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Background@#/Aim: Radiotherapy (RT) is an effective local treatment for hepatocellular carcinoma (HCC). However, whether additional RT is safe and effective in patients with advanced HCC receiving atezolizumab plus bevacizumab remains unclear. This retrospective cohort study aimed to evaluate the feasibility of additional RT in these patients. @*Methods@#Between March and October 2021, we retrospectively analyzed seven patients with advanced HCC who received RT during treatment with atezolizumab plus bevacizumab. The median prescribed RT dose was 35 Gy (range, 33–66). Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) after RT were analyzed. @*Results@#The median follow-up duration after RT was 14.2 months (range, 10.0–18.6). Of the seven patients, disease progression was noted in six (85.7%), the sites of disease progression were local in two (28.6%), intrahepatic in four (57.1%), and extrahepatic in four (57.1%). The median time of FFLP was not reached, and PFS and OS times were 4.0 (95% confidence interval [CI], 3.6–4.5) and 14.8% (95% CI, 12.5–17.2) months, respectively. The 1-year FFLP, PFS, and OS rates were 60% (95% CI, 43.8–76.2), 0%, and 85.7% (95% CI, 75.9–95.5), respectively. Grade 3 or higher hematologic adverse events (AEs) were not observed, but grade 3 nonhematologic AEs unrelated to RT were observed in one patient. @*Conclusions@#The addition of RT may be feasible in patients with advanced HCC treated with atezolizumab plus bevacizumab. However, further studies are required to validate these findings.
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Background/Aims@#Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. @*Methods@#This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). @*Results@#In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28–0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0–56.7%, whereas that of the TKI group was 12.3–15.0%. @*Conclusions@#For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.
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Hepatocellular carcinoma (HCC) is highly prevalent and the third most common cause of cancer-related death in Asia. In contrast to the West, the main etiology of HCC in many Asian countries except Japan is chronic hepatitis B virus infection. Differences in the major causes of HCC lead to significant clinical and treatment differences. This review summarizes and compares guidelines on managing HCC from China, Hong Kong, Taiwan, Japan, and South Korea. From oncology and socio-economic perspectives, factors such as underlying diseases, staging methods, government policies, insurance coverage, and medical resources contribute to varying treatment strategies among countries. Furthermore, the differences in each guideline are fundamentally caused by the lack of incontrovertible medical evidence, and even existing results of clinical trials can be interpreted differently. This review will provide a complete overview of the current Asian guidelines for HCC in recommendations and in practice.
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Peritoneal seeding of hepatocellular carcinoma (HCC) is incurable and has poor prognosis. A 68-year-old man underwent surgical resection for a 3.5 cm single nodular HCC at the tip of segment 3 and transarterial chemoembolization for a 1.5 cm-sized recurrent HCC at the tip of segment 6. 3 months later, an increasing 1 cm pelvic nodule on the rectovesical pouch warranted radiotherapy. Although it stabilized, a new 2.7 cm-sized peritoneal nodule in the right upper quadrant (RUQ) omentum appeared 3.5 years after radiotherapy. Hence, omental mass and small bowel mesentery mass excision were performed. 3 years later, recurrent peritoneal metastases in the RUQ omentum and rectovesical pouch progressed. 33 cycles of atezolizumab and bevacizumab treatment elicited stable disease response. Finally, laparoscopic left pelvic peritonectomy was performed without tumor recurrence. Herein, we present a case of HCC with peritoneal seeding that was successfully treated with surgery after radiotherapy and systemic therapy, leading to complete remission.
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The incidence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide, including Asia. Most patients with NAFLD-related HCC are at a much-advanced stage and older age at the time of diagnosis than those with virus-related HCC because they have not undergone HCC surveillance. This review provides an overview of the mechanism of hepatocarcinogenesis in NAFLD, preventive strategies for NAFLDrelated HCC, and strategies for the surveillance of patients with NAFLD.
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The prognosis of patients with advanced hepatocellular carcinoma (HCC) with tumor thrombus extending to the inferior vena cava (IVC) is extremely poor. Herein, we present a rare case of advanced HCC that was treated with sorafenib and radiotherapy, leading to complete remission. This patient had a 9 cm infiltrative HCC occupying almost the entire left lobe with a tumor thrombus extending through the hepatic vein, IVC, and left portal vein. The patient received 400 mg sorafenib twice daily. One year after the start of sorafenib, intensity-modulated radiation therapy for viable HCC and tumor thrombus was performed with a dose of 5,500 cGy. Twenty-seven months after the starting date of sorafenib, there was no intratumoral arterial enhancement, which suggested a complete response according to the modified RECIST criteria. This case suggests that the combination of sorafenib and radiotherapy might provide clinical benefits in patients with advanced HCC with IVC tumor thrombus.
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Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate secondline systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents.
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Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate secondline systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents.
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Spontaneous tumor rupture is a serious but rare complication of hepatocellular carcinoma (HCC) and has a low survival rate. Here, we report a case of massive HCC that ruptured and was treated successfully with transarterial chemoembolization (TACE). A 55-year-old man with abdominal pain was diagnosed with a 12-cm-wide ruptured HCC at segment 8. The overall liver function was scored as Child–Pugh A, but the single nodule tumor had ruptured; therefore, TACE treatment was initiated. After the first TACE treatment, residual tumors were found; thus, secondary TACE was performed 5 months later. No new lesions or extrahepatic metastases were found 16 months after the first TACE treatment, so hepatic resection was performed for curative treatment. The postoperative pathology results did not reveal any cancer cells; hence, TACE alone resulted in a cure. We report this case because the cure has been maintained for more than 3 years after resection.
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Background/Aims@#Multiple meta-analyses and observational studies have reported that alcohol is a risk factor for liver cancer. However, whether there is a safe level of alcohol consumption remains unclear. We performed a systematic review and meta-analysis of the correlation between low-level alcohol consumption and the risk of liver cancer. @*Methods@#Nested case-control studies and cohort studies involving the general population published prior to July 2019 were searched. In total, 28 publications (31 cohorts) with 4,899 incident cases and 10,859 liver cancer-related deaths were included. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. @*Results@#Compared with those with low levels of alcohol consumption, moderate and heavy drinkers (≥1 drink/day for females and ≥2 drinks/day for males) had pooled ORs of 1.418 (95% CI, 1.192 to 1.687; p<0.001) for liver cancer incidence and 1.167 (95% CI, 1.056to 1.290; p=0.003) for liver cancer mortality. The pooled OR for liver disease-related mortality for those with more than low levels of alcohol consumption was 3.220 (95% CI, 2.116 to 4.898; p<0.001) and that for all-cause mortality was 1.166 (95% CI, 1.065 to 1.278; p=0.001). The sensitivity analysis showed that none of the studies had a strong effect on the pooled OR. The Egger test, Begg rank correlation test, and the funnel plot showed no overt indication of publication bias. @*Conclusions@#Continuous consumption of more than a low-level of alcohol (≥1 drink/day for females and ≥2 drinks/ day for males) is related to a higher risk of liver cancer.
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BACKGROUND/AIMS: Sorafenib remains the only approved molecular targeted agent for hepatocellular carcinoma (HCC); however, reliable biomarkers that predict its efficacy are still lacking. The aim of this study was to explore whether cancer stem cell (CSC) markers have a predictive role with regard to the sorafenib response in HCC patients. METHODS: We enrolled 47 patients with HCC for whom tumor samples obtained before starting sorafenib treatment were available. RNA was extracted from formalin-fixed, paraffin-embedded samples, and real-time polymerase chain reaction was used to quantify mRNA expression of the CSC genes EpCAM, CD13, CK8, CD24, CD44, CD90, CD133, SALL4, ALDH1A1, ALB, and AFP. RESULTS: Of 47 patients, 14.9% and 74.5% had vascular invasion and extrahepatic spread, respectively. Patients with low CD133 expression tended to have longer progression-free survival (PFS) than those with high CD133 expression (5.5 months vs 4.0 months), although without statistical significance. The expression levels of other markers were not associated with PFS. When examining markers in combination, patients with high CD133 and CD90 expression had shorter PFS rates than those with low expression (2.7 months vs 5.5 months; p=0.04). Patients with low CD133 and EpCAM expression demonstrated better PFS than those with high expression (7.0 months vs 4.2 months; p=0.04). Multivariable analysis indicated that an Eastern Cooperative Oncology Group performance status score of 1 and high CD133/CD90 expression were significantly associated with shorter PFS. CONCLUSIONS: Overexpression of the CSC markers CD133 and CD90 in HCC was associated with poorer response to sorafenib. These two genes may serve as predictive biomarkers for sorafenib therapy.
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Humanos , Biomarcadores , Carcinoma Hepatocelular , Supervivencia sin Enfermedad , Células Madre Neoplásicas , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , ARN , ARN Mensajero , Células MadreRESUMEN
BACKGROUND/AIMS: There have been no nationwide studies to investigate the trends in incidence and 5-year survival rates of intra- and extrahepatic bile duct cancers and gall-bladder cancer. Therefore, our study aimed to describe the incidence and 5-year survival rates of biliary tract cancers by subsites in South Korea. METHODS: A total of 86,134 patients with biliary tract cancers were selected from the National Health Information Database. Age-standardized incidence rates and annual percentage changes were calculated. Life-table methods and log-rank tests were used to determine the differences in survival rates. Cox-proportional hazard models were used to estimate the hazard ratio of the patients with biliary tract cancers. RESULTS: The incidence rate of intra-hepatic bile duct cancer decreased by 1.3% annually from 8.8 per 100,000 in 2006 to 7.8 per 100,000 in 2015. Extrahepatic bile duct cancer also showed a decreasing trend by 2.2% per year from 8.7 per 100,000 in 2006 to 6.7 per 100,000 in 2015. Gallbladder cancer showed the greatest decline, with an annual percentage change of 2.8% from 6.3 per 100,000 to 5.2 per 100,000 during the same period. The 5-year survival rates were 30.0% in gallbladder cancer, 27.8% in extrahepatic bile duct cancer, and 15.9% in intra-hepatic bile duct cancer. CONCLUSIONS: The overall incidence rates of intrahepatic and extrahepatic bile duct cancer and gallbladder cancer decreased from 2006 to 2015. Among biliary tract cancers, intrahepatic bile duct cancers exhibited the highest incidence rate and the worst survival rate.
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Humanos , Neoplasias de los Conductos Biliares , Conductos Biliares Extrahepáticos , Conductos Biliares Intrahepáticos , Neoplasias del Sistema Biliar , Sistema Biliar , Colangiocarcinoma , Neoplasias de la Vesícula Biliar , Incidencia , Corea (Geográfico) , Modelos de Riesgos Proporcionales , Tasa de SupervivenciaRESUMEN
PURPOSE: Although there are several prospective clinical studies comparing radiofrequency ablation (RFA) and hepatic resection (HR) for the treatment of hepatocellular carcinoma, there are few trials that have been performed in strictly homogeneous patients. METHODS: Patients who were newly diagnosed with a solitary hepatocellular carcinoma were randomized to the HR or RFA group. Inclusion criteria were as follows: age ≥ 20 years but ≤ 70 years, Child-Pugh class A, maximal diameter of the tumor ≥ 2 cm but ≤ 4 cm, no previous treatment history, and platelet count > 80,000/mm3. RESULTS: Although the study was early terminated, 29 and 34 patients were enrolled in the HR and RFA groups, respectively, and prospectively followed on an intention-to-treat basis. The 5-year overall survival rates were 83.4% and 86.2% in the HR and RFA groups, respectively, which were not significantly different (P = 0.812 by log-rank, P = 0.990 by Breslow). The 3- and 5-year disease-free survival rates in the HR group were significantly superior to those in the RFA group (66.7%, 44.4% vs. 44.1%, 31.2%, P = 0.071 by log-rank, P = 0.023 by Breslow). Intrahepatic local recurrence tended to develop more frequently in the RFA group (P = 0.042), while the frequency of intrahepatic distant and extrahepatic recurrence was similar bet ween the 2 groups. There were no significant differences in the frequency and severity of complications between the 2 groups. CONCLUSION: HR was significantly superior to RFA in terms of disease-free survival; however, the overall survival was excellent in both groups.
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Humanos , Carcinoma Hepatocelular , Ablación por Catéter , Supervivencia sin Enfermedad , Hepatectomía , Recuento de Plaquetas , Estudios Prospectivos , Recurrencia , Tasa de SupervivenciaRESUMEN
Liver cancer is the sixth most common cancer (fourth in men and sixth in women) and the second largest cause of cancer mortality in South Korea. The crude incidence rate of liver cancer was 31.9/100,000 (47.5/100,000 in men and 16.2/100,000 in women) and the age-standardized incidence rate was 19.9/100,000 (32.4/100,000 in men and 8.8/100,000 in women) in 2014. The crude incidence rate increased from 1999 to 2011 and thereafter showed a subtle decreasing tendency. The crude prevalence rate was 113.6/100,000 (170.2/100,000 in men and 57.1/100,000 in women) and the age-standardized prevalence rate was 72.6/100,000 (115.7/100,000 in men and 33.7/100,000 in women) in 2014, which increased from 2010 to 2014. Survival from liver cancer has improved over the last two decades. The 5-year relative survival rate was markedly increased from 10.7% in those diagnosed with liver cancer between 1993 and 1995 to 32.8% in those diagnosed between 2010 and 2014. The epidemiology of liver cancer is influenced by that of underlying liver diseases such as viral hepatitis. Substantial progress has been made in the prevention and treatment of viral hepatitis; however, uncontrolled alcoholic liver disease, obesity and diabetes appears to have the potential to emerge as major causes for liver cancer. Depending on the success of the control of risk factors, the epidemiology of liver cancer in Korea may change.
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Humanos , Masculino , Carcinoma Hepatocelular , Epidemiología , Hepatitis , Incidencia , Corea (Geográfico) , Hepatopatías , Hepatopatías Alcohólicas , Neoplasias Hepáticas , Hígado , Mortalidad , Obesidad , Prevalencia , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Systemic therapy for hepatocellular carcinoma (HCC) has markedly changed since 2007, with the approval of sorafenib. Sorafenib improved the overall survival of patients with advanced HCC; however, the modest efficacy and toxicity of this therapy present unmet needs. Subsequently, a variety of molecular targeted agents have been tested as first-line or second-line therapies but have failed, and sorafenib has remained the only approved systemic agent for almost 10 years. Recently, regorafenib significantly improved overall survival and was approved for patients with HCC who have been previously treated with sorafenib. Nivolumab, a programmed death protein-1 inhibitor, was also approved as second-line therapy, based on remarkable response rates.
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Humanos , Carcinoma Hepatocelular , Inmunoterapia , Terapia Molecular DirigidaRESUMEN
The original article contained incorrect figure captions.
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PURPOSE: We developed a new method of detecting circulating tumor cells (CTCs) in liver cancer patients by constructing cell blocks from peripheral blood cells, including CTCs, followed by multiple immunohistochemical analysis. MATERIALS AND METHODS: Cell blockswere constructed from the nucleated cell pellets of peripheral blood afterremoval of red blood cells. The blood cell blocks were obtained from 29 patients with liver cancer, and from healthy donor blood spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, α-fetoprotein (AFP), Glypican 3, and HepPar1. RESULTS: The average recovery rate of spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2 cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18 (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1, and Glypican3 were expressed only in tissue. Only EMA was significantly associated with the expressions in CTC and tissue. CTC detection was associated with higher T stage and portal vein invasion in HCC patients. CONCLUSION: This cell block method allows cytologic detection and multiple immunohistochemical analysis of CTCs. Our results show that tissue biomarkers of HCC may not be useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in patients with HCC.
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Humanos , Anticuerpos , Biomarcadores , Células Sanguíneas , Carcinoma Hepatocelular , Línea Celular , Colangiocarcinoma , Células Epiteliales , Eritrocitos , Glipicanos , Inmunohistoquímica , Queratinas , Neoplasias Hepáticas , Hígado , Métodos , Mucina-1 , Células Neoplásicas Circulantes , Vena Porta , Donantes de TejidosRESUMEN
Hepatocellular carcinoma (HCC) can be diagnosed based on characteristic findings of arterial-phase enhancement and portal/delayed "washout" in cirrhotic patients. Several countries and major academic societies have proposed varying specific diagnostic criteria for HCC, largely reflecting the variable HCC prevalence in different regions and ethnic groups, as well as different practice patterns. In 2014, a new version of Korean practice guidelines for management of HCC was released by the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC). According to the KLCSG-NCC Korea practice guidelines, if the typical hallmark of HCC (i.e., hypervascularity in the arterial phase with washout in the portal or 3 min-delayed phases) is identified in a nodule > or = 1 cm in diameter on either dynamic CT, dynamic MRI, or MRI using hepatocyte-specific contrast agent in high-risk groups, a diagnosis of HCC is established. In addition, the KLCSG-NCC Korea practice guidelines provide criteria to diagnose HCC for subcentimeter hepatic nodules according to imaging findings and tumor marker, which has not been addressed in other guidelines such as Association for the Study of Liver Diseases and European Association for the Study of the Liver. In this review, we briefly review the new HCC diagnostic criteria endorsed by the 2014 KLCSG-NCC Korea practice guidelines, in comparison with other recent guidelines; we furthermore address several remaining issues in noninvasive diagnosis of HCC, including prerequisite of sonographic demonstration of nodules, discrepancy between transitional phase and delayed phase, and implementation of ancillary features for HCC diagnosis.
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Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Carcinoma Hepatocelular/diagnóstico , Medios de Contraste , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Hígado/patología , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética/métodos , Guías de Práctica Clínica como Asunto , República de CoreaRESUMEN
PURPOSE: The purpose of this study is to determine the optimal dose of proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: Inoperable HCC patients who had naive, recurrent, or residual tumor to treatment were considered eligible for PBT. Patients received PBT with 60 GyE in 20 fractions (dose level 1; equivalent dose in 2 Gy fractions [EQD2], 65 GyE10); 66 GyE in 22 fractions (dose level 2; EQD2, 71.5 GyE10); or 72 GyE in 24 fractions (dose level 3; EQD2, 78 GyE10). Dose-limiting toxicity was determined by grade > or = 3 acute toxicity. RESULTS: Twenty-seven patients were enrolled; eight, seven, and 12 patients were treated with dose levels 1, 2, and 3, respectively. Overall, treatment was well tolerated, with no dose-limiting toxicities. The complete response (CR) rates of primary tumors after PBT for dose levels 1, 2, and 3 were 62.5% (5/8), 57.1% (4/7), and 100% (12/12), respectively (p=0.039). The 3-and 5-year local progression-free survival (LPFS) rates among 26 patients, excluding one patient who underwent liver transplantation after PBT due to its probable significant effect on disease control, were 79.9% and 63.9%, respectively, and the 3-and 5-year overall survival rates were 56.4% and 42.3%, respectively. The 3-year LPFS rate was significantly higher in patients who achieved CR than in those who did not (90% vs. 40%, p=0.003). CONCLUSION: PBT is safe and effective and an EQD2 > or = 78 GyE10 should be delivered for achievement of local tumor control.