bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of prognostic factors after esophagectomy in which preoperative chemotherapy was successful.
Authors: Ogata Takashi , Shimoda Yota , Nagasawa Shinsuke , Nakazono Masato , Hara Kentaro , Kumazu Yuta , Hayashi Tsutomu , Yamada Takanobu , Oshima Takashi 
Published: May 2019

e15568 Background: Current standard treatment for Stage IB/II/III Japanese squamous cell carcinoma of the esophagus is esophagectomy after two courses preoperative chemotherapy with 5-FU/CDDP. Prognosis of cases in which preoperative chemotherapy was successful is usually good, but some cases were recurrence. On the other hand, some reports showed that the negative survival impact of infectious complications after esophagectomy is canceled out by succeeding preoperative chemotherapy. So we evaluate of prognostic factors after esophagectomy in which preoperative chemotherapy was successful. Methods: Between 2011 and 2015, 122 cases were performed esophagectomy after two courses of preoperative chemotherapy using 5-FU/CDDP for stage IB / II / III esophageal cancer, and 46 cases were achieved Grade 2 histopathological effect(2/3 or more disappearance of tumor). We examined 3-year survival rate and 3-year RFS in this 46 cases and examined what could be a prognostic factor. PS, ASA, sex, operation time, volume of bleeding , postoperative complications(C-D classification≧G2), pT, pN, tumor wall retentivity, preoperative nutritional status(Albumin, CRP, Prealbumin, RBP), nutritional indicators at discharge (weight change rate, fat mass change rate, muscle mass change rate) were evaluated as recurrence prediction factor. Results: 3-year OS of histological Grade2 cases were 84.5%, and 3 -year RFS were 88.8%. In 46 cases, relapse was found in 12 cases, and univariate analysis showed pT, pN as a risk of relapse, and multivariate analysis showed only pT as a risk of relapse. There were 5 cases of recurrence within 1 year after esophagectomy, and there was a significantly poor prognosis compared with recurrent cases later than 1 year after esophagectomy. Conclusions: The risk factor of recurrence in patients with squamous cell carcinoma after preoperative chemotherapy followed by esophagectomy was pathological T factor, and recurrent case within 1 year after esophagectomy was significantly poor prognosis.
The characterization of ERBB family mutations in Chinese biliary tract cancers.
Authors: Song Tianqiang , Zhang Wei , Li Huikai , Chen Ping , Chen Xiaoqian , Shi Junping , Zhang Shuirong , Yao Ming , Wang Kai 
Published: May 2019

e15595 Background: Next generation sequencing has been applied to identify actionable mutations in biliary tract cancers (BTCs). ERBB family genes, especially ERBB2 and ERBB3, serve as effective biomarkers for BTCs targeted therapy as shown in MyPathway and SUMMIT clinical trials. However, the distribution and major mutation types of ERBB family genes were not clear in Chinese BTC patients. Methods: Deep sequencing targeting 450 cancer genes was performed on FFPE and matching blood samples collected from a cohort of 716 Chinese BTC patients. Genomic alterations including single nucleotide variations (SNV), short and long insertions/deletions (Indels), copy number variations, gene rearrangements and fusions were analyzed. Results: A total of 14% (101/716) of patients with a median age of 62 years old, including 45 males and 56 females, were identified harboring ERBB family mutations. Somatic ERBB family mutations occurred with a rate of 29% in gallbladder carcinoma (GBCA), 13% in extrahepatic cholangiocarcinoma (EHCCA), 12% in hilar cholangiocarcinoma (HCCA) and 8% in intrahepatic cholangiocarcinoma (IHCCA). No germline mutation was detected. A high rate of ERBB2 gene amplification was observed in GBCA (17%). In IHCCA and EHCCA, SNV/Indel accounted for 3% and 5%, respectively, and was the major variation in ERBB2. In HCCA, SNV/Indel was the most common mutation in ERBB3 (8%). In BTC patients, TP53 (81%) and CDK12 (36%) were the top-ranked co-mutant genes with ERBB2. The mutant frequency of CDK12 was significantly different between patients with or without an ERBB2 mutation ( p< 0.001). ERBB2 S310F/Y, ERBB3 V104L/M were hotspot mutations within the ERBB family in BTCs. Conclusions: ERBB family mutations were detected in 14% of Chinese BTC patients. Similar to Western populations (PMID: 27622582), ERBB2 gene amplification was the most common mutation in GBCA in Chinese patients. Unlike ERBB2/ ERBB3 amplification which has been reported as the major mutation in previous studies, our study of other BTC types revealed ERBB2/ ERBB3 SNV/Indel as the major mutation. BTC patients harboring ERBB family mutations have the potential to benefit from pan-HER inhibitors.
Microvascular invasion may guide selection of candidates for combination treatment with sorafenib and TACE for intermediate recurrent hepatocellular carcinoma.
Authors: Peng Zhen-Wei , Chen Shuling , Han Xiao , Wang Yuanqi , Kuang Ming 
Published: May 2019

e15601 Background: To investigate the role of sorafenib combined with transarterial chemoembolization (TACE) for the treatment of intermediate recurrent hepatocellular carcinoma (rHCC) after initial hepatectomy and whether the status of microvascular invasion (MVI) could help screen out the appropriate candidates for the combination treatment. Methods: The study was approved by the ethics committee of two tertiary medical centers in China. From Jan 2010 to Dec 2016, 260 consecutive patients with intermediate rHCC after initial hepatectomy who underwent combination treatment or TACE were enrolled. Overall survival (OS) and progression-free survival (PFS) were compared between these two treatments according to MVI status. Results: The 1-, 3-, 5-year OS (77.1% vs. 62.0%, 49.3% vs. 35.2%, 38.9% vs. 20.5%, P = 0.011) and PFS (74.2% vs. 56.5%, 37.5% vs. 18.7%, 37.5% vs. 18.7%, P = 0.003) rates were significantly higher in the combination group than those in the TACE group for intermediate rHCC. For MVI-positive patients, the median OS (17.2 months vs. 12.1 months, P = 0.024) and PFS (17.0 months vs. 11.0 months, P = 0.022) after combination treatment (n = 55) were significantly longer than those after TACE alone (n = 72). For MVI-negative patients, the median OS (42.7 months vs. 32.6 months, P = 0.247) and PFS (24.6 months vs. 17.2 months, P = 0.113) were comparable between combination therapy (n = 73) and TACE alone (n = 60). Multivariate analysis revealed that tumor number, MVI status and treatment allocation were significant predictors of OS and PFS, while the tumor size was another prognostic factor for PFS. Conclusions: Patients with intermediate rHCC can benefit from sorafenib plus TACE treatment, while MVI-positive patients were good candidates for combination treatment.
Density of CD8+ and CD68+ lymphocyte cell infiltration is associated with clinic outcome in hepatocellular carcinoma.
Authors: Xin Haibei , Chen Huan , Wu Lihong , Chen Yanhui , Luo Hongli , Zhang Henghui , Li Nan 
Published: May 2019

e15612 Background: The achievements of immune checkpoint blockade strengthen the concept that tumor outgrowth and development are comprehensively regulated by immune system. The aim of the study was to explorer whether distinct infiltrated immune cell features differentially affect clinical outcome in hepatocellular carcinoma (HCC). Methods: We obtained respectable stage II HCC specimens, along with adjacent para-tumor tissues from 221 patients who underwent surgical resection at Eastern Hepatobiliary Surgery Hospital, (in Shanghai, China) from 2015 through April 2018. CD8+ and CD68+ tumor-infiltrating lymphocytes (TILs) in the cancer area (CA) and stroma area (SA), as well as PD-1/PD-L1 expression, were analyzed by multiple immunohistochemistry. Results: The density of CD8+ TILs were significantly associated with gender, tumor size, and cirrhosis; while the density of CD68+ TILs were associated with copies of HBV DNA and anti-viral treatment. Multivariate Cox regression analysis revealed that high densities of CD8+ TILs and low densities of CD68+/CD8+ ratios independently predicted better outcomes. Of note, a prognostic signature combining clinic features [portal vein tumor thrombus (PVTT) and tumor size (TS)] and CD8+ TILs densities discriminated HCC patients into four subtypes with increasing risk of mortality: PVTT-negative/TS-small/CD8-high (6.8% of cases), PVTT-negative/TS-small/CD8-low (45.7%), PVTT-negative/TS-large (34.4%) and PVTT-positive (13.1%). Further association studies suggested that the four subgroups correlated with gender, tumor envelope, microvascular invasion (MVI), and SA-PD1 expression. Similarly, a prognostic signature combining PVTT, TS and CD68+/CD8+ ratios discriminated HCC patients into four subtypes with increasing risk of recurrence. Conclusions: Combined immune features including CD8+ and CD68+ lymphocyte infiltration and clinic characteristics are useful prognostic biomarkers for HCC patients.
Randomized phase II trial of sorafenib, capecitabine, and oxaliplatin (SECOX) versus single agent sorafenib in patients with advanced hepatocellular carcinoma.
Authors: Kwok Gin Wai , Tang Vikki , Leung Roland Ching-Yu , Lee Ann-Shing , Law Ada , Chiu Joanne Wing Yan , Li Bryan , Cheung Tan To , Yau Thomas 
Published: May 2019

e15630 Background: We aimed to compare the efficacy and tolerability of SECOX regimen with sorafenib alone as first-line treatment of advanced hepatocellular cancer (HCC) in a multicenter, open-label and randomized setting. Methods: Patients not suitable for surgery or various loco-regional therapies and no prior systemic therapy for advanced HCC were recruited in 3 centres. Eligible patients were randomly assigned to receive either SECOX (sorafenib 400 mg BD continuously, oxaliplatin 85 mg/m2 on D1, and capecitabine 1700 mg/m2 on D1-7 q2w) or sorafenib alone continuously in 1:1 ratio. Primary endpoint was time-to-progression (TTP). Secondary endpoints were tolerability, overall tumor response rate, overall survival (OS) and progression-free survival (PFS). Results: Forty-six patients were randomized and treated, of whom 22 were in the SECOX arm. Median age was 64 years and majority of the patients were male (72%). 40 patients (87%) were hepatitis B carrier, and 42 patients (91%) had Child-Pugh A liver function. Thirty patients (65%) had received prior non-systemic treatment for HCC. Median duration of follow-up was 7.8 months (mos) (range 0.3-25.8). At the time of analysis,one patient in the SECOX arm is still receiving treatment. Median TTP was 3.2 mos (95% CI 1.7-5.8) for SECOX vs 2.8 mos (95% CI 1.8-4.0) for sorafenib. The hazard ratio (HR) for TTP was 0.91 (95% CI 0.5-1.7; p = 0.77; predetermined futility boundary HR ≥ 0.86). Median OS was 7.1 mos (95% CI 3.0-15.3) for SECOX vs 12.5 mos (95% CI 7.2-15.4) for sorafenib (p = 0.29). Median PFS was 3.1 mos (95% CI 1.6-5.8) for SECOX vs 2.7 mos (95% CI 1.8-4.0) for sorafenib. 2 patients (9%) and no patients achieved partial response in the SECOX and sorafenib arms, respectively. The clinical benefit rate (CR+PR+SD) was 36% for the SECOX arm and 21% for the sorafenib arm (p = 0.50). Incidence of treatment-related adverse events (trAEs) was common in both SECOX and sorafenib arms (64% and 71% respectively, p = 0.75). The most common grade 3-4 trAE was ALP increase (14%) for SECOX and hand-foot skin reaction (25%) for sorafenib. Conclusions: The addition of capecitabine and oxaliplatin to sorafenib did not result in significant improvement in TTP. Clinical trial information: NCT02716766.
Impact of HCV treatment in patients with advanced hepatocellular carcinoma on sorafenib.
Authors: Herman Michael , Zhang Yuhua , Wang Lisa , Sim Hao-Wen , Knox Jennifer J. 
Published: May 2019

e15645 Background: Hepatocellular carcinoma (HCC) is the 4th leading cause of global cancer deaths. In North America, HCC is most commonly caused by Hepatitis C virus (HCV). Direct acting antivirals (DAAs) have dramatically increased sustained virologic response (SVR) rates for HCV. Studies of DAAs in early stage HCC have had conflicting results on HCC outcomes. A small Asian study of 58 advanced HCC patients treated with sorafenib demonstrated SVR improved survival, but whether the same effect occurs in North American patients is unknown. Methods: Inclusion criteria for this retrospective study were: biopsy or clinically proven advanced incurable HCC, sorafenib treatment at Princess Margaret Cancer Centre between January 1 2008-June 30 2018 and a history of HCV. Survival was analyzed using the Kaplan Meier method and a cox proportional hazards model was fit to determine the effect of SVR on OS. Results: 93 patients were included with a median duration of sorafenib therapy of 3 months. 89% were ECOG 0-1 and 96% were BCLC-C (See table 1). Of those receiving antivirals, 95% were given before sorafenib. Overall, SVR was achieved in 23 (50%) patients. Median OS of patients achieving SVR vs not in SVR was 10.3 vs 8.9 months respectively (HR 0.67, 95% CI 0.36-1.24, p = 0.20). Median PFS was 6.4 vs 5.0 months in patients with or without SVR (HR 0.66, 95% CI 0.39-1.13, p = 0.13). There was no significant difference between mean dose of sorafenib or discontinuation due to toxicity in patients by SVR status. Conclusions: Antiviral therapy with SVR lead to a non-statistically significant improvement in OS in patients with Child-Pugh A-B liver disease, advanced HCC treated with sorafenib and HCV. These results should be validated in larger data-sets. [Table: see text]
The combined treatment of 150 kHz tumor treating fields (TTFields) and sorafenib inhibits hepatocellular carcinoma in vitro and in vivo.
Authors: Weinberg Uri , Davidi Shiri , Tempel- Brami Catherine , Munster Mijal , Gotlib Karnit , Zeevi Einav , Schneiderman Rosa S. , Voloshin Tali , Giladi Moshe , Kinzel Adrian , Kirson Eilon David , Palti Yoram 
Published: May 2019

e15653 Background: Hepatocellular carcinoma (HCC) is the third cause of cancer related mortality and the primary cause of cancer death. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. Sorafenib, an oral multikinase inhibitor is approved for patients with advanced HCC, yet its survival benefit is still limited. In this work we explored the potential of the use of TTFields alone and in combination with Sorafenib as a treatment for HCC. Methods: HepG2 and Huh-7D12 cells were treated with various TTFields frequencies for 72 hours using the inovitro system. Efficacy of the combined treatment of TTFields and Sorafenib (36-3000 nM) was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, induction of apoptosis, cell cycle and clonogenic potential were determined. TTFields (1.2 V/cm) and Sorafenib (10 mg/kg) were applied for 6 days to rats injected to the liver with N1S1 HCC cells. Tumor growth was followed using MRI. Results: The optimal TTFields frequency was 150 kHz for both cell lines. TTFields application (1.0 - 1.7 V/cm, 72 hours) at 150 kHz led to 36-40% reduction in cell counts and to additional reduction of over 70% in the clonogenic potential. The combined treatment of TTFields and Sorafenib led to a significant reduction in the number of cells (p < 0.001) as compared to each treatment alone. The averaged tumor volume fold increase of the combination treatment group was significantly lower than the one observed in the: control group, the TTFields group and the Sorafenib group. Conclusions: The results presented in this work demonstrate that TTFields can be an effective treatment against HCC cells and that the combination with Sorafenib may further enhance treatment efficacy.
Association of liver-directed local therapy with overall survival in metastatic intrahepatic cholangiocarcinoma.
Authors: Sebastian Nikhil , Miller Eric David , Williams Terence M , Noonan Anne M. , Hays John L. , Diaz Pardo Dayssy Alexandra 
Published: May 2019

e15659 Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive hepatobiliary malignancy characterized by local infiltration and lymph node, lung, and bone metastases. The majority of patients die from tumor-related liver failure. The standard of care for metastatic ICC is chemotherapy (CHT) and the role of local therapy to the liver is unclear. We used the National Cancer Database (NCDB) to compare overall survival (OS) of patients treated with CHT, with and without local radiotherapy (RT) or surgery of the liver. Methods: We evaluated patients with metastatic ICC who received CHT with or without hepatic surgery or external beam RT to a dose ≥ 45 Gy. We used multiple imputation followed by cox proportional hazards and nearest neighbor propensity score matching (1:1, caliper = 0.1) on the basis of age, sex, race, comorbidity score, T-stage, tumor size, N-stage, primary tumor focality, primary tumor vascular invasion, year of diagnosis, insurance status, and treatment facility, as well as presence of bone, lung, and lymph node metastases. Results: We identified 2201 patients who received either CHT alone (n = 2097), or with hepatic surgery (n = 76) or RT (n = 28). Liver-directed local therapy was associated with improved OS on univariate (hazard ratio [HR] = 0.57; 95% CI 0.15 - 0.71; p < 0.001) and multivariate analysis (HR = 0.61; 95% CI 0.49 - 0.75; p < 0.001). There was no difference in OS between RT versus surgery (HR = 1.37; 95% CI 0.76 - 2.46; p = 0.30). After propensity score matching, there were 104 patients in each cohort. Liver therapy continued to be associated with improved OS (HR = 0.60; 95% CI 0.45 - 0.81; p = 0.001). Conclusions: We found that addition of local therapy to the liver with surgery or RT is associated with higher OS when compared to CHT alone in metastatic ICC. These findings should be validated in an independent cohort.
RISE-HEP project part 1: Treatment sequences evaluation in hepatocellular carcinoma cell lines.
Authors: Faloppi Luca , Nabissi Massimo , Santoni Matteo , Maggi Federica , Galizia Eva , Miccini Francesca , Bianconi Maristella , Puzzoni Marco , Astara Giorgio , Battelli Nicola , Santoni Giorgio , Scartozzi Mario 
Published: May 2019

e15663 Background: For over ten years the most stimulating results in systemic therapy for advanced HCC derived from the use of sorafenib (S). But in the last two years several drugs, in particular other multikinase inhibitors like lenvatinib (L), regorafenib (R), cabozantinib (C), proved to be effective both as an alternative or a sequential therapy to sorafenib. In this widened and rapidly increased scenario, without any head-to-head trial, clinicians struggle to define the best drug and the best treatment sequence. Aim of the first part of this project is to evaluate the activity of different treatment sequences in HCC cell lines to pave the way to a future clinical trial investigating their efficacy. Methods: Compounds of S, R, L and C were dissolved in DMSO and aliquoted. HepG2 cell line, obtained from ECACC (Salisbury, UK), was seeded at the density of 3 x 104 cells/ml. After 24 h of incubation, compounds or vehicle (DMSO) were added. Treatments were performed in single administration and six replicates were carried out for each dose. At 48h post-treatment, cells were fixed and stained with acid solution. The absorbance was measured at 520 nm using an ELISA reader (BioTek Instruments, USA). The assay was also performed with the sequences of: S-R, S-C, L-R, L-C (first line treatments for 48h followed by the second compound for 48h). Higher doses than the minimum inhibiting one were tested. Results: S showed superior activity than L as first line compound. In the sequence assay S-C and S-R seems to have the best results in terms of cell viability. After L the best compound appears to be R. See table. Conclusions: Our results showed relevant variations in cell viability with different drug sequences. Already planned analyses in the RISE-HEP project in vivo and in humans are mandatory to confirm which sequence would have the highest efficacy.[Table: see text]
Clinical predictors of radiographic progression of a hepatic lesion from Li-RADS 3 to Li-RADS 5 among a population of individuals at high risk of hepatocellular carcinoma.
Authors: Hannan Lindsay Marie , Ojeda Patricia I , Hippe Daniel S , Mieloszyk Rebecca , Johnson Guy E , Park James Oh , Harris William Proctor , Bhargava Puneet 
Published: May 2019

e15668 Background: We sought to identify clinical predictors of radiographic progression of a Li-RADS (LR) 3 lesion (i.e. indeterminate for hepatocellular carcinoma (HCC)) to a LR 5 lesion (i.e. definitely HCC) among patients (pts) at high risk of HCC. Methods: Radiology reports from the University of Washington with an LR assignment, 2013-2017, were reviewed (5037 reports, 1954 patients(pts)). Pts with an LR 3 lesion, a follow-up scan within 1 year of date of LR 3 lesion detection, and radiographic evidence of cirrhosis OR a diagnosis of chronic HBV were included in the analysis. Results: Of the 167 pts, 38 (23%) progressed to LR 5 status, 10 progressed to LR 4, and 12 were downgraded to LR 1-2. The remaining 64% were unchanged at LR 3. Radiographic data including year of LR 3 detection (2013-2014 47%) and LR 3 imaging modality (CT 50.3%, MR 49.7%) were obtained. Clinical data were abstracted from medical record review, including sex (65% male), age (80% < 65), race (66% White), cirrhosis etiology (45% HCV, 27% EtOH, 22% NASH, 8% HBV), HCV genotype, HCV treatment status, AFP, and ALBI score (G2 54%, G3 16%, unk 15%). Variables of interest (age, sex, race, cirrhosis etiology, AFP, ALBI score, year of LR 3 detection, imaging modality) were included in proportional hazards modeling with the underlying time metric defined as time from LR 3 detection to date of LR 5 detection or date of last scan up to one year after LR 3 identification. Backwards elimination modeling was performed until remaining variables were associated with the outcome at a level of significance of p < 0.05 (Table 1). Among those with chronic HCV, risk of progression to LR 5 did not differ by HCV genotype (1a, 1b, 2, 3, other, unknown) or sustained viral response status at the time of LR 3 detection. Table 1: Multivariate hazard ratios (HR) and 95% confidence interval (CI) estimates. Conclusions: Chronic HCV, older age at LR 3 detection, earlier year of LR 3 detection, and male sex appear independently associated with risk of progression to LR 5. The identification of clinical factors associated with LR 3 progression may allow for the development of risk modeling tools to assist clinicians in determining frequency of follow-up imaging and optimal timing of intervention.[Table: see text]