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  • 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
    Prognostic significance of periostin 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. e16143-e16143
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e16143-e16143
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.e16143
    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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  • 3
    Online Resource
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    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.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e15662-e15662
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e15662-e15662
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e15662
    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
    Online Resource
    Online Resource
    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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  • 5
    Online Resource
    Online Resource
    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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  • 6
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    Online Resource
    Quantitative CT imaging features for hepatocellular carcinoma (HCC) with b-catenin (CTNNB1) gene mutation.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 4_suppl ( 2017-02-01), p. 253-253
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. 253-253
    Abstract: 253 Background: To determine whether CT imaging features can provide quantitative biomarkers to differentiate HCC with pathologic B-catenin gene mutation and those without mutation. Methods: Quantitative imaging features were extracted from a database of manually labeled liver with enhancing and non-enhancing tumor tissue,which were established using multiphasic CT images from 17 patients. CT studies were done before each patient underwent surgical removal of the HCC, which were subjected to pathologic analysis to evaluate B-catenin mutation.The mean period between the CT studies and the pathologic analyses was 18 days. According to the pathology results, the patients were divided into two groups: HCC with CTNNB1 mutation and HCC without. Image feature extraction included image gradients, co-occurrence matrix, and pixel neighborhood statistics of the first, second, and third moments. Pairwise analyses of the imaging features were performed on the mutated and non-mutated HCC images and the background liver tissue of both groups. Independent samples t-test and Mann Whitney U test were performed to quantitatively compare between the means of the imaging features extracted from the tumor tissues of both groups and those extracted from the background liver tissue of both groups. Results: Imaging feature analysis of the pairwise difference between the mutated and non-mutated HCC scans for multiple pixel-neighborhood image features are statistically significant.The top stratifying image features include the skewness (p = 0.02), energy (p = .03), and entropy (p = .03) during the venous and arterial phase. Conclusions: This preliminary study demonstrates the feasibility of quantitative imaging feature extraction from CE-CT imaging to differentiate between HCC with proven B-catenin gene mutation and those without mutation. Non-invasive methods of identifying HCC with B-catenin mutations may be clinically beneficial since B-catenin is an important potential target in novel cancer therapies, and identifying B-catenin mutations may also help provide information regarding prognosis.Verifying the quantitative features in larger patient populations is needed to confirm the results of this study.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.4_suppl.253
    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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  • 7
    Online Resource
    Online Resource
    The differential clinicopathologic features and survival outcome between hepatitis C–related HCC patients in the United States versus Egypt.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. e15128-e15128
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e15128-e15128
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.e15128
    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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  • 8
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    Online Resource
    Clinical and Prognostic Biomarker Value of Blood Circulating Inflammatory Cytokines in Hepatocellular Carcinoma
    S. Karger AG ; 2023
    In:  Oncology
    Details
    In: Oncology, S. Karger AG
    Abstract: Circulating inflammatory cytokines play critical roles in tumor-associated inflammation and immune responses. Recent data has suggested that several interleukins (ILs) mediate carcinogenesis in hepatocellular carcinoma (HCC). However, the predictive and prognostic value of circulating ILs has yet to be validated. Our study aimed to evaluate the association of the serum ILs with overall survival (OS) and clinicopathologic features in a large cohort of HCC patients. We prospectively collected data, and serum samples from 767 HCC patients treated at The University of Texas MD Anderson Cancer Center between 2001 and 2014, with a median follow-up of 67.4 months (95% CI: 52.5, 83.3). Biomarker association with overall survival (OS) was evaluated by the Log-rank method. The median OS in this cohort was 14.2 months (95% confidence interval [CI]: 12, 16.1 months). Clinicopathologic features were more advanced, and OS was significantly inferior in patients with high circulating levels of IL1-R1, IL-6, IL-8, IL-10, IL-15, IL-16, and IL-18. In conclusion, our study shows that several serum IL levels are valid prognostic biomarker candidates and potential targets for therapy in HCC.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000531870
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 9
    Online Resource
    Online Resource
    IGF-Child-Turcotte-Pugh score as a predictor of treatment outcome in Child-Pugh A, advanced hepatocellular carcinoma patients undergoing sorafenib therapy.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e16660-e16660
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16660-e16660
    Abstract: e16660 Background: Sorafenib is the first systemic therapy approved for advanced HCC treatment; with no accurate tool available to help predict survival and treatment outcome and to guide therapy decisions. Our novel blood-based insulin-like growth factor-1 (IGF)-Child-Turcotte-Pugh (CTP) score comprises levels of IGF-1, bilirubin, INR, and albumin. IGF-CP score significantly improved the prediction of HCC survival in our recently published studies. The current prospective study aimed to compare the overall survival (OS) and progression free survival (PFS) of 116 patients with CTP-A HCC treated with sorafenib whose score is reclassified as IGF-A (AA) to that of patients whose score is reclassified as IGF-B/C (AB/AC). Methods: After the approval of the institutional review boards and signing written informed consent, a total of 116 patients with HCC were prospectively enrolled and started on sorafenib and followed until progression or death. 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: 116 patients were CTP class A, 87 of the patients with CTP class A were classified as IGF-CTP-A and had median OS of 13.16 ms (95% CI = 12.04 to 22.6 ms), and a median PFS of 5.82 months (ms) (95% CI = 4.34 to 9.14 ms), whereas 29 patients were reclassified as intermediate risk (IGF-CTP-B) and had had a higher risk of death with a shorter OS of 7.6 months (95% CI = 5.23 to 24.47 months) and shorter PFS of 3.49 months (95% CI = 2.53 to 5.26 months). There was higher overall rate of adverse events in the CTP-A patients reclassified as IGF-CTP B than IGF-CTP A especially in grade III-IV adverse events, upper GI Bleeding, lower GI Bleeding, nose bleeding, renal failure, liver failure, encephalopathy, fatigue, weight loss, anorexia, and vomiting. Conclusions: The results of this study support our biologically-driven hypothesis that among HCC patients with CTP-A class treated with sorafenib, those reclassified as IGF-CTP-B/C will have poorer prognosis in terms of shorter OS and PFS. Thus, our study provides an objective non-invasive strategy to better predict the outcome in HCC patients undergoing systemic therapy. Future validation 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.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e16660
    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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    Online Resource
    The association between statin use and hepatocellular cancer outcome.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 4_suppl ( 2013-02-01), p. 165-165
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 165-165
    Abstract: 165 Background: Preclinical evidence supports anti-tumoral activity of statins. Several observational studies have shown inverse association between statin use and hepatocellular cancer (HCC) incidence. However, little is known as to whether statins can delay the progression of HCC. Therefore, we investigated the association between statin use and the outcome of patients with HCC. Methods: 644 patients diagnosed with pathologically confirmed HCC were followed up from 2000 till 2011. Survival analysis was done using Cox regression model. Results: The mean age of the HCC cohort was 63.1 years (SD, ±11.5). 73.4% were men and 65.5% were Caucasians. 70.7% were diagnosed at TNM stage III and IV. 52.6% had no evidence of hepatitis B or C virus infection. 81.7% had local and systemic therapy, while 18.3% underwent surgical resection. The median survival of HCC patients was 19.2 months. 10.7% of patients reported statin use. We observed significant difference in overall survival between statin non-users and users; the median overall survival (95% CI) were 18.5 (16.4-20.5) months and 25.4 (19.8-31.1) months, respectively (log rank test p = 0.04). 30% mortality reduction was observed in statin users versus non-users (HR = 0.7, 95% CI, 0.5-0.9). This significant association was also observed in patients who received systemic and local therapy (p = 0.04). HCC patient without liver cirrhosis showed 40% mortality reduction (HR = 0.6, 95% CI, 0.4-0.9, P = 0.04) while patient with liver cirrhosis did not. History of hepatitis did not affect the association. Even after controlling for various clinical variables including age, sex, race, staging, HCV, HBV, liver cirrhosis, treatment, alcohol use and diabetes, statin use was still associated with favorable overall survival in HCC patients (HR = 0.7, 95% CI, 0.5-0.9, P=0.03). Conclusions: This is the largest study to date to evaluate the effect of statins on the outcomes of HCC patients. We found that statin use may reduce the risk of death in patients with HCC. Validation of our finding is warranted in a large prospective study.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.4_suppl.165
    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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