bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conversion hepatectomy for hepatocellular carcinoma with inadequate future- remnant- liver after portal vein ligation in combination with apatinib plus camrelizimab: A single-arm prospective pilot study (PLACES).
Authors: Zeng Zhiming , Zhu Guangzhi , Huang Huasheng , Jiang Yangfeng , Ye Xinping , Zeng Jie , Liu Cuizhen , Su Hao , Su Ming , Mo Ning , Liao Xiwen , Ma Fuchao , Peng Minhao , Ma Jie , Peng Tao 
Published: June 2021

e16132 Background: A variety of staged hepatic resection has been applied in patients (pts) with hepatocellular carcinoma (HCC) who had an inadequate future-remnant-liver (FRL), but the clinical outcomes remain unsatisfactory. Based on the clinical data of apatinib (a highly selective VEGFR-2 inhibitor) and camrelizimab (anti‐PD‐1 antibody) in HCC pts, we therefore evaluated the safety and efficacy of portal vein ligation (PVL) in combination with apatinib plus camrelizimab for primary HCC with insufficient residual liver volume. Methods: Pts aged 18-75, with HCC, Child-Pugh A status, BCLC stage A-C, preoperative indocyanine green retention rate at 15 min < 10%, and preoperative FLR/standardized liver volume (SLV) < 30% (for pts without cirrhosis ) and < 40% (for pts with cirrhosis ) were enrolled. Pts received PVL followed by camrelizimab (200mg, iv, d1 q2w) plus apatinib (250mg, po, pd, q2w) until surgical criteria were met. Pts underwent second-stage hepatic resection 4 weeks after treatment discontinuation, and continued treatment with apatinib plus camrelizimab for 1 year or endpoints occurred. The primary endpoints were resection rate of conversion surgery and ORR (objective response rate). Results: Between Apr 21, 2020 to Jan 20, 2021, 14 pts were enrolled in this trial. The estimated median preoperative FLR/SLV for all pts was 34.6%. Among the 10 evaluable pts, 7 met the criteria for surgery and 5 completed second-stage hepatectomy except for 2 pt who refused and waited for surgery, respectively. The median interval time of the two stages of surgery was 138.8 days. ORR was 40%, and disease control rate (DCR) was 100% (4 pts with partial response and 6 pts with stable disease). The other 4 pts are waiting for the evaluation. No adverse events (AEs) of grade 3 or worse occurred after PVL. The most common treatment-related AEs in pts during treatment with apatinib plus camrelizimab included hypoalbuminemia (36%), increased aspartate aminotransferase (AST) (100%) and rash (29%). Major AEs in pts underoing second-stage hepatectomy were pneumonia (100%), increased AST (100%), increased alanine transaminase (100%) and anemia (100%). One patient died of postoperative pulmonary infection. Conclusions: PVL in combination with apatinib plus camrelizimab followed by staged resection may be a safe and effective treatment option for HCC pts with insufficient FLR. Clinical trial information: ChiCTR2000033692.
A phase 2 trial of apatinib combined with intensity modulated radiation therapy for patients with unresectable hepatocelluar carcinoma.
Authors: Ke Shaobo , Qiu Hu , Peng Jin , Cai Gaoke , Zhangcai Yutian , Cheng Hao , Cai Yuxin , Xia Lingling , Luo Xixi , Wu Yong , Gong Yi , Wang Jing , Shi Wei , Chen Jiamei , Zhao Wensi , Ruan Shasha , Chen Yongshun 
Published: June 2021

e16136 Background: To estimate the clinical outcomes and safety for patients with unresectable advanced hepatocelluar carcinoma (HCC) treated with apatinib in combination with intensity modulated radiation therapy (IMRT). Methods: This study was an open-label, single-arm, phase 2 clinical trial of apatinib combined with IMRT for treatment of patients with unresectable advanced HCC. Patients aged between 18 and 75 years with adequate hematologic, liver, and renal functions, and ECOG performance status of 1 or less were included in the study between March 2017 and September 2020. Patients received IMRT (biologically effective dose(BED): 46-60Gy), and continuous apatinib (250-500 mg/d) orally until disease progression or unacceptable toxic effects. The primary end point was progression-free survival(PFS), the secondary end points included overall survival(OS), disease control rate (DCR), objective response rate(ORR) and safety. The data were analyzed for this report with cutoff on February 1, 2021. Results: A total of 46 patients were screened and 33 were enrolled in this study. The cohort had a median age of 56.7 years (range 21-77), 28(84.85%) were men. 25(75.76%) patients had hepatitis B, 32(96.7%) were BCLC stage B-C, 31(93.9%) were Child-Pugh A-B，and 8(24.2%) had portal vein involvement. Receiving first-line and second- or later-line treatment were 21(63.6%) and 12(36.4%), respectively. At a median follow-up of 11.6 months, the median PFS was 7.68 months(95% confidence interval:5.39-9.76) .The 6-month and 12-month overall survival rates were 100% and 96.2%, respectively. According to Response Evaluation Criteria in Solid Tumors Version 1.1, the ORR and DCR were 15% and 82%, respectively. There were 15 (15.2%) grade 3-4 treatment-related adverse events including neutropenia, thrombocytopenia, hypertension, proteinuria and hand and foot syndrome. There were no treatment-related deaths. Conclusions: Apatinib in combination with IMRT was safe and effective in improving PFS and DCR, and suggested an encouraging anti-tumor activity in patients with unresectable advanced HCC. Clinical trial information: ChiCTR-OPC-17011890.
Acceleration of blood-based circulating cell-free DNA epigenetic age among HIV-infected patients with hepatocellular carcinoma in Nigeria.
Authors: Zheng Yinan , Hawkins Claudia , Okeke Edith , Lesi Olufunmi A. , Qu Yishu , Roberts Lewis R. , Gursel Demirkan , Abdulkareem Fatimah Biade , Akanmu Alani , Imade Godwin , Wei Jian-Jun , Kocherginsky Masha , Kim Kwnag-Youn , Adeyemo Wasiu Lanre , Wehbe Firas Hazem , Achenbach Chad , Sagay Atiene , Ogunsola Folasade , Murphy Robert , Hou Lifang 
Published: June 2021

e16137 Background: Hepatocellular Carcinoma (HCC) is the leading cause of cancer-related mortality in Nigeria. HIV and viral hepatitis B (HBV) and C (HCV) co-infection are common in Nigeria that significantly accelerates liver disease progression including HCC. Aging-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (ccfDNA) extracted from serum/plasma are promising minimally-invasive biomarkers that may inform HIV-associated HCC. We examined the epigenetic age acceleration (EpiAgeAccel) in ccfDNA in HCC patients with HIV. Methods: The study included three groups of participants: a) HIV positive with HCC (n=7); b) HIV positive and cancer-free (n=45); and c) HIV negative with HCC (n=33). Epigenetic age was estimated by Horvath’s calculator using genome-wide ccfDNA methylation data profiled by Illumina EPIC array. EpiAgeAccel was computed as the residuals of a linear model of epigenetic age on chronological age, namely the unexplained portion of epigenetic age by chronological age. We used multiple linear regression to compare EpiAgeAccel between HIV/HCC groups, adjusting for sex, age, education, alcohol intake, and HBV/HCV infection. Results: Among HIV positive participants, there was a higher percentage of men (57% vs. 22%, p<0.001), HBV infection (29% vs. 11%, p=0.004), and HCV infection (57% vs. 2%, p<0.001) in the HCC group compared to the cancer-free group. EpiAgeAccel was 4.8 years higher in HIV positive patients with HCC compared to cancer-free HIV positives (p=0.02). Among HCC patients, EpiAgeAccel was 2.1 years higher in HIV positives compared to HIV negative but not statistically significant. Conclusions: Epigenetic age in ccfDNA is accelerated in HIV-positive HCC patients. EpiAgeAccel measured in ccfDNA may be developed into a surrogate biomarker for minimally invasive HCC detection among HIV-infected patients in low- and middle-income countries.
Utilization of hepatocellular carcinoma surveillance programs in patients with cirrhosis: A systematic review and meta-analaysis.
Authors: Singh Jameel Kenneth , Ramai Daryl , Tartaglia Nicola , Ambrosi Antonio , Khan Shahab R. , Chandan Saurabh , Facciorusso Antonio 
Published: June 2021

e16141 Background: Patients with cirrhosis are advised to undergo hepatocellular carcinoma (HCC) surveillance every six months. Routine screening is associated with early tumor detection and improved survival. However, surveillance is underutilized. We aimed to characterize the impact of HCC surveillance interventions on patient uptake and concomitant detection of HCC. Methods: We performed a comprehensive literature search of major databases (from inception to October 2020) to identify studies which assess the impact of HCC surveillance programs in patients with cirrhosis. Our primary endpoint was uptake of screening defined as having an abdominal sonogram every at least every 6 months. Secondary endpoint was the detection of HCC following screening. Pooled data was assessed using a random-effects model expressed in terms of odds ratio (OR) and 95% confidence interval (CI). Results: Nine studies were included for meta-analysis which involved 5,021 patients with cirrhosis. Patients with a history of hepatitis B or C accounted for 40.5% of the study cohort. Comparing both screening and control groups, patients were 5 times more likely to undergo abdominal sonography if they participated in surveillance programs versus usual care (OR 4.69; CI: 2.41 – 9.13, I2: 94%). Overall, the mean difference in patients who did undergo screening versus those who did not participate in surveillance was 30.6% (CI: 19.2% – 41.9%, P < 0.001). Comparing both screening and control groups, patients were 1.5 times more likely to be diagnosed with HCC if they participated in surveillance programs (OR 1.49; CI: 0.57 – 3.89, I2: 65%). On subgroup analysis, comparing type of intervention program, dedicated surveillance programs showed a higher uptake compared to clinical reminders, though not statistically significant (dedicated programs OR 62.6, CI: 1.53 – 2559.5 vs clinical reminders OR 2.63, CI: 1.82 – 3.79). Conclusions: Patient uptake in HCC surveillance remains underutilized. Interventions such as dedicated surveillance programs and clinical reminders systems can significantly increase uptake of abdominal sonography and cancer detection.
Evaluation of somatic and germline mutations in Chinese patients with gallbladder carcinoma reveals clinically actionable targets.
Authors: Yang Wenhui , Liu Si , Li Xiaomo , Gao Hongjian , Ma Tonghui , Liu Rong 
Published: June 2021

e16143 Background: Gallbladder cancer (GBC) is an aggressive gastrointestinal cancer and the median survival of GBC patients is less than one year. Given the rarity of this disease, there is no enough evidence to guide the precision therapy for GBC patients. Therefore, it is urgent to identify therapeutic targets in GBC to help physicians to enroll patients in clinical trials. In this study, we aimed to characterize clinically actionable mutations in a large cohort of patients with GBC. Methods: To characterize therapeutic targets in 118 Chinese GBC patients, a deep sequencing panel (OncoPanscan, Genetronhealth) was applied to explore somatic alterations including point mutations, indels, copy number alterations and gene fusions, as well as possible pathogenic germline variants respectively from their tumor tissues and matched genomic DNA sample. Results: Recurrent somatic mutations were identified in TP53 (65%), ERBB2 (18%), ARID2 (13%), ELF3 (13%), CDKN2A (12%), ARID1A (10%), KRAS (10%) and KMT2C (10%). Of the entire cohort, the most frequently mutated genes were in the ErbB pathway including EGFR, ERBB2, ERBB3, and ERBB4. For the patients with ERBB2 genetic aberrations, 67% (14/21) patients had gene amplification and 29% (6/21) patients had the oncogenic S310F/Y (n = 6) mutation which may be eligible for HER2-targeted therapy clinical trial. Importantly, 9% (10/118) patients carried activating PIK3CA mutations including P104L, E110del, E545K/Q/G, E542K, E726K and T1025S which may be targeted by PIK3CA inhibitor alpelisib. Additionally, patients with loss-of-function mutation in NF1 (n = 6), STK11 (n = 5) and PTEN (n = 2) can be respectively targeted with MEK inhibitor and mTOR inhibitor. Furthermore, patients with MET amplification (n = 3) may be eligible for clinical trials of MET inhibitor carbozantinib. There were four patients (3.4%) carried loss-of-function germline mutations in DNA repair genes ( BRCA1, BRCA2 and PALB2) and 19 patients (16%) harbored somatic loss-of-function mutations in BRCA1 (n = 2), BRCA2 (n = 2), ARID1A (n = 12) and ATM (n = 3). These patients may benefit from platinum chemotherapy or targeted therapy with PARP inhibitors. Interestingly, 13% (15/118) patients in our cohort carried ELF3 inactivating mutations which was reported as a potential GBC vaccine candidate. Taken together, at least 54 (46%) patients in our cohort had actionable genetic alterations. Conclusions: Our results indicated that activating mutations in the ErbB and PI3K signaling pathways are the major driving events of GBC. The results of genomic profiling can guide physicians to enroll a significant portion of GBC patients into genomically matched clinical trials.
Treatment patterns and outcomes of locally advanced gall bladder cancer: A National Cancer Database (NCDB) analysis.
Authors: Kancharla Pragnan , Alnimer Lynna , Samhouri Yazan , Shankar Karthik , Bakalov Veli , Jayakrishnan Thejus Thayyil , Peterson Chelsea , Huffman Deanna , Wegner Rodney E. , Monga Dulabh K. 
Published: June 2021

e16147 Background: Gall bladder (GB) cancer is rare but an aggressive disease especially when presenting at an advanced stage. There is controversy regarding the best treatment approach for locally advanced disease. In this NCDB analysis, we aim to study treatment patterns for T3, T4, and/or N1 GB cancer and estimate survival for each treatment modality. We also sought to investigate clinical and socioeconomic predictors of treatment selection. Methods: We conducted a retrospective cohort analysis using de-identified data accessed from the NCDB. The NCDB provided records of 39,229 patients diagnosed with GB cancer between 2004-2017. We excluded patients who were not treated at the reporting facility, those with no histologic confirmation of the diagnosis, those with no survival data available and those with T1, T2 and metastatic disease. We did exploratory analysis and divided patients into six arms based on treatment modality (Table). Stepwise multivariable regression models were used to analyze predictors of treatment selection. Survival estimates were calculated using the Kaplan Meier and proportional Cox hazard regression methods. Results: We identified 7,004 patients with GB cancer who fulfilled the inclusion and exclusion criteria. Median age was 68 years. There were 69.5% females, and the majority of patients were white (66.1%). Receiving treatment at an academic/research center (OR 0.37, 95% CI 0.19-0.73, p <0.01), black patients (OR 0.55 95% CI 0.36-0.85, p <0.01) and higher education (OR 0.58, 95% CI 0.37-0.91, p 0.02) decreased the odds of receiving surgery. Meanwhile, the presence of lymphovascular invasion was seen more amongst patients with receipt of surgery. For patients who underwent radiation, increasing age (OR 0.97, 95% CI 0.97-0.98, p <0.01) and higher histologic grade (OR 0.65, CI 0.46-0.92, p .02) were associated with less radiation use. Median income between $50,354-$63,332 (OR 1.28, 95% CI 1.02-1.60, p 0.04) was associated with more radiation use. Patient who received triple therapy had improved survival compared with other modalities (HR 0.51, CI 0.46-0.57, p <0.01). Median overall survival (OS) for the whole population was 13.0 months (CI 12.6-13.5) (Table) Conclusions: American patients with T3, T4, and/or N1 GB cancer received variable treatment modalities. Patients who underwent triple-modality therapy in our analysis had improved adjusted-overall survival compared with other modalities. Limitations include unmeasured confounding factors, selection bias and the retrospective design. We also identified clinical and socioeconomic factors that affect treatment selection.[Table: see text]
The comparative efficacy of atezolizumab and bevacizumab versus lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC).
Authors: Trueman David , Liu Yifeng , Lucero Melanie , Meier Genevieve 
Published: June 2021

e16151 Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, comprising 90% of all cases. In the phase III IMbrave150 trial, combination of atezolizumab and bevacizumab (atezo+bev) resulted in improved overall survival (OS) and progression-free survival (PFS) compared with sorafenib for patients with unresectable hepatocellular carcinoma (uHCC). In the phase III REFLECT trial, lenvatinib met the primary endpoint of non-inferiority in OS versus sorafenib, and demonstrated superiority in secondary endpoints; PFS, time to progression and objective response rate (ORR). Furthermore, post-hoc analyses strongly suggest that the original non-inferiority trial likely underestimated the true effect of lenvatinib on OS due to imbalances in baseline prognostic covariates and the comparatively greater use of post-treatment anti-cancer therapies in the sorafenib arm. In the absence of a head-to-head comparison between atezo+bev and lenvatinib, the objective of this analysis was to estimate their comparative efficacy as first-line treatments for patients with uHCC. Methods: A network meta-analysis (NMA) was conducted based on a de novo systematic literature review which identified evidence for licensed therapies in first-line uHCC. This was supplemented with data from the extended IMbrave150 study findings (clinical cut-off on 31 August 2020). Median hazard ratios (HR) with corresponding 95% credible intervals (CrI) were estimated for OS and PFS. HRs for OS and PFS from REFLECT were taken from multivariable analyses which adjusted imbalances in baseline prognostic covariates. All analyses were conducted in a Bayesian generalised linear model framework. Model selection was based on deviance information criterion (DIC). Results: Four eligible phase III studies (REFLECT, SHARP, Asia-Pac and IMbrave150) were included. Using a fixed-effects model, the estimated median HRs for atezo+bev compared with lenvatinib were 0.81 (95%CrI: 0.61, 1.08; posterior p=0.078) and 0.99 (95%CrI: 0.76, 1.28; posterior p=0.454) for OS and PFS, respectively. The results obtained were similar to those observed by Vogel et al, who reported an OS HR of 0.63 (95% CI: 0.32, 1.25), and a PFS HR of 0.91 (95% CI: 0.23, 3.65). Conclusions: While the NMA respects the randomization of the included studies, it does not represent direct evidence and should therefore be considered exploratory in nature. The results of this NMA suggest that the benefit of atezo+bev is not statistically significant compared to lenvatinib, as the differences between atezo+bev and lenvatinib fell within the Bayesian range of equivalence (upper limit of Crl ≥ 1 for OS and PFS) and were subject to a high degree of uncertainty. The results of the NMA were consistent for all the publicly available data cuts from IMbrave150.
Combined treatment with iodine-125 (125I) seed strand and transarterial chemoembolization (TACE) plus lenvatinib with anti-PD-1 antibodies in patients with unresectable hepatocellular carcinoma (uHCC) and portal vein tumor thrombus (PVTT): Real-world experience in China.
Authors: Zhang Zi-Han , Zhang Wen , Liu Qing-Xin , Liu Ling-Xiao , Luo Jian-Jun , Qu Xu-Dong , Yan Zhi-Ping 
Published: June 2021

e16152 Background: We reviewed real-world outcomes for patients with uHCC and PVTT receiving TACE with 125I seed and stent implantation combined with lenvatinib plus anti-PD-1 antibodies. Methods: We retrospectively reviewed medical records from 62 consecutive adult (≥18 to ≤75 years) patients with HBV-related HCC and type III and IV PVTT with Child-Pugh class A or B liver function and ECOG performance status of 0-2 who received 125I seed strand and stent implantation combined with TACE at our center between November 2018 and May 2020. Patients were divided into two groups; those who had received adjuvant lenvatinib plus anti-PD-1 inhibitors, initiated 3 days after the first interventional procedure (Group A; n=18), and those who only received locoregional therapy (Group B; n=44). Propensity score matching (PSM) with a 1:1 ratio was used to reduce selection bias. Tumor response, progression-free survival (PFS, time from the first interventional procedure to progression or death for both Group A and Group B) and time-to-progression (TTP) were assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Time to untreatable progression (TTUP) and overall survival (OS) were also assessed. Adverse events (AEs) were graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) v4.0. Results: PSM resulted in 15 matched pairs of patients, and baseline demographic parameters were comparable between the two groups. The median follow-up time was 12.4 ± 4.6 and 9.4 ± 4.8 months for patients in Groups A (n=15) and B (n=15) after PSM, respectively. Compared with patients in Group B, those in Group A had a higher overall response rate (66.7 vs. 18.2%; p=0.001) and disease control rate (72.2 vs. 43.2%; p=.038) and a longer median PFS, TTP, TTUP and OS (Table). No serious complications related to locoregional procedures were reported in either group. In Group A, 13% (n=2) of patients experienced ≥1 AE but the majority were Grade <3; one patient had Grade 2 hyperthyroidism and one had Grade 2 enteritis, which were both considered related to immunotherapy. Conclusions: These real-world data show that 125I seed strand and stent implantation combined with TACE plus adjuvant lenvatinib and anti-PD-1 antibodies led to better treatment responses and survival outcomes compared with locoregional treatment alone in patients with uHCC and PVTT, with an acceptable safety profile. Summary of survival outcomes in propensity score matched groups.[Table: see text]
A prognostic model to predict survival after hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein invasion.
Authors: He Jian , Mo Zhiqiang , Mai Qicong , Shi Feng , Chen Xiaoming 
Published: June 2021

e16157 Background: We aimed to establish a prognostic model to predict survival for the patient with advanced hepatocellular carcinoma (HCC) after the treatment with hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin. Methods: 164 patients diagnosed of HCC with portal vein invasion and treated with HAIC of oxaliplatin plus fluorouracil/leucovorin between 1/2018 and 1/2021 at the Guangdong provincial people’s hospital and were randomly divided to training(N=82) and validation(N=82) cohort. We investigated the impact of baseline characteristics and tumour load on overall survival (OS, log-rank test) and developed a prognostic model in the training cohort by using a stepwise Cox regression model and validated in validation cohort. Results: The final presentation of the model was “NCV-score= 0.974* serum neutrophil/lymphocyte ratio+ 1.239* Child-pugh stage+ 0.661* portal Vein invasion grade”, which further selected the first quartile of the linear predictor, namely 5.7, as cut-off values. The NCV-score differentiated two risk categories(≥5.7, ＜5.7) with distinct prognosis (median OS: 6.6 vs. 11.2 months, p <0.001). The prognostic model was used to develop nomogram for predicting individual survival of HAIC candidates and was validated in validation cohort to identify patients who obtain satisfying survival benefit for HAIC. Conclusions: The NCV-score identifies advanced HCC patients who obtain satisfying survival benefit for HAIC of oxaliplatin plus fluorouracil/leucovorin and provides individual survival predicting.[Table: see text]