Updated treatment recommendations for hepatocellular carcinoma (HCC) from the ESMO Clinical Practice Guidelines

Vogel, Arndt; Martinelli, Erika; Cervantes, A.; Chau, Ian; Daniele, Bruno; Llovet, Josep M.; Meyer, Tim; Nault, Jean‐Charles; Neumann, Ursula; Ricke, Jens; Sangro, Bruno; Schirmacher, Peter; Verslype, Chris; Zech, Christoph J.; Arnold, Dirk

doi:10.1016/j.annonc.2021.02.014

Cited by 246 publications

(207 citation statements)

References 13 publications

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“…Thus, (i) comparisons between two or more combinations should be performed to find better efficacious and tolerable drugs in future studies. (ii) According to the statement of the ESMO guideline [4], all the available firstand second-line drugs for HCC should be treated in a secondline setting. This means that along with atezolizumabbevacizumab or alisertib-lenvatinib combinations, more combinations such as lenvatinib-pembrolizumab should be investigated for more first-line setting.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Marasco et al assessed the performance of several prognostic scores. They reported poor performance outcomes of HCC patients treated with sorafenib [4]. European Society for Medical Oncology (ESMO) guideline recommended considering all of these approved agents mentioned above in the second-line setting after atezolizumab-bevacizumab combination was more efficacious; median progression-free survival is only 6.8 months [3].…”

Section: Introductionmentioning

confidence: 99%

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Antitumor Effect of Lenvatinib Combined with Alisertib in Hepatocellular Carcinoma by Targeting the DNA Damage Pathway

Hao

Peng

Wang

et al. 2021

BioMed Research International

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Background and Aim. Although a strong antitumor effect of lenvatinib has been noted for patients with unresectable hepatocellular carcinoma (HCC), its efficacy requires improvement. It is imperative to seek therapeutic strategies that combine Lenvatinib with other anticancer agents. In this study, we investigated the anticancer effect of combining lenvatinib with alisertib, aurora A kinase (AURKA) target drug, against HCC in vitro and in vivo. Methods. Immunohistochemical staining, sequencing, and genetic analysis of liver cancer tissues were performed. The antitumor efficacy of single-agent or combination treatment was measured by cell counting kit-8 assay and colony formation assays. Their antiproliferative and apoptosis activity is evaluated by cell cycle analyses and wound healing assays. The DNA-related proteins were also measured by Western blotting and immunohistochemical staining. The HepG2 xenograft model was used to detect the effects of lenvatinib-alisertib on the antitumor activity. Results. AURKA was found to be upregulated in HCC tissues (77.3%, 17/22). Combined alisertib and lenvatinib treatment significantly enhanced the inhibition of proliferation and migration in HepG2 and Hep3B cell lines compared to single-agent treatments (all P s < 0.01 ). Alisertib alone or in combination with lenvatinib demonstrated a significant increase in the percentage of super-G2 cells (lenvatinib 1 μM vs. lenvatinib 1 μM + alisertib 0.1 μM 8.84 ± 0.84 vs. 34.0 ± 1.54 , P < 0.001 ). Discontinuous spindles and missegregated chromosomes in HCC cells treated with alisertib in combination with lenvatinib were observed. We further revealed that combined treatment inhibited the expression of DNA damage pathway proteins compared to those of single-agent treatments. In nude mice, combined administration of alisertib combined with lenvatinib significantly enhanced the suppression of tumor growth and induced apoptosis (all P s < 0.01 ). Conclusions. Our findings provide evidence for the possible use of alisertib in combination with lenvatinib in the treatment of HCC for better therapeutic outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antitumor Effect of Lenvatinib Combined with Alisertib in Hepatocellular Carcinoma by Targeting the DNA Damage Pathway

Hao

Peng

Wang

et al. 2021

BioMed Research International

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“…With the continuous progress of research, small molecule type V tyrosine kinase inhibitors lenvatinib and atilizumab combined with bevacizumab have achieved better results than sorafenib and because of their superior advantages, have quickly become the standard first-line treatment. According to the latest ESMO clinical practice guidelines, for patients with portal vein invasion and extrahepatic metastasis, atilizumab combined with bevacizumab is the first-line treatment option ( 138 ). In terms of combined use, the remission rate of lenvatinib combined with pembrolizumab in the phase Ib trial reached 46%, although further exploration is needed ( 139 ).…”

Section: Preventionmentioning

confidence: 99%

Risk Factors and Prevention of Viral Hepatitis-Related Hepatocellular Carcinoma

et al. 2021

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Hepatocellular carcinoma (HCC) is a common cancer in the world, and its incidence is increasing yearly. Hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection are important causes of HCC. Liver cirrhosis, age, sex, smoking and drinking, and metabolic risk factors will increase the risk of cancer in HBV/HCV patients. And viral load, APRI, FIB-4, and liver stiffness can all predict the risk of HCC in patients with viral infection. In addition, effective prevention strategies are essential in reducing the risk of HCC. The prevention of HCC involves mainly tertiary prevention strategies, while the primary prevention is based on standardized vaccine injections to prevent the occurrence of HBV/HCV. Eliminating the route of transmission and vaccination will lead to a decrease in the incidence of HCC. Secondary prevention involves effective antiviral treatment of HBV/HCV to prevent the disease from progressing to HCC, and tertiary prevention is actively treating HCC to prevent its recurrence.

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“…Current guidelines recommend TACE as first-line therapy for BCLC-B disease and as an alternative treatment option for earlystage disease in patients unsuitable for surgical therapies or thermal ablation. 11,14 TACE is, however, recognised as a non-curative procedure in guidelines with reported recurrence rates of 25% and above. 9,11,15 The evidence supporting the role of SBRT as definitive treatment is building, with a recent systematic review of SBRT in early-stage HCC reporting 3 year local control of 93% and overall survival of 73% comparable to surgical resection or radiofrequency ablation.…”

Section: Increased Utilisation and Incorporation Into Guidelinesmentioning

confidence: 99%

Stereotactic body radiotherapy in the management of hepatocellular carcinoma: An Australian multi‐institutional patterns of practice review

et al. 2021

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IntroductionStereotactic body radiotherapy (SBRT) is an emerging, therapeutic option in the management of hepatocellular carcinoma (HCC). A multicentre Liver Ablative Stereotactic Radiation (LASR) database was established to provide a collaborative platform for Australian institutions to define the practice of liver SBRT for HCC. This study explores the patterns of SBRT practice amongst Australian institutions.MethodsThis was a multi‐institutional retrospective study of patients treated with SBRT for HCC at 10 institutions between January 2013 and December 2019. Patients' demographics, disease characteristics and SBRT details were evaluated.ResultsThree hundred and seventeen patients were evaluated with a median age of 67 years (range, 32–90). Liver cirrhosis was present in 88.6%, baseline Child‐Pugh score was A5/6 in 85.1% and B7/8 in 13.2%. Median size of HCC treated was 30 mm (range, 10–280). 63.1% had early‐stage disease (Barcelona clinic liver cancer (BCLC) stage 0/A) and 36% had intermediate/advanced‐stage disease (BCLC B/C). In 2013/2014, six courses of SBRT were delivered, increasing to 108 in 2019. SBRT was prescribed in five fractions for 71.3% of the cohort. The most common dose fractionation schedule was 40 Gy in five fractions (24.3%). Median biologically effective dose (BED10) delivered was 85.5 Gy for early‐stage and 60 Gy for intermediate/advanced disease, respectively. The most common prescription range was 100–120 Gy BED10 (32.8%).ConclusionSBRT utilisation for HCC is increasing in Australia. There was wide variation in size of tumours and disease stages treated, and prescription patterns. Uniform reporting of clinical and dosimetric details are important in refining the role of liver SBRT.

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Updated treatment recommendations for hepatocellular carcinoma (HCC) from the ESMO Clinical Practice Guidelines

Cited by 246 publications

References 13 publications

Antitumor Effect of Lenvatinib Combined with Alisertib in Hepatocellular Carcinoma by Targeting the DNA Damage Pathway

Antitumor Effect of Lenvatinib Combined with Alisertib in Hepatocellular Carcinoma by Targeting the DNA Damage Pathway

Risk Factors and Prevention of Viral Hepatitis-Related Hepatocellular Carcinoma

Stereotactic body radiotherapy in the management of hepatocellular carcinoma: An Australian multi‐institutional patterns of practice review

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