bluuebunny/crossref_metadata_2025_split huggingface dataset:
A MRI-based radiomics model for preoperative prediction of five-year survival status in hepatocellular carcinoma.
Authors: Wang Xiao-Hang , Long Liu-Hua , Cui Yong , Jia Angela Y , Zhu Xiang-Gao , Wang Hong-Zhi , Wang Zhao-Hai , Wang Wei-Hu 
Published: May 2019

e15596 Background: Recurrence is the major cause of mortality in resected hepatocellular carcinoma (HCC) patients. However, without a standard approach to evaluate prognosis, it is difficult to select potential candidates for additional therapy. We aim to develop and evaluate a magnetic resonance imaging (MRI)-based radiomics model to predict 5-year survival status of HCC patients in the preoperative setting. Methods: A total of 201 HCC patients who were followed up for at least 5 years (unless death occurred) after curative hepatectomy were enrolled in this retrospective multicenter study. 3144 radiomics features were extracted from four conventional sequences of preoperative MRI (T1WI, T2WI, DWI and dynamic contrast-enhanced MRI). The random forest method was used for feature selection and radiomics signature building. 5-fold cross validation was used for robust estimation. A radiomics model incorporating the radiomics signature and clinical risk factors was developed. The model performance was evaluated by its discrimination and calibration. Results: Patients were divided into survivor (n = 97) and non-survivor (n = 104) groups based on survival status at 5 years from surgery. The 30 most survival-related radiomics features were selected to develop the radiomics signature. The preoperative alpha-fetoprotein level was integrated into the model as an independent clinical risk factor in multivariable logistic regression analysis (OR = 3.764; 95% CI 1.997-7.096). The radiomics model demonstrated good calibration and satisfactory discrimination, with the mean area under the curve of 0.9340 (95% CI 0.9222-0.9458) in training set and 0.7383 (95% CI 0.6914-0.7852) in validation set. Conclusions: The MRI-based radiomics model represents a valid method to predict 5-year survival status in HCC patients in the preoperative setting, and may be used to guide neoadjuvant or adjuvant treatment decisions in high-risk patients.
Additional prognostic value of metabolic parameters measured by dual time point pretreatment F-18 FDG PET/CT in patients with intrahepatic cholangiocarcinoma.
Authors: Hwang Jae Pil , Choi Seo Youn , Kim Hee Kyung , Moon Jong Ho , Park Jung Mi 
Published: May 2019

e15598 Background: The aim of this retrospective study was to determine whether delayed glucose metabolism assessed by dual time point F-18 FDG PET/CT provides additional prognostic information independent of established prognostic factors in patients with intrahepatic cholangiocarcinoma (IHCC). Methods: We reviewed retrospectively the medical records of 96 patients (men 57, women 39, mean age 66 ± 10 years) with pathologically proven IHCC. They underwent dual time point F-18 FDG PET/CT as part of a pretreatment workup from July 2012 to December 2017. For the analysis, patients were classified by age, sex, stage, serum CA19-9, early SUVmax (eSUV), delayed SUVmax (dSUV), delta SUVmax (ΔSUV, difference between early and delayed SUVmax) and histopathology (pCEA, p53, Ki-67 index). The relationship between FDG uptake and survival was analyzed using the Kaplan-Meier with log-Rank test and Cox’s proportional-hazard regression methods. Results: Median survival for all 96 study subjects was 303 days and median SUVmax was 7.2 (range: 2.5 – 21.7). The survival was found to be significantly related to eSUV ( p < 0.0001), age ( p = 0.017), LN metastasis ( p = 0.03) and p53 index ( p = 0.04) and multivariate analysis study revealed that the patients with a higher SUVmax ( p = 0.0001, 95%CI = 1.80 to 5.89, HR = 3.26), prescence of LN metastasis ( p = 0.031), higher age ( p = 0.044) and a higher p53 index ( p = 0.007) showed worse overall survival. In addition, we carried out a subgroup analysis targeting the 55 patients with delayed SUVmax to evaluate a prognostic value of delayed image parameter. In univariate analysis, dSUV (cut-offvalue 7.3, p = 0.0006) and ΔSUV (cut-off value 3.2, p = 0.035), age ( p < 0.0001) and sCA19-9 ( p = 0.018) showed significant correlation and dSUV was an independent factor of overall survival in multivariate analysis. ( p = 0.014, 95%CI = 1.30 to 10.7, HR = 3.74) And then, we analyzed combinations of eSUV, dSUV and ΔSUV each other to evaluate additional prognostic information. The result revealed that higher dSUV ( p = 0.0001, AUC = 0.68) and ΔSUV ( p = 0.0002, AUC = 0.71) showed a poorer overall survival although the eSUV of IHCC was low. Conclusions: Higher delayed SUVmax and ΔSUVmax on pretreatment dual time point F-18 FDG PET/CT can predict poorer survival and additional information of risk stratification in patients with IHCC.
Nemesis: Non-inferiority meta-analysis of selective internal radiation therapy with yttrium-90 resin microspheres versus sorafenib in advanced hepatocellular carcinoma: A preliminary analysis.
Authors: Venerito Marino , Pech Maciej , Canbay Ali , Donghia Rossella , Guerra Vito , Chatellier Gilles , Pereira Helena , Gandhi Mihir , Chow Pierce K. H. , Vilgrain Valérie , Ricke Jens , Leandro Gioacchino 
Published: May 2019

e15604 Background: No survival benefit has been observed for selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres versus (vs.) sorafenib in patients with advanced hepatocellular carcinoma (HCC). In NEMESIS, we assessed by an individual patient data meta-analysis whether SIRT, either as monotherapy or followed by sorafenib, is non-inferior to sorafenib and compared safety profiles. Here we present preliminary data. Methods: A systematic search of MEDLINE, EMBASE, and the Cochrane Library, up to 6 December 2018, found three randomized trials comparing SIRT as monotherapy, or followed by sorafenib, to sorafenib monotherapy among patients with advanced HCC. The main outcomes were overall survival (OS) and frequency of adverse events (AEs). Survival data were pooled (fixed effect analysis). The primary population for non-inferiority analysis was the per-protocol (PP) population. The non-inferiority margin for the hazard ratio (HR) upper boundary was set at 1.08 as specified in EASL guidelines. Results: The three included trials compared sorafenib to SIRT (SIRveNIB and SARAH) or to SIRT followed by sorafenib (SORAMIC) in 1243 patients. After randomization, 23.3% vs. 7.1% of patients (p < 0.0001) did not receive the allocated intervention, and 542/608 (89.1%) vs. 418/635 (65.8%), (odds ratio [OR] 4.3, 95% CI: 3.2-5.8, p < 0.0001) completed the study without major protocol deviations (PP population), in the SIRT and sorafenib arms, respectively. Baseline characteristics of the PP population did not differ between the two comparison groups. Median OS with SIRT followed or not by sorafenib was non-inferior to sorafenib (HR 0.90, 95% CI 0.78–1.02). Treatment-related AEs grades ≥3 were reported in 109/356 (30.6%) patients who received SIRT and 197/378 (52.1%) patients in the sorafenib arm (SIRveNIB and SARAH only, p = 0.0002). Conclusions: SIRT as initial therapy for advanced HCC is non-inferior to sorafenib in OS, and offers a better safety profile.
Epidemiology, prevalence and national trends of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) in hospitalized US patients between 2002-2014.
Authors: Elkafrawy Ahmed , Othman Hasan F. , Asif Samia , Al-Sayyed Leen , Shrestha Anuj 
Published: May 2019

e15616 Background: cHCC-CCA represents a rare type of primary liver cancer that was first identified in 1949. The aim of this study is to evaluate epidemiology, clinical outcomes and national trends of cHCC-CCA in hospitalized US patients using the Nationwide Inpatient Sample database (NIS). Methods: NIS database was inquired to identify patients with HCC between 2002 and 2014 using ICD9-CM codes. Patients with HCC were classified into two groups, one group with cholangiocarcinoma (CCA) and the other group without CCA. SPSS version 25 was used for statistical analysis. Results: We identified 525,699 patients with HCC between 2002-2014. Of them, 2,158 patients (0.4%) had CCA. In the cHCC-CCA group, 87.8% of the patients were above 50 years old, 58.1% were male, 63.7% were Caucasian, and 10% were African American. Mortality in patients hospitalized with cHCC-CCA was 8.5% compared to 11.1% in patients with HCC (OR 0.74, 95% CI 0.64-0.86, P < 0.0001). Mortality in cHCC-CCA patients decreased from 19.1% in 2002 to 7.9% in 2014. The median length of stay (LOS) in patients with cHCC-CCA was 6 days compared to 4 days in patients with HCC (P < 0.0001). Median LOS for patients with cHCC-CCA was unchanged between 2002 and 2014. The median hospitalization cost of charge in cHCC-CCA patients was 41,012 USD compared to 28,371 USD in HCC patients. In the cHCC-CCA group, it increased from 17,243 USD in 2002 to 37,234 USD in 2014. Only 0.9% of patients with cHCC-CCA underwent liver transplantation compared to 3.5% of HCC patients (OR 0.26, 95% CI (0.17-0.41), P < 0.0001). Conclusions: Prevalence of cHCC-CCA was 0.4% of patients with HCC during the study period. cHCC-CCA was unexpectedly associated with less mortality; possibly because of limitations in comparison due to the smaller number of patients compared to HCC alone. cHCC-CCA was also associated with lower rates of liver transplantation but more prolonged LOS and higher hospitalization cost of charge compared to HCC patients. In the same period, mortality decreased in cHCC-CCA patients and cost of charge increased while prevalence and LOS were unchanged. Further studies are needed to evaluate and understand cHCC-CCA as a separate entity.
Outcomes of treatment of carcinoma gall bladder undergoing curative intent surgery.
Authors: Chaturvedi Arun , Kumar Vijay , Gupta Sameer , Akhtar Naseem , Saini Shiv Rajan , Prakash Puneet 
Published: May 2019

e15621 Background: Gall bladder carcinoma (GBC) is the most common malignancy of the biliary tract. North India reports one of the highest incidences of GBC in the world. Majority of patients present with advanced disease where surgery is not possible. We report the results of patients undergoing curative intent surgery at a tertiary care University hospital in North India. Methods: Data of 270 patients undergoing curative intent surgery for GBC at the Department of Surgical Oncology, King George’s Medical University, Lucknow (India) between January 2014 and December 2018 was retrospectively studied. We have analysed the collected data using descriptive and survival statistics. Results: During the period of study 270 patients were operated for GBC. Mean age of patients was 50.2 years and majority (75.2%) were females. On surgical exploration 82 (30.4%) had unresectable disease and only a biopsy or palliative procedure was done. Simple cholecystectomy was done where frozen section showed benign calculus cholecystitis in 26 (9.6%) patients. Radical cholecystectomy was performed in 162 (60%) patients. Final histopathology revealed Xanthogranulomatous cholecystitis in 28 (17.3%) of these 162 patients. Adjacent organ resection was done in 29 of the 134 (24.1%) patients undergoing radical cholecystectomy for pathologically proven GBC. Colon and CBD were the most common adjacent organs resected. Completion radical cholecystectomy was done in 22 patients with incidental GBC. Adjuvant chemotherapy as per our institutional protocol was given to 68 (50.7%) patients having Stage 3 or more disease. After a mean follow-up of 19 months the median disease free interval (DFI) is 38 months and the median overall survival (OS) has not been reached. Patients undergoing adjacent organ resection had an inferior median OS of 20 months compared to those without it where the median has not been reached (Log Rank P = 0.006). Conclusions: Nearly a third of GBC patients planned for curative intent surgery are found to have unresectable disease on exploration. This proportion needs to be brought down. Radical cholecystectomy in properly selected GBC patients without adjacent organ involvement gives satisfactory survival outcomes.
Health-related quality-of-life in patients with cholangiocarcinoma: Results of a systematic literature review.
Authors: Cho Yohan , Chadwick Claire , Barrett Scott , Bibeau Kristen , El-Hadi Wissam , Hopkinson Devan 
Published: May 2019

e15623 Background: Cholangiocarcinoma (CCA) is a rare biliary tract cancer (BTC) with a historically poor prognosis and limited treatment options. Both quality and quantity of life can be important factors when deciding treatment, thus assessment of health-related quality-of-life (HRQoL) is needed to justify the use of novel therapies. HRQoL questionnaires are a standardized way to understand the patients’ perspective and treatment experience. The objective of this review was to examine the published literature specific to HRQoL in CCA. Methods: A systematic literature search was conducted using EMBASE and MEDLINE from Jan 2008 to June 2018 to identify abstracts with published HRQoL data in CCA patients. This review also included global conference proceedings (2015-2018) and HTA websites. Articles were considered relevant if they reported HRQoL data in patients with CCA, bile duct carcinoma, and/or hepatobiliary system cancer. Results: Of the 2,933 studies initially identified, 7 ongoing or completed studies met the scoping criteria to be included in the review. No articles in this literature review reported data from clinical trials. Multiple HRQoL measures were utilized; however within the studies, EORTC QLQ-BIL21 was the only HRQoL measure developed and validated specifically for BTC (CCA, gallbladder, or ampulla vater) identified in this review. 3/7 studies included information on CCA subtypes (intrahepatic, extrahepatic) with 2/3 studies reporting HRQoL by subtype. Patient symptoms were reported in 4/7 studies, including gastrointestinal distress, abdominal pain, fatigue, fever, itching, difficulty sleeping, anxiety, jaundice and weight loss. Conclusions: Within this literature review, few studies have been published with HRQoL data in CCA patients. Data from the existing published literature is generally from a heterogeneous patient population, and not consistently specified for CCA stage or subtype. To better understand HRQoL in CCA patients, more data needs to be generated that include clinical trials for novel therapies.
Molecular pathway activation-based analysis for personalized prescription of tyrosine kinase inhibitors for advanced solid tumor patients.
Authors: Poddubskaya Elena , Baranova Madina , Allina Daria , Sekacheva Marina , Makovskaia Lyudmila , Albert Eugene , Suntsova Maria , Aleshin Alexey 
Published: May 2019

e15636 Background: Tyrosine-kinases (TKs) play key roles in cancer by acting as major components of various signaling pathways. Tyrosine kinase inhibitors (TKIs) act by inhibiting TKs, thereby modulating downstream signaling. Here we report a molecular pathway analysis-based approach to personalize prescription of TKIs for advanced and recurrent solid tumors, exemplified by successful cases of off-label prescriptions of TKIs to unresectable metastatic cholangiocarcinoma (MCC) and to recurrent ovarian granulosa cell tumor (GCT) patients. Methods: To isolate RNA, we used patient’s tumor histologically verified formalin fixed, paraffin embedded (FFPE) tissue blocks containing > 75% tumor cells. Gene expression levels were established using CustomArray platform. Tumor expression was compared with the corresponding normal tissues and a second-opinion platform Oncobox (Omicsway, USA) was applied for finding abnormally activated molecular pathways and for the corresponding ranking of target drugs. Results: For a 26-year-old woman with progressive ovarian GCT despite multiple previous lines of therapy who underwent salvage therapy selection, the following target drugs could be potentially most effective for treatment according to the Oncobox test: Regorafenib, Sorafenib, Sunitinib, Pazopanib, Axitinib, Imatinib. In Oct 2015, patient was administered Sorafenib, but it was not well tolerated, and this therapy was terminated after 2 months. However, ultrasound examination indicated an associated decrease in the size of neoplasms. Therapy regimen was switched to Imatinib, which was well tolerated and resulted in a disease stabilization. As for Feb 2019, Imatinib administration is continued and patient is physically active with Karnofsky scale index 90%. Another patient with MCC was prescribed with subsequent TKI monotherapies for Sorafenib and Pazopanib that occupied, respectively, 2nd and 4th positions of the Oncobox drug rating. It resulted in a two-year stabilization. Conclusions: Our results evidence that sequential personalized prescription of different TKIs based of gene expression tests may be a perspective avenue of further clinical investigations.
Myopenia as a significant prognostic factor in BCLC-B intermediate-stage hepatocellular carcinoma treated with sorafenib.
Authors: Okada Mao , Nakanishi Hiroyuki , Kurosaki Masayuki , Kirino Sakura , Osawa Leona , Watakabe Keiya , Wang Wan , Shimizu Takao , Takaura Kenta , Takada Hitomi , Kaneko Shun , Tamaki Nobuharu , Yasui Yutaka , Tsuchiya Kaoru , Itakura Jun , Takahashi Yuka , Izumi Namiki 
Published: May 2019

e15639 Background: Tyrosine kinase inhibitors (TKI) are important treatment options for unresectable hepatocellular carcinoma (HCC). The survival benefit of sorafernib was demonstrated not only in advanced stage but also for BCLC-B intermediate stage who are refractory to transcatheter arterial chemoembolization by OPTIMIS study. Skeletal muscle mass depletion (Myopenia) is a poor prognostic factor in HCC treated by resection or loco-reginal ablation, but its effect on survival in TKI treated patients, especially in those within BCLC-B stage remains unclear. The aim of the present study is to elucidate the impact of myopenia on survival among HCC treated with sorafenib, especially in BCLC-B stage. Methods: In 213 patients who started treatment with sorafenib between 2009 and 2016, myopenia at baseline was determined by using skeletal muscle index calculated from CT images of the third lumber vertebra level. The impact of myopenia on survival was analyzed in whole patients, after stratification by BCLC stage, and after matching for backgrounds within BCLC-B patients. Results: The median survival in whole, BCLC-C, and –B was 13.7, 8.7 and 15.2 months, respectively. Myopenia was not a significant prognostic factor in whole patients and in BCLC-C stage. However, among BCLC-B patients (n = 104), survival was significantly better in patients with no myopenia (p = 0.05). Among them, 85 patients who continued sorafenib for more than 8 weeks were extracted and those with or without myopenia were matched for backgrounds by propensity score. Backgrounds including etiology, Child-Pugh score, BMI, AFP and PIVKA-Ⅱwas not different between myopenia (n = 30) and no myopenia group (n = 30) after matching. The overall survival at 6-, 12-, and 24-months was 96%, 74%, and 62% in no myopenia group which was significantly better compared to 89%, 64%, and 28% in myopenia group (p = 0.019). The hazard ratio was 2.12 (95% CI 1.11-4.03). Conclusions: Absence of myopenia predicts favorable outcome in sorafenib treated HCC patients within BCLC-B intermediate stage.
High spatiotemporal heterogeneity, clonal selection and neoantigen evolution in acquired sorafenib-resistant patient-derived xenograft models of hepatocellular carcinoma.
Authors: Yang Xin-Rong , Hu Bo , Zhou Jian , Fan Jia 
Published: May 2019

e15641 Background: Patient-derived xenograft (PDX) models have been regarded as valuable preclinical models for oncology drug development and exploring underlying mechanism of drug resistance. As the standard treatment option for advanced hepatocellular carcinoma (HCC), the survival benefit of sorafenib is modest. Even among those who initially responded well to sorafenib treatment, most patients ultimately develop progressive disease owing to acquired drug resistance. Understanding how selective pressure from sorafenib directs the evolution of HCC and shapes its clonal architecture is a central biological question with important clinical implications to combat acquired drug resistance. Methods: Three sorafenib-resistant PDX models were generated by continuous sorafenib treament for more than six months. Whole exome sequencing (WES) and RNA sequencing were performed. The subclone of mutation, fusion genes, and the evolving landscape of tumor neoantigens were further explored. Finally, the antitumor efficacy of recombinant mouse PD-1 antibody was evaluated in sorafenib resistance syngeneic tumors model by immune-competent C57BL/6J mice with Hepa 1-6. Results: High spatiotemporal heterogeneity was observed in engraftment among pre- and post- sorafenib resistance in established acquired-resistance PDX models. Clonal selection on engraftment was observed in established acquired-resistance PDX models. There are many high expressed genes, which showed subclone expansion with the emergence of sorafenib resistance. There is vary difference of neoantigens between pre- and post-resistance engraftment as well as sampling points in same tissues. It was presented that a high burden of clonal neoantigens in sorafenib resistant tissues (P < 0.05), while there has no difference in tumor mutation burden. Moreover, the intra-tumor heterogeneity upon the neoantigen landscape was much bigger than that upon tumor mutation burden. We found that fusion subclone sizes were increased significantly after sorafenib resistance (P < 0.05). Finally, the antitumor efficacy of recombinant mouse PD-1 antibody was confirmed in sorafenib resistance syngeneic tumors mice model (P < 0.001). Conclusions: High spatiotemporal heterogeneity, clonal selection and neoantigen evolution was observed in acquired sorafenib-resistant PDX model of HCC. Immunotherapy such as immune checkpoint inhibitors might be a promising strategy for HCC patients with acquired sorafenib resistance. .