS and RFS (55.4% and 35.1%, respectively) compared to overweight patients (71.3% and 55.6%, P = 0.017 and P = 0.002), with outcomes comparable to obese patients (48.5% and 38.2%, P = 0.939 and P = 0.442). Multivariable Cox-regression analysis revealed lean BMI, but not obese BMI, as an independent predictor of decreased OS (HR: 1.69; 95%CI: 1.06-2.71; P = 0.029) and RFS (HR: 1.72; 95% CI: 1.17-2.52; P = 0.006). Conclusions: This study challenges conventional perceptions of BMI in cancer prognosis, revealing that lean NAFLD-HCC patients have poorer long-term surgical outcomes compared to their overweight and obese counterparts. These findings underscore the need for a nuanced understanding of BMI’s role in NAFLD-HCC management and prompt further investigation into the underlying biological mechanisms of this paradox.
Survival outcomes in patients with non-metastatic intrahepatic cholangiocarcinoma in United States: A nationwide analysis.
Authors: Mohsin Aleenah , Ahmad Shahzaib , Khan Hadin Darain , Aziz Nouman , Naeem Hamza , Bellur Shreyas S. , Ganiyani Mohammad Arfat , Jayram Diya , Ahluwalia Manmeet Singh 
Published: July 2024

e16277 Background: Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive primary liver malignancies contributing to notable morbidity and mortality. Surgical resection (Sx) is the mainstay of treatment for non-metastatic ICC. However, it is unclear if augmenting resection with chemotherapy (CT), radiotherapy (RT) or chemoradiation (CRT) confers survival benefit in non-metastatic ICC. This study aims to assess effective therapeutic option for non-metastatic ICC. Methods: We queried the National Cancer Database to identify patients diagnosed with non-metastatic (stage 0-3, M0) ICC between 2004 and 2020. We reported survival outcomes in the study cohort in concordance with STROBE guidelines. We analyzed median overall survival (mOS) and differences in survival using the Kaplan-Meier (KM) methodology and pair-wise log-rank test, respectively in 6 groups based on treatment: Sx, CT, RT, Sx+CT, Sx+CRT, and CRT. Results: The analysis included 20,005 patients diagnosed with non-metastatic ICC with a median age of 66 years (range: 15-90+ years). The population included White (83.6%), Black (8.3%), and Asian (3.9%). 50% of the patients were male, 91.9% were non-Hispanic, 88.8% had Charlson-Deyo score (CDS) of 0-1, 11.2% had CDS ≥2, 51.6% were treated at academic/tertiary care program. 24.0% of the cases had positive lymph nodes. 3,394 patients (23.9%) of the total patients underwent Sx, 4,313 (30.4%) patients underwent CT alone, 1,023 (7.2%) patients underwent RT, 2753 (19.3%) patients underwent Sx+CT, 1100 (7.7%) patients underwent Sx+CRT, and 1629 (11.5%) patients underwent CRT alone. Patients who underwent Sx alone had better mOS (46.3 months, 95% CI 42.8-48.9) than all other modalities, including Sx+CT (46.0 months, 95% CI 43.9-48.0, P = 0.10), Sx+CRT (44.5 months, 95% CI 35.6-50.4, P = 0.11), CT (12.4 months, 95% CI 11.9-12.8, P < 0.01), RT (18.3 months, 95% CI 16.3-19.8, P < 0.01), and CRT (18.1 months, 95% CI 17.0-19.4, P < 0.01). Conclusions: Our study indicates that surgical resection yields the best survival outcomes when compared to other treatment modalities for nonmetastatic ICC. However, there is no significant difference in survival when surgery is combined with chemotherapy or chemoradiation in nonmetastatic ICC. Further prospective research is needed to refine treatment strategies and enhance outcomes for ICC patients. [Table: see text]
Survival outcomes associated with treatment modalities in stage 4 gallbladder neuroendocrine tumors: A nationwide analysis.
Authors: Aziz Nouman , Ahmad Shahzaib , Ganiyani Mohammad Arfat , Ozair Ahmad , Sarwar Muhammad Zeeshan , Jayram Diya , Khan Hadin Darain , Ahluwalia Manmeet Singh 
Published: July 2024

e16295 Background: Gallbladder neuroendocrine tumors (GNETs) are rare, heterogeneous, and aggressive tumors of the gallbladder. GNETs usually present in the elderly ( > 60 years) and there are no clear clinical guidelines to treat stage 4 GNETs due to rarity. We evaluated therapeutic options for stage 4 GNETs. Methods: We included stage 4 GNETs diagnosed between 2004-2020 in the National Cancer Database. Treatment was stratified into combination therapy (Comb) - surgery (Sx) and chemotherapy (CT), Sx alone and CT alone. Survival outcomes were expressed as Kaplan-Meier curves and Cox proportional hazard model adjusting for age, Charlson-Deyo score (CDS) and sociodemographic variables like sex, race, ethnicity, insurance status, and facility location. We expressed survival outcomes as median overall survival (mOS, 95% CI) and time-dependent survival as hazard ratio (HR, 95% CI). Results: Of 242 patients with stage 4 GNETs, the median age was 64 years (range 29-90+ years), 62.4% were female, 66.9% had CDS of 0, 22.4% had CDS of 1, 10.8% had CDS ≥2, 98.7% had poorly differentiated tumor (grade 3 or 4), 70.3% were White, 85.9% were non-Hispanic, median size of the primary tumor was 10.7 cm (range 0.8-14.1 cm) and 47.8% were treated at academic or research program. 46 (19.0%) patients received Comb, 171 (70.7%) received CT and 25 (10.3%) patients received Sx alone. The mOS was 11.5 months (9.3-18.4), 9.4 months (7.9-11.2), 4.2 months (2.3-6.3) for Comb, CT and Sx, respectively (P < 0.001). Pairwise log-rank revealed no significant differences between Comb and CT groups (P = 0.07). In univariate Cox analysis, CDS ≥2 showed HR of 1.6 (1.0-2.4; p = 0.04), Sx showed HR of 1.7 (1.1-2.7; P = 0.02), and Medicare had HR of 1.35 (1.02-1.78; p = 0.037). However, on multivariate analysis, uninsured patients (HR = 5.16; 95% CI 1.50-17.7; P = 0.009) and those receiving Sx alone (HR = 2.09; 95% CI 1.27-3.46; P = 0.004) had unfavorable outcomes. Conclusions: The combination of primary site surgery with CT improves survival in stage 4 GNETs as compared to resection alone. However, there is no significant difference in survival in combination therapy and CT. We emphasize the need for robust prospective studies comparing the efficacy of chemotherapy, neoadjuvant and adjuvant chemotherapy for stage 4 GNETs.[Table: see text]