bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter study on adjuvant chemotherapy of S-1 versus observation for resected perihilar cholangiocarcinoma.
Authors: Hosokawa Isamu , Higuchi Ryota , Homma Yuki , Takayashiki Tsukasa , Ome Yusuke , Matsuyama Ryusei , Takano Shigetsugu , Uemura Shuichiro , Yabushita Yasuhiro , Suzuki Daisuke , Miyake Kentaro , Honda Goro , Endo Itaru , Ohtsuka Masayuki 
Published: June 2023

e16201 Background: The prognosis of perihilar cholangiocarcinoma (PHC) is poor even after curative resection. The efficacy of adjuvant S-1 chemotherapy for resected PHC is unclear. This study aimed to assess the efficacy of adjuvant S-1 chemotherapy after major hepatectomy for PHC. Methods: Consecutive patients with PHC who underwent major hepatectomy (hemihepatectomy or trisectionectomy extending to segment 1 with extrahepatic bile duct resection) at three high-volume centers in Japan from 2007 to 2020 were retrospectively evaluated. Patients with Clavien-Dindo grade V complications, pStage I or IVB disease, and those who underwent adjuvant radiation therapy were excluded from analysis. Propensity score matching analysis was performed to compare the disease-specific survival (DSS) of patients who underwent adjuvant S-1 chemotherapy with those who underwent observation. Results: Of 480 patients, 373 were eligible for the study, 81 of whom underwent adjuvant S-1 chemotherapy, and 146 underwent observation. In the global cohort, DSS in the S-1 and observation groups were similar ( P = 0.18). In the matched cohort as well (S-1: n=44, Observation: n=44), DSS was similar between the S-1 and observation groups ( P = 0.09). On multivariate analysis, performance of percutaneous biliary drainage, CA19-9 levels at operation ≥ 300 U/ml, and lymph node (LN) metastasis were independent predictors of poor survival following major hepatectomy for PHC. In subgroup analysis of patients with LN metastasis, DSS in the S-1 group was better than in the observation group ( P = 0.001). Conclusions: Adjuvant S-1 chemotherapy after major hepatectomy might be effective in PHC patients with LN metastasis.
Association between autologous transfusion and recurrence-free survival in patients with hepatocellular carcinoma after resection: A prospective nonrandomized controlled trial.
Authors: Zhong Jian-Hong , Xie Si , Huang Jian-Li , Yang Da-Long , Chen Zu-Shun , Ma Liang 
Published: June 2023

e16206 Background: To investigate whether preoperative stored autologous transfusion has a significant effect on recurrence-free survival of patients with primary hepatocellular carcinoma (HCC). Methods: Recurrence-free survival (RFS), overall survival, and perioperative morbidity were compared among patients with or without autologous transfusion at our medical center between January 2019 and December 2021. Patients who received autologous transfusion were matched based on propensity scores to patients who did not, in order to reduce confounding due to baseline differences. This study was registered on ClinicalTrials.gov (NCT02654028). Results: Of the 618 patients in the analysis, 399 (64.6%) received autologous transfusion and 219 (35.4%) did not receive autologous transfusion. By 30 July 2022, the median RFS time had been achieved. Patients with or without autologous transfusion had similar RFS before (hazard ratio 1.01, 95%CI 0.82-1.24) or after propensity score analysis (hazard ratio 1.04, 95%CI 0.82-1.31). However, the median overall survival was not achieved. Patients with or without autologous transfusion also had similar overall survival before (hazard ratio 1.15, 95%CI 0.84-1.56) or after propensity score analysis (hazard ratio 1.26, 95%CI 0.88-1.79). Moreover, subgroup analyses found that patients with or without autologous transfusion had similar RFS or overall survival among those with early, intermediate, or advanced stage disease. The two groups also had similar rates of perioperative mortality and morbidity. Conclusions: Preoperative stored autotransfusion had no significant effect on survival in patients with HCC who underwent liver resection. Clinical trial information: NCT02654028 .
EGFR/ERBB2 aberrations in Chinese biliary tract carcinomas.
Authors: Wu Xiaobing , Zhao Yaping , Wang Chenxi , Ding Ran , Deng Wanglong , Bu Fanfeng 
Published: June 2023

e16208 Background: Biliary tract carcinoma (BTC) accounts for 3% gastrointestinal cancers in China. BTCs are mainly classified as gallbladder cancer (GBC) and cholangiocarcinomas (CCA) with dismal prognosis. Current chemotherapy regimens for BTC yield poor outcomes. We aimed to describe the genomic landscape of a BTC patient cohort using next-generation sequencing (NGS), focusing on the EGFR/ERBB2 aberrations and exploring the possibility of therapeutic intervention. Methods: We analyzed BTC tissue/blood samples including GBCs and CCAs with targeted sequencing (NGS) for EGFR/ERBB2 activating mutations, copy number amplifications (copy number≥5) and rearrangements (containing the kinase domain). A cohort of 1033 Chinese BTC patients were analyzed including 783 GBC patients and 250 CCA patients. Results: Data analysis revealed EGFR/ERBB2 alteration rates were 9.0% in Chinese BTC patients. The majority of these alterations were in fact ERBB2 alterations at a rate of 15.8% in GBC and 6.4% in CCA（P<0.05). A further subanalysis of ERBB2 mutation types showed that 46.7% in GBC and 64.6% in CCA were activating mutations, 37.8% in GBC and 31.3% in CCA were gene amplifications, 8.9% in GBC and 2.1% in CCA were gene rearrangements and 6.7% of GBC and 2.1% of CCA cases had multiple ERBB2 alterations. The top activating ERBB2 mutation were p.S310F（10/45） followed by p.R678Q(4/45) in GBC and were p.S310F (11/48) followed by p.V777L(5/48) in CCA. EGFR alteration rates were 3.5% in GBC and 1.3% in CCA（P<0.05). Among these, 30% of the GBCs and 60% of the CCAs had an activating EGFR mutation, 70% of the GBCs and 30% of the CCAs had EGFR copy number amplification and 10% of the GBCs and no CCA case had an EGFR rearrangement. Three EGFR activating mutations detected in GBC were p.G719A, p.L861Q, p.A289V. Six EGFR activating mutations detected in CCA were p.G719D, p.E746_S752delinsV, p.L858R, p.N771_H773dup, p.D770_N771insG, p.R222C. Conclusions: We report characteristics of EGFR/ERBB2 alterations in Chinese GBC and CCA patients. In general, 19.4% of GBC and 7.7% CCA may benefit from EGFR/ERBB2 targeted therapy. EGFR/ERBB2 targeted therapies should be further explored in Chinese BTC patients.
Evaluating triple therapy with lenvatinib, PD-1 inhibitor and transarterial chemoembolization for unresectable intrahepatic cholangiocarcinoma: A retrospective study.
Authors: Tu Jianfei , Ying Xihui , Lai Lingqiang , Huang Chaoming , Liu Shuang , Chen Li , Zhang Dengke , Wu Jiahao , Chen Jie 
Published: June 2023

e16210 Background: Cholangiocarcinoma has a poor prognosis and responds poorly to intravenous chemotherapy. This study evaluated the efficacy and safety of a triple therapy combining transarterial chemoembolization (TACE) with lenvatinib and programmed cell death protein (PD)-1 inhibitors for treating unresectable intrahepatic cholangiocarcinoma (ICCA). Methods: This retrospective study included a total of 15 patients with unresectable ICCA who were initially treated with TACE. One week later, they received lenvatinib 8 mg/day orally and PD-1 inhibitors for 21 days/cycle. The primary endpoint was the objective response rate (ORR); secondary endpoints included disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and the incidence of treatment-related adverse events (TRAEs). Results: At 1-month post-treatment, the ORR was 73.3% and the DCR was 86.7%. The median PFS was 10.4 months (95% confidence interval [CI]: 6.73, not reached), and the median OS was 16.9 months (95% CI: 9.2, not reached). Compared with pre-treatment data, post-treatment levels of the tumor serum markers carcinoembryonic antigen and carbohydrate antigen 19-9 had decreased significantly (P<0.05). However, 13 patients experienced Grade 1–2 TRAEs, including decreased appetite (n=8 [53.3%]), fatigue (n=3 [20.0%]), weight-loss (n=3 [20.0%]), hypertension (n=2 [13.3%]), hand–foot syndrome (n=2 [13.3%]), diarrhea (n=1 [6.7%]), dysphonia (n=1 [6.7%]), and hypothyroidism (n=1 [6.7%]). No patient experienced Grade ≥3 TRAEs during treatment or follow-up. Conclusions: Triple therapy with TACE, lenvatinib and PD-1 inhibitors showed promising antitumor activity as well as a tolerable safety profile in patients with ICCA. Larger clinical studies investigating this treatment combination should be considered.
Huaier granules for hepatocellular carcinoma recurrence after ablation: A multicenter prospective cohort study.
Authors: Han Yue , Zheng Jiasheng , Wan Chidan , Li Zixiang , Zhai Bo , Li Jiaping , Li Yuliang , Li Hailiang , Ma Liwei , Liu Ruibao , Zhou Jun , Shi Lei , Song Lei , Wang Shuai , Han Juqiang , Zhang Bo , Li Qingdong , Ye Xin , Fan Weijun 
Published: June 2023

e16216 Background: Clinical trials had confirmed the efficacy and safety of Huaier granules in the treatment of hepatocellular carcinoma (HCC), but real-world evidence is still lacking. This prospective study aimed to evaluate the real-world effectiveness and safety of Huaier granules for HCC recurrence after ablation. Methods: Post-ablation patients with no residual lesions confirmed by imaging were enrolled in this study and divided into the Huaier granule group and the control group based on receiving Huaier granules or not. Propensity-score matching was performed according to age, gender, TACE within 3 months before ablation, alpha-fetoprotein level, time interval between ablation and enrollment, and Child-Pugh Grade in 1-(up)-to-2 ratio. The primary outcome was progression-free survival (PFS), and the secondary outcomes were local recurrence-free survival (LRFS) and adverse events (AEs). Results: There were 340 patients in the Huaier granule group and 141 patients in the control group. After propensity score matching, 189 patients and 111 patients were selected for the Huaier granule group and the control group, respectively. There was no significant difference in baseline characteristics between two groups after matching. The median follow-up time of the Huaier granule group and the control group were 49.14 weeks and 73.29 weeks, respectively. The number of PFS events were 29 (15.34%) and 27 (24.32%) in the Huaier granule group and the control group, respectively. The 48, 72, and 96-week PFS rates were 87.4%, 79.4% and 75.2% in the Huaier granule group, and 79.9%, 70.1% and 66.5% in the control group, respectively ( P=0.1649). The number of LRFS events were 27 and 25 in the Huaier granule group and the control group, respectively. In the pre-matching Huaier granule cohort, the incidence of AEs, serious AEs, and grade ≥ 3 AEs were 54 (16.56%), 30 (9.20%) and 14 (4.30%), respectively. Conclusions: This study suggested potential benefit in PFS and RFS and favorable safety profile of Huaier granules in patients with HCC after ablation. Longer-term follow-up is needed to confirm this finding.[Table: see text]
Using machine learning-based boosting algorithm to predict hepatotoxicity after local therapy and association with survival in patients undergoing liver directed therapy.
Authors: Mo Allen , Velten Christian , Tang Justin , Ohri Nitin , Kalnicki Shalom , Mirhaji Parsa , Kaubisch Andreas , Soby Selvin , Peshansky Alexandre , Henninger Erin , Garg Madhur , Guha Chandan , Kabarriti Rafi 
Published: June 2023

e16229 Background: Hepatocellular carcinoma typically arises in the setting of chronic liver disease. In carefully selected patients, liver directed therapy has been demonstrated to improve survival; however, this benefit from cancer specific survival may be offset by increased mortality from diminished hepatic functional reserve. Treatment-related hepatotoxicity also may vary between liver directed treatment modalities for a given tumor. Our aim was to determine if a machine learning approach could estimate hepatotoxicity prior to treatment. Methods: We identified all patients with hepatocellular carcinoma who underwent liver directed therapy at a large urban academic health system who also had post-treatment laboratory follow-up at 6 months. Patients were categorized as having worse liver function if they experienced a decline in albumin-bilirubin (ALBI) grade or more than 0.5 absolute decline in ALBI score at post treatment follow-up. A machine learning, extreme-gradient boosting (XGBoost) approach was employed to identify predictive features for hepatotoxicity using fine-tuned hyperparameters. Results: The study cohort consisted of 269 patients. 48 (18%) were categorized as having worsened hepatic function after liver directed therapy, with an average decline of -0.72 in ALBI score. Median survival after liver directed therapy was 5.8 years, with worsening hepatic function associated with a 5 month decline in overall survival. 158 (59%) patients received transarterial chemoembolization, 99 (37%) patients received stereotactic body radiotherapy and 12 (7%) patients received Y-90. A machine learning model was developed resulting in an Area Under the ROC Curve (AUC) of 0.894 in a 10-point decision tree model. On SHAP analysis, the features with the largest impact on hepatotoxicity prior to treatment was pretreatment T-stage followed by Child-Pugh Score. Conclusions: A machine learning model was developed to accurately classify patients who sustained treatment related hepatotoxicity. Significant decline in ALBI score or grade was associated with a worsening of overall survival. Future studies in larger prospective clinical trials utilizing this machine learning-based methodology of assessing liver dysfunction after focal therapy are required to validate these findings.
Survival outcomes with observation or adjuvant therapy in elderly patients with biliary tract cancer.
Authors: Gbolahan Olumide B. , Zhi Xiaojie , Botrus Gehan , Shah Mihir Maheshkumar , Sarmiento Juan , Russell Maria C. , Kooby David A. , Maithel Shishir K. , Alese Olatunji B. 
Published: June 2023

e16230 Background: The impact of adjuvant therapy (AT) on overall survival (OS) for biliary tract cancer (BTC) is contested. The BILCAP study suggested an improvement in OS with adjuvant capecitabine compared to observation. This was not apparent in the intention to treat population. Importantly, none of the patients in the study was older than 70 years. Considering the toxicity of AT and conflicting results of efficacy, the role of AT in older adults with BTC needs to be thoroughly assessed. We hypothesized that AT is not associated with significant benefit in the elderly. Methods: We performed a retrospective review of patients with resected BTC; gall bladder cancer (GBC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) using the National Cancer Database (NCDB) PUFs (2004-2019). We limited analysis to patients aged >= 70 years. We compared clinical characteristics and outcomes in those who received AT (including chemotherapy and chemotherapy + radiation) within 6 months after resection, and those who did not (Obs). We performed propensity score matching analysis of both groups (matched for age, sex, race, Charleson-Deyo score, AJCC pathologic T stage among others) and assessed survival by Kaplan-Meier analysis. Results: We identified 8,091 elderly patients with T1-T3/N1-N2 resected BTC. The majority had GBC (76.7%), and 3, 041 (38%) were aged >= 80 years (median 78 years). Only 2, 632 (32.5%) received AT. Of these, 1,304 (50%) received chemotherapy and radiation. Median OS was higher in the Obs vs the AT group (24.3 months, vs 20.2 months, P < 0.0001) and the five-year survival was also higher in the Obs group (29.1% vs 22.6%, P<0.001). Survival also favored the Obs group in a propensity score matched cohort of 835 patients per group (median OS 33.1 vs 19.5 months, P <0.0001). On multivariable analysis AT was associated with a higher hazard of death (HR 1.21, CI 1.13-1.29, P <0.001). Age >=80 (HR 1.39, CI 1.32-1.47, P<0.001), GBC ( HR 1.29, CI 1.20-1.39, P<0.001) were also associated with worse survival. Compared to diagnosis between 2004-2009 diagnosis in 2010- 2015 (HR 0.83, CI 0.78- 0.89) and 2016- 2019 (HR 0.74 CI 0.67-0.8, P <0.001) were associated with improved OS. Conclusions: In patients >=70, AT for BTC was not associated with improved OS and was actually associated with a higher hazard of death compared Obs. Based on these results, the role of AT for BTC in the elderly needs to be examined prospectively.
Trends in utilization of first-line palliative care in non-metastatic hepatocellular carcinoma.
Authors: Ozer Muhammet , Goksu Suleyman Yasin , Sahin Ilyas 
Published: June 2023

e16234 Background: Palliative care therapies are known to improve the quality of life and even the survival of some patients. Although non-metastatic (stages I-III) hepatocellular carcinoma (HCC) patients often present with significant symptoms, first-line palliative care treatment is uncommon in this setting. Here we characterized rates of palliative care utilization among non-metastatic HCC patients and determined factors associated with palliative care receipt. Methods: We conducted a retrospective review of adult National Cancer Database patients diagnosed with metastatic HCC between 2004 and 2019. We used descriptive analysis for determining palliative care utilization, including palliative chemotherapy, surgery, radiotherapy, and pain management. We performed multivariable logistic regression analysis to assess the association of characteristics with palliative treatment utilization. Results: Among 121,151 patients diagnosed with stage I-III HCC, the utilization of first-line palliative care subsets was only a small portion of 3966 (3.3%). The most commonly used palliative care treatment was pain management (37.4%), followed by systemic chemotherapy (31.1%), radiotherapy (13%), surgery (9.9%), and combination therapies (8.6%). The higher stage, high comorbidity score, and decreased life expectancy were more likely to be associated with received PC. Stage 2 and 3 diseases were associated with increased odds of PC receipt compared to stage 1 disease (odds ratio [OR] = 1.63 [1.45-1.83] and OR = 3.57 [3.22-3.95]; respectively). Comorbidity score 3 was significantly more likely to receive PC than comorbidity score 0 (OR = 1.54 [1.41–1.69]). In addition, life expectancy >24 months was significantly less associated with PC receipt compared to life expectancy < 6 months (OR: 0.23 [0.20-0.26]). Conclusions: First-line palliative care subsets are underutilized to control symptoms among patients with non-metastatic HCC. Targeted efforts should be focused on increasing palliative care delivery in this group which has a vast potential to benefit.
Comprehensive analysis of molecular characteristics, TMB, and MSI in Chinese patients with neuroendocrine neoplasms.
Authors: Li Xiaohan , Xiao Yun , Ma Juan , Ding Ran , Wang Chenxi , Deng Wanglong , Bu Fanfeng 
Published: June 2023

e16236 Background: Neuroendocrine neoplasms (NENs) is a heterogeneous and rare tumor type. To date, most genomic profiling studies on NENs have mainly focused on pancreatic NENs (PanNENs), less is known about nonpancreatic NENs (NP-NENs). We explored the molecular characteristics, tumor mutational burdens (TMB) and microsatellite instability (MSI) in Chinese NENs patients based on different primary lesions to discover genomic profiles. Methods: We retrospectively analyzed molecular characteristics, TMB and MSI in 155 Chinese NENs patients from laboratory of Simcere Diagnosis (Nanjing, China) during 2019 to 2022. Tissue and plasma samples were profiled using the 551-gene panel next-generation sequencing (NGS). Results: The median age of 155 patients was 61 years old (range, 22-85 years old), the male to female ratio was 1.63:1. 118 cases with known primary lesions could be divided into PanNENs(n=22) and NP-NENs (n=96). There were no differences in age and ratio of PanNENs and NP-NENs. The most common SNV and indel mutations were TP53(23%), DAXX (22.7%), MEN1 (18.2%), KRAS (18.2%), ATM (13.6%), SMAD4 (13.6%) and TSC2 (13.6%) in PanNENs, in which CDK4/6 amplifications were often detected (31.8%, 27.3%). Gene fusions rarely occurred in this cohort. For NP-NENs, we identified TP53 (58.3%), MUC16 (29.2%), RB1(31.3%), LRP1B (22.9%), SMARCA4 (10.4%), SPTA1 (10.4%) and FAT3 (10.4%) as the most common SNV and indel mutations, with MYC (26%) and CDK4 (15.6%) amplifications. CCNE1 high-level amplification was especially common in digestive system NENs. Multiple gene fusions were found in NP-NENs. 13/155 (8.4%) patients carried pathogenic/likely pathogenic germline mutations in MUTYH(n=3), MSH3 (n=2), FANCG (n=2), RAD51D (n=1), CDH1 (n=1), ERCC3 (n=1), ATM (n=1), MEN1 (n=1), RECQL4 (n=1), most of them were associated with DNA damage repair (DDR) pathway. 92.3% (12/13) patients were NP-NENs with only one PanNENs harboring MUTYH germline mutation. 155 NEN patients could be evaluated for TMB, 24 (15.5%) patients had TMB≥10Muts/Mb, 7% (10/24) were lung-derived NENs. TMB was significantly higher in NP-NENs compared to PanNENs (4.26 muts/Mb vs. 2.13muts/Mb, P<0.01). 138 patients could be evaluated for MSI status, only one NEN whose primary site was liver was MSI-H, the others were all MSS. Conclusions: Our data showed that PanNENs and NP-NENs had different mechanisms of tumorigenesis: DAXX and MEN1 alterations commonly identified in PanNENs primarily mediate DDR and PI3K-mTOR pathway. Frequent TP53, RB1 and CCNE1 aberrations in NP-NENs were associated with CDK signaling pathway. TMB was low in almost all NENs exclude lung-derived NENs. It revealed distinct drivers in different subtypes, potentially being used as relevant therapeutic targets.