scholarly journals Diagnosis, Staging, and Patient Selection for Locoregional Therapy to Treat Hepatocellular Carcinoma

2020 ◽  
Vol 37 (05) ◽  
pp. 441-447
Author(s):  
Zachary T. Berman ◽  
Isabel Newton
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Options ◽  
Intermediate Stage ◽  
Family Education ◽  
Locoregional Therapy ◽  
Stage Disease ◽  
Incidence And Mortality ◽  
Tumor Boards ◽  
Diagnostic Approaches ◽  
Locoregional Therapies

AbstractHepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality and the only cancer for which the incidence and mortality are on the rise. Sensitive and specific screening and diagnostic approaches, robust staging regimens, multidisciplinary tumor boards, and patient/family education and engagement in the shared decision-making process help to identify a patient's optimal treatment options. Locoregional therapies have been the mainstay for treating intermediate-stage disease, but they are finding special applications for early and advanced disease. This review discusses the diagnosis of HCC, current accepted staging models, and treatment of HCC, with a focus on locoregional therapies.

New advances in the diagnosis and management of hepatocellular carcinoma

BMJ ◽  
2020 ◽  
pp. m3544 ◽  
Author(s):  
Ju Dong Yang ◽  
Julie K Heimbach
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Treatment ◽  
Early Stage ◽  
Treatment Options ◽  
Intermediate Stage ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Long Term Outcomes ◽  
Stage Disease

ABSTRACT Hepatocellular carcinoma is one of the leading causes of cancer related death in the world. Biannual surveillance for the disease in patients with cirrhosis and in high risk carriers of hepatitis B virus allows early stage cancer detection and treatment with good long term outcomes. Liver ultrasonography and serum α fetoprotein are the most commonly used surveillance tests. If suspicious results are found on the surveillance test, multiphasic computed tomography or magnetic resonance imaging should be undertaken to confirm the diagnosis of hepatocellular carcinoma. If radiologic tests show inconclusive results, liver biopsy or repeat imaging could be considered for confirmation of hepatocellular carcinoma. Management of the disease is complex. Patients should be evaluated by a multidisciplinary team, and the selection of treatment should consider factors such as tumor burden, severity of liver dysfunction, medical comorbidities, local expertise, and preference of patients. Early stage hepatocellular carcinoma is best managed by curative treatment, which includes resection, ablation, or transplantation. Patients with intermediate stage disease often receive locoregional treatment. Systemic treatment is reserved for patients with advanced disease. Several positive, phase III, randomized controlled trials have expanded the systemic treatment options for advanced hepatocellular carcinoma with promising long term outcomes, especially trials using combination treatments, which could also have eventual implications for the treatment of earlier stage disease.

scholarly journals Selecting the first line treatment in non-metastatic hepatocellular carcinoma - comparing clinical practice guidelines

2020 ◽  
Vol 14 (2) ◽  
Author(s):  
Soumya Jogi ◽  
Radha Varanai ◽  
Sravani S. Bantu ◽  
Ashish Manne
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Practice ◽  
Systemic Therapy ◽  
Residual Disease ◽  
Disease Process ◽  
Locoregional Therapy ◽  
Line Treatment ◽  
First Line ◽  
Tumor Boards ◽  
First Line Treatment

Primary malignancy of the liver or hepatocellular carcinoma (HCC) is unique in its presentation, disease process, and management. Unlike breast or colon cancer, the staging of HCC depends on performance status and baseline liver function along with pathological characteristics. Apart from traditional options like surgery and systemic therapy, effective management can be achieved in selected cases with liver transplant and locoregional therapy (LRT) like transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and ablation. Liver study societies and cancer groups across the globe proposed guidelines to aid the treating physicians in choosing first-line treatment for liver cancer. It is tough to compare these guidelines as they differ not only in treatment recommendations but also in risk assessment (and staging). The approach to the same patient may be different in the country he or she is managed. In clinical practice, decisions are usually taken on the consensus of multidisciplinary tumor boards and do not necessarily adhere to any guidelines. In the early (and very early) stage HCC, curative options like surgery, transplant, and ablation are recommended. In intermediate stage HCC, LRT (TACE and TARE) is preferred in the first line and systemic therapy for treatment failure or residual disease. Systemic therapy, including the atezolizumab/bevacizumab combination and tyrosine kinase inhibitors (TKI) like sorafenib and lenvatinib, is used for advanced stages. Supportive care is advised for terminal stage HCC.

Cancer Immunotherapy-Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

2021 ◽  
Vol 16 ◽  
Author(s):  
Jing Bai ◽  
Ping Liang ◽  
Qian Li ◽  
Rui Feng ◽  
Jiang Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Locoregional Therapy ◽  
Incidence And Mortality

: Hepatocellular Carcinoma (HCC) is one of the most common malignancies, the incidence and mortality of which are increasing worldwide. Cancer immunotherapy has revolutionized cancer treatment in recent years. In particular, Immune Checkpoint Inhibitors (ICIs) as new therapeutic tools have demonstrated encouraging antitumor activity and manageable tolerability in HCC. Immunologic checkpoint blockade with antibodies targeting Programmed cell Death-1 (PD-1), Programmed cell Death Ligand-1 (PD-L1), and Cytotoxic T Lymphocyte-Associated protein-4 (CTLA-4) strengthens tumor immunity by restoring exhausted T cells. Although the efficacy of combination treatment strategies using ICIs combined with other ICIs, molecular targeted agents, systemic therapy, or locoregional therapy has been well documented in numerous preclinical and clinical studies on several types of cancers, most HCC patients do not benefit from ICI treatment. This review highlights recent developments and potential opportunities related to ICIs and their combination in the management of HCC. The present article also includes recent patent review coverage on this topic.

Myopenia as a significant prognostic factor in BCLC-B intermediate-stage hepatocellular carcinoma treated with sorafenib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15639-e15639
Author(s):  
Mao Okada ◽  
Hiroyuki Nakanishi ◽  
Masayuki Kurosaki ◽  
Sakura Kirino ◽  
Leona Osawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Prognostic Factor ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Intermediate Stage ◽  
Significant Prognostic Factor ◽  
Poor Prognostic Factor ◽  
Skeletal Muscle Index ◽  
The Impact

e15639 Background: Tyrosine kinase inhibitors (TKI) are important treatment options for unresectable hepatocellular carcinoma (HCC). The survival benefit of sorafernib was demonstrated not only in advanced stage but also for BCLC-B intermediate stage who are refractory to transcatheter arterial chemoembolization by OPTIMIS study. Skeletal muscle mass depletion (Myopenia) is a poor prognostic factor in HCC treated by resection or loco-reginal ablation, but its effect on survival in TKI treated patients, especially in those within BCLC-B stage remains unclear. The aim of the present study is to elucidate the impact of myopenia on survival among HCC treated with sorafenib, especially in BCLC-B stage. Methods: In 213 patients who started treatment with sorafenib between 2009 and 2016, myopenia at baseline was determined by using skeletal muscle index calculated from CT images of the third lumber vertebra level. The impact of myopenia on survival was analyzed in whole patients, after stratification by BCLC stage, and after matching for backgrounds within BCLC-B patients. Results: The median survival in whole, BCLC-C, and –B was 13.7, 8.7 and 15.2 months, respectively. Myopenia was not a significant prognostic factor in whole patients and in BCLC-C stage. However, among BCLC-B patients (n = 104), survival was significantly better in patients with no myopenia (p = 0.05). Among them, 85 patients who continued sorafenib for more than 8 weeks were extracted and those with or without myopenia were matched for backgrounds by propensity score. Backgrounds including etiology, Child-Pugh score, BMI, AFP and PIVKA-Ⅱwas not different between myopenia (n = 30) and no myopenia group (n = 30) after matching. The overall survival at 6-, 12-, and 24-months was 96%, 74%, and 62% in no myopenia group which was significantly better compared to 89%, 64%, and 28% in myopenia group (p = 0.019). The hazard ratio was 2.12 (95% CI 1.11-4.03). Conclusions: Absence of myopenia predicts favorable outcome in sorafenib treated HCC patients within BCLC-B intermediate stage.

Role of hepatologists in management of hepatocellular carcinoma in the new era of transplant oncology.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 501-501
Author(s):  
Divya Ashat ◽  
Mark Karwal ◽  
Shiliang Sun ◽  
Sandeep Laroia ◽  
Tomohiro Tanaka
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multidisciplinary Approach ◽  
Complete Response ◽  
Meld Score ◽  
Locoregional Therapy ◽  
Direct Role ◽  
New Era ◽  
Tumor Boards ◽  
Median Diameter

501 Background: There have been global efforts to manage hepatobiliary malignancies such as hepatocellular carcinoma (HCC) in a multidisciplinary setting under the concept of transplant oncology. We published preliminary data of hepatology-directed treatment of HCC (Ann Hepatol 2019). However, the actual role of hepatologists in this setting is not well defined. Methods: We evaluated 107 patients with newly diagnosed HCC, undergoing locoregional therapy (LRT) as a first therapy (microwave ablation, TACE, TARE or SBRT) in our institution between 1/2017 to 2/2019 and being followed until 8/2019. Patients were divided into three groups based on referral pathways: outside referral directly to oncologists (O-group, n=24), internal referral from hepatologists to oncologists (H/O-group, n=62) and hepatologist directed HCC treatment (H-group, n=21). The hepatologist performed all microwave ablations in H-group; rest of the LRTs were performed by either interventional radiology or radiation oncology. Results: The baseline gender, etiology of liver disease, MELD score, Child-Pugh score, BCLC stage, CLIP score, AFP and proportion of patients within Milan criteria were similar between 3 groups ( p=n.s.). However, O-group included older patients (median 70 vs 63/62 y.o., p<0.01), and had larger HCC size (median diameter 41 vs 26/28mm, p<0.01). In H-group, there were more cases discussed in multidisciplinary tumor boards (77% vs 46%, p=0.012) and referrals for liver transplantation (71% versus 50%, p=0.046). Time between the diagnosis and the first procedure was shorter in H-group than others (median 53 vs 69 days, p=0.048). The rate of complete response/partial response per mRECIST criteria was highest in H-group (91 vs 66%, p=0.024). The 2-year cumulative survival was comparable among three groups (70, 74 and 76% in O-group, H/O-group and H-group, respectively, p=0.4). Conclusions: Hepatologists are often the first point of contact and can play a key (and even more direct) role in subsequent management of HCC. To further accomplish the concept of multidisciplinary approach and transplant oncology, primary/secondary care institutions might be a potential target for intervention for outreach.

scholarly journals Analyses of Intermediate-Stage Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization prior to Designing Clinical Trials

Liver Cancer ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 596-612
Author(s):  
Keisuke Koroki ◽  
Sadahisa Ogasawara ◽  
Yoshihiko Ooka ◽  
Hiroaki Kanzaki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Transarterial Chemoembolization ◽  
Checkpoint Inhibitors ◽  
Intermediate Stage ◽  
Tumor Burden ◽  
Durable Response ◽  
High Burden ◽  
High Tumor Burden ◽  
Stage Disease

Background: Intermediate-stage hepatocellular carcinoma (HCC) has a high frequency of recurrence and progression to advanced stage after transarterial chemoembolization (TACE), particularly in patients with high tumor burden. Promising new results from immune checkpoint inhibitors (ICIs) and ICI-based therapies are expected to replace TACE, especially in HCC patients with high tumor burden. Aims: The present study aimed to evaluate the effectiveness of TACE with a view to design clinical trials comparing TACE and ICIs. Methods: We retrospectively identified intermediate-stage HCC patients undergoing TACE from our database and subdivided patients into low- and high-burden groups based on three subclassification models using the diameter of the maximum tumor and the number of tumors. Clinical outcomes were compared between low- and high-burden intermediate-stage HCC. Results: Of 1,161 newly diagnosed HCC patients, 316 were diagnosed with intermediate-stage disease and underwent TACE. The median overall survival from high-burden intermediate-stage disease was not significantly different by clinical course, reaching high tumor burden in all subclassification models. The prognosis of high-burden patients after initial TACE was poor compared with low-burden patients for two models (except for the up-to-seven criteria). In all three models, high-burden patients showed a poor durable response rate (DRR) both ≥3 months and ≥6 months and poor prognosis after TACE. Moreover, patients with confirmed durable response ≥3 months and ≥6 months showed better survival outcomes for high-burden intermediate-stage HCC. Conclusions: Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.

scholarly journals Combining Chemistry and Engineering for Hepatocellular Carcinoma: Nano-Scale and Smaller Therapies

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1243
Author(s):  
Danielle L. Stolley ◽  
Anna Colleen Crouch ◽  
Aliçan Özkan ◽  
Erin H. Seeley ◽  
Elizabeth M. Whitley ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Residual Disease ◽  
Primary Liver Cancer ◽  
Intermediate Stage ◽  
Model Systems ◽  
Current Status ◽  
Label Free ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Stage Disease ◽  
New Applications

Primary liver cancer, or hepatocellular carcinoma (HCC), is a major worldwide cause of death from carcinoma. Most patients are not candidates for surgery and medical therapies, including new immunotherapies, have not shown major improvements since the modest benefit seen with the introduction of sorafenib over a decade ago. Locoregional therapies for intermediate stage disease are not curative but provide some benefit. However, upon close scrutiny, there is still residual disease in most cases. We review the current status for treatment of intermediate stage disease, summarize the literature on correlative histopathology, and discuss emerging methods at micro-, nano-, and pico-scales to improve therapy. These include transarterial hyperthermia methods and thermoembolization, along with microfluidics model systems and new applications of mass spectrometry imaging for label-free analysis of pharmacokinetics and pharmacodynamics.

scholarly journals Ramucirumab for Patients with Intermediate-Stage Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Results from Two Phase 3 Studies (REACH and REACH-2)

Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Masatoshi Kudo ◽  
Richard S. Finn ◽  
Manabu Morimoto ◽  
Kun-Ming Rau ◽  
Masafumi Ikeda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Intermediate Stage ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Locoregional Therapy ◽  
Hazards Model ◽  
Bclc Staging

<b><i>Background:</i></b> Intermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. <b><i>Methods:</i></b> A pooled meta-analysis of independent patient data (stratified by study) from REACH (AFP ≥ 400 ng/mL) and REACH-2 was performed. All patients had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0–1, prior sorafenib treatment, and either HCC BCLC stage B (refractory/not amenable to locoregional therapy) or BCLC stage C. Patients were randomized to ramucirumab 8 mg/kg or placebo every 2 weeks. Median overall survival (OS) and progression-free survival were estimated by the Kaplan-Meier method. Treatment effects in BCLC stage B and C were evaluated by Cox proportional-hazards model; prognosis of BCLC staging for OS was evaluated by multivariate Cox proportional-hazards model. Tumor responses were evaluated according to Response Evaluation in Solid Tumors v1.1. Liver function was assessed with albumin-bilirubin score. <b><i>Results:</i></b> Baseline characteristics were generally balanced between treatment arms in each BCLC stage. BCLC staging trended as an independent prognostic factor for OS (B vs. C; hazard ratio [HR] 0.756 [95% CI 0.546–1.046]). Consistent treatment benefit was observed for ramucirumab versus placebo across BCLC stages. Median OS for ramucirumab versus placebo was 13.7 versus 8.2 months; HR (95%): 0.43 (0.23–0.83) and 7.7 versus 4.8 months; HR (95%): 0.72 (0.59–0.89) for BCLC stage B and C, respectively. Adverse events (AEs) were consistent with observations from both studies; hypertension was the most frequent grade ≥3 AE. Liver function was preserved throughout the study and similar between treatment arms in both BCLC stages. <b><i>Conclusions:</i></b> Ramucirumab provided a better survival benefit irrespective of BCLC stage and was well tolerated without compromising liver function during treatment.

scholarly journals Locoregional Combined With Systemic Therapies for Advanced Hepatocellular Carcinoma: An Inevitable Trend of Rapid Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Xin Li ◽  
Yaxi Wang ◽  
Xin Ye ◽  
Ping Liang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rapid Development ◽  
Locoregional Therapy ◽  
Current Status ◽  
Advanced Hepatocellular Carcinoma ◽  
Antitumor Effects ◽  
Primary Tumors ◽  
Advanced Hcc ◽  
Number Of Patients ◽  
Locoregional Therapies

Despite the application of antiviral drugs and improved surveillance tools, the number of patients diagnosed with hepatocellular carcinoma (HCC) at an advanced stage and with a dismal prognosis is still on the rise. Systemic treatment with multiple multitargeted tyrosine kinase inhibitors (TKIs), such as sorafenib, has been a widely utilized approach for a decade. In addition, the use of a combination of TKIs with other types of compounds, including immune checkpoint inhibitors (ICIs) and antiangiogenic inhibitors, has shown efficacy in treating advanced HCC. However, the presence of intolerable adverse events, low disease response and control rates, and relative short overall survival of such combinatory therapies makes novel or optimized therapies for advance HCC urgently needed. Locoregional therapy (transarterial chemoembolization, and thermal ablation) can destroy primary tumors and decrease tumor burden and is widely used for HCC management. This type of treatment modality can result in local hypoxia and increased vascular permeability, inducing immunogenic effects by releasing tumor antigens from dying cancer cells and producing damage-associated molecular patterns that facilitate antiangiogenic therapy and antitumor immunity. The combination of systemic and locoregional therapies may further produce synergistic effects without overlapping toxicity that can improve prognoses for advanced HCC. In preliminary studies, several combinations of therapeutic modes exhibited promising levels of safety, feasibility, and antitumor effects in a clinical setting and have, thus, garnered much attention. This review aims to provide a comprehensive, up-to-date overview of the underlying mechanisms of combined systemic and locoregional therapies in the treatment of advanced HCC, commenting on both their current status and future direction.

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