Recently, the efficacy of immuno-oncologic agents for advanced hepatocellular carcinoma (HCC) has been proven in several trials. In particular, atezolizumab with bevacizumab (AteBeva), as a first-line therapy for advanced HCC, has shown tremendous advances in the IMBrave150 study. However, second or third-line therapy after treatment failure with AteBeva has not been firmly established. Moreover, clinicians have continued their attempts at multidisciplinary treatment that includes other systemic therapy and radiotherapy (RT). Here, we report a case that showed a near complete response (CR) of lung metastasis to nivolumab with ipilimumab therapy after achieving a near CR of intrahepatic tumor using sorafenib and RT in a patient with advanced HCC who had experienced treatment failure of AteBeva.
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Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update John D. Gordan, Erin B. Kennedy, Ghassan K. Abou-Alfa, Eliza Beal, Richard S. Finn, Terence P. Gade, Laura Goff, Shilpi Gupta, Jennifer Guy, Hang T. Hoang, Renuka Iyer, Ishmael Jaiyesimi, Minaxi Jhawer, Asha Karippot, Ahmed O. Kaseb, R. Kate Kelley, Jerem Journal of Clinical Oncology.2024; 42(15): 1830. CrossRef
Prognostic significance of combined PD-L1 expression in malignant and infiltrating cells in hepatocellular carcinoma treated with atezolizumab and bevacizumab Jaejun Lee, Jae-Sung Yoo, Ji Hoon Kim, Dong Yeup Lee, Keungmo Yang, Bohyun Kim, Joon-Il Choi, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Ji Won Han, Pil Soo Sung Frontiers in Immunology.2024;[Epub] CrossRef
Sorafenib is the oldest first line systemic treatment in patients with advanced hepatocellular
carcinoma (HCC) and has been used exclusively for nearly 10 years. The superiority of
administering a combination of atezolizumab plus bevacizumab (AteBeva) compared to
sorafenib as first line systemic treatment for unresectable HCC was recently proven during
the IMbrave150 Phase III randomized trial. While clinicians can expect improved responses
and treatment outcomes due to the good results of the IMbrave 150 trial, they must also
consider that atezolizumab can cause various immune-related adverse events (IrAEs). Based
on the above suggestions, we herein present a case of HCC with lymph node metastasis
who achieved complete remission following treatment with AteBeva and developed an IrAE
(adrenal insufficiency). Further study of real-life data regarding combination therapy with
AteBeva is needed to manage patients with advanced HCC.
Sorafenib is a well-known approved systemic therapeutic agent used in patients with advanced hepatocellular carcinoma (HCC). Regorafenib and nivolumab are approved as second-line therapeutic drugs in patients showing disease progression after sorafenib therapy. However, there is no established third- or fourth-line therapy in patients with progression after regorafenib or nivolumab treatment. Recently, the combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICPIs) has been attempted as a firstline treatment strategy in advanced HCC patients based on the hypothesis that combination therapy may overcome resistance in ICPI monotherapy. On the basis of this suggestion, we herein describe the case of an HCC patient demonstrating macrovascular invasion, whereby partial remission was achieved via the combination of sorafenib and nivolumab following disease progression after nivolumab therapy. Further studies on the combination of TKIs and ICPIs are necessary to determine ways to manage HCC patients showing disease progression after ICPI therapy.
Sorafenib is the only approved targeted agent as the first line systemic therapy for treatment of
advanced hepatocellular carcinoma (HCC). However, the improvement of survival duration under
3 months is far from clinical satisfactory and most patients experience disease progression within
6 months after sorafenib therapy. Unfortunately, second line systemic therapy after treatment
failure of sorafenib was not established and there were no clear guidelines for salvage treatment
modalities. Recently, studies suggests that combination of sorafenib and single cytotoxic agent
can be relatively effective and safe strategy that achieves promising rates of local and systemic
control in advanced HCC patients. Based on above suggestions, we herein offer our experience
of a case achieved complete remission by combination therapy of sorafenib and tegafur in the
patient with progressed disease after sorafenib therapy.
Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) have a
extremely poor prognosis. According to the Barcelona Clinic Liver Cancer guideline, sorafenib
is a standard therapy in this situation, but many clinicians still select locoregional therapy (LRT)
such as transarterial therapy, external beam radiation therapy (EBRT), even surgical resection
(SR) or combination of LRTs because the survival improvement by sorafenib is unsatisfactory.
Based on recent meta-analysis and prospective study, transarterial chemoembolization (TACE)
and transarterial radioembolization seem to be effective and safe therapeutic option that
have comparable outcome to sorafenib. Recently large nationwide studies demonstrated
that SR can be a potentially curative treatment in selected patients. Hepatic arterial infusion
chemotherapy (HAIC) can be also good option, especially in Child class B patients based
on small volume prospective studies. Moreover, multidisciplinary strategies based on the
combination of LRTs (SR plus TACE, TACE + EBRT, TACE + Sorafenib, HAIC + EBRT etc.) may
improve survival of HCC patients with PVTT. Finally we discuss individualized and tailored
treatment strategies for different clinical situations.
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Progress in Non-Surgical Treatment of Primary Hepatocellular Carcinoma with Combined Portal Vein Carcinoma Thrombosis 文豪 寇 Advances in Clinical Medicine.2023; 13(07): 11779. CrossRef
Transarterial chemoembolization (TACE) is the worldwide procedure performed for patients
with various stage hepatoceullar carcinoma (HCC), but is not yet considered as curative
treatment because of relatively high local recurrence rate. Moreover, many clinicians
frequently experience treatment failure (incomplete necrosis or stage progression etc.) after
repeated TACE, but no clear guidelines have been recommended about salvage treatment
modalities for this situation. Recently, studies for combination of radiation therapy and TACE
for HCC with TACE refractoriness have been tried and reported better therapeutic efficacy.
Based on above suggestions, we herein offer our experience of a patient with macrovascular
invasion developed after repeated TACE that achieve complete remission by stereotactic
body radiation therapy. Further study, maybe regarding a combination of locoregional and
systemic therapy, is necessary on how to manage HCC patients with TACE refractoriness.
Infiltrative hepatocellular carcinoma (HCC) patients have a poor prognosis because most
patients present with advanced disease. Although tumor size is small, ablation therapy
is difficult because it is difficult to delineate tumor boundary and tumor often combined
vascular invasion. Therefore many clinicians still try locoregional therapy (LRT) such as
transarterial chemoembolization (TACE), radiation therapy (RT), or combination with LRT
and sorafenib in this situation. Stereotactic body radiation therapy (SBRT) is new technology
providing very highly conformal ablative radiation dose and is expected to salvage modality
for HCC showed incomplete response of TACE due to combined arteriovenous (AV) shunts.
Based on above suggestions, we herein offer our experience of a complete remission of tumor
by combination of SBRT and TACE in a patient with infiltrative HCC. Further study, maybe
regarding a combination of locoregional and systemic therapy is necessary on how to manage
infiltrative HCC with AV shunts.
Reserved liver function is one of the most important determinants of survivial in advanced
hepatocellular carcinoma (HCC). Especially in cirrhotic patient with decompensated liver
function, sorafenib for HCC with main portal vein invasion have limited efficacy and survival
benefit. Therefore many clinicians or centers still try locoregional therapy (LRT) such as
transarterial chemoembolization (TACE), radiation therapy (RT), or combination with LRT
and sorafenib in this situation. However this multidisciplinary approach may increase
treatment related toxicity such as liver failure, etc. Recently, studies for combination of RT
and sorafenib for HCC with portal vein invasion have been tried and reported not only better
therapeutic efficacy, but also more hepatic toxicity.Based on above suggestions, we herein
offer our experience of a patient that although achieved survival gain via partial remission
of intrahepatic tumor and main portal vein thrombosis and metastatic lymph node by
combination therapy of RT and sorafenib, finally expired due to hepatictoxicity. Further study,
maybe regarding a combination of locoregional and systemic therapy, is necessary on how to
manage decompenstated cirrhotic patients with HCC with main portal vein invasion. (J Liver
Cancer 2014;14:120-126)
Hepatocellular carcinoma (HCC) patients with bile duct invasion have a poor prognosis because many do not receive effective treatment. Surgical resection is thought to be only option of curative treatment, increasing chance of survival, but it is possible to minor group of patients because of poor reserved liver function associated with underlying liver disease and obstructive jaundice. Therefore many clinicians or centers still select locoregional therapy such as transarterial chemoembolization (TACE), radiation therapy (RT) etc. Stereotactic body radiation therapy (SBRT) is new technology providing very highly conformal ablative radiation dose for a small numbers (1-5 fractions) of large fraction size and is expected to salvage modality for HCC showed incomplete response of TACE due to vascularity or accessibility of feeding artery. Based on above suggestions, we herein offer our experience of a patient with partial remission of tumor by combination therapy of TACE, SBRT and sorafenib. Further study, maybe regarding a combination of locoregional and systemic therapy (so called multidisciplinary approach), is necessary on how to manage HCC patients with bile duct invasion or sparse vascularity.
Extrahepatic metastasis (EHM) associated with hepatocellular carcinoma (HCC) has been increasing due to prolonged
survival with recent advances in therapeutic approaches including locoregional therapy such as transarterial chemoemoblization
(TACE), radiofrequency ablation and radiation therapy (RT). Though many guidelines recommended systemic therapy such as
sorafenib in this situation, some clinicians or centers still select locoregional therapy because the survival improvement of 2 or 3
months by sorafenib is far from optimal. Moreover, some studies showed that complete and partial response of intrahepatic
tumors can result in significant improvement of patient survival even in situation of EHM. Based on above suggestions, we herein
offer our experience of a patient with complete remission of intrahepatic tumor and adrenal gland metastasis treated with
combination therapy of TACE and RT and sorafenib. Further study, maybe regarding a combination of locoregional and systemic
therapy (so called multidisciplinary approach), is necessary on how to manage HCC patients with EHM.