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  • American Society of Clinical Oncology (ASCO)  (65)
  • 1
    Online Resource
    Online Resource
    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
    Online Resource
    Online Resource
    In Reply
    American Society of Clinical Oncology (ASCO) ; 2009
    In:  Journal of Clinical Oncology Vol. 27, No. 4 ( 2009-02-01), p. 648-649
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 4 ( 2009-02-01), p. 648-649
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2008.20.8587
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2009
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Prognostic effect of angiotensin-converting-enzyme inhibitors in HCC patients treated with sorafenib.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 4_suppl ( 2013-02-01), p. 328-328
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 328-328
    Abstract: 328 Background: Experimental studies indicated that angiotensin-converting-enzyme inhibitors (ACEs) or angiotensin receptor blockers (ARBs) has a role in reducing malignant changes of the liver and may significantly improve the mortality in patients with other cancers. However it is not known whether ACE and ARB inhibitors may have prognostic impact on HCC survival outcome. We aimed at evaluating the role of ACE inhibitors and ARB blockers on the prognosis of HCC patients who have been treated by Nexavar (sorafenib). Methods: Using resources of our case-control study at MD Anderson, total of 187 (males, 76.5%; females, 23.5%) pathologically confirmed HCC had been treated by sorafenib. The overall mean age (±SD) was 62.5years ± 9.6. The majority of patients were Caucasians (62.6%) who were diagnosed at TNM stage III and IV (79.2%). Total of 89 (47.6%) patients had no evidence of hepatitis C virus (HCV) or hepatitis B virus (HBV). Median survival was calculated using Kaplan Meier product-limit method and survival rates were compared using the log rank test. Cox proportional hazards model was used to estimate the univariate and multivariate Hazard Risk Ratios (HRR) and 95% Confidence Interval (CI). Results: The overall median survival of HCC patients was 19.9 months (95% CI, 16.1-23.6). Intake of ACEs or ARBs inhibitors was reported in 94 patients (50.3%). We observed significant difference in overall median survival (months) between patients who had ACE/ARB inhibitors versus those who did not, median survival (95% CI) were 21.5 (17.1-25.8) and 14.6 (12.4-16.7), respectively, p=0.04. After adjustment for HCC prognostic factors and demographic factors, we observed 30% reduction in HCC mortality among those who received ACEs/ARBs inhibitors, the estimated HR was 0.7 (95% CI, 0.4-1), p=0.05. Conclusions: Our results may indicate that HCC patients under anti-angiogenic therapy (sorafenib) and have been under anti-hypertensive therapy like ACE/ARB may assist in depleting the collagen and may improve host matrix and tumor microenvironment to enhance drug delivery. Future analysis in a larger sample is warranted
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.4_suppl.328
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Retrospective evaluation of Middle Eastern patients (pts) with type II diabetes mellitus (DM) and colorectal cancer (CRC): Validation of metformin effect on overall survival (OS).
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 3_suppl ( 2014-01-20), p. 478-478
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 478-478
    Abstract: 478 Background: Epidemiologic data suggest that anti-DM medications may impact OS in CRC pts who have type 2 DM. Although type 2 DM and CRC are major health problems in the Middle East, little data exists on pts with both conditions from this region. Methods: Medical records from 1,835 CRC pts seen at King Hussein Cancer Center between 1/1/2004 and 12/31/2012 were evaluated for prevalence of type 2 DM; those with both conditions were evaluated for anti-diabetic therapy and treatment outcomes (OS and progression-free survival [PFS]). Results: 285 type 2 DM CRC patients were identified (prevalence 15.5%); 19 pts were censored as their anti-DM medications were not known. Median age of 266 pts analyzed was 62.1 years (± 8.9), M: F ratio 1.6:1, non-metformin (n = 109, 41%), metformin only (n = 43, 16%), metformin + insulin (n = 11, 4%), metformin + another oral agent (n = 104, 39%). Metformin use increased over time (19% in 2004 to 71% in 2012). Adjusting for age, gender, body mass index, and stage, type 2 DM pts treated with metformin had a 40% improvement in OS (hazard ratio 0.624, 95% confidence interval 0.44-0.97). Conclusions: These data support previous findings that metformin use in CRC pts with type 2 DM is associated with a superior PFS and OS. Contrary to previously published data there was a statis tically significant OS benefit in stage IV pts, while the trend toward OS benefit in stage I-III pts was not statistically significant (see Table). This study was supported by the King Hussein Cancer Center/MD Anderson Sister Institution Network Fund. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.3_suppl.478
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    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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  • 6
    Online Resource
    Online Resource
    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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  • 7
    Online Resource
    Online Resource
    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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  • 8
    Online Resource
    Online Resource
    The association of family history of primary liver cancer with cholangiocarcinoma: USA case-control study.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 4_suppl ( 2022-02-01), p. 403-403
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 4_suppl ( 2022-02-01), p. 403-403
    Abstract: 403 Background: The incidence of cholangiocarcinoma (CCA), particularly intrahepatic cholangiocarcinoma (IHC) has exponentially increased in the United States since 2007. While cholangiocarcinomas share some common characteristics, increasing evidence suggests that different subtypes of CCA have divergent tumor microenvironments, pathobiology and distinct epidemiologic features and risk factors. The correlation between family history of cancer and cholangiocarcinoma remains to be determined. This study aims to address the connection between positive family history of primary liver cancer and development of cholangiocarcinoma, including intrahepatic cholangiocarcinoma (IHC) and extrahepatic cholangiocarcinoma (EHC), in USA. Methods: At The University of Texas M. D. Anderson Cancer Center, we studied 429 patients with pathologically confirmed cholangiocarcinoma (308 IHC, 121 EHC) and 1,075 healthy controls. All subjects were interviewed for their family history of cancer, including the number of relatives with cancer, the type of cancer, the subjects’ relationship with the relative, and the age at which the relative was diagnosed. Results: Independent of hepatitis B virus (HBV) and hepatitis C virus (HCV), a family history of cancer was significantly associated with IHC and EHC, the estimated ORs and 95% CI were 1.6 (1.2-2.2) and 1.6 (1.1-2.5) for IHC and EHC respectively. Primary liver cancer in first-degree relatives was significantly associated with EHC development (OR 9.4 [95% CI, 2.9-30.7]). No significant association was observed for IHC, (OR 1.7 [95% CI, 0.5-5.9] ). The prevalence of family history of primary liver cancer in first-degree members was recorded in 6.6% of EHC patients and in 1.6% of IHC patients. Multiple relatives with primary liver cancer were observed in 5 patients (4.1%) among EHC subjects but less common in IHC (1%). All estimated ORs were adjusted for age, sex, race, smoking, alcohol, Hepatitis virus infection, diabetes, and obesity. Conclusions: First-degree family history of primary liver cancer is associated with EHC development in USA independent of known risk factors for CCA. Further research exploring the genetic–environment interactions associated with EHC is warranted. Focused efforts in identifying the population at increased risk for developing EHC are necessary and may lead to new screening and surveillance strategies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.4_suppl.403
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    Early obesity and risk of cholangiocarcinoma in the United States.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 4_suppl ( 2017-02-01), p. 239-239
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. 239-239
    Abstract: 239 Background: In the United States, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing over the last few decades. Despite the public health problem of obesity and the increasing incidence of ICC, the relationship between early adulthood obesity and ICC has never been examined in the American population. Methods: At the University of Texas MD Anderson Cancer Center we conducted a case-control study aimed at examining relationship between ICC and history of obesity after controlling for the potential confounding of several risk factors. Cases were patients with pathologically confirmed diagnosis of ICC. Controls were healthy subjects recruited from spouses of patients at MD Anderson who had cancers other than liver or gastrointestinal. Each case was frequency matched to 4 controls by age (± 5 years), sex, and race. Case patients and controls were interviewed for risk factors of liver cancer. A self-reported weight and body size pictogram at ages 20, 30, 40, 50, 60 was obtained from each participant. In 2016 we recruited 63 newly diagnosed patients with ICC who were compared to 252 healthy controls. Obesity was defined as body mass index (BMI) ≥ 30.0. Results: There was a significant 3 fold increase in ICC risk for obese individuals compared to those with normal weight. The estimated odds ratio (OR), 95%; confidence interval (CI) was 3.3 (1.3-9.1); P = .02. Obesity at the mid-20s, mid-30s, and mid- 40s was significantly associated with ICC risk; the estimated OR (95% CI) was 7.3 (2.8-19.7), 7 (2.4-20.9), and 4.8 (2-11.4), respectively. In addition, viral hepatitis, heavy alcohol use ( 〉 40 ml ethanol/day), and family history of cancer were significantly associated with ICC. Underlying radiological, pathological, or clinical evidence of steatosis, fibrosis, and cirrhosis was significantly observed in 25% ICC patients with early obesity. Conclusions: We concluded that early adulthood obesity is a significant risk factor for ICC in USA where underlying fatty liver diseases can be a significant factor for ICC progression. Integration of obesity with other ICC risk factors into a risk model may lead to identify high-risk individuals. Future collaboration with other US institutions is highly warranted to highlight the mechanism of obesity-induced ICC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.4_suppl.239
    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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  • 10
    Online Resource
    Online Resource
    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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