Optimal subsequent treatments for patients with hepatocellular carcinoma resistant to anti-PD-1 treatment

Immunotherapy ◽  
2021 ◽  
Author(s):  
Xuqi Sun ◽  
Ziliang Yang ◽  
Yuhao Tang ◽  
Sihan Mao ◽  
Peiyao Xiong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Progressive Disease ◽  
Subsequent Treatment ◽  
Locoregional Therapy ◽  
Resistant Group

Aim: The subsequent treatments for patients with hepatocellular carcinoma (HCC) resistant to immunotherapy remain unclear. This study aimed to identify optimal treatments for HCC patients with progression after anti-PD-1 therapy. Methods: The authors retrospectively analyzed 197 HCC patients with progressive disease after anti-PD-1 treatment. These patients were classified into initial resistant and secondary resistant groups. Results: In the initial resistant group, subsequent treatment with PD-1 antibody plus locoregional therapy prolonged post-progression survival and overall survival (p = 0.025 and 0.029, respectively). In the secondary resistant group, subsequent treatment did not improve the prognosis of patients. Conclusion: Subsequent PD-1 antibody plus locoregional therapy could achieve survival benefits in HCC patients initially resistant to anti-PD-1 immunotherapy.

scholarly journals Pretransplant Locoregional Therapy for Hepatocellular Carcinoma: Evaluation of Explant Pathology and Overall Survival

2016 ◽  
Vol 6 ◽  
Author(s):  
Eliza W. Beal ◽  
Kristin M. Dittmar ◽  
A. James Hanje ◽  
Anthony J. Michaels ◽  
Lanla Conteh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Locoregional Therapy

scholarly journals The Dynamic Changes of AFP From Baseline to Recurrence as an Excellent Prognostic Factor of Hepatocellular Carcinoma After Locoregional Therapy: A 5-Year Prospective Cohort Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Qi Wang ◽  
Biyu Liu ◽  
Wenying Qiao ◽  
Jianjun Li ◽  
Chunwang Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Value ◽  
Locoregional Therapy ◽  
Dynamic Changes ◽  
Risk Of Death ◽  
Increased Risk ◽  
Medical University ◽  
Newly Diagnosis

BackgroundAlthough many studies have confirmed the prognostic value of preoperative alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC), the association between AFP at baseline (b-AFP), subsequent AFP at relapse (r-AFP), and AFP alteration and overall survival in HCC patients receiving locoregional therapy has rarely been systematically elucidated.Patients and MethodsA total of 583 subjects with newly diagnosis of virus-related HCC who were admitted to Beijing You ‘an Hospital, Capital Medical University from January 1, 2012 to December 31, 2016 were prospectively enrolled. The influence of b-AFP, subsequent r-AFP, and AFP alteration on relapse and post-recurrence survival were analyzed.ResultsBy the end of follow-up, a total of 431 (73.9%) patients relapsed and 200 (34.3%) died. Patients with positive b-AFP had a 24% increased risk of recurrence compared with those who were negative. Patients with positive r-AFP had a 68% increased risk of death after relapse compared with those who were negative. The cumulative recurrence-death survival (RDS) rates for 1, 3, 5 years in patients with negative r-AFP were 85.6% (184/215), 70.2%(151/215), and 67.4%(145/215), while the corresponding rates were 75.1% (154/205), 51.2% (105/205), and 48.8% (100/205) in those with positive AFP (P<0.001). 35 (21.6%) of the 162 patients with negative b-AFP turned positive at the time of recurrence, and of this subset, only 12 (34.3%) survived. Of the 255 patients with positive b-AFP, 86 (33.7%) turned negative at the time of relapse, and of this subset, only 30 (34.9%) died. The 1-, 3-, and 5-year cumulative RDS rates were also compared among groups stratified by AFP at baseline and relapse. The present study found that patients with positive AFP at baseline and relapse, as well as those who were negative turned positive, had the shortest RDS and OS.ConclusionsNot only AFP at baseline but also subsequent AFP at relapse can be used to predict a post-recurrence survival, which can help evaluate mortality risk stratification of patients after relapse.

Comparison of a new prognostic system and five current staging systems in predicting the survival rate of patients with advanced hepatocellular carcinoma.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 193-193
Author(s):  
Zhan-Hong Chen ◽  
Xing Li ◽  
Min Dong ◽  
Xiao-Kun Ma ◽  
Xiang-Yuan Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Survival Rate ◽  
Liver Cancer ◽  
Staging System ◽  
Locoregional Therapy ◽  
Score System ◽  
Advanced Hcc ◽  
Prognostic System ◽  
Staging Systems

193 Background: Prognosis of patients with advanced HCC is very poor, median overall survival varies from 3 to 6 months. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical tirals. We have established a new prognostic system called SYSU system (variables and risk classification criteria are listed below, reported in MASCC 2013) and now we want to compare this new prognostic system and 5 current staging systems in predicting the survival rate of patients with advanced HCC. Methods: From September 2008 to June 2010, a total of 253 patients with advanced HCC who were not amendable to locoregional therapy were analyzed. The median follow-up is 38.5 months and the median survival is 7 months. Data were collected to classify patients according to our new system(SYSU system), Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma (BCLC), Advanced Liver Cancer Prognostic System (ALCPS), Chinese University Prognostic Index staging system for HCC (CUPI), OKUDA score system and French scoring system(GETCH) at diagnosis. OS and 3-month OS were the end points used in the analysis. Results: When predicting 3-month survival, ROC analysis show AUC of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 0.822,0.821,0.777,0.756,0.688 and 0.621. AUC of SYSU system and ALCPS is similar and they are significantly better than the other four staging system (p<0.05). When predicting overall survival, likelihood ratio test show χ2 of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 97.7,85, 50.5, 46.4,22.6 and 8.4 and AIC of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 1939,1952,1986,1990,2014 and 2028. Our SYSU system has best performance in terms of discriminatory ability, homogeneity and monotonicity. Conclusions: Our SYSU system is the best score system in prediction of OS and 3-month OS among the 6 systems analyzed for Chinese advanced HCC patients. [Table: see text]

scholarly journals Targeted Inhibition of FGF19/FGFR Cascade Improves Anti-Tumor Immunity and Response Rate in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
David Wai Meng Tai ◽  
Thi Bich Uyen Le ◽  
Aldo Prawira ◽  
Rebecca Zhi Wen Ho ◽  
Hung Huynh
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
T Cells ◽  
Progressive Disease ◽  
Response Rate ◽  
Acquired Resistance ◽  
Proliferation And Metastasis ◽  
New Treatment ◽  
Targeted Inhibition ◽  
Pdx Models

Abstract Background Hepatocellular carcinoma (HCC) is the most common liver cancer globally, claiming nearly 1 million lives each year. Overexpression of fibroblast growth factor (FGF) receptors (FGFRs) signaling cascade has been shown to contribute to tumorigenesis, metastasis, and poor prognosis in HCC. Therefore, targeted inhibition of the FGF/FGFR cascade may represent a new treatment strategy for HCC patients. Methods HCC patient-derived xenograft (PDX) models were implanted into either severe combined immunodeficient (SCID) or CD34 + hu-NSG (humanized) mice and subsequently treated with vehicle, infigratinib (FGFR1-3 inhibitor), FGF401 (FGFR4 inhibitor), or the combination of infigratinib and FGF401. Tumor progressions, overall survival of mice, lung metastasis, and drug resistance were monitored, and samples collected at the end of the treatment cycle were subjected to Western blot analyses and immunohistochemistry. Results HCC PDX models expressing high levels of FGF19/FGFR4 or FGFR2/3 showed favorable initial treatment response to FGF401 and infigratinib, respectively. However, progressive disease due to acquired resistance was observed. Combination infigratinib/FGF401 augmented the antitumor activity, response rate, and overall survival of mice. This combination significantly increased the infiltration of B-cells, macrophages, CD8 + T-cells, and CD4 + T-cells associated with granzyme-B mediated apoptosis, delayed onset of resistance, and inhibited metastasis by potently inhibiting several critical signaling pathways involved in proliferation and metastasis. Conclusions Our findings suggest that HCC patients with high FGFR2/3 or FGF19/FGFR4 expressing tumors might benefit from a combination infigratinib/FGF401, thus supporting its evaluation in clinical trials.

scholarly journals Complex treatment of hepatocellular carcinoma at early (BCLC-A) and intermediate (BCLC-B) stages

2020 ◽  
Vol 25 (2) ◽  
pp. 55-66
Author(s):  
B. N. Kotiv ◽  
I. I. Dzidzava ◽  
S. A. Alent’yev ◽  
A. V. Smorodsky ◽  
K. I. Makhmudov ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Targeted Therapy ◽  
Radiofrequency Ablation ◽  
Liver Resection ◽  
Transarterial Chemoembolization ◽  
Survival Rates ◽  
Locoregional Therapy ◽  
Group 2 ◽  
Group 1

Аim. Evaluation of the effectiveness of hepatocellular carcinoma treatment at early BCLC-A and intermediate BCLC-B stages by the combined use of liver resections and locoregional therapy.Materials and methods. The study included 142 patients with hepatocellular carcinoma. At the BCLC-A stage – 46 observations, at the BCLC-B stage – 96 observations. Chronic hepatitis and cirrhosis of various etiologies were detected in 58 (40.8%) patients. Liver resection of various volumes, transarterial chemoembolization and radiofrequency ablation were used for treatment. With the tumor progression and the ineffectiveness of locoregional therapy, targeted therapy was prescribed.Results. Four groups of patients were identified depending on treatment tactics. In group 1, 28 patients underwent radical liver resections; in group 2, 37 patients underwent preoperative transarterial chemoembolization and liver resection. In group 3, 63 patients underwent therapeutic transarterial chemoembolization and radiofrequency ablation. In group 4, 14 patients underwent transarterial chemoembolization followed by hepatic arterial infusion of chemotherapy and targeted therapy. Overall survival in groups 1 and 2 significantly exceeds survival rates in groups 3 and 4. The median overall survival in groups 1–4 was 39, 37.5, 19.5, and 7.5 months (p1–3 = 0.0001 ; p1–4 = 0.0009, p2–3 = 0.018 , p 2–4 = 0.001). The cumulative one, three and five year survival rates in groups 1 and 2 did not significantly differ (87.8% and 80.0%, 82.5% and 75.0%, 68.2% and 58.0%, 54.5% and 41.0%, respectively, p1–2 = 0.076). However, group 1 consisted exclusively of patients with BCLC-A stages with solitary tumors less than 6.5 cm in diameter, group 2 included large BCLC-A tumors and multiple tumors BCLC-B stages (67.6%).Conclusion. For the treatment of patients with hepatocellular carcinoma BCLC-A and BCLC-B stages, a multimodal approach should be applied, including differential use and a rational combination of regional chemotherapy and resection techniques, taking into account the functional state of the liver.

scholarly journals Clinical value evaluation of microRNA-324-3p and other available biomarkers in patients with HBV-infection-related hepatocellular carcinoma

2021 ◽  
Author(s):  
Li Zhao ◽  
Qian Yang ◽  
Jianbo Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatitis B ◽  
Diagnostic Performance ◽  
Cox Regression ◽  
Hbv Infection ◽  
Healthy Controls ◽  
Survival Prognosis ◽  
Diagnosis And Prognosis ◽  
Hcc Cells

Abstract Background Patients with hepatitis B virus (HBV) infection are at high risk of hepatocellular carcinoma (HCC). This study aimed to evaluate the expression of microRNA-324-3p (miR-324-3p) in HBV-related HCC, and explore the clinical significance of serum miR-324-3p and other available biomarkers in the diagnosis and prognosis of HBV-related HCC. Methods Expression of miR-324-3p in HBV-infection-related cells and patients was estimated using quantitative real-time PCR. The receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance of serum miR-324-3p, AFP and PIVKA-II in the differentiation of HBV-related HCC from healthy controls and chronic hepatitis B (CHB). The relationship between serum miR-324-3p and patients’ clinical features was assessed using Chi-square test, and the value of miR-324-3p to predict overall survival prognosis was evaluated using Kaplan-Meier methods and Cox regression assay in patients with HBV-related HCC. Results HBV-related HCC cells had significantly increased miR-324-3p compared with normal and HBV-unrelated HCC cells, and serum miR-324-3p in HCC patients with HBV infection was also higher than that in healthy controls and CHB. Serum miR-324-3p had relatively high diagnostic accuracy for the screening of HCC case with HBV infection, and the combination of miR-324-3p, AFP and PIVKA-II showed the improved diagnostic performance. Additionally, high serum miR-324-2p in HBV-related HCC patients was associated with cirrhosis, tumor size, clinical stage and poor overall survival prognosis. Conclusion Serum increased miR-324-3p may be involved in the progression of HBV-related hepatitis to HCC, and may serve as a candidate biomarker for the diagnosis and prognosis of HBV-related HCC.

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