Purpose
This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE).
Materials and Methods
From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA).
Results
Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness.
Conclusion
Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.
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Purpose
The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is often uncertain. We aimed to utilize analytic morphomics, a high-throughput imaging analysis, to assess if body composition is predictive of post-TACE survival.
Materials and Methods
We included patients from a single center (Ann Arbor VA)who had TACE as the primary treatment forHCC and had a pre-treatment computed tomography scans. Univariate analysis and multivariate conditional inference tree analysis were utilized to identify the morphomic characteristics predictive of 1-year survival. Resultswere validated in an external cohort(University of MichiganHealth System) ofHCC patientswho underwent TACE as their primary treatment.
Results
In the 75 patients in the derivation cohort, median survival was 439 (interquartile range, 377 to 685) days from receipt of TACE, with 1-year survival of 61%. Visceral fat density (VFD) was the only morphomic factor predictive of overall and 1-year survival (p < 0.001). Patients with VFD above the 56th percentile had a 1-year survival of 39% versus 78% for those below the 56th percentile. VFD also correlated with 1-year survival in the external validation cohort (44% vs. 72%, p < 0.001). In a secondary analysis, patients with higher VFD were significantly more likely to experience hepatic decompensation after TACE (p < 0.001).
Conclusion
VFD served as an objective predictor of mortality in patients undergoing TACE, possibly through its ability to predict hepatic decompensation. VFD may serve as a radiographic biomarker in predicting TACE outcomes.
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Purpose
In this study, we retrospectively investigated the prevalence of arterioportal (AP) shunts in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and evaluated the changes in AP shunts after chemoembolization followed by external beam radiation therapy (EBRT).
Materials and Methods
We analyzed 54 HCC patients with PVTT who were treated with chemoembolization followed by EBRT. EBRT was uniformly delivered at a total dose of 30 to 45 Gy (median, 35 Gy), with a daily dose of 2 to 4.5 Gy. Angiographic images of chemoembolization before and after radiation therapy (RT) were reviewed to investigate the AP shunt.
Results
During the initial session of chemoembolization, 33 of 54 patients (61%) had an AP shunt. After EBRT, 32 out of 33 patients had an additional session of chemoembolization and were evaluated for a change in the AP shunt. The AP shunt decreased in 20 of 32 patients (63%) after chemoembolization followed by EBRT. The 1-year calculated overall survival (OS) rate for all patients was 52.6% and the 2-year OS was 36.4%. The median OS in all patients was 13 months. Patients with AP shunt showed poorer median OS than those without AP shunt, but there was no statistically significant difference (median, 12 months vs. 17 months).
Conclusion
The AP shunt frequently occurs in HCC patients with PVTT. This study suggests that a poor prognosis is associated with an AP shunt. Chemoembolization followed by RT may produce a decrease in AP shunts.
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Hepatocellular carcinomas are one of the most common malignancies in the world. However, no effective therapeutic modality has been proven to prolong the survival of patients in an inoperable stage. The purpose of this study was to determine the response rate and the toxicities of a combination of pirarubicin, UFT and leucovorin in patients with non-embolizable hepatocellular carcinomas, or who had progressed during their transcatheter arterial chemoembolization treatment. MATERIALS AND METHODS Of 23 patients with a hepatocellular carcinoma, 11 had progressed during a transcatheter arterial chemoembolization, with the other 12 being transcatheter arterial chemoembolization-naive. All the patients were treated with pirarubicin (70 mg/m2 i.v., day 1), UFT (350 mg/m2 P.O., day 1~21), and leucovorin (25 mg/m2 P.O., day 1~21). RESULTS Twenty patients were able to be evaluated, with a partial response being achieved in four, giving an overall response rate of 20% (95% confidence interval, 7~44%). The median overall survival time was 6 months, and the median survival time of the transcatheter arterial chemoembolization-naive patients was significantly longer than that of those treated by transcatheter arterial chemoembolization (p=0.012). The most significant dose-limiting toxicity was leucopenia and thrombocytopenia. CONCLUSION The combination of pirarubicin, UFT and leucovorin therapies showed marginal antitumor activity and significant toxicity in patients with non-embolizable or failed transcatheter arterial chemoembolization hepatocellular carcinomas.
PURPOSE Although transarterial chemoembolization (TACE) has been widely used for the treatment of unresectable hepatocellular carcinoma, it has not been determined yet which chemotherapeutic agents were best for TACE. To determine the best chemotherapeutic regimen for TACE, we performed a prospective randomized study comparing 3 chemo- therapeutic regimen (adriamycin alone vs. cisplatin alone vs. adriamycin + cisplatin). MATERIALS AND METHODS The patients with unresectable hepatocellular carcinoma were eligible for this study and were randomly assigned to three treatment groups (A: adriamycin 30 mg/m(2), B: cisplatin 60 mg/m(2), C: adriamycin 30 mg/m(2) + cisplatin 60 mg/m(2)). The TACE were performed by administering the mixture of lipiodol and the assigned chemotherapeutic drugs through the hepatic artery, followed by embolization with gelfoam powder. The treatment was planned to be repeated every 4 weeks. RESULTS After 40 patients (14 in group A, 16 in group B, 10 in group C) entered, the study was stopped prematurely because of serious treatment-related complications including 15% of local complications, 18% of hepatic encephalopathy, and 8% of deaths. Because TACE could result in necrosis without reduction of mass size, the response could not be evaluated by the change of mass size, but by the change of serum alpha-fetoprotein level. Of 25 patients who had elevated serum alpha-fetoprotein and were assessable for response, there were one complete response (CR) and 5 partial responses (PR) out of 10 in group A, 5 PRs out of 10 in group B, and 2 PRs out of 5 in group C. There was no difference in response rates among the 3 treatment groups (p > 0.05). The response rate in patients treated with gelform embolization was higher than patients without embolization (63% (12/19) vs 19% (1/6): p<0.05). The median survival (OS) was 23 weeks for all 40 patients, 15 weeks for group A, 42 weeks for group B and 24 weeks for group C. The difference of OS between group A and B was statistically significant (p=0.02). However, the OS was not associated with any prognostic factors including treatment group in multivariate analysis. CONCLUSION Although cisplatin seemed to be more effective in TACE than adriamycin, no firm conclusion could be drawn from this prematurely ended study. However, we could conclude that the TACE with gelform powder is so toxic that it could not be given safely to the patients with unresectable hepatocellular carcinoma
Purpose We have investigated the annual frequency of recurrent intrahepatic tumors and the doubling time of regrowing tumors after transhepatic arterial chemoembolization (TAE) to know the proper time for subsequent TAE. Materials and Methods: Among cases in which a previous TAE was performed, 28 cases showed definite intrahepatic recurrence and 7 cases showed a regrowing tumor in the follow-up liver CT scan and/or hepatic angiography. Resnlts: The annual frequency of intrahepatic recurrence in the 28 tumors was 71.4% (20/28) within one year and 100% within 6 years. The mean doubling time of 7 regrowing tumors was 68.3 days. Conclusion: We concluded that periodically repeated TAE is needed for further treatment of the recurrent and regrowing tumors.
In order to evaluate the effect of preoperative transcatheter arterial chemoembolization on recurrence rate and survival after curative resection in patients with hepatocellular carcinoma, a retrospective clinical study of 57 patients underwent curative resection was performed. Fifty seven patients with hepatocellular carcinoma, underwent curative liver resection at Yongdong Severance Hospital from June 1985 to June 1995, were divided into two different treatment groups. Of the 57 patients, 25 patients(Group I) had received preoperative transcatheter arterial chemoembolization and 32(Group II) had not received. In any of the variables considered, age, sex, HBsAg, Child class, tumor number, tumor size, a- FP, operative method, no significant difference of patient characteristics between the two groups was found(p>0.05). Using the Kaplan-Meier Product-limit method and log-rank test, the differences of 1, 3, 5-year overall survival and disease-free survival rates, between these comparable groups were analyzed. The l, 3, 5-year overall survival rates in Group I and Group II were, respectively, 95.2%, 59.5%, 39.7% and 76.6%, 58.7%, 44.0%. Furthermore, the disease-free survival rates were, respectively, 81.5%, 50.3%, 50.3% and 69.4%, 43.9%, 30.8 %. This result indicates that there was no statistical significant difference between two groups in overall and disease-free survival. But, we gained a better results in Group I patients especially with total necrosis of tumor. So, further study, when & how we obtained total necrosis of hepatocellular carcinoma preoperatively, will be needed.