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  • 1
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    Molecular profiling by circulating tumor DNA (ctDNA) and benefit from anti-PD-1 in HCC.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e15679-e15679
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e15679-e15679
    Abstract: e15679 Background: Molecular profiling has defined actionable mutations in HCC, and has the potential to be used for selection of targeted therapies, as well as for the characterization of predictive biomarkers from approved treatments. Noninvasive strategies are critical to HCC given the challenge of obtaining liver biopsies. We investigated whether profiling by ctDNA could provide predictive and/or prognostic information for HCC patients (pt) treated with immune checkpoint inhibitors. Methods: We analyzed blood samples from 22 HCC pt who underwent treatment with anti-PD-1 using comprehensive genomic testing of ctDNA with a commercially-available platform (Guardant Health, CA). Demographic and treatment data were retrospectively collected with the goal of correlating treatment outcomes and drug response (by imaging and/or AFP) with molecular abnormalities. Results: 17/22 (77.3%) were men; median age was 66 years. 21 patients received nivolumab and 1 received pembrolizumab. 9 were HCV positive and 5 were HBV positive. 15/22 patients had 〉 1 alteration identified. The median number of alterations/pt was 3 (range, 1-8). TP53 was the common altered gene (n = 11) followed by CTNBB1 (n = 8) , TERT (n = 5) KRAS (n = 3) , GNAS (n = 2). Mutations were also seen (n = 1) in KIT, PIK3CA, PTEN, EGFR, NTRK, FGFR2 among others. 6 pt (27.3%) had AFP response and 8 (36.4%) achieved disease control 〉 12 weeks. Mutations involving KIT, PIK3CA and PTEN were associated with shorter progression-free (PFS) (p 〈 .001 for all) and overall survival (OS) (p = .028 for all), whereas GNAS mutation was associated with shorter PFS (p = 0.019) but not OS. No differences in OS or PFS was observed for other alterations, including the presence of CTNNB1 mutation. There were no correlations between specific alterations and objective tumor response (either by imaging or AFP). 32% of pt were progression-free at 6 months. Median OS was not reached, and 62% were alive after 1 year. Conclusions: Identifying non-invasive predictive biomarkers of benefit to immunotherapy is a priority in HCC. Our data suggest that specific ctDNA alterations can provide predictive information for survival (OS and PFS) on immune checkpoint inhibitors. Further larger studies are warranted for confirmation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e15679
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Risk factors associated with neuroendocrine tumors: A U.S.‐based case–control study
    Wiley ; 2008
    In:  International Journal of Cancer Vol. 123, No. 4 ( 2008-08-15), p. 867-873
    Details
    In: International Journal of Cancer, Wiley, Vol. 123, No. 4 ( 2008-08-15), p. 867-873
    Abstract: Carcinoids are rare neuroendocrine tumors (NETs); however, their incidence has significantly increased in the United States over the past 30 years. Little is known about the epidemiology of these cancers and their associated risk factors. We evaluated the independent effects of multiple risk factors associated with NETs arising at 5 disease sites (small intestine, stomach, lung, pancreas and rectum). We conducted a retrospective, hospital‐based, case–control study involving 740 patients with histologically confirmed NETs and 924 healthy controls. Information on different risk factors was collected, and unconditional logistic regression analysis was used to determine adjusted odds ratios (AORs) and 95% confidence interval (CI) by the maximum‐likelihood method. Smoking and alcohol consumption were not associated with NETs development in either men or women. However, a family history of cancer was a significant risk factor for all NETs. A long‐term history of diabetes mellitus was a significant risk factor for gastric NETs (AOR = 5.6; 95% CI, 2.1–14.5), particularly in women (AOR = 8.4; 95% CI, 1.9–38.1). Diabetes modified the risk among women with a positive family history of cancer for the development of gastric NETs (AOR = 52.2; 95% CI, 5.5–491.5). Our results suggest that the risk of NETs may mostly explained by genetic factors. The increased risk of gastric NETs in women with both diabetes and a positive family history of cancer suggest that women may have a greater genetic susceptibility to NETs than men. © 2008 Wiley‐Liss, Inc.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    URL: Article
    DOI: 10.1002/ijc.v123:4
    DOI: 10.1002/ijc.23529
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2008
    detail.hit.zdb_id: 218257-9
    detail.hit.zdb_id: 1474822-8
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  • 3
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    Association of elevated alpha-1 antitrypsin with advanced clinicopathologic features of hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 4_suppl ( 2017-02-01), p. 289-289
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. 289-289
    Abstract: 289 Background: Alpha-1 Antitrypsin (A1AT) is a circulating liver derived protease inhibitor. There is an evolving evidence that elevated level of A1AT stimulate tumor cell proliferation, and invasion in different cancers. Despite A1AT well-known involvement in hepatic fibrosis, its role in hepatocellular carcinoma (HCC) pathogenesis is not well characterized. The current study aimed to investigate the association between A1AT and clinicopathologic features and prognosis of patients with HCC. Methods: Between 2001 and 2014, total of 766 HCC patients from MD Anderson Cancer Center were enrolled. Under IRB approval, baseline patients’ clinical characteristics were retrieved from medical records. The normal level of plasma A1AT was defined based on the Mayo clinic reference value (1 – 1.9 mg/ml). Survival analysis included Kaplan Meier statistic and Cox regression analysis. Multivariate Hazard Ratio (HR) and 95% Confidence interval (CI) were estimated to determine the independent effect of A1AT on HCC prognosis. Results: The mean and standard deviation of plasma A1AT level was 2.7 ± 0.98 mg/mL. All patients were categorized into 2 groups: group 1 (N = 156) with normal serum level ( ≤ 1.9) and group 2 (N = 610) with higher values ( 〉 1.9). Median survival (months), 95% CI were 24.4 (18.02 – 30.7) and 11.6 (9.6 – 13.6) in group 1 and 2 respectively, (P 〈 .0001). Patients in group 2 experienced poor clinical characteristics than group 1. The estimated multivariate HR (95% CI) for A1AT is 1.4 (1.1 – 1.7) after adjustment for age, sex, race, cirrhosis, AFP, TNM staging, and treatment exposure. Conclusions: High plasma level of A1AT is associated with higher α-feto protein, advanced TNM and Barcelona clinic liver cancer (BCLC) staging and poor survival of HCC patients. Recent preliminary studies suggested that changes in glycosylaion of production of A1AT by HCC cells correlates with the microenvironment inflammatory and proteolytic activities, which are probably linked to advanced clinicopathologic features and poorer survival. Future excremental studies are warranted to understand the mechanistic pathways of potential A1AT involvement in HCC initiation and progression.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.4_suppl.289
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Global Protein Aberration Score (GloPAS): A comprehensive risk score to predict hepatocellular carcinoma biology and estimate patients’ survival.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 4_suppl ( 2018-02-01), p. 287-287
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 4_suppl ( 2018-02-01), p. 287-287
    Abstract: 287 Background: Existing hepatocellular carcinoma (HCC) staging systems use a small number of empirically selected clinical/biological variables. We hypothesize that GloPAS (global protein aberration score) will capture a more global measurement of disease biology that can partition HCC into three subsets: (1) essentially normal profiles, (2) extremely aberrant profiles, and (3) slightly aberrant profiles. Methods: We collected plasma samples and clinical data prospectively from 767 HCC patients (pts) and 200 healthy controls, and quantified 317 pts using Myriad RBM CLIA-certified panel, Austin, TX. We applied a deconvolution algorithm, originally developed for determining percent normal contamination for tumor, to quantify the degree of global protein aberration for each pt relative to normal controls. We defined three distinct groups of pts with low ( 〈 0.3), medium (0.3-0.8), and high ( 〉 0.8) GloPAS and assessed GloPAS association with overall survival (OS) and other prognostic factors using log-rank tests and compared the prognostic abilities of GloPAS vs. existing systems using concordance index(C-index). We developed a single-sample GloPAS (ssGloPAS) using an algorithm that can be applied to single sample setting. Results: Although determined without using information about OS or any pt-level clinical or demographic factors (i.e. unsupervised), GloPAS showed remarkable prognostic separability (low/med/high GloPAS, with median OS 38.2mo/18.3mo/7.1mo, p 〈 0.0001). GloPAS prognostic ability was far above any existing HCC staging system (C-index = 0.75 vs. 0.58-0.70 p 〈 0.0001), demonstrating even more prognostic information than key factors as metastatic status and vascular invasion. The ssGloPAS was able to recapitulate the global signal captured by the GloPAS score with a much smaller subset of 14 proteins. Conclusions: GloPAS significantly improved prediction of OS and prognostic stratification of HCC. After further validation, ssGloPAS could be used to guide therapy decisions and stratify HCC pts in clinical trials. The novel concept underlying GloPAS methodology can be applied to other cancers to build disease-specific prognostic scores.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.4_suppl.287
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Evaluating clinical and prognostic implications of Glypican 3 in hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. e15619-e15619
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e15619-e15619
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.e15619
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Utility of Neuropilin-1 in predicting survival in patients with hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. e16142-e16142
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e16142-e16142
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.e16142
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Molecular Profiling of Hepatocellular Carcinoma Using Circulating Cell-Free DNA
    American Association for Cancer Research (AACR) ; 2019
    In:  Clinical Cancer Research Vol. 25, No. 20 ( 2019-10-15), p. 6107-6118
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 20 ( 2019-10-15), p. 6107-6118
    Abstract: Molecular profiling has been used to select patients for targeted therapy and determine prognosis. Noninvasive strategies are critical to hepatocellular carcinoma (HCC) given the challenge of obtaining liver tissue biopsies. Experimental Design: We analyzed blood samples from 206 patients with HCC using comprehensive genomic testing (Guardant Health) of circulating tumor DNA (ctDNA). Results: A total of 153/206 (74.3%) were men; median age, 62 years (range, 18–91 years). A total of 181/206 patients had ≥1 alteration. The total number of alterations was 680 (nonunique); median number of alterations/patient was three (range, 1–13); median mutant allele frequency (% cfDNA), 0.49% (range, 0.06%–55.03%). TP53 was the common altered gene [ & gt;120 alterations (non-unique)] followed by EGFR, MET, ARID1A, MYC, NF1, BRAF, and ERBB2 [20–38 alterations (nonunique)/gene] . Of the patients with alterations, 56.9% (103/181) had ≥1 actionable alterations, most commonly in MYC, EGFR, ERBB2, BRAF, CCNE1, MET, PIK3CA, ARID1A, CDK6, and KRAS. In these genes, amplifications occurred more frequently than mutations. Hepatitis B (HBV)-positive patients were more likely to have ERBB2 alterations, 35.7% (5/14) versus 8.8% HBV-negative (P = 0.04). Conclusions: This study represents the first large-scale analysis of blood-derived ctDNA in HCC in United States. The genomic distinction based on HCC risk factors and the high percentage of potentially actionable genomic alterations suggests potential clinical utility for this technology.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-18-3341
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 8
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    Association between Expression of Transcription Factor Sp1 and Increased Vascular Endothelial Growth Factor Expression, Advanced Stage, and Poor Survival in Patients with Resected Gastric Cancer
    American Association for Cancer Research (AACR) ; 2004
    In:  Clinical Cancer Research Vol. 10, No. 12 ( 2004-06-15), p. 4109-4117
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 10, No. 12 ( 2004-06-15), p. 4109-4117
    Abstract: The biological and clinical behaviors of cancer are affected by multiple molecular pathways that are under the control of transcription factors. Improved understanding of how transcription factors affect cancer biology may lead to improved ability to predict clinical outcome and discovery of novel therapeutic strategies. We evaluated the relationship between Sp1 and vascular endothelial growth factor (VEGF) expression, as well as their effect on survival in 86 cases of resected human gastric cancer. The degree of VEGF expression correlated highly with Sp1 expression (P & lt; 0.01). Patients with high Sp1 expression were 98 times more likely to have high VEGF expression compared with those with negative Sp1 expression. Clinically, negative or weak Sp1 expression was associated with early stage (IA) in gastric cancer. Strong Sp1 expression was more frequently observed among patients with stage IB–IV disease (P = 0.035). Similarly, whereas strong Sp1 expression was uncommonly observed among patients with N0 or N1 disease (19 and 16%), N2/N3 gastric cancer was associated with strong Sp1 expression (48%; P = 0.034). Strong Sp1 expression was also associated with inferior survival. The median survival duration in patients who had a tumor with a negative, weak, and strong Sp1 expression was 44, 38, and 8 months (P = 0.0075), respectively, whereas patients with strong VEGF expression had a shorter survival duration; the difference was not statistically significant. When Sp1 and VEGF expression, stage, completeness of resection, histology, and patient age were entered in a Cox proportional hazards model, strong Sp1 expression (P = 0.021) and an advanced disease stage (P & lt; 0.001) were independently prognostic of poor survival. Given the importance of Sp1 in the expression of VEGF, our data suggest that dysregulated Sp1 expression and activation play important roles in VEGF overexpression and, thus, gastric cancer development and progression.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-03-0628
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2004
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 9
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    IGF-1 Child-Turcotte-Pugh score as a predictor of overall survival to therapy in CTP-A, BCLC stage C patients with advanced hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 4_suppl ( 2020-02-01), p. 488-488
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. 488-488
    Abstract: 488 Background: Child-Turcotte-Pugh (CTP) A is the standard population for active HCC therapy. The IGF-CTP score, comprises levels of type 1 insulin-like growth factor (IGF-1), bilirubin, INR, and albumin, significantly improved the prediction of overall survival (OS) in recently published studies. Our current study aimed to investigate the accuracy of the IGF-CTP score in predicting OS in HCC Child-Pugh A patients (pts) treated with local and/or systemic therapies (tx). The overall hypothesis is that the IGF-CTP score can further distinguish CP-A pts in terms of overall survival, PFS. Methods: Between 2014 and 2018, a total of 274 pts with new advanced HCC BCLC stage who had available baseline plasma IGF-1 level were retrospectively enrolled. Clinicopathologic features and treatment history were collected. We calculated IGF-CTP scores, used Kaplan-Meier method and log rank test to estimate and compare time to event outcomes between subgroups of patients. Results: 198 pts were CTP Class A, 209 patient underwent systemic tx, 65 underwent local tx [see table] ; 161 were re-classified as IGF-CTP-A with a median OS of 16.09 months (95% CI = 13.06 to 23.29 months) (p 〈 0.0001), whereas 37 patients were reclassified as intermediate risk (IGF-CTP-B) and had significantly shorter OS of 10.66 months (95% CI = 5.49 to 26.51) (p 〈 0.0001). Conclusions: The results of this study support our biologically-driven hypothesis that IGF-CTP score is predictive of overall survival to therapy in advanced HCC treated with local and/or systemic therapy. Among HCC pts with CTP-A class, some are reclassified as IGF-CP-B/C and were found to have significantly poorer prognosis in terms of shorter OS. Future validation of the predictive ability of our IGF-1 score may lead to adopting it as a stratification tool in clinical trials as well as to predict HCC outcome and guide therapy decision in routine practice. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.4_suppl.488
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 10
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    IGF-Child-Pugh score as a predictor of treatment outcome in advanced hepatocellular carcinoma patients treated with sorafenib.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 4076-4076
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 4076-4076
    Abstract: 4076 Background: Our recent published studies concluded that Lower levels of Insulin like growth factors-I (IGF-I) is correlated with shorter overall survival (OS) in HCC, and IGF-CP scores assigned based on serum bilirubin, serum albumin level, prothrombin time, and plasma IGF-1 provides better prognostic stratification. Sorafenib is the first frontline drug approved for the treatment of CP class A patients with advanced HCC. CP class A is the standard criterion for active therapy and trials entry in HCC. In this study we aimed at evaluating the predictive ability of IGF-CP to sub-stratify old CP classes and better predict sorafenib outcomes. Methods: Total of101 patients were prospectively enrolled from MD Anderson Cancer Center (MDACC). Blood sample were collected and tested for IGF-I and IGF-CP was calculated into class A, B and C. Median OS and progression free survival (PFS) were analyzed, and log rank test was used to compare PFS and OS between subgroups of IGF-CTP score of patients. Results: Among CP class, patients who were reclassified as IGF-CP (B) (Old A/new B) had significantly shorter OS in months (m) was 7.6m (95% CI= 5.23-26.51m ) and PFS of 2.99m (95% CI=2.53-5.26m) with (P 〈 0.001) in both, as compared to patients’ who classified as class A by both scoring systems (AA), who had OS of 15.43m (95% CI=12.3-31.18m) and PFS of 4.97m (95% CI=3.26-7.2m), (P 〈 0.001) in both. Conclusions: IGF-CTP score sub-stratified CP A class, and provided better prognostic stratification and accuracy than CP score in predicting sorafenib survival outcomes in HCC. This approach may lead to a paradigm shift in predicting efficacy and toxicity of systemic HCC therapies and in stratifying patients for active therapy and selection in HCC clinical trials.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.4076
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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