bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of circulating tumor DNA for prediction and surveillance of tumor recurrence after liver transplantation: A pilot study.
Authors: Huang Ao , Guo De-Zhen , Zhang Xuan , Sun Ying , Zhang Xin , Fu XiuTao , Wang Yupeng , Yang Guo-Huan , Sun Qiman , He Yifeng , Song Kang , Huang Xiao-Wu , Liu Wei-Ren , Ding Zhen-Bing , Shi Ying-Hong , Fan Jia , Zhou Jian 
Published: June 2022

e16149 Background: Emerging data suggest that circulating tumor DNA (ctDNA) could detect minimal residual disease (MRD) and reflect tumor recurrence after radical resection in hepatocellular carcinoma (HCC). However, most reported ctDNA measurements are based on hotspot mutations and their predictive value in liver transplantation (LT) are still undetermined. We conducted a pilot study investigate ctDNA fingerprint as the detection marker of MRD in HCC patients undergoing LT. Methods: We enrolled 74 patients in HCC and monitored their ctDNA changes along the course of treatment at both pre- and post-operation by serial sampling of peripheral blood. All of the patents were treated by LT, and their ctDNA variations were used to assess the recurrence. We analyzed the correlation between ctDNA levels and recurrence-free survival (RFS) of the patients. Results: We monitored the ctDNA value of each patient before and after LT and found that the ctDNA-positive group was associated with higher recurrence rate (31.7% vs 11.5%), and has a shorter RFS than that of the ctDNA-negative group at baseline (preopreation) (HR, 3.25; CI 95% 1.18-8.97; p = 0.019). The conclusion also stands in patients at first timepoint follow-up after LT (postoperation) (recurrence rate, 46.2% vs 21.3%; HR, 4.26; CI 95% 1.62-11.2; p = 0.010). Moreover, changes of ctDNA were associated with RFS during the course after LT, both the ctDNA-decreased group and ctDNA-negative group have favorable clinical benefit than ctDNA-increased group. Conclusions: This study confirming the association between baseline levels of ctDNA and RFS in HCC undergoing LT. More importantly, it suggests the change of ctDNA level in plasma is a promising biomarker of MRD detection and patient prognosis in early HCC.
Lenvatinib plus PD-1 inhibitors in 378 unresectable hepatocellular carcinoma: A large real-world study from two centers.
Authors: Yang Xu , Chen Bowen , Wang Yanyu , Wang Yunchao , Long Junyu , Zhang Nan , Xue Jinnan , Xun Ziyu , Zhang Linzhi , Cheng Jiamin , Lei Jin , Pan Jie , Hu Ke , Guan Mei , Huo Li , Mao Yilei , Sang Xinting , Lu Yinying , Zhao Hai-Tao 
Published: June 2022

e16155 Background: Combining lenvatinib (a multikinase inhibitor) with programmed cell death protein-1 (PD-1) inhibitor has been explored in Unresectable hepatocellular carcinoma (uHCC) in phase 1b trials. This study aimed to investigate the real-word efficacy and safety of lenvatinib plus PD-1 inhibitor for large Chinese patients uHCC cohorts. Methods: BCLC stage B or C uHCC patients were included. Data was collected from Oct 2017 to Nov 2021 retrospectively. Patients were treated with lenvatinib and PD-1 inhibitor (pembrolizumab or nivolumab or camrelizumab or sintilimab or toripalimab or tislelizumab). The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and objective response rate (ORR) evaluated by RECIST v1.1 criteria. Adverse events (AEs) were assessed using CTCAE v5.0. Prognostic factors of survival were also analyzed. Results: 378 uHCC patients of BCLC stage B (12.7%) and C (87.3%) from two medical centers were included in China. The median age was 55 (range 18-89) years and 86.5% patients were male. ECOG scores were 0 (43.7%), 1 (43.4%) and 2 (13.0%), while Child-pugh grade were A (77.5%) and B (22.5%) respectively. The median OS was 17.8 (95% CI 14.0-21.6) months. The median PFS was 6.9 (95% CI 6.0-7.9) months. The best objective response rate (ORR) and disease control rate (DCR) was 74/378 (19.6%) and 278/378 (73.5%) respectively. Child-pugh grade (A vs. B), ECOG score (0 vs. 1-2), BCLC stage (B vs. C) and achieve response (yes vs. no) were the prognostic factors for both OS and PFS. All (100%) experienced all-grade adverse events (AE). The most frequent AEs were fatigue, diarrhea, hypertension, decreased appetite. The most common ≥Grade 3 AEs were hypertension (13.2%), fatigue (7.1%), decreased platelet count (6.3%), increased blood bilirubin (6.1%), diarrhea (6.1%) and gastrointestinal hemorrhage (4.8%). Conclusions: This real-world study of lenvatinib plus PD-1 inhibitors achieved long survival and considerable ORR for uHCC patients in China. The tolerability of combination therapy was acceptable but should be still monitored closely. Clinical trial information: NCT03892577. [Table: see text]
Genetic profile and survival outcomes in a modern cohort of patients with biliary tract cancers (BTC): Single center experience in New York City.
Authors: Kaur Anahat , Bteich Fernand , Brodin Patrik , Kabarriti Rafi , Goel Sanjay , Kaubisch Andreas 
Published: June 2022

e16157 Background: BTCs are the second most common primary hepatobiliary malignancy with rising incidence and mortality worldwide. Individual characterization of BTCs at a genomic level is critical to tailor management strategies. Currently available data stem from studies in predominantly White populations. We conducted a retrospective study to determine the demographic, clinical and survival profiles of patients with BTCs seen in our center, who had been tested for genomic alterations. Methods: We identified 69 patients with BTCs diagnosed between 2015-2022 who had tissue-based genomic results available. Chi-square test was used to compare frequency distributions. Univariate analysis with cox regression model and multivariate cox proportional hazards test were conducted. Kaplan-Meier curves were used to assess overall survival (OS). Results: Median age at diagnosis was 67 years and median follow-up time was 15.5 months. Racial and ethnic minority populations were highly represented with 41% Hispanic, 29% Black and 17% White patients. ECOG performance status (PS) ranged between 0-2 at diagnosis. Most patients (40%) had stage IV BTC, with intrahepatic cholangiocarcinoma (CCA) being most prevalent (48%). On univariate modeling, variables associated with a shorter OS were age (HR 1.03, 95% CI 1.00-1.07, p = 0.05) and ECOG PS of 2 (HR 7.03, 95% CI 1.49-33.3, p = 0.014). In a multivariate model, ECOG PS 2 was independently associated with a shorter OS. The most common mutations (N, %) found on NGS were TP53 (28, 41%), KRAS (13, 19%), ARID1A (11, 16%), PIK3CA (9, 13%), ERBB2 (5, 7%) and FGFR2 (5, 7%). Median tumor mutation burden (TMB) was 4 Mut/Mb, with 18.9% having hypermutated (≥10 Mut/Mb) BTCs. Potentially actionable targets were found in 40 (58%) patients, 5.8% of which received targeted therapies with a median OS of 27 months (median OS of entire cohort was 22.8 months). KRAS mutation was significantly less common in intrahepatic CCA compared to the other BTC subtypes (p = 0.016). Race or ethnicity were not found to have a significant association with mutation frequency (Table). TP53 and ARID1A mutations were associated with a trend towards reduced OS in univariable analysis, with HR = 1.46 (p = 0.29) and HR = 1.64 (p = 0.28) respectively. Conclusions: Extensive genomic diversity was observed among BTC patients in our center which serves a large minority population. Studies with larger sample size are required to expand our understanding of the genomic spectrum in BTCs, its therapeutic and survival implications. [Table: see text]
Biomarker analysis of first-line camrelizumab plus apatinib in patients with advanced biliary tract cancers: Results from a phase II study.
Authors: Rao Jian-hua , Chen Dong-sheng , Song Yunjie 
Published: June 2022

e16164 Background: The prognosis of immunotherapy for patients with unresectable or metastatic biliary tract cancers (BTCs) was not very optimistic, exploring the potential biomarkers associated with tumor response in advanced BTCs may further improve the clinical benefits from immunotherapy. Methods: Fourteen advanced BTCs patients from the single-arm phase II study (ChiCTR2000034283) receiving camrelizumab (anti-PD-1 antibody) plus apatinib (VEGFR2 inhibitor) as first-line combination therapy, were included for the current biomarkers analysis. Exploratory points mainly focused on differentiated immune-related gene expression and immune pathway signatures using a 289-gene immune-related RNA panel sequencing on baseline tumor samples. Differential gene expression analysis was performed between responders (tumor regression) and non-responders (tumor extension) using Wilcoxon rank-sum test. Signature scores were calculated using the Gene Set Variation Analysis package with publicly available gene signatures. Results: Of all enrolled patients with clinical response evaluations, twelve patients had available RNA-sequencing data (6 responders vs. 6 non-responders) on baseline tumor samples. Differential gene expression analysis revealed a significantly higher BRCA2, RAD51, BRIP1 expression (p < 0.001) and decreased TGF β 1, IT GAX, ITGB2 expression (p < 0.001) in responder tumors compared with non-responder tumors. Differentiated genes were significantly enriched in receptor metabolic process pathway in responder tumors. Extensive analyses on immune cell types score were also calculated, CD8 positive T cells (p = 0.022) were significantly increased in baseline responder tumors, and Macrophages M2 cells (p = 0.008) were significantly increased in baseline non-responder tumors. Conclusions: Some differentially expressed genes and immune-related cell types were founded in defined groups, both immune- and tumor-intrinsic factors may be considered for validation in a larger study. Clinical trial information: ChiCTR2000034283.
Sintilimab plus bevacizumab as maintenance therapy for patients with unresectable hepatocellular carcinoma treated with transarterial chemoembolization: A phase Ib study.
Authors: Cai Mingyue , Liang Wei , Huang Wensou , Guo Yongjian , Liang Licong , Zhou Jingwen , Lin Liteng , Deng Haihui , Zhu Kangshun 
Published: June 2022

e16165 Background: Sintilimab (a PD-1 inhibitor) plus bevacizumab (Sin-Bev) has been demonstrated to confer a significant survival benefit over sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). This phase Ib study (NCT04592029) aimed to evaluate the safety and efficacy of Sin-Bev for patients with uHCC who received transarterial chemoembolization (TACE). Methods: The key eligibility criteria were: age ≥ 18 years; BCLC B/C stage uHCC; no prior systemic therapy and non-curative local treatments; Child-Pugh score ≤7; ECOG PS ≤1. This study included dose escalation and dose expansion stages. In the dose escalation stage, a 3+3 design was employed to determine the safety of a standard dose of sintilimab (200 mg Q3W) plus two possible doses of bevacizumab (group A: 7.5 mg/kg Q3W; group B: 15.0 mg/kg Q3W) after TACE. In the dose expansion stage, additional 30 patients were randomized 1:1 to each group. Sintilimab and bevacizumab was started at 3-7 days after the first TACE (TACE was repeated on demand). The primary endpoints were the incidence of adverse events (AEs) and progression free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: At the time of data cutoff (January 20th, 2022), 36 patients were enrolled (18 in each group). One patient in group A withdrew from the study after the first cycle of treatment. Of the remaining 35 patients, 20 (57.1%) had disease at BCLC C stage, 15 (42.9%) had macroscopic vascular invasion and 11 (31.4%) had extrahepatic metastasis. The mean largest tumor size was 10.5±5.2 cm. The median follow-up was 9.57 (range, 4.4-15.6) months. Thirty-one patients (86.1%, n=36) had treatment-related AEs (83.3% in group A vs. 88.9% in group B, P=1.000). All the AEs were mild (<grade 2) and manageable. During follow-up, 19 patients (54.3%) experienced disease progression (per RECIST 1.1 or mRECIST). The median PFS was 7.2 (95% CI 3.6-10.8) months (6.7 [95% CI 4.7-8.8] months in group A vs. 8.4 [95% CI 3.9-12.8] months in group B, P=0.832). The median PFS in this report was immature due to some later enrolled patients were censored. Thus, it is likely to improve with longer follow-up. The ORR per RECIST 1.1 and mRECIST was 37.1% (41.2% in group A vs. 33.3% in group B, P=0.733) and 80.0% (88.2 in group A vs. 72.2% in group B, P=0.402), respectively. The DCR per RECIST 1.1 or mRECIST was 91.4% (94.1% in group A vs. 88.9% in group B, P=1.000). The median OS was not reached. Conclusions: Sin-Bev showed preliminary clinical benefits and an acceptable safety profile in uHCC patients treated with TACE. The study is still ongoing and further follow-up is required to obtain the final survival results. Clinical trial information: NCT04592029.
Prognostic factors, and survival difference in gastrointestinal extrapulmonary small cell carcinoma using SEER database.
Authors: Ulanja Mark Bilinyi , Alese Olatunji B. 
Published: June 2022

e16170 Background: Gastrointestinal extrapulmonary small cell carcinoma (GI EPSCCa) is a rare and aggressive tumor. Current treatment guidelines are extrapolated from small cell lung cancer. Factors affecting survival, and the role of primary tumor location are currently unknown. Methods: Using the SEER database to identify patients diagnosed from 2000 to 2018, we used Cox proportional hazard models to assess prognostic factors based on primary tumor location. Results: Of the 1,687 patients included in the analysis, 79.7% were White and 56.9% male. Distribution of the primary location were 31.5% colorectal (CRC), 22.1% Esophagus, 20.6% pancreas, 13.3% hepatobiliary (HB), 10.6% stomach, and 1.8% small intestine (SI). Patients ≥65 years were more likely to have esophago-gastric, SI, HB and pancreatic EPSCCa (P<0.001). Males were more likely to have esophago-gastric, CRC and pancreatic EPSCCa (P<0.001). While Blacks were more likely to have esophago-gastric and SI EPSCCa, Whites were more likely to have CRC, HB and pancreas EPSCCa (P=0.012). There were no racial differences in overall survival (OS) for GI EPSCCa. Male gender (adjusted Hazard Ratio(aHR)=1.12, 95%CI:1.00-1.24, P=0.042), and age ≥65 (aHR)=1.21, 95%CI:1.09-1.35, P=0.001) were associated with inferior OS. Advanced stage at presentation, or not receiving radiation therapy/ chemotherapy were also associated with worse OS. Surgical intervention, and treatment period after 2006 were associated with superior OS (Table) Regarding GI site, HB EPSCCa was associated with inferior OS compared with esophageal EPSCCa (aHR)=1.21, 95%CI:1.00-1.46, P=0.048). SI EPSCCa had a trend toward improved OS (compared to esophageal EPSCCa) (P= 0.237). Conclusions: Chemotherapy, surgery, radiation therapy, female gender, younger age were associated with superior OS for GI EPSCCa, while advanced stage, HB sites (compared to esophageal EPSCCa) were associated with poorer outcome. OS for GI EPSCCa has improved over time. Prospective studies are needed to guide therapy for this aggressive tumor. [Table: see text]
Efficacy and safety of transcatheter arterial chemoembolization in combination with camrelizumab and targeted agents in intermediate-stage unresectable hepatocellular carcinoma: A single-arm, prospective, real-world study.
Authors: Li Jinpeng , Shi Jutian , Song Jinlong 
Published: June 2022

e16190 Background: The prognosis for advanced hepatocellular carcinoma (HCC) is still very poor. This study aimed to explore the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with camrelizumab plus targeted therapy for the treatment of patients with advanced HCC. Methods: In this single-arm, prospective, real-world study, patients with intermediate-stage unresectable HCC who had a Child-Pugh score ≤ 7 and had not received prior systemic anti-cancer treatment would receive comprehensive treatment with TACE followed by immunotherapy with camrelizumab 200 mg every 3 weeks plus a tyrosine kinase inhibitor (TKI) agent selected from lenvatinib (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight < 60 kg), sorafenib 400 mg twice-daily or donafenib 200 mg twice-daily until intolerable toxicity or disease progression. During the study treatment, patients assessed as eligible for resection would undergo surgery. The primary endpoint was objective response rate (ORR) assessed by an independent review committee per modified RECIST. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: From September 2020 to November 2021, 49 patients were enrolled. Among them, 45 (91.8%) patients were male, 41 (83.7%) patients were aged ≤65 years, 30 (61.2%) patients had extrahepatic metastases, and 41 (83.7%) patients had HBV infection. The ORR and DCR were 69.4% (34/49) and 87.8% (43/49), respectively. Five (10.2%) patients were assessed as eligible for surgery, and one of them already received surgery successfully and achieved pathological complete response. The median OS was not reached, and the median PFS was 6.1 months (95%CI, 1.4 -10.8). After 3 months, the alpha-feto-protein decreased compared with before treatment (p < 0.05). All patients had adverse events (AEs) of any grade. The most common AEs were reactive cutaneous capillary endothelial proliferation (30, 61.2%), abdominal pain (25, 51.0%), thyroid dysfunction (20, 40.8%) and fever (18, 36.7%). The majority of treatment-related AEs (TRAEs) were mild or moderate. Grade 3 TRAEs occurred in 3 (6.1%) patients, grade 4 TRAEs occurred in 1 (2.0%) patient, and no deaths occurred. Conclusions: TACE combined with camrelizumab plus targeted therapy in the treatment of advanced HCC shows good efficacy in controlling tumor progression and may provide opportunity of resection. Clinical trial information: ChiCTR2000039508.
Response to systemic treatments in advanced fibrolamellar carcinoma: A French multicenter retrospective cohort of the AGEO.
Authors: Ye-Tran Xixi , Bouattour Mohamed , Perret Audrey , Turpin Anthony , Walter Thomas , Vitellius Carole , Coriat Romain , Lequoy Marie , Blanc Jean Frederic , Regnault Hélène , Pietrasz Daniel , Sefrioui David , Lecomte Thierry , Moati Emilie , Caliez Olivier , Nguyen-Khac Eric , Fresneau Brice , Hautefeuille Vincent 
Published: June 2022

e16194 Background: Fibrolamellar carcinomas (FLC) are rare hepatic malignancies affecting young patients without chronic liver disease, often diagnosed at an advanced stage. Few data are available regarding efficacy of systemic anti-tumor treatments. Main objective was to explore response according to RECIST 1.1 criteria in the first line setting in advanced FLC patients. Methods: This retrospective multicentric French cohort included 44 patients with advanced FLC who received at least one systemic treatment and had one morphological evaluation, performed every 2-3 months. Results: Median age at diagnosis was 24 years (range 13-62), 59.1% were female, 38% were at stage IVa (lymph node involvement) and 42% at stage IVb (metastatic involvement). Responses were analyzed in 42 patients, 7 receiving neoadjuvant treatment and 35 patients receiving a first line palliative treatment. There was no complete response, 14.3% (n = 5) had a partial response (PR), 37.1% (n = 13) had stable disease (SD) and 48.6% (n = 17) had progressive disease. GEMOX was the most prescribed regimen (n = 8) with a disease control rate (PR+SD) at 25% (PR = 12.5% and SD = 12.5%). Doxorubicine-platine was the second most prescribed association (n = 5) with a disease control rate at 80% (PR = 40% and SD = 40%). Tyrosine kinase inhibitors, i.e. sorafenib (n = 10) and sunitinib (n = 3) showed no response and a rate of SD of 40% and 33% respectively. The association of doxorubicine-platine plus sorafenib was used in 4 patients, with one PR and three SD. Only one patient received immunotherapy (nivolumab and ipilimumab), but progressed at first evaluation at two months. Median overall survival was 3.3 years. Five years overall survival was 35% (95%CI = 0.23-0.54). Patients who underwent surgery had a better prognosis (55 months vs 15.5 months). Unfortunately, disease relapsed quickly after surgery, with a median relapse-free survival of 11 months. Conclusions: Advanced fibrolamellar carcinomas have a low chemosensitivity to either cytotoxic chemotherapy or tyrosine kinase inhibitors. Larger studies are warranted to define a standard of care for these rare tumors requiring treatment in an expert centre, either with a molecular screening.
Combination of donafenib and anti-PD-1 antibody plus trans-arterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (uHCC).
Authors: Gu Shanzhi , Tan Yulin , Zhou Huan , Hu Hongtao , Zheng Tongsen , Zheng Zhendong , Zhu Xu , Yuan Mu 
Published: June 2022

e16197 Background: Donafenib (Dona), a multikinase inhibitor recently marketed in China for advanced HCC with its superiority in overall survival (OS) over Sorafenib from a large head-to-head Phase 3 study. The clinical experience of triple therapy (TKIs + ICIs + TACE) in the treatment of patients (pts) with uHCC is limited. We assessed the safety and efficacy of triple therapy [Dona +anti-PD-1+ TACE] in uHCC in this Phase 1 study. Methods: The objective of this Phase 1, open-label, multicenter, dose-escalation and expansion study was to assess the MTD/recommended dose for Dona in combination of a fixed-dose anti-PD-1 plus TACE in uHCC. The primary endpoint was DLT occurring in the first treatment cycle. Secondary endpoints included the overall safety and tolerability, ORR and PFS by mRECIST. Qualified pts (age 18-75) were enrolled if uHCC without macrovascular invasion (VP3/4) or extrahepatic spread; measurable disease by mRECIST; ECOG 0 to 1; Child-Pugh A; systemic therapy naive. Results: At the cut-off date (Dec 31 2021), data of 25 pts who underwent triple therapy from 6 cancer centers in China were analyzed (Table). The median duration of follow-up was 105 days (1-358 days). No DLTs were observed [Dona 50 mg Bid (n=3); 150 mg Qd (n=3); 100 mg Bid (n=6)]. Additional 13 pts were treated with the recommended dose of Dona 100 mg Bid. Treatment-related adverse events (TRAE) occurred in 24 pts (Grade 3, 36%; no Grade 4). 16 pts had at least one response assessment, the ORR was 62.5%; in 12 pts with BLCL B, the ORR was 83.3%. mPFS was not reached. Conclusions: Combination of Dona, anti-PD-1 and TACE showed a high rate of tumor response and good safety profile in uHCC. Clinical trial information: NCT04605185. [Table: see text]