Application of GPS marker to the local treatment of hepatocellular carcinoma -GPS markers two-point method-

Choonpa Igaku ◽  
2011 ◽  
Vol 38 (5) ◽  
pp. 585-594
Author(s):  
Yasuhide MITSUMOTO ◽  
Ryuuki MINAMI ◽  
Takahiro MORI ◽  
Takuya UCHIDA ◽  
Koji FUJITA ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Local Treatment ◽  
Point Method

Phase II HEPANOVA trial of tumor treating fields concomitant with sorafenib for advanced hepatocellular carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS470-TPS470 ◽  
Author(s):  
Anca Grosu ◽  
Eleni Gkika ◽  
Thomas B. Brunner ◽  
Robert Thimme ◽  
Uri Weinberg
Keyword(s):  
Hepatocellular Carcinoma ◽  
Sample Size ◽  
Disease Progression ◽  
Standard Dose ◽  
Local Treatment ◽  
Weighted Average ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Exact Test ◽  
Tumor Treating Fields

TPS470 Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of hepatocellular carcinoma (HCC), leading to a significant increase in cell death. The Phase 2 HEPANOVA study is the first trial testing TTFields in HCC patients, and is designed to test the safety and efficacy of adding TTFields to sorafenib in advanced HCC. Methods: Patients (N = 25) with unresectable HCC who are not amenable to any local treatment will be enrolled in this prospective, single-arm study. The study enrolls patients with ECOG score of 0-2 and Barcelona clinic liver cancer (BCLC) stage 0-C. Patients must have a measurable disease per RECIST Criteria. Having implanted electronic devices in the torso is exclusionary. Sorafenib will be administered at standard dose (400 mg twice daily). TTFields (150 kHz) will be delivered for 18 hours/day until local disease progression per RECIST Criteria. Clinical follow up will be performed q4w, and a CT/MRI scan q12w. Following disease progression in the liver, patients will discontinue TTFields and be followed monthly for survival. Overall response rate will be the primary endpoint and in-field control rate, progression-free survival rate at 12 month (PFS12), OS rate at 1 year and toxicity will all be secondary endpoints. Sample size was calculated using an Exact test for proportions considering the weighted average of ORR of patients who had either complete or partial response per RECIST criteria in historical studies with sorafenib is 4.5%. A sample size of 25 patients was required to achieve a power of approximately 80% at a one-sided alpha level of 0.05 using a single sample Exact test for proportions. Clinical trial information: NCT03606590.

Randomized, Multicenter, Open-Label Study of Oxaliplatin Plus Fluorouracil/Leucovorin Versus Doxorubicin As Palliative Chemotherapy in Patients With Advanced Hepatocellular Carcinoma From Asia

2013 ◽  
Vol 31 (28) ◽  
pp. 3501-3508 ◽  
Author(s):  
Shukui Qin ◽  
Yuxian Bai ◽  
Ho Yeong Lim ◽  
Sumitra Thongprasert ◽  
Yee Chao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Palliative Chemotherapy ◽  
Locally Advanced ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
End Point

Purpose To determine whether FOLFOX4 (infusional fluorouracil, leucovorin, and oxaliplatin) administered as palliative chemotherapy to patients with advanced hepatocellular carcinoma (HCC) provides a survival benefit and efficacy versus doxorubicin. Patients and Methods This multicenter, open-label, randomized, phase III study in mainland China, Taiwan, Korea, and Thailand involved 371 patients age 18 to 75 years who had locally advanced or metastatic HCC and were ineligible for curative resection or local treatment. They were randomly assigned at a ratio of one to one to receive either FOLFOX4 (n = 184) or doxorubicin (n = 187). The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), response rate (RR) by RECIST (version 1.0), and safety. Results At the prespecified final analysis, median OS was 6.40 months with FOLFOX4 (95% CI, 5.30 to 7.03) and 4.97 months with doxorubicin (95% CI, 4.23 to 6.03; P = .07; hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.02). Median PFS was 2.93 months with FOLFOX4 (95% CI, 2.43 to 3.53), and 1.77 months with doxorubicin (95% CI, 1.63 to 2.30; P < .001; HR, 0.62; 95% CI, 0.49 to 0.79). RR was 8.15% with FOLFOX4 and 2.67% with doxorubicin (P = .02). On continued follow-up, the trend toward increased OS with FOLFOX4 was maintained (P = .04; HR, 0.79; 95% CI, 0.63 to 0.99). Toxicity was consistent with previous experiences with FOLFOX4; proportions of grade 3 to 4 adverse events were similar between treatments. Conclusion Although the study did not meet its primary end point, the trend toward improved OS with FOLFOX4, along with increased PFS and RR, suggests that this regimen may confer some benefit to Asian patients, but an OS benefit cannot be concluded from these data.

scholarly journals Therapeutic Potential of (−)-Agelamide D, a Diterpene Alkaloid from the Marine Sponge Agelas sp., as a Natural Radiosensitizer in Hepatocellular Carcinoma Models

Marine Drugs ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. 500
Author(s):  
Changhoon Choi ◽  
Yeonwoo Cho ◽  
Arang Son ◽  
Sung-Won Shin ◽  
Yeon-Ju Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Marine Sponge ◽  
Therapeutic Potential ◽  
Apoptotic Cell ◽  
Local Treatment ◽  
Predictive Biomarkers ◽  
Apoptotic Cell Death ◽  
Tumor Growth Inhibition ◽  
Radiation Induced

Radiation therapy (RT) is an effective local treatment for unresectable hepatocellular carcinoma (HCC), but there are currently no predictive biomarkers to guide treatment decision for RT or adjuvant systemic drugs to be combined with RT for HCC patients. Previously, we reported that extracts of the marine sponge Agelas sp. may contain a natural radiosensitizer for HCC treatment. In this study, we isolated (−)-agelamide D from Agelas extract and investigated the mechanism underlying its radiosensitization. (−)-Agelamide D enhanced radiation sensitivity of Hep3B cells with decreased clonogenic survival and increased apoptotic cell death. Furthermore, (−)-agelamide D increased the expression of protein kinase RNA-like endoplasmic reticulum kinase/inositol-requiring enzyme 1α/activating transcription factor 4 (PERK/eIF2α/ATF4), a key pathway of the unfolded protein response (UPR) in multiple HCC cell lines, and augmented radiation-induced UPR signaling. In vivo xenograft experiments confirmed that (−)-agelamide D enhanced tumor growth inhibition by radiation without systemic toxicity. Immunohistochemistry results showed that (−)-agelamide D further increased radiation-induced ATF4 expression and apoptotic cell death, which was consistent with our in vitro finding. Collectively, our results provide preclinical evidence that the use of UPR inducers such as (−)-agelamide D may enhance the efficacy of RT in HCC management.

Stereotactic body radiotherapy: an effective local treatment modality for hepatocellular carcinoma

2014 ◽  
Vol 10 (14) ◽  
pp. 2227-2241 ◽  
Author(s):  
Jonathan Klein ◽  
Renee Korol ◽  
Simon S Lo ◽  
William Chu ◽  
Michael Lock ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stereotactic Body Radiotherapy ◽  
Treatment Modality ◽  
Local Treatment

Clinical characteristics and outcomes of patients with advanced hepatocellular carcinoma treated with immunotherapy: A “real world” retrospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16644-e16644
Author(s):  
Adel Chergui ◽  
Eswar Gadde ◽  
Ana Acuna-Villaorduna ◽  
Rafi Kabarriti ◽  
Sanjay Goel ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Real World ◽  
Clinical Characteristics ◽  
Treatment Initiation ◽  
Local Treatment ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
Male Predominance ◽  
Dismal Prognosis

e16644 Background: Advanced hepatocellular carcinoma (HCC) is an aggressive malignancy with dismal prognosis. Newer agents, including immunotherapy (IO), have been granted accelerated approval for patients previously treated or unable to tolerate sorafenib. However, information outside clinical trials is scarce. This study aims to describe clinical characteristics and outcomes of HCC patients treated with IO. Methods: HCC patients treated with IO were identified using the institutional software, Clinical Looking Glass. Data regarding demographics, clinical and treatment characteristics were collected by chart review. Neutrophil/lymphocyte ratio (NLR) and AFP were collected at IO treatment initiation and considered low if below 4 and 400, respectively. Progression-free survival (PFS) was defined as time from treatment initiation to progression of disease or death, and overall-survival (OS) as time from IO initiation to death from any cause. Disease characteristics were analyzed using descriptive statistics, PFS and OS were plotted using Kaplan-Meier curves. Results: 52 patients with a median age of 64.5 years and male predominance (38, 73.1%) were identified. There were 24 (54.5%) Hispanics, 9 (20.5%) Non-Hispanic Blacks, 7 (15.9%) Non-Hispanic White and 4 (9.1%) Asians. Cirrhosis present in 41 (83.7%), median MELD of 8 (IQ: 7-10). 37 (77.1%) patients had ECOG 0-1. Hepatitis B and C and B infection were encountered in 12 (24.5%) and 22 (44%) patients, respectively. Intravascular invasion present in 16 (34.8%) and extrahepatic metastases in 7 (14.9%). Local treatment was provided to 29 (59.2%) and radiation to 14 (28.6%). First line treatment (tx1) was Sorafenib in 29 (55.8%) and Nivolumab in 21 (40.4%). Nivolumab was second line treatment or beyond (tx2) in 31 (59.6%). Median PFS was 6.2 (3.1-10.6) months and it did not differ between tx1 and tx2 (8 vs 5.9 months, p = 0.90). Median OS was 13.2 months; there was a tendency towards higher survival rates in patients that were treated in tx2 (11.8 vs 14.3 months, 0 = 0.59) and in patients with low NLR (14.8 vs 9.2 months, p = 0.14). Median OS was higher in patients with low AFP at IO treatment initiation (15.7 vs. 9.2 months, p = 0.03). Conclusions: In this multiethnic cohort, the “real world” experience of the benefit of IO in HCC is encouraging, with a median OS exceeding one year. NLR showed potential as a possible biomarker. Expanded data may elucidate the differences if any, between use of IO as front vs. second line therapy, in PFS and OS.

Laparoscopic local treatment for hepatocellular carcinoma under general anesthesia

2003 ◽  
Vol 21 ◽  
pp. 75-78
Author(s):  
Norio Isoda ◽  
Kenichi Ido ◽  
Kazunori Ono ◽  
Hideaki Inamori ◽  
Yasuhiro Onobuchi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
General Anesthesia ◽  
Local Treatment

Randomized Controlled Trial of Tamoxifen in Advanced Hepatocellular Carcinoma

2005 ◽  
Vol 23 (19) ◽  
pp. 4338-4346 ◽  
Author(s):  
Jean-Claude Barbare ◽  
Olivier Bouché ◽  
Franck Bonnetain ◽  
Jean-Luc Raoul ◽  
Philippe Rougier ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Performance Status ◽  
Univariate Analysis ◽  
Local Treatment ◽  
Cox Proportional Hazards Model ◽  
Tamoxifen Treatment ◽  
Control Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Pugh Class

Purpose Randomized studies on tamoxifen treatment of hepatocellular carcinoma (HCC) produced conflicting results. The aim of this study was to assess the efficacy of tamoxifen administration in improving overall survival of patients with advanced HCC. Patients and Methods A total of 420 patients with HCC who were not suitable for surgery or local treatment were randomly assigned between April 1995 and May 2000: 210 in the control group and 210 in the tamoxifen group (20 mg/d orally). Patients with WHO performance status greater than 2, belonging to Child-Pugh class C, or with serum creatinine greater than 130 μmol/L were not eligible. Results Tolerance was good and the main reported adverse effects were thrombophlebitis (three patients), nausea (two patients), and hot flushes (three patients). Outcome did not differ between the two treatment arms: estimated median survival was 4.8 and 4.0 months in the tamoxifen and in the control groups, respectively (P = .25). Univariate analysis showed significant association of survival with age, Okuda stage, WHO performance status, Child-Pugh class, intrahepatic tumor stage, alpha-fetoprotein serum concentration, and presence of extrahepatic spread, portal vein thrombosis, hepatomegaly, or hepatalgia. In a Cox proportional hazards model we found a significant beneficial effect of tamoxifen on survival in patients belonging to Okuda I or II stages. Conclusion In this large study, tamoxifen did not improve the survival of patients with advanced HCC, but there is a suggestion that patients without major hepatic insufficiency seem to have some survival benefit. New trials involving this specific population are warranted.

scholarly journals The role of a multidisciplinary approach in the treatment of hepatocellular carcinoma

2020 ◽  
Vol 21 (4) ◽  
pp. 10-14
Author(s):  
Oleg I. Kit ◽  
Liubov Iu. Vladimirova ◽  
Anna E. Storozhakova ◽  
Tatiana A. Snezhko ◽  
Elena A. Kalabanova ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Practice ◽  
Targeted Therapy ◽  
Surgical Treatment ◽  
Viral Hepatitis ◽  
Multidisciplinary Approach ◽  
Local Treatment ◽  
Treatment Methods ◽  
Viral Hepatitis C ◽  
Advanced Stages

Aim. Evaluation of treatment options and efficacy in patients with hepatocellular carcinoma based on data from the FSBI Rostov Cancer Research Institute using a multidisciplinary approach to the problem. Materials and methods. 124 cases of hepatocellular carcinoma were analyzed. In 79.8% of patients (average age of 61.4 years) the disease was diagnosed at advanced stages (IIIIV). Antibodies to viral hepatitis B were detected in 18 (14.5%) patients, and antibodies to viral hepatitis C in 35 (28.2%) patients. Liver cirrhosis occurred in 38 (30.6%) cases, and ChildPugh class A in 20 (16.1%) cases. In the FSBI RCRI, a multidisciplinary approach has been introduced into clinical practice; decision on treatment tactics is made with a close cooperation of several specialists. The use of special treatment methods was available in 67 (54%) patients. 32 patients with Barcelona Clinic Liver Cancer (BCLC) stage A (early) or stage B (intermediate), had surgical treatment or hepatic arterial chemoembolization (HACE) with lipiodol or microspheres using various cytostatics (18 and 14 patients, respectively). 35 patients with advanced stage C were given a systemic therapy with various cytostatics (gemcitabine, oxaliplatin, doxorubicin) or targeted therapy with sorafenib. The treatment efficacy was assessed according to mRECIST. Results. The best median overall survival (OS) up to 21 months was in the group of patients (n=18) who underwent volume resection surgery. In this group, sorafenib was prescribed to 2 patients after surgery. When performing HACE, the median OS was 14.2 months. In 6 patients, HACE was performed 2 or more times. Among the 14 patients who had HACE, sorafenib was prescribed in 8 cases, and the median OS in this group was 16.3 months. 20 patients were given targeted therapy with sorafenib. Following 3 months of taking the drug, 16 patients achieved stabilization of the disease according to the mRECIST, in 1 patient a partial response, in 3 patients disease progression. Median OS was 9.1 months; progression-free survival among patients treated with sorafenib was 5.4 months. Conclusions. The use of a multidisciplinary approach in clinical practice makes it possible to choose the optimal treatment option for hepatocellular carcinoma and contributes to the improvement in OS. The combination of local treatment methods (surgical treatment, HACE) with effective drug therapy is the most optimal approach to treating patients with advanced stages of hepatocellular carcinoma.

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