Hepatocellular carcinoma (HCC) is a cytotoxic chemotherapy-resistant tumor and most HCCs arise in a background of liver cirrhosis of various causes. Although the IMBrave150 trial showed remarkable advancements in the treatment of unresectable HCC with atezolizumab plus bevacizumab (AteBeva), therapeutic outcomes were unsatisfactory in more than half of the patients. Accordingly, many ongoing trials combine conventional modalities with new drugs such as immune checkpoint inhibitors for better treatment outcomes, and they are expected to benefit patients with limited responses to conventional treatment. Here, two patients with advanced stage HCC with preserved liver function and good performance status showed partial response after treatment with combination or sequential therapy of AteBeva, hepatic arterial infusion chemotherapy, radiation therapy, and transarterial chemoembolization. These findings indicate the efficacy of multidisciplinary treatment against advanced HCC. Additional studies are required to establish optimal treatment strategies.
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Complications of immunotherapy in advanced hepatocellular carcinoma Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim Journal of Liver Cancer.2024; 24(1): 9. CrossRef
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Background/Aims Lenvatinib was recently proven to be non-inferior to sorafenib in treating unresectable hepatocellular carcinoma (HCC) in a phase-3 randomized controlled trial. In this study, we investigated whether the response to lenvatinib was affected by tumor immunogenicity.
Methods Between May 2019 and April 2020, nine patients with intermediate-to-advanced HCC, who were treated with lenvatinib after liver biopsy, were enrolled. Immunohistochemical staining and multi-color flow cytometry were performed on specimens obtained from liver biopsy.
Results Among the nine patients enrolled, four showed objective responses (complete responses+partial responses). Immunohistochemical staining for CD3, CD68, and programmed cell death ligand 1 (PD-L1) demonstrated that patients with objective responses showed marked infiltration of T cells and PD-L1-expressing macrophages in intra-tumoral and peri-tumoral tissues compared to those without objective responses. A significant difference in the numbers of infiltrated T cells, both in the intra-tumoral (P<0.01) and peri-tumoral regions (P<0.05), were identified between responders and non-responders. Regarding the number of infiltrated macrophages, no significant difference was found between the responders and non-responders, although the number of PD-L1-expressing tumor-associated macrophages was significantly higher in responders than that in non-responders (P<0.05).
Conclusions Tumor immunogenicity, as indicated by T cell and PD-L1-positive macrophage infiltration, affects lenvatinib response in unresectable HCC.
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Despite recent advances in the treatment of hepatocellular carcinoma (HCC), the prognosis
of patients with extrahepatic metastasis from HCC still remains dismal. The current study
presents a case of HCC that was metastatic to the pelvis and describes successful treatment
with multidisciplinary approach to the skeletal metastasis. The patient was a 67-year-old
male who presented with right pelvic pain 28 months following right hepatectomy for HCC.
Computed tomography and magnetic resonance imaging indicated a solitary bone metastasis
without intrahepatic recurrence. Complete response was achieved with multidisciplinary
management including sorafenib, transarterial embolization, surgery to remove the
metastatic mass and radiotherapy after surgery. A post-operative follow-up 15 months later
found that the patient remained in good health with maintained complete response. This case
suggests that a multidisciplinary approach can achieve long-term cancer-free survival and
prolonged life expectancy beyond palliative care for patients with solitary bone metastasis
after curative surgery for HCC.
Background/Aims Metronomic (MET) chemotherapy is a treatment characterized by
frequent infusion of low doses of chemotherapeutic agent without extended break. The aim
of this study is to evaluate the efficacy of MET chemotherapy compared with transarterial
chemoembolization (TACE) in patients with child B class advanced hepatocellular carcinoma
(HCC). Methods Seventy-three patients with child B class advanced HCC were analyzed between
April, 2007 and August, 2013 according to two treatment groups: (i) MET chemotherapy group
(n=43, Epirubicin 35 mg/body surface area [BSA] every 4 weeks, and cisplatin 15 mg/BSA and
5-fluorouracil 50 mg/BSA weekly for 3 weeks) via an implantable port system with 1 week
break. (ii) TACE group (n=30, Adriamycin 20-50 mg) every 4 weeks. Primary endpoint was
overall survival (OS). Results The median survival times in the MET and TACE groups were 4.5 months and
3.1 months, respectively. The overall survival rate showed significantly better in the MET
treatment group than in the TACE group (P=0.039). When the factors affecting patient
OS were analyzed, MET chemotherapy (P=0.038, hazard ratio {HR} 0.538 [95% confidence
interval {CI} 0.299-0.967]) was independently associated with OS. Larger maximal tumor size,
extrahepatic metastasis and advanced stage also were significant factors for OS (P=0.009, HR
1.064 [95% CI 1.014-16.064]; P=0.014, HR 2.120 [95% CI 1.164-3.861]; P=0.019, HR 2.046 [95% CI
1.125-3.720], respectively). Conclusions MET chemotherapy showed survival benefit than TACE in patients with child
class B advanced HCC. Therefore, MET chemotherapy may be considered as a treatment
option for advanced HCC with poor liver function. (J Liver Cancer 2015;15:92-99)
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A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma with poor liver function Hyun Yang, Hyun Young Woo, Soon Kyu Lee, Ji Won Han, Bohyun Jang, Hee Chul Nam, Hae Lim Lee, Sung Won Lee, Do Seon Song, Myeong Jun Song, Jung Suk Oh, Ho Jong Chun, Jeong Won Jang, Angelo Lozada, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon Clinical and Molecular Hepatology.2017; 23(2): 128. CrossRef