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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
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    Online Resource
    Retrospective study to evaluate variables predicting no-show international patients.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. e17528-e17528
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e17528-e17528
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.e17528
    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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  • 3
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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
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    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
    Refining prognosis in patients with hepatocellular carcinoma through incorporation of metabolic imaging biomarkers
    Springer Science and Business Media LLC ; 2017
    In:  European Journal of Nuclear Medicine and Molecular Imaging Vol. 44, No. 6 ( 2017-6), p. 969-978
    Details
    In: European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 44, No. 6 ( 2017-6), p. 969-978
    Type of Medium: Online Resource
    ISSN: 1619-7070 , 1619-7089
    URL: Article
    DOI: 10.1007/s00259-016-3583-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2098375-X
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  • 7
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    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-10-6)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-10-6)
    Abstract: Hepatocellular carcinoma (HCC) is an aggressive neoplasm with poor clinical outcome because most patients present at an advanced stage, at which point curative surgical options, such as tumor excision or liver transplantation, are not feasible. Therefore, the majority of HCC patients require systemic therapy. Nonetheless, the currently approved systemic therapies have limited effects, particularly in patients with advanced and resistant disease. Hence, there is a critical need to identify new molecular targets and effective systemic therapies to improve HCC outcome. The liver is a major target of the growth hormone receptor (GHR) signaling, and accumulating evidence suggests that GHR signaling plays an important role in HCC pathogenesis. We tested the hypothesis that GHR could represent a potential therapeutic target in this aggressive neoplasm. We measured GH levels in 767 HCC patients and 200 healthy controls, and then carried out clinicopathological correlation analyses. Moreover, specific inhibition of GHR was performed in vitro using siRNA and pegvisomant (a small peptide that blocks GHR signaling and is currently approved by the FDA to treat acromegaly) and in vivo , also using pegvisomant. GH was significantly elevated in 49.5% of HCC patients, and these patients had a more aggressive disease and poorer clinical outcome (P & lt;0.0001). Blockade of GHR signaling with siRNA or pegvisomant induced substantial inhibitory cellular effects in vitro. In addition, pegvisomant potentiated the effects of sorafenib (P & lt;0.01) and overcame sorafenib resistance (P & lt;0.0001) in vivo. Mechanistically, pegvisomant decreased the phosphorylation of GHR downstream survival proteins including JAK2, STAT3, STAT5, IRS-1, AKT, ERK, and IGF-IR. In two patients with advanced-stage HCC and high GH who developed sorafenib resistance, pegvisomant caused tumor stability. Our data show that GHR signaling represents a novel “druggable” target, and pegvisomant may function as an effective systemic therapy in HCC. Our findings could also lead to testing GHR inhibition in other aggressive cancers.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.986305
    DOI: 10.3389/fonc.2022.986305.s001
    DOI: 10.3389/fonc.2022.986305.s002
    DOI: 10.3389/fonc.2022.986305.s003
    DOI: 10.3389/fonc.2022.986305.s004
    DOI: 10.3389/fonc.2022.986305.s005
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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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
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    Online Resource
    I-CLIP: Improved Stratification of Advanced Hepatocellular Carcinoma Patients by Integrating Plasma IGF-1 into CLIP Score
    S. Karger AG ; 2011
    In:  Oncology Vol. 80, No. 5-6 ( 2011), p. 373-381
    Details
    In: Oncology, S. Karger AG, Vol. 80, No. 5-6 ( 2011), p. 373-381
    Abstract: 〈 i 〉 Objective: 〈 /i 〉 Improving the prognostic stratification of unresectable hepatocellular carcinoma (HCC) patients is critically needed. Since patients’ survival is closely linked to the severity of the underlying liver disease, and insulin-like growth factor-1 (IGF-1) is produced predominantly in the liver, we hypothesized that IGF-1 may correlate with patients’ survival and hence improve the prognostic ability of the Cancer of the Liver Italian Program (CLIP) score. 〈 i 〉 Methods: 〈 /i 〉 Baseline plasma IGF-1 and clinicopathologic parameters were available from 288 patients. Multivariate Cox regression models, Kaplan-Meier curves, and the log-rank test were applied. Recursive partitioning was used to determine the optimal cut point for IGF-1 using training/validation samples. Prognostic ability of the I-CLIP (I = IGF) was compared to CLIP using C-index. 〈 i 〉 Results: 〈 /i 〉 IGF-1 significantly correlated with the clinicopathologic features. With an optimal IGF-1 cut point of 26 ng/ml, the overall survival of patients with IGF-1 〉 26 was 17.7 months (95% CI 13.6–22.8), and with IGF-1 ≤26 was 5.8 months (95% CI 4.0–12.5), p 〈 0.0001. The concordance probabilities for CLIP and I-CLIP were 0.7037 and 0.7096, respectively (p 〈 0.0001). 〈 i 〉 Conclusions: 〈 /i 〉 Our preliminary results indicate that I-CLIP significantly improved prognostic stratification of patients with advanced HCC. However, independent validation of our study is warranted.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000329040
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2011
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 10
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    Online Resource
    Reassessing Hepatocellular Carcinoma Staging in a Changing Patient Population
    S. Karger AG ; 2014
    In:  Oncology Vol. 86, No. 2 ( 2014), p. 63-71
    Details
    In: Oncology, S. Karger AG, Vol. 86, No. 2 ( 2014), p. 63-71
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 Hepatocellular carcinoma (HCC) staging systems were developed using data predominantly from patients who had hepatitis and cirrhosis. Given the recent change in prevalence of viral hepatitis and cirrhosis at oncology centers, which has altered the natural history of HCC, we aimed at comparing the accuracy of HCC staging systems in patients with or without hepatitis and cirrhosis. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A total of 438 patients were enrolled. Baseline clinicopathologic parameters, Barcelona Clinic Liver Cancer stage, Cancer of the Liver Italian Program score, TNM (6th edition) stage, Okuda stage, and Chinese University Prognostic Index score were prospectively obtained for all patients, and retrospectively analyzed. Kaplan-Meier analysis was used to determine overall survival (OS), Cox regression analyses were performed, and Harrell's Correspondence Index compared the staging systems' ability to predict OS duration. Subgroup analyses of patients with or without hepatitis or cirrhosis were performed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Median patient OS was 13.9 months; 165 patients (37.7%) had no cirrhosis and 256 patients (58.4%) had no hepatitis. Overall, all staging systems were significantly less predictive of OS in patients who did not have cirrhosis or hepatitis. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our results advocate the need to further stratify HCC based on cirrhosis and hepatitis status, which may change patient risk-stratification and, ultimately, treatment decisions.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000356573
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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