318 Effects of Radiologic Tumor Response of Anti-Glypican-3 GC33 and Multi Tyrosine Kinases Inhibitor Sorafenib in Hepatocellular Carcinoma

Background: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. Methods: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. Results: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4–8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8–15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. Conclusions: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

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997 TUMOR RESPONSE EVALUATION ACCORDING TO MRECIST CRITERIA IN PATIENTS WITH HEPATOCELLULAR CARCINOMA TREATED WITH TACE-DRUG ELUTING BEADS

Journal of Hepatology ◽

10.1016/s0168-8278(12)61009-5 ◽

2012 ◽

Vol 56 ◽

pp. S390

Author(s):

A.L. Chagas ◽

L. Kikuchi ◽

N.S. Freitas ◽

A.C.B. Santos ◽

R.S.S.M. Alencar ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Response ◽

Response Evaluation ◽

Tumor Response Evaluation ◽

Drug Eluting Beads ◽

Drug Eluting

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Predictive factors of tumor response to trans-catheter treatment in cirrhotic patients with hepatocellular carcinoma: A multivariate analysis of pre-treatment findings

World Journal of Gastroenterology ◽

10.3748/wjg.v13.45.6022 ◽

2007 ◽

Vol 13 (45) ◽

pp. 6022 ◽

Cited By ~ 5

Author(s):

Roberto Miraglia ◽

Giada Pietrosi ◽

Luigi Maruzzelli ◽

Ioannis Petridis ◽

Settimo Caruso ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Multivariate Analysis ◽

Predictive Factors ◽

Tumor Response ◽

Cirrhotic Patients ◽

Pre Treatment

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Radiological Appearance of Hepatocellular Carcinoma Predicts the Response to Trans-arterial Chemoembolization in Patients Undergoing Liver Transplantation

10.21203/rs.2.11764/v3 ◽

2019 ◽

Author(s):

Wei Zhang ◽

An-Hui Xu ◽

Wei Wang ◽

Yan-Hui Wu ◽

Qian-Ling Sun ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Tumor Necrosis ◽

Tumor Response ◽

Locoregional Therapy ◽

Arterial Phase ◽

Radiological Appearance ◽

Explant Analysis ◽

Complete Tumor ◽

Arterial Chemoembolization

Abstract Background: The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE. Methods: From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT. Results: Eighty nine TACE procedures (1.35±0.67; 1-4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P=0.002), “typical tumor enhancement” (P=0.010) and smooth tumor margins (p=0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis. Conclusion s : The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation.

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3-Formylchromone Counteracts STAT3 Signaling Pathway by Elevating SHP-2 Expression in Hepatocellular Carcinoma

Biology ◽

10.3390/biology11010029 ◽

2021 ◽

Vol 11 (1) ◽

pp. 29

Author(s):

Chakrabhavi Dhananjaya Mohan ◽

Min Hee Yang ◽

Shobith Rangappa ◽

Arunachalam Chinnathambi ◽

Sulaiman Ali Alharbi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathway ◽

Tyrosine Kinases ◽

Present Report ◽

Migration And Invasion ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway ◽

Substantial Toxicity ◽

Transcription 3 ◽

Constitutive Phosphorylation

Hepatocellular carcinoma (HCC) is one of the leading cancers that contribute to a large number of deaths throughout the globe. The signal transducer and activator of transcription 3 (STAT3) is a tumorigenic protein that is overactivated in several human malignancies including HCC. In the present report, the effect of 3-formylchromone (3FC) on the STAT3 signaling pathway in the HCC model was investigated. 3FC downregulated the constitutive phosphorylation of STAT3 and non-receptor tyrosine kinases such as JAK1 and JAK2. It also suppressed the transportation of STAT3 to the nucleus and reduced its DNA-binding ability. Pervanadate treatment overrode the 3FC-triggered STAT3 inhibition, and the profiling of cellular phosphatase expression revealed an increase in SHP-2 levels upon 3FC treatment. The siRNA-driven deletion of SHP-2 led to reinstate STAT3 activation. 3FC downmodulated the levels of various oncogenic proteins and decreased CXCL12-driven cell migration and invasion. Interestingly, 3FC did not exhibit any substantial toxicity, whereas it significantly regressed tumor growth in an orthotopic HCC mouse model and abrogated lung metastasis. Overall, 3FC can function as a potent agent that can display antitumor activity by targeting STAT3 signaling in HCC models.

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Safety, tolerability and efficacy of transarterial chemoembolization using anthracyclines-loaded drug eluting microspheres for treatment of patients with unresectable hepatocellular carcinoma: Pooled analyses.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.287 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 287-287

Author(s):

Thierry De Baere ◽

Filipe Veloso Gomes ◽

Gontran Verset ◽

Gerardo Tovar-Felice ◽

Katerina Malagari ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Function ◽

Transarterial Chemoembolization ◽

Tumor Response ◽

Objective Response ◽

Progression Free Survival ◽

Close Monitoring ◽

Bridge To Transplant ◽

Level Data ◽

Drug Eluting

287 Background: Transarterial chemoembolization either with Lipiodol (cTACE) or with drug eluting microspheres (DEM-TACE) is indicated for the treatment of hepatocellular carcinoma (HCC) not amenable to curative treatments in patients with preserved liver function. Safety of TACE is becoming more important with its increased use as a bridge to transplant or downstaging to resection, but also for preservation of liver function in case of subsequent immuno-combination therapies. LifePearl microspheres is a novel DEM comprised of polyethylene-glycol with reported good safety profile and efficacy in smaller series. Our purpose was to assess safety and efficacy of TACE using anthracycline loaded LifePearl for the treatment of patients with unresectable HCC in a pooled analysis of studies with available more than 500 patient’s level data. Methods: We pooled patient level data from 5 single arm studies. Safety was assessed by close monitoring of adverse events according to CTCAE (v4.03). Tumor response was assessed, according to mRECIST and RECIST1.1 and analyzed as best overall response to account for differences in time of imaging follow-up between studies. The Kaplan-Meier method was used to estimate event rates for time to event outcomes: progression free survival (PFS), time to unTACEable progression (TTUP) and overall survival (OS) censoring patients at time of surgery or transplantation. Results: Out of 586 patients, 85.5%, 13.5% and 1.0% were Child Pugh A, B and C, respectively. BCLC stages 0, A, B and C were 13.6%, 43.4%, 41.1% and 1.9% respectively. The mean number of HCC lesions was 2.1±1.5 and mean sum of tumor diameters was 49.3±32.9mm. In 19% of patients alpha-feto protein level was > 200ng/ml. A mean of 1.9±1.3 DEM-TACEs were performed per patient. A total of 197 events were reported including 2.6 % grade 4 and 1.5% grade 5, mostly related to post-embolization syndrome. Complete response, partial response and stable disease were 60.2%, 27.1% and 7.4% respectively providing an objective response and disease control rates of 87,3% and 94,7% respectively. 10% of patients were transplanted or resected. Median OS, PFS and TTUP is indicated in the table below. OS was 89.2%, 80.2% and 69.7% at 12, 18 and 24 months respectively. Conclusions: The treatment of patients with unresectable HCC with anthracycline loaded LifePearl showed good tolerance with acceptable toxicity and high tumor response rate that translated into promising PFS, TTUP and OS. [Table: see text]

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