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481 Background: We sought to identify predictors of progression of LR3 lesions (i.e. indeterminate for HCC) to LR5 lesions (i.e. definitely HCC) on follow-up imaging among cirrhotic pts. Methods: Imaging reports with LR assignments were identified among pts seen at the University of Washington, 2013-2017. Cirrhotic pts with a LR3 lesion and follow-up scan within 1 year (yr) of LR3 lesion date were included (n = 313). Clinical features were abstracted from chart review. Survival analyses employing interval censoring were performed. Variables as potentially predictive of LR3 progression were identified in univariate analyses, with backwards elimination done (p < 0.05) to obtain the final multivariate model. Results: 20.4% of LR3 lesions progressed to LR5 within 1 yr; 73% were still LR3, 8% progressed to LR4. The population was predominantly male (61%), Caucasian (71%), older than 55 (63%). The most common cirrhotic etiologies were HCV (46.7%), alcohol (32.6%), and NASH (12.8%), not mutually exclusive. AFP at the time of LR3 scan was low if available (39% with AFP 2cm. Men (HR 2.0, p = 0.02), earlier scan yr (HR 0.47 per yr, p < 0.0001), older age (HR 1.42 per 15 yr, p = 0.047), lesion size (HR 1.21 for 2cm+, global p = 0.02) appeared as independent predictors of LR3 to LR5 progression based on the final model. Of 16 variables examined, men were more likely to have chronic HCV, history of alcohol use and less likely to have autoimmune hepatitis. No other differences were seen. In an a priori analysis, risk of male sex (HR 1.99, p = 0.03) persisted despite control for HCV, alcohol, age, race, scan yr, lesion size, and number of lesions. Conclusions: Identification of clinical factors associated with LR3 progression may allow for risk modeling tools that may assist in determining imaging frequency and timing of intervention. The increased risk among men vs women is not explained by clinical or radiographic features listed above.

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]

e24276Background: Hepatocellular carcinoma (HCC), the most common hepatic malignancy, is the second leading cause of cancer-related death worldwide. China accounts for more than 50% of new HCC cases and deaths in the world. The genomic profiles of HCC in Chinese patients had not been thoroughly elucidated to facilitate diagnosis and treatment. Methods: FFPE tumor and matched blood samples of 181 Chinese HCC patients, including 152 males (median age of 54) and 29 females (median age of 52), were collected for next-generation sequencing-based 450 genes panel assay. Genomic alterations (including single base substitutions, short and long insertions/deletions, copy number variations, and gene rearrangement in selected genes) and tumor mutational burden were assessed. In addition, the expression of tumor cell PDL1 was also evaluated by FDA-cleared DAKO 22c3 antibody. Results: The most frequently mutated genes in 181 Chinese HCC were TP53 (59.7%), TERT (34.3%), CTNNB1 (21.5%), AXIN1 (12.2%), RB1 (11.0%), STK24 ...

e15582Background: The presence of ascites has been considered a relative contraindication for performing percutaneous thermal ablation of hepatic tumors due to concerns for hemorrhage. The purpose ...

11064 Background: [Y-90]-SIRT has an established role in managing patients with primary and secondary hepatic neoplasia. Recently, imaging of the regional distribution of the implanted [Y-90]-micro...

e15177 Background: About 80%-90% of primary hepatic malignancy is hepatocellular carcinoma (HCC). Patients with HCC can be identified as negative for both hepatitis B surface antigen and anti-hepat...

295 Background: Previously treated Hepatic Colorectal Metastases (CRC) and advanced hepato cellular cancer (HCC) are tumor challenges frequently unresponsive to systemic chemo therapy (CT). We reviewed survival outcome in chemo resistant / high risk patients following hepatic artery infusion (HAI) in 21 CRC pts, 10 HCC pts, and 6 miscellaneous metastatic cancers. Methods: Patient groups: 21 CRC pts (16M, 5 F), mean age 63: 16 had metachronous (DFI-17 mos), and 5 Synchronous CA; liver extent: 76% multiple (>5) mets or extensive bilateral; CEA (ng/m), >100, 8 pts > 50 (3 pts) ;< 5 (3 pts),UNK(7 pts). Previous CT:FU/LV (11pts), Oxaliplatin (OX) or Irinotecan (IR) (10 pts). Liver surgery: Partial Resection/RFA – 9 pts. HCC – (9 PTS), cholangioCA(1pt); M/F 5/5; av.age 63yr.. Previous RX Hepatic lobectomy 4 pts, RFA/TACE – 3 patients. Miscellaneous GP (therapy): Hepatic lobectomy + HAI were in metastatic lung (1), Breast (1), advanced gall bladder Ca (GBCA) (T 3-4) (2 pts); HAI alone was done in Br. CA (1) carcinoid (1) Treatment Protocols: CRC: HAI-FUDR 12/15mg/kg/d, dexamethasone 2mg.kg/d, leukovorin (20mg/M2/d) X14 d plus bolus (d1), oxaliplatin OX 130 mg/M2 cisplatin CIS, 100 mg/M2; Systemic RX: d20-30. OX I.V. 130mg/M2, capecitabine 750-1,000 mg/M2/d x 10 days (also used in Miscel. Grp.) HCC Protocol: HAI-14 d as in CRC Protocol. Bolus infusion d1-doxorubicin 75mg/M2or OX or CIS as in CRC schema. Results: CRC:OS-CRC post start HAI = med/16 mos., 2yr/5yr = 27%/6%. HCC OS = 9 mos.( Median); 3->41mos in 9 evaluable pts.; 1 HCC pt with recurrence 2 yr. post hepatectomy survived over 3.5 yrs. with HAI + RFA/TACE – (OS-67mo).Miscellaneous group included lung (11 mos) Br CA (23, 9 mos) adv. Carcinoid (3 mos), GBCA (2 pts > 60 mos), Major Complications; Pump malfunction (4 pts), misperfusion (2) pts, infected pocket (2) pt, duodenal fistula (1) pt. Conclusions: Hepatic artery infusion alternating with systemic chemo therapy has apparent survival benefit in selected patients with persistent or progressive chemo resistant malignancy from metastatic CRC, HCC, or selected miscellaneous cancers (breast, lung, liver, gall bladder cancer) and warrants further study.

10611 Background: Cholangiocarcinoma (CCA) is an aggressive tumor arising from biliary tract epithelium.CCA is the second most common primary hepatic malignancy, with a progressive increasing incidence in western countries. Polycomb group protein Enhancer of Zeste homolog 2 (EZH2) is overexpressed in several human carcinomas, including CCA, where EZH2 overexpression is associated with tumor progression. The aim of this study is to evaluate the correlation between candidate EZH2 Single Nucleotide Polymorphisms (SNPs) with clinical outcome in CCA patients. Methods: Genomic DNA was extracted from blood samples of 75 patients [44 male and 31 female, with average age of 62.3 (range, 26-80 years)] affected by hystologically confirmed advanced CCA, treated with the epirubicin-cisplatin-xeloda (ECX) regimen. We performed an in silico characterization to select EZH2 SNPs (rs2302427 C/G, rs6464926 C/T, rs17171119 T/G and rs887569 C/T) from 26 EZH2 SNPs described previously. Genotyping was performed through Taqman PCR. Prognostic value of selected EZH2 SNPs was assesses by correlation with time to progression (TTP) and overall survival (OS). OS and TTP curves were obtained through Kaplan-Meier method, and comparison with survival distribution was evaluated with logrank test. Results: Through specific software (PROMO 3.0, MicroSNiper and Gene Card) we performed an in silico analysis based on functional characterization criteria (transcription factor binding-TFB, miRNA binding and missense mutations). We selected 4 EZH2 SNP alleles showing specific relevance in CCA because of their differential TFB affinity (PPARα/RXRα, E2F-1, Pax-5 and p53). The rs887569 C/T SNP was significantly associated with clinical outcome. The TT genotype predicted a significantly longer OS in CCA patients (TT vs CT-CC p=0.026). Moreover, the TT genotype showed a trend-like association with reduced risk of death (HR=0.59, 95%CI=0.33-1.05, p=0.075), at multivariate analysis. Conclusions: These results suggest the role of rs887569 EZH2 SNP as a possible predictive marker of OS in advanced CCA patients treated with ECX regimen, and offer a potential new tool for treatment optimization.

e14151 Background: Previously treated hepatic colorectal metastases (CRC) and advanced hepato cellular cancer (HCC) are tumor challenges frequently unresponsive to systemic chemo therapy (CT). We reviewed survival outcome in chemo-resistant/high-risk patients following hepatic artery infusion (HAI) in 21 CRC pts, 10 HCC pts, and 6 miscellaneous metastatic cancers. Methods: Patient groups: 21 CRC pts (16M, 5 F), mean age 63, 16 had metachronous (DFI-17 mos), and 5 synchronous CA; liver extent: 76% multiple (>5) mets or extensive bilateral, CEA (ng/m), >100, 8 pts > 50 (3 pts) < 5 (3 pts) and , NA – 7 pts. Previous CT: FU/LV (11pts), oxaliplatin (OX) or irinotecan (IR) (10 pts). Liver surgery: partial resection/RFA – 9 pts. HCC: (9 PTS), cholangio CA(1), M/F 5/5; av. age 63. Previous RX hepatic lobectomy 4 pts, RFA/TACE – 3 patients. Miscellaneous GP (therapy): Hepatic lobectomy + HAI were done in metastatic lung (1), Breast (1), advanced gall bladder cancer (GBCA; T 3-4; 2 pts); HAI alone was done in Br. C...

10036 Background: Cholangiocarcinomas (CCC) are the second most common primary hepatic malignancy with a still poor prognosis and arise from biliary epithelia or cholangiocytes. Until now, less is known about the molecular pathways leeding to CCC. Methods: Oligonucleotide arrays were used to analyze gene expression profiles of 8 intrahepatic CCCs. After isolation of tRNA and transcription into cDNA, biotin-labelled cRNA probes were hybridized to GeneArrays (Affymetrix U 133A) containing probes of more than 22.000 genes/ESTs. For two-dimensional cluster analysis we used special software programs (Genexplore, GeneSpring). Dysregulated genes were determined by presence in more than 70% and a 2-fold change in relation to the corresponding non-malignant liver tissue. Lightcycler analysis were performed to validate the expression datas of dysregulated genes. Results: A total of 694 dysregulated genes (330 up-/364 down-regulated, compared with corresponding non-malignant tissue) were detected. As the gene with the highest and most consistent upregulation we were able to identify osteopontin (OPN) with an average 5-fold overexpression in all CCC tissues. OPN is an acidic phosphoprotein that is secreted by osteoblasts, macrophages and many other cell types and binds to a variety of cell surface receptors (integrins/CD44). OPN is multifunctional, with activities in cell migration, regulation of bone metabolism, immune cell function and control of tumor cell phenotype. Elevated OPN levels were seen in different tumors but until now no data exist about the expression in CCCs. As one possible interaction in human carcinogenesis, OPN has recently been shown to be a novel substrate for some MMPs, which play an importand role in tumor invasion and metastasis. Conclusions: This is the first report about an overexpression of OPN in CCC and our data indicate an important role in cholangiocarcinogenesis. Further studies are needed to illucidate the moleculargenetic mechanisms of OPN interactions in CCC. No significant financial relationships to disclose.