bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sorafenib treatment in recurrent hepatocellular carcinoma post liver transplantation.
Authors: Fallah-Rad Nazanin , Cao Yanshuo , Sapisochin Gonzalo , Dhani Neesha C. , Knox Jennifer J. , Grant David , Jang Raymond Woo-Jun , Greig Paul David , Lilly Leslie , Chen Eric Xueyu 
Published: September 2018

e15613 Background: Liver transplantation (LT) is a potentially curative treatment for patients (pts) with selective hepatocellular carcinoma (HCC). HCC recurrence post LT is estimated to be 15-20%. Data on systemic therapy post-recurrence is scarce and limited case series suggest that sorafenib (SOR) may have benefit in this population. We reviewed a single center experience with SOR in recurrent HCC post LT Methods: A retrospective review was conducted on pts with recurrent HCC post LT at University Health Network (UHN) who were treated with SOR. Pt characteristics were collected including age, gender, comorbidities, background liver disease, type of LT, and time to recurrence after LT. Treatment information collected included: initial SOR dose (and adjustments), adverse events (AEs), duration of treatment and survival. Results: Between 2006 and 2016, 24 pts were identified. The average age was 60 years (range: 18-72), most pts were male (20/4), living/cadaveric transplant: 11/13. HCC etiology included hepatitis B (10), alcohol (4), NASH (3), hepatitis C (2), hemochromatosis (2), Budd-Chiari (2) and unknown (1). The average time to recurrence of HCC was 16.08 (range: 1.5-60) months post OLT. There was a bimodal time to recurrence with a median of 6 months. SOR starting doses were 200 mg BID in 18 pts, 300 mg BID in 1 and 400 mg BID in 4. 14 pts required dose adjustment due to AEs, mainly relating to fatigue and palmar-plantar syndrome. The median time on treatment was 2.5 (range: 0.25-37) months. The average time to progression on SOR and/or discontinuation due to AEs was 4.30 (+/- 7.2) months. Conclusions: SOR is reasonably tolerated in pts with recurrent HCC post LT, with expected AE profiles. In this small case series, the median time on SOR was short and estimated time to progression was shorter than that in non-transplant HCC population. Overall, SOR has limited activity in this population, but selected pts may derive extended benefit. Better understanding of responders and investigations of other therapies are needed for this population.
CT-based radiomic analysis of hepatocellular carcinoma patients to predict key genomic information.
Authors: West Derek L , Kotrotsou Aikaterini , Niekamp Andrew Scott , Idris Tagwa , Giniebra Camejo Dunia , Mazal Nicolas James , Cardenas Nicolas James , Goldberg Jackson L. , Colen Rivka R. 
Published: September 2018

e15623 Background: The utilization of computed tomography (CT) has virtually replaced the need for tissue diagnosis in hepatocellular carcinoma (HCC). Imaging features (e.g. size, shape and vascularity) have been associated with patient survival. However, the full potential of CT in HCC diagnosis may not be reached, as high-throughput computing allows for extraction of quantitative features that are not part of radiologists’ lexicon. The purpose of this study was to investigate the ability of radiomic analysis to successfully identify specific doxorubicin chemoresistant genes on CT images of treatment-naïve hepatocellular carcinoma (HCC). Methods: We identified 27 treatment-naïve patients with a single HCC tumor from The Cancer Genome Atlas (TCGA) whom had gene expression profiles. Baseline CT images were obtained from The Cancer Imaging Archive (TCIA). 3D Slicer software was used for manual tumor segmentation and final segmented images were reviewed by a board-certified radiologist. Following tumor segmentation, texture analysis was performed on MATLAB environment. A total of 310 rotation invariant texture features, which measure tumor heterogeneity, were obtained (first-order histogram and grey level co-occurrence matrix). The mRMR method was used to select the most relevant radiomic features. ROC analysis and LOOCV were used to assess the performance of five specific genes known to confer doxorubicin chemoresistance (TP53, TOP2A, CTNNB1, CDKN2A and AKT1). Results: Radiomic analysis identified TP53 (AUC = 86.61%, Specificity = 92.31%, Sensitivity = 92.9%), TOP2A (AUC = 78.0%, Specificity = 69%, Sensitivity = 85.7%), CTNNB1 (AUC = 86.8%, Specificity = 92.3%, Sensitivity = 85.7%), CDKN2A (AUC = 76.9%, Specificity = 76.9%, Sensitivity = 78.6%) and AKT1 (AUC = 72.5%, Specificity = 69.2%, Sensitivity = 85.7%) in treatment-naïve HCC CT studies. Conclusions: The identification of specific genes that confer chemoresistance to doxorubicin can be reliably ascertained via the use of radiomic analysis. This study may help tailor future treatment paradigms via the ability to categorize HCC tumors on genetic level and identify tumors which may not have a favorable response to doxorubicin based therapies.
Hepatocellular carcinoma outcomes at an academic transplant center: A single-institution retrospective study.
Authors: Kurkul Charles Vincent , Ryer Elizabeth , Maheswaran Abiramy , Holzwanger Erik , Switzer Bradley Alan 
Published: September 2018

e15624 Background: Although there have been recent advances in locoregional therapies, liver transplant remains the only curative treatment for hepatocellular carcinoma. Previous single-institution studies suggest that despite aggressive management, OS for non-transplantable patients remains poor. It has been proposed that multidisciplinary evaluation at a high volume academic center will improve outcomes, though this has not been well reported. Methods: 249 patients with diagnosed HCC evaluated in the UMass multidisciplinary HCC clinic between 2006 and 2016 were identified. Patient demographics, interventions, and outcomes were documented through chart review. Kaplan-Meier survival curves were calculated to compare outcomes. Results: Of the 249 patients, 77% were male and the median age was 64 (22-83). Child-Pugh score at diagnosis was 53% A/32% B/13% C. Comorbidities included hepatitis C (54%), hepatitis B (9%), and NASH (1.2%). Alcoholic liver disease was present in 45% of patients (25% HCV+EtOH). The stage at diagnosis was I/II/III/IV in 43/37/16/4% respectively. 101 patients were eligible for transplant. 54 received a liver. 38 remain on the waiting list. In the 169 non-transplant patients, multiple modalities were utilized including resection (3%), Y90 (6%), TACE (40%), RFA (30%), EtOH ablation (1%), and SBRT (19%). 38% of patients received sorafenib, and 3.5% cytotoxic chemotherapy. 40% of patients had one intervention, 21% had two, 16% had three, and 7% had four or more. 16% of patients received only active surveillance. The median OS for all patients was 4.4 years. Transplanted patients had a 5 year OS of 80%. The median OS for non-transplant patients was 36 months. Median OS by C-P in non-transplant patients was 52/24/11 months (A/B/C). Median OS by stage in the same population was NR/32/11/6 months. Conclusions: While patients with very advanced and severe disease still did poorly, this aggressively treated group demonstrated favorable outcomes when compared to the historically poor survival without transplant.This would imply that multidisciplinary treatment in a high volume center improves outcomes. Further prospective and comparative work is pending.
Utility of CT texture for identification of FGFR2 fusion in cholangiocarcinoma: A radiogenomic pilot study.
Authors: DeLeon Thomas , Borad Mitesh J. , Wu Teresa , Li Jing , Zwart Christine M. , Yang George , Holeman Scott , Silva Alvin C. 
Published: September 2018

e15626 Background: FGFR2 fusions are found in 10-15% of intrahepatic cholangiocarcinomas. Individuals with FGFR2 fusions have a better prognosis and more indolent natural history. More recently FGFR2 fusions have been described as a predictive marker for tyrosine kinase inhibitors targeting the FGFR2 pathway. Texture analysis from CT imaging has been used in the past to estimate degree of fibrosis and angiogenesis in various tumors types; however, texture analysis has not been used in the past to detect FGFR2 rearrangements. Methods: This is a retrospective study of 33 patients with intrahepatic cholangiocarcinoma who were previously tested for FGFR2 fusions with either a FISH break apart assay or with clinically available next generation sequencing assays. All patients had a contrast enhanced CT performed. To address physiological and pathological variations, matched-size regions of interest (ROIs) over areas of non-necrotic tumor and unaffected liver during the portal venous phase were drawn. The paired ROIs for each patient were then processed via an imaging analytic pipeline for (1) ROI normalization, (2) texture panel creation, and (3) machine learning predictive model development. Results: Fifteen patients with FGFR2 fusions and 18 patients without FGFR2 fusions were included in the study. Using the developed predictive model, accurate FGFR2 fusion classification in 90% of cases was achieved (sensitivity = 87%, specificity = 94%). Conclusions: Utilizing advanced analytics with machine learning techniques, multi-textural data obtained from conventional CT images has the capability to detect genetic aberrations in intrahepatic cholangiocarcinoma, including FGFR2 gene fusions. Radiogenomic evaluation has several attractive benefits including the cost effective and expeditious detection of actionable mutations such as FGFR2 fusions as well as avoidance of invasive procedures such as percutaneous core biopsies. [Table: see text]
Phase I study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma patients.
Authors: Shen Jie , Wang Lifeng , Zou Zhengyun , Wei Jia , Liu Baorui 
Published: September 2018

e15628 Background: Advanced hepatocellular carcinoma is a challenging disease to treat because of its late stage, rapid progression. We conducted a new treatment modality, meaning a cellular immune therapy based on personalized peptide vaccination (PPV-DC-CTL) combined with radiotherapy, to treat advanced hepatocellular carcinoma. It integrates personalized peptide vaccination in tumor immunotherapy, takes full advantages of the immune modulation of radiotherapy, promotes tumor cells releasing antigens and results in more effective therapeutic strategy in local control and system treatment. Methods: A total of 9 patients with advanced hepatocellular carcinoma were admitted. Multidisciplinary consultation confirmed that all the patients were clearly no surgical opportunity. 4 patients with multiple liver metastases (liver lesions > 3 pieces), 1 patient with liver metastases and portal vein tumor thrombosis, 1 patient with lung and bone metastasis, 2 patients with liver and lung metastasis, and 1 patients with liver metastases and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL. Results: After radiotherapy and 1-3 cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in 6 patients, of which, imaging assessment of lesions researched PR for 3 patients and SD for another 3 patients. Response rate (RR) was 33%, and disease control rate (DCR) was 66%. This scheme is safe and well tolerated. None of the patients had side effects on liver and kidney function. Only one patient had Grade2 of bone marrow suppression, and the rest had no significant side effects on hemogram. Conclusions: Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced hepatocellular carcinoma, which is well tolerated, safe, feasible, and effective. Clinical trial information: ChiCTR-OIC-16010025.
GALNT14 genotype-guided, sorafenib in combination with transarterial chemoembolization in hepatocellular carcinoma: An interim report of a prospective randomized controlled trial.
Authors: Yeh Chau-Ting , Lee Wei-Chen , Lin Shi-Ming , Lin Chih-Lang , Hsu Chao-Wei , Wu Ting-Jung , Yu Ming-Chin , Hung Chien-Fu , Tseng Jeng-Hwei , Lin Chen-Chun , Chen Wei-Ting , Teng Wei , Chen Yi-Cheng , Chang Ming-Ling 
Published: September 2018

e15657 Background: Sorafenib is the only approved targeted agent for treatment of unresectable hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is the mainstay of treatment for advanced HCC patients in Barcelona Clinical Liver Cancer (BCLC) stage B. Previous randomized controlled trials did not show definite beneficial effect for TACE + sorafenib combination therapy in Asian HCC patients. Recently, an SNP marker on GALNT14gene, rs9679162, was found associated with therapeutic outcomes in HCC patients receiving chemotherapy or chemoembolization, wherein rs9679162-TT genotype was associated with a favorable therapeutic response. In this study, we examined whether this marker could be used as a guide for TACE + sorafenib therapy. Methods: From 2015-Aug, HCC patients in BCLC stage B were genotyped for GALNT14-rs9679162. Patients with genotype TT were treated with TACE alone. Patients with non-TT (CT or CC) were randomized 1:1 to receive TACE + sorafenib treatment or TACE treatment alone (NCT02504983). Results: Interim analysis was performed on 2017-Jan. Totally 40 patients were enrolled. Of them, 16 and 24 patients had GALNT14-TT and non-TT genotypes, respectively. Of the non-TT patients, 11 and 13 patients were randomized into TACE alone (TACEA) and TACE + sorafenib (TACE+S) group. TACEA patients had significant shorter time-to-tumor progression compared with TACE+S (P = 0.019) and GALNT14-TT patients (P < 0.001). No significant difference was found for time-to-therapeutic response (CR + PR) between the three groups. However, when evaluating the time-to-therapeutic response occurring > 3 m of the first TACE (excluding early response), it was found that TACEA patients had significant longer time-to-therapeutic response compared with TACE+S (P = 0.046) and GALNT14-TT patients (P = 0.034). Conclusions: The interim analysis confirmed that patients with GALNT14-TT genotype had a favorable TACE response compared with the non-TT genotype. In addition, in patients with non-TT genotype, TACE + sorafenib combination therapy had a significantly better therapeutic response compared with TACE alone. Clinical trial information: NCT02504983.
Anti-mitochondrial therapy in bile duct cancer.
Authors: Alistar Angela Tatiana , Pasche Boris , Morris Bonny , Desnoyer Rodwige , D'Agostino Ralph 
Published: September 2018

e15661 Background: Biliary duct carcinoma is a rare but highly fatal malignancy. The five-year survival rate for advanced bile duct cancer is 2%, per SEER data. As such, new treatment options are desperately needed. CPI-613, a novel anticancer agent that selectively inhibits mitochondrial metabolism in cancer cells, was employed in this study. Methods: This phase 1 study utilized a two-stage dose-escalation schema to determine the maximum-tolerated dose (MTD) and safety of single agent CPI-613 in patients with locally advanced or metastatic bile duct cancers. The 1st cohort enrolled 4 patients at 2300 mg/m2, with no dose-limiting toxicities (DLT) observed. The 2nd cohort enrolled patients at 1200 mg/m2/day for pre-cycle (days 1-5) and 3000 mg/m2 on days 1 and 4 weekly for 3 weeks (28 day cycle). The 5th and 6th patient experienced a DLT. The 3rd cohort was initiated at 600 mg/m2 pre-cycle and 3000 mg/m2 weekly with no other DLTs observed. Results: To-date, 14 patients have been enrolled in the study. The MTD was determined at 600 mg/m2/day pre-cycle and 3000 mg/m2 as per schedule. Once the MTD was determined, the cohort was expanded and, 8 patients have been treated at the MTD with no DLTs observed. Two additional patients are planned to be enrolled at this dose prior to trial completion. Of these 8 patients, 3 are still alive with 1 having prolonged survival (15 months) and the other 2 still on treatment. The most commonly observed toxicities were mild, such as anemia, anorexia, dehydration, fatigue, nausea and thrombocytopenia. Conclusions: Treatment with CPI-613 was well tolerated by patients with heavy tumor burden and refractory disease. CPI-613 has recently been shown to be well tolerated in combination with FOLFIRINOX in pancreatic cancer patients. Due to the low toxicity of CPI-613 in this study, even among highly symptomatic patients, it is anticipated that combination with other active agents is feasible in patients with advanced bile duct cancer. CPI-613 represents a novel treatment that could prove to be an exciting therapeutic alternative for patients with previously limited options and poor survival. Clinical trial information: NCT01766219.
A prospective biomarker study to assess IGF-1 score ability to sub-stratify Child-Turcotte-Pugh classes and predict response to systemic therapy in hepatocellular carcinoma.
Authors: Kaseb Ahmed Omar , Abdel-Wahab Reham , Hassan Manal , Xiao Lianchun , Raghav Kanwal Pratap Singh , Girard Lauren , Amin Hesham M. , Morris Jeffrey , Wolff Robert A. , Yao James C. 
Published: September 2018

e15662 Background: Our recent studies showed that lower insulin like growth factors-I (IGF-I) associated with shorter overall survival (OS) in HCC. Furthermore, integrating IGF-I into Child Pugh Score (CTP) (IGF-CTP) led to better prognostic stratification (Kaseb et al., JNCI 2014). Since CTP class A is the standard criterion for active therapy and trials entry, we aimed at assessing the ability of IGF-CTP to predict systemic therapy outcome. Methods: 78 patients were prospectively enrolled and treated with sorafenib. Pre-treatment blood sample were tested for IGF-I and IGF-CTP was calculated after study completion. Survival analysis was done to measure the estimated median OS and progression free survival (PFS), and log rank test was used to compare PFS and OS between subgroups of IGF-CTP score of patients. Results: For CTP A patients, the estimated median OS in months (95% confidence interval, CI) was 9.1m (5.3 – 19.7) and PFS was 5.6m (3.8 – 7.9). Patients who were reclassified as IGF-CTP (B) (OldA/newB = AB) had significantly shorter OS 5.2m (2.8 - NA) and PFS of 4.3m (2.1 – NA), as compared to patients’ who classified as class A by both scoring systems (AA), who had OS of 11.1m (5.7 – 21.3) and PFS of 7.2 m (3.9 – 15.1), P < .001. Interestingly, patients who classified as CTP-B but IGF-CTP-A ( = BA) had significantly longer OS 10.2 (2.89 – NA) and PFS 8.1 (2.9 – NA), as compared to (BB) patients who had OS of 5.8 (3.2 –NA) and PFS of 5.1 (3.19 – NA), P < .001 Conclusions: Our study concluded that IGF-CTP score was more accurate than original CTP score in predicting survival outcomes of systemic therapy in HCC. If validated, this approach may change the standard stratification criteria for active therapy in routine clinical practice and patient selection for clinical trial entry in HCC.
Osteoponstin expression and presence of EGFR-positive liver macrophage to predict outcome after liver transplantation for hepatocellular carcinoma.
Authors: Tsuchiya Kaoru , Sieghart Wolfgang , Herac Merima , Hucke Florian , Oberhuber Georg , Sibilia Maria , Peck-Radosavljevic Markus 
Published: September 2018

e15664 Background: Orthotopic liver transplantation (OLT) is the most effective therapy for patients with hepatocellular carcinoma (HCC) of limited extent. We focused on biomarkers, which could serve as tools for patient selection for OLT with good outcome even when transplanted beyond the standard size limits. Methods: Osteopontin(OPN) expression and presence of Epidermal Growth Factor Receptor (EGFR)-positive liver macrophage had been shown previously to be associated with the risk of tumor recurrence post OLT and were investigated immunohistochemically in 125 HCC-patients undergoing OLT between 1982 and 2002. Multivariate analyses of these and other well-described factors associated with median overall survival (OS) and time to recurrence (TTR) were performed. Results: The OS rates of the 125 patients at 1, 3, 5, 7 and 10 years were 77%, 52%, 43%, 37% and 32%. The 3-, 5-, and 7-year survival rates for patients without expression of both biomarkers (OPN and EGFR-positive liver macrophage) were 66.1%, 61.0% and 54.1%. These were significantly better than for the other groups (p < .0001), whereas the 3- and 7-year survival rates for patients with expression of both biomarkers were 25.0% and 5.0%. Fifty-eight patients (38.4%) developed tumor recurrence.There was no significant difference in OS and TTR between the patients beyond the Milan criteria (MC) without expression of both biomarkers (n = 26) and the patients within MC with expression of one or two biomarkers (n = 20).On multivariate analysis, vascular invasion and presence of EGFR-positive liver macrophage in HCC were independent factors associated with OS. Both biomarkers were independent factors associated with TTR.On multivariate analysis, morphologic criteria including MC and Up-to-7 criteria were not significantly associated with OS and TTR once OPN and EGRF+ macrophage presence was introduced into the analysis. Conclusions: Staining for OPN and EGFR-positive liver macrophage in HCC can give important prognostic information. The discussion about the selection for OLT in HCC patients should likely consider the expression of biomarkers in addition to relying on morphologic criteria.
Effect of adjuvant therapy on resected gallbladder adenocarcinoma: A propensity score matched analysis of national data.
Authors: Kasumova Gyulnara G. , Tabatabaie Omidreza , Miksad Rebecca A. , Ng Sing Chau , Hidalgo Manuel M. , Tseng Jennifer F. 
Published: September 2018

e15669 Background: There is a paucity of data and no consensus regarding administration of adjuvant therapy after resection of gallbladder cancer. In the absence of a completed clinical trial, we retrospectively reviewed US cancer data. Methods: National Cancer Data Base was queried for patients diagnosed with gallbladder adenocarcinoma between 2004-2014 who underwent definitive resection for non-metastatic disease (pT1b, pT2, pT3, pN0, pN1, pNX) and had R0 and R1 resection margins. One-to-one propensity score matching was used to account for potential selection bias in patient and tumor characteristics. Kaplan-Meier method was used to compare overall survival. Results: Of 4830 patients identified, 1489 (30.8%) received adjuvant chemotherapy. Patients who received adjuvant chemotherapy were more likely to be younger, have private insurance or Medicare, have no comorbidities, higher T stage, and moderately to poorly differentiated tumors (all p-values < 0.0001). The majority of patients who received adjuvant chemotherapy also received adjuvant radiation (58.0%). On unadjusted analysis, patients who received adjuvant chemotherapy had no difference in median overall survival compared to those who did not (25.8 vs 29.0 mo; p = 0.3060). After matching for sex, age, race, insurance, comorbidity, facility type, pT stage, lymph node status, resection margins (R0 vs R1), adjuvant radiation, and tumor grade no difference in median overall survival remained between patients who did (21.8 mo) and did not (22.6 mo) receive adjuvant chemo (p = 0.6843). However, after matching on the propensity to receive adjuvant radiation in addition to the above covariates, receipt of adjuvant radiation resulted in a persistently significant increase in median overall survival (27.8 vs 22.2 mo; p = 0.0005). Conclusions: After matching for potential confounders, there is no difference in overall survival for patients who did and did not receive adjuvant chemotherapy after R0/R1 resection for pT1b, pT2, and pT3 gallbladder adenocarcinoma; however, adjuvant radiation does appear to confer a survival advantage. These results support the current treatment guidelines until evidence from RCTs becomes available.