scholarly journals Biopsy for advanced hepatocellular carcinoma: results of a multicentre UK audit

2021 ◽  
Author(s):  
Alexa Childs ◽  
Nekisa Zakeri ◽  
Yuk Ting Ma ◽  
Joanne O’Rourke ◽  
Paul Ross ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Performance Status ◽  
Clinical Excellence ◽  
Case Report Form ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Analysis ◽  
Radiological Criteria ◽  
Histological Data ◽  
Histological Confirmation

Abstract Background Advanced hepatocellular carcinoma (HCC) is commonly diagnosed using non-invasive radiological criteria (NIRC) defined by the European Association for the Study of the Liver or the American Association for the Study of Liver Diseases. In 2017, The National Institute for Clinical Excellence mandated histological confirmation of disease to authorise the use of sorafenib in the UK. Methods This was a prospective multicentre audit in which patients suitable for sorafenib were identified at multidisciplinary meetings. The primary analysis cohort (PAC) was defined by the presence of Child-Pugh class A liver disease and performance status 0–2. Clinical, radiological and histological data were reported locally and collected on a standardised case report form. Results Eleven centres reported 418 cases, of which 361 comprised the PAC. Overall, 76% had chronic liver disease and 66% were cirrhotic. The diagnostic imaging was computed tomography in 71%, magnetic resonance imaging in 27% and 2% had both. Pre-existing histology was available in 45 patients and 270 underwent a new biopsy, which confirmed HCC in 93.4%. Alternative histological diagnoses included cholangiocarcinoma (CC) and combined HCC-CC. In cirrhotic patients, NIRC criteria had a sensitivity of 65.4% and a positive predictive value of 91.4% to detect HCC. Two patients (0.7%) experienced mild post-biopsy bleeding. Conclusion The diagnostic biopsy is safe and feasible for most patients eligible for systemic therapy

Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

2009 ◽  
Vol 27 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Melanie B. Thomas ◽  
Jeffrey S. Morris ◽  
Romil Chadha ◽  
Michiko Iwasaki ◽  
Harmeet Kaur ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Study Objective ◽  
Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

2017 ◽  
Vol 36 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Christian Labenz ◽  
Vera Prenosil ◽  
Sandra Koch ◽  
Yvonne Huber ◽  
Jens U. Marquardt ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Hepatocellular Carcinoma ◽  
Metabolic Syndrome ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
The Metabolic Syndrome ◽  
The Impact

Background/Aim: Individual components of the metabolic syndrome (MS) such as obesity or diabetes mellitus impair the prognosis of patients with hepatocellular carcinoma (HCC) following curative treatment approaches or transarterial therapies. The aim of this retrospective study was to assess the impact of these factors on the overall survival (OS) of patients with advanced HCC treated with sorafenib. Methods: Univariate and multivariate analyses were performed to assess the impact of individual components of the MS on the OS of 152 consecutive patients with advanced HCC treated with sorafenib. Results: The presence of overweight/obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and of the MS itself did not impair the median OS. Multivariate analysis showed that Eastern Cooperative Oncology Group Performance Status ≥1 (hazards ratio [HR] 2.03), presence of macrovascular invasion (HR 1.71), Child-Pugh score B/C (HR 2.19), tumor grading G3 (HR 2.17), no prior HCC treatment (HR 2.34), and the presence of 2 or more out of 5 individual components of the MS (HR 0.65) were independent prognostic factors regarding the median OS. Conclusions: Our investigations do not confirm a negative prognostic role of individual components of the MS or the MS itself for patients with advanced HCC treated with sorafenib.

Transition of molecular target agent therapy in advanced hepatocellular carcinoma: A multicenter, retrospective study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 317-317
Author(s):  
Kazufumi Kobayashi ◽  
Sadahisa Ogasawara ◽  
Aya Takahashi ◽  
Yuya Seko ◽  
Satoshi Tsuchiya ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Staging System ◽  
Sequential Therapy ◽  
Molecular Target ◽  
Advanced Hepatocellular Carcinoma ◽  
Entire Cohort ◽  
Significant Difference

317 Background: There have been considerable advances in systemic chemotherapy for hepatocellular carcinoma (HCC) in recent times. Currently, four molecular target agents (MTA) are available for HCC treatment in Japan. Sequential therapy using multiple MTAs is being considered as the gold standard of treatment. However, the effectiveness of the treatment strategy transition for HCC remains unclear. The present study aimed to clarify the current practical use of MTAs and its effectiveness in HCC treatment. Methods: In this multicenter, retrospective study, we collected and analyzed the clinical data of 877 patients who underwent MTA therapy for HCC from June 2009 to March 2019 at several institutes in Japan. The patients were classified into 3 groups as per the period of initial MTA treatment beginning (period 1: 2009–2012, n = 267; period 2: 2013–2016, n = 352; period 3: 2017–2019, n = 258). These 3 periods were defined to have approximately same term. Period 3 means the era of multiple MTAs because of the approval of regorafenib in Japan in 2017. We assessed the patient characteristics, MTA use, and prognosis of the 3 groups. Results: The proportion of patients with advanced-stage HCC, defined according to the Barcelona Clinic Liver Cancer staging system, in each period was 70.1%, 66.5%, and 62.0% in period 1, 2, and 3, respectively. MTA use for intermediate stages increased with the passage of time ( p = 0.052). The proportion of multiple MTAs use was remarkably increased in the 3 groups (1.1%, 10.2%, and 42.6%, respectively, p < 0.0001). Child-Pugh score, proportion of macrovascular invasion, extrahepatic metastasis, and α-fetoprotein (AFP) ≥400 ng/mL showed no significant difference among the 3 groups. The median overall survival was 11.9 months for the entire cohort and 10.4, 11.3, and 15.2 months, for period 1, 2, and 3, respectively. It is noteworthy that the prognosis of patients with HCC improved over time ( p = 0.016). With respect to progression-free survival, the median value was 3.0 months for the entire cohort and 2.7, 2.8, and 4.7 months for period 1, 2, and 3, respectively ( p < 0.0001). The treatment duration was also prolonged with time (2.7, 3.2, and 6.6 months for period 1, 2, and 3, respectively; p < 0.0001). Multivariate analysis using Cox proportional hazard model showed that HCV infection, Child-Pugh score, performance status, α-fetoprotein ≥400 ng/mL, presence of macrovascular invasion, and period 3 for initial MTA introduction were independent prognostic factors. Conclusions: Sequential therapy with multiple MTAs has gained popularity with time and is considered to improve patient prognosis. The development of MTA therapy for HCC is expected to continue. Therefore, further studies are needed to help determine the appropriate drugs, the sequence of MTA use, and the precise transition time.

Radioembolization in Advanced Hepatocellular Carcinoma

2018 ◽  
Vol 36 (19) ◽  
pp. 1898-1901 ◽  
Author(s):  
Ahsun Riaz ◽  
Robert Lewandowski ◽  
Riad Salem
Keyword(s):  
Hepatocellular Carcinoma ◽  
Portal Vein ◽  
Group Performance ◽  
Performance Status ◽  
Relevant Literature ◽  
Eastern Cooperative Oncology Group ◽  
Distant Metastases ◽  
Advanced Hepatocellular Carcinoma ◽  
Vein Thrombosis ◽  
Management Approaches

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 68-year-old man with a remote history of alcohol abuse presented with vague abdominal pain. A review of systems suggested the patient had an Eastern Cooperative Oncology Group performance status 1 (restriction of strenuous physical activity). There were no physical examination findings of note. Laboratory studies disclosed Child-Pugh A liver status (no ascites; no encephalopathy; total bilirubin, 1 mg/dL; albumin, 3.5 g/dL; and international normalized rato, 1.2). The alpha-fetoprotein was mildly elevated (19.5 ng/mL). Magnetic resonance imaging with contrast disclosed an infiltrative mass with extensive malignant right and left portal vein thrombosis ( Fig 1A ) with cavernous transformation of the portal vein. The infiltrative mass ( Fig 2A ) was biopsied, revealing hepatocellular carcinoma. No distant metastases were found on a bone scintigraphy or computerized tomography scan. Given these features, this patient was classified as Barcelona Clinic for Liver Cancer stage C. The patient was referred for management of advanced hepatocellular carcinoma.

Assessment of radioembolization among patients who met the inclusion criteria for Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14654-e14654 ◽  
Author(s):  
Bruno Sangro ◽  
Livio Carpanese ◽  
Roberto Cianni ◽  
Daniele Gasparini ◽  
Rita Golfieri ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Function ◽  
Median Overall Survival ◽  
Performance Status ◽  
Advanced Hepatocellular Carcinoma ◽  
Inclusion Criteria ◽  
Ecog Performance Status ◽  
Advanced Hcc ◽  
Good Liver Function

e14654 Background: SHARP was pivotal in determining the safety and efficacy of sorafenib in advanced hepatocellular carcinoma (HCC) in patients with predominately good liver function. In practice, many patients with advanced HCC receive radioembolization (RE). Investigators from the European Network on RE with yttrium-90 resin microspheres (ENRY) group conducted an analysis of safety and survival among consecutive patients who met the SHARP inclusion criteria. Methods: 58% of patients (189 of 325) who had received RE between 09/2003 and 12/2009 were considered SHARP-equivalents. Of these, 11.6% received sorafenib 4.7 months (median) after RE for a median duration of 2.8 months. Safety and tolerability analyses were conducted up to day 90 post RE; changes from baseline were recorded and transitions in CTCAE grades >3 tested. Statistical analyses used SAS (SAS, Cary NC) version 9.2 XP Pro. Results: Like the SHARP sorafenib cohort, most patients had advanced HCC (BCLC stage C: 72.5%), good liver function (Child–Pugh class A: 100%) and ECOG performance status (0–1: 90.5%). Macroscopic vascular invasion (MVI), extrahepatic spread (EHD) or both was present in 33.9%. 20.1% had received prior surgical procedures, 8.5% prior ablative procedures and 33.3% prior vascular [chemo]embolization. RE was predominantly a single whole-liver procedure (median activity 1.7 GBq). Median overall survival was 10.8 months (95% CI: 8.8–12.8) in the SHARP-equivalent cohort, 10.2 months (8.3–11.8) in patients with MVI/EHD, 9.7 months (7.6–10.9) in advanced HCC (BCLC stage C) and 16.6 months (11.2–22.8) in intermediate HCC (BCLC stage B). Treatment-related adverse events (all grades; grade >3) were: fatigue (50.3%; 2.1%), abdominal pain (25.9%; 2.1%), nausea/vomiting (31.2%; 0.5%) and GI ulcer (3.2%; 1.0%). At baseline, raised bilirubin (all grades) was present in 20.3%, increasing to 49.4% of patients evaluated up to day 90. Bilirubin grade was unchanged in 58.1% and increased in 37.8%; 4.0% had ≥grade 3 events. Conclusions: In patients matching the inclusion criteria for SHARP, RE was well tolerated with a median overall survival which compares favorably with sorafenib.

KEYNOTE-224: Phase II study of pembrolizumab in patients with previously treated advanced hepatocellular carcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS504-TPS504 ◽  
Author(s):  
Andrew X. Zhu ◽  
Jennifer J. Knox ◽  
Masatoshi Kudo ◽  
Stephen L. Chan ◽  
Richard S. Finn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Ecog Performance Status ◽  
Previously Treated

TPS504 Background: The tyrosine kinase inhibitor sorafenib is the standard of care for first-line hepatocellular carcinoma (HCC). For patients with HCC after disease progression on sorafenib or for those with intolerance to sorafenib, no approved therapies are available. Because HCC is often driven by inflammation and is also associated with a suppressed immunoenvironment, there is a strong rationale to evaluate immunotherapy in patients with this type of cancer. The single-arm, multisite, phase 2 KEYNOTE-224 study (ClinicalTrials.gov, NCT02702414) was designed to evaluate the efficacy and safety of the anti–PD-1 antibody pembrolizumab in patients with previously treated advanced HCC. Methods: Approximately 100 patients will be enrolled. Inclusion criteria include age ≥18 years, histologically or cytologically confirmed diagnosis of HCC Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to or refractory to locoregional therapy, and disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation). Patients must also have measurable disease based on RECIST v1.1 as confirmed by central imaging vendor review, documented objective radiographic progression after stopping treatment with sorafenib or intolerance to sorafenib, Child-Pugh liver score A, ECOG performance status 0-1, and predicted life expectancy > 3 months. Patients will be allocated to receive pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles (~2 years) or until disease progression, unacceptable toxicity, patient withdrawal of consent, or investigator decision. Response will be assessed every 9 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. The primary end point is objective response rate per RECIST v1.1 by central imaging vendor review. Secondary end points are overall survival; safety and tolerability; and duration of response, disease control rate, time to progression, and progression-free survival per RECIST v1.1 by central imaging vendor review. Enrollment in KEYNOTE-224 is ongoing. Clinical trial information: NCT02702414.

Real-world treatment characteristics for first-line therapy (1L) of advanced hepatocellular carcinoma (HCC) in Canada and Europe.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 353-353
Author(s):  
Sharlene Gill ◽  
Dena H Jaffe ◽  
Marc DeCongelio ◽  
Arnold N. DuBell ◽  
Jing Shi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Function ◽  
Portal Vein ◽  
Real World ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Unmet Need ◽  
Advanced Hepatocellular Carcinoma ◽  
Portal Vein Invasion

353 Background: Sorafenib is indicated for the treatment of HCC. This study captures and describes real-world use of 1L therapy for advanced unresectable or metastatic HCC across Canada and Europe. Methods: A retrospective, non-interventional survey of 278 physicians in Canada (7.5%) and Europe (92.5%) (France, Germany, Italy, Spain and UK) was conducted between Feb-Mar 2018. Clinical and treatment data were collected from medical charts for patients aged ≥18y, who initiated and completed systemic 1L treatment for HCC within 2 years of data collection, and a Child-Pugh [CP] A/B at 1L initiation. Descriptive statistics compared 1L systemic therapy, sorafenib vs. other. Results: 706 patients were included (n = 504 sorafenib; n = 202 other [83% chemotherapy; 10% targeted therapy; 7% checkpoint inhibitors]) with a mean age at 1L of 62.7±9.3y and 79% males. Comorbidities did not differ by sorafenib vs. other for alcoholism (33%), Hepatitis C (14%), and nonalcoholic steatohepatitis and/or nonalcoholic fatty liver disease (9%) but did for Hepatitis B (12% vs. 6%) and cirrhosis (31% vs. 18%) (both p < 0.05). At diagnosis, more patients treated with sorafenib vs. other had portal vein invasion (56% vs. 35%, p < 0.001). At 1L initiation, sorafenib patients had better performance status (PS) (ECOG 0-1: 80% vs. 67%, p < 0.05) and preserved liver function (CP A: 58% vs. 47%, p < 0.05). The results indicated that sorafenib was used less compared to other systemic therapies among those with poor performance (ECOG 2-4) and poor liver function (CP B) (71% vs. 83%, p = 0.068). Median treatment duration was shorter for sorafenib (2 vs. 4 months, p < 0.001). The most common grade 3 adverse events were fatigue (9%), diarrhea (5%), and hand/foot skin reaction (4%). Conclusions: In this real-world chart survey of Canadian and European physicians, sorafenib remains the most commonly used 1L systemic therapy for advanced HCC. Patients treated with sorafenib were more likely to have cirrhotic liver disease, portal vein invasion, better PS and preserved liver function, but sorafenib use was not limited to CP A. Understanding determinants of 1L therapy is important as the treatment landscape of HCC is evolving to address unmet need.

Cabozantinib in advanced hepatocellular carcinoma: Efficacy and safety data from an international multicenter real-world cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16668-e16668
Author(s):  
Fabian Finkelmeier ◽  
Bernhard Scheiner ◽  
Catherine Leyh ◽  
Jan Best ◽  
Thorben Wilhelm Fründt ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Disease ◽  
Side Effects ◽  
Real World ◽  
Advanced Hepatocellular Carcinoma ◽  
Duration Of Treatment ◽  
Advanced Liver Disease ◽  
Advanced Hcc ◽  
International Multicenter

e16668 Background: The multikinase inhibitor cabozantinib has been approved by the European Medicines Agency in November 2018 for hepatocellular carcinoma (HCC) prior treated with sorafenib. We report, to our knowledge, for the first time safety and efficacy data of an international, multicenter, real-world cohort of patients with advanced HCC treated with cabozantinib. Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 10 centers in Austria and Germany. Patients´ characteristics, side effects, duration of treatment and survival data were analyzed until January 17, 2020. Results: 74 patients were identified of whom 65 patients were male (88%) and 9 were female (12%). The median age at the start of cabozantinib treatment was 66 years. The most common underlying liver diseases included hepatitis C in 15 (20%), hepatitis B in 6 (8%), alcohol in 17 (23%) and NAFLD/NASH in 20 (27%) patients, respectively. 64 patients (86%) had BCLC stage C and 43 patients (58%) were Child Pugh A. Cabozantinib was used as systemic second- and third-line treatment in 37 (50%), and 25 (34%) patients, respectively. In the remaining patients cabozantinib was used in further lines. The median starting dose was 40 mg (20-60 mg). In 26 patients (35%) a dose reduction due to side effects was performed. Following best responses under cabozantinib were documented: partial response in 4 (5%), stable disease in 22 (30%), and progressive disease in 24 (32%) patients, respectively. 24 patients (32%) had not yet been evaluable. The median duration of cabozantinib treatment was 4.4 months. 35 patients (47%) had died at day of data analysis. The median overall survival from start of cabozantinib treatment was 7.7 months. Most common adverse events were fatigue and diarrhea. Conclusions: Cabozantinib treatment was effective, safe and feasible in patients with advanced HCC. Patients in the real life setting had more advanced liver disease – only 58% of patients were Child A. Duration of treatment was similar to the phase 3 trial (CELESTIAL). However, overall survival was shorter, probably due to more advanced liver disease.

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