Comparative efficacy and safety of multimodality treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus: patient-level network meta-analysis
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ABSTRACT:
SUBMITTER: Leung J
PROVIDER: S-EPMC10905023 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:IntroductionPrevious trials demonstrated that anti-angiogenesis or anti-programmed death protein 1 (PD-1) monotherapy showed unsatisfied effect in advanced hepatocellular carcinoma (HCC). No study existed that focus on the effects of camrelizumab and apatinib ("C+A") combination therapy for HCC patients with the location and extent of portal vein tumor thrombus (PVTT) as the main variable being assessed. This study was to compare the efficacy and tolerability of "C+A" for HCC patients with PVTT.MethodsWe retrospectively analyzed patients with advanced HCC and PVTT who underwent "C+A" therapy in a multicenter retrospective cohort from Jan 2019 to July 2020. Outcomes of patients who underwent "C+A" were analyzed by using the Kaplan-Meier method according to types of PVTT: PVTT in the main portal vein (type A), PVTT in the first-order portal vein branch (type B), and PVTT in second- or lower-order portal vein branches (type C).ResultsSixty-three patients were finally included and the mean duration of follow-up was 12.6 ± 4.5 months. The objective response rate (ORR) and disease control rate (DCR) for the whole cohort were 44.0% and 75.0%, respectively. The median overall survival (OS), progression-free survival (PFS) and time to progression (TTP) were 14.8 months, 11.8 months and not yet reached (NR), respectively. Patients with type B (OS, 15.9 months; PFS, 14.0 months; TTP, NR) or type C (OS, 16.0 months; PFS, 14.9 months; NR) PVTT appear to have better survival benefits compared with type A (OS, 5.8 months; PFS, 5.0 months; TTP, 7.0 months). Along with AFP, the absence of main PVTT was an independent predictive factor for survival at uni- and multivariate analysis.ConclusionCamrelizumab and apatinib yielded a promising outcome in patients with advanced HCC who developed a tumor thrombus in the first lower-order portal vein branches and was generally safe and had manageable side effects.
| S-EPMC7734076 | biostudies-literature
Project description:The optimal treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains controversial. We aimed to investigate the best treatment for patients with HCC with PVTT. From January 2002 to January 2014, the data from all consecutive patients with HCC with PVTT who underwent surgical treatment (ST),TACE,TACE combined with sorafenib (TACE-Sor), or TACE combined with radiotherapy (TACE-RT) in the 4 largest tertiary hospitals in China were analyzed retrospectively. The patients were divided into 3 subtypes according to the extent of PVTT in the portal vein (type I-III). The primary endpoint was overall survival (OS). A total of 1580 patients with HCC with PVTT were included in the study. The median survival times (MST) for ST (n = 745) for type I, II, and III patients (95% CI) were 15.9 (13.3-18.5), 12.5 (10.7-14.3), and 6.0 (4.3-7.7) months, respectively. The corresponding figures for patients after TACE (n = 604) were 9.3 (5.6-12.9), 4.9 (4.1-5.7), and 4.0 (3.1-4.9), respectively; for patients after TACE-Sor (n = 113) 12.0 (6.6-17.4), 8.9 (6.7-11.1), and 7.0 (3.0-10.9), respectively; and for patients after TACE-RT (n = 118) 12.2 (0-24.7), 10.6 (6.8-14.5), and 8.9 (5.2-12.6), respectively. Comparison among the different treatments for the 3 subtypes of PVTT patients after propensity score (PS) matching showed the effectiveness of ST to be the best for type I and type II PVTT patients, and TACE-RT was most beneficial for type III patients. Treatment was an independent risk factor of OS. ST was the best treatment for type I and II PVTT patients with Child-Pugh A and selected B liver function. TACE-RT should be given to type III PVTT patients.
| S-EPMC4839896 | biostudies-literature
Project description:Background and aimsThe safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of symptomatic portal hypertension (SPH) caused by hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) of main trunk remains unclear. The purpose of this study was to initially explore the safety and efficacy of TIPS for SPH caused by HCC with PVTT of main trunk.MethodsThis retrospective study analyzed 16 patients who underwent TIPS for SPH caused by HCC with PVTT of main trunk. The evaluated outcomes were technical success rate, SPH control rate, stent patency rate, overall survival (OS), and complications.ResultsFrom July 2018 to February 2023, sixteen consecutive HCC patients with PVTT of main trunk and SPH were retrospectively identified. Technical success was 93.75 %. All patients had complete or partial remission of clinical symptoms, and there were no incidents of acute variceal rebleeding and re-exacerbation of ascites during follow-up. There had no intraoperative TIPS-related complications occurred. One patient developed mild hepatic encephalopathy after TIPS placement during the follow-up period. During follow-up, 13 of 16 patients died of advanced HCC progression, the median OS was 10.0 months, and the cumulative OS of 0.5-, 1-, and 2 years were 66.67 %, 45.00 %, and 11.25 %, respectively.ConclusionsTIPS for SPH caused by HCC with PVTT of main trunk may be safe and effective.
| S-EPMC10733097 | biostudies-literature
Project description:Portal vein tumor thrombus (PVTT) frequently occurs with the progression of hepatocellular carcinoma (HCC) and is an important factor in determining the prognosis of HCC. In many cases of HCC with advanced PVTT, treatment is difficult because the tumor has considerable extension into the liver, and portal hypertension is a frequent complication. The standard therapy for unresectable HCC with advanced PVTT is sorafenib therapy in patients with good hepatic function. However, the outcomes of sorafenib therapy are not completely satisfactory, making the development of another therapy an urgent task. Therefore, this review aims to summarize non-operative treatments for HCC with advanced PVTT and discuss future perspectives based on those therapies, including therapies still being developed.
| S-EPMC5472939 | biostudies-literature
Project description:BackgroundWe aimed to investigate the efficacy of a novel regimen, external beam radiation (RT) combined with trans arterial chemoembolization (TACE) and lenvatinib (LEN), in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus.MethodsWe prospectively observed 102 participants from three tertiary medical centers in China between October 2018 and October 2020, who chose either RT plus TACE and LEN (RT-TACE-LEN) or TACE and LEN (TACE-LEN). LEN (12 mg or 8 mg daily) was administrated orally and continued until progression or intolerable side effects were noted. TACE was given one day after administration of LEN, and RT began within 4 weeks after the first TACE. The median dose/fraction of RT was 50 Gy/25 fractions (range: 45-60 Gy/25 fractions). Overall survival and progression free survival were compared between two groups, and complications were assessed.ResultsBoth 51 patients received RT-TACE-LEN and TACE-LEN, respectively. Most patients had tumor size> 5 cm (73.8%) and tumor number≥ 2 (69.9%). The overall incidence of toxicities was significantly higher in RT-TACE-LEN group than TACE-LEN group (100% vs. 64.7%, p< 0.001), but incidences of grade 3-4 toxicities were comparable (54.9% vs. 49.0%, p= 0.552). Both median overall survival (22.8 vs. 17.1 months, p= 0.031) and median progression-free survival (12.8 vs. 10.5 months, p= 0.035) were significantly longer after RT-TACE-LEN treatment than TACE-LEN.ConclusionsThe addition of RT to TACE and LEN was safe, and might improve clinical outcomes of patients with advanced HCC, which needs conformation from further studies.
| S-EPMC10763235 | biostudies-literature
Project description:IntroductionVascular invasion and metastasis are poor prognostic factors in patients with hepatocellular carcinoma (HCC). The efficacy of available therapeutic regimens for unresectable HCC is not satisfactory in HCC with portal vein tumour thrombosis (PVTT). Therefore, this open-label, single-arm phase II clinical trial aims to investigate the efficacy and safety of radiotherapy combined with atezolizumab plus bevacizumab in treating HCC patients with PVTT.Methods and analysisWe plan to enrol patients diagnosed with unresectable HCC complicated by PVTT. Intensity-modulated radiotherapy (IMRT) combined with atezolizumab plus bevacizumab will be administered for treatment. Patients will initially receive radiotherapy, with each IMRT cycle lasting for 28 days and the total dose of tumour (DT) of 40 Gy/20 f/26 d. CT scan will be performed again, and the treatment plan will be reformulated after field constriction. The treatment will continue until the total DT is up to 54-56 Gy/27-28 f. The treatment with atezolizumab plus bevacizumab will be started at 3±1 days after the initiation of radiotherapy and will continue until unacceptable toxicity or disease progression. The primary endpoint is objective response rate (ORR), while the secondary endpoints include overall survival, disease control rate, progression-free survival, time to progression, duration of response and the rate of surgical conversions. Assuming an ORR of 47%, with a two-sided alpha error of 0.1, 90% power, and a 10% drop-out rate, the required number of evaluable patients is 42.Ethics and disseminationThis study will be conducted according to the standards of Good Clinical Practice and in compliance with the principles of the Declaration of Helsinki. The Ethics Committee of our Hospital has approved the protocol (EHBHKY2021-K-017). All participants are required to provide written informed consent. The results of the trial will be published in peer-reviewed journals and presented at international conferences.Trial registration numberChiCTR2100049831.
| S-EPMC9756192 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) with main portal vein tumor thrombus (mPVTT) has a poor prognosis even after surgical resection. Whether neoadjuvant radiotherapy improves surgical outcomes is currently unknown. The aim of this study was to compare the survival of patients with resectable HCC and mPVTT who underwent neoadjuvant therapy to those who underwent surgery alone.MethodsA non-randomized comparative study was performed. For patients in the neoadjuvant radiotherapy group, three-dimensional conformal radiotherapy was administrated with a daily fraction of 300 cGy in 6 consecutive days. Hepatectomy was carried out 4 weeks after completion of irradiation.Results95 patients were enrolled into this study. In the neoadjuvant radiotherapy group (n = 45), 12 patients showed gross radiological reduction in extent of PVTT. In 6 patients, the extent of PVTT was reduced to be within the ipsilateral side of the portal vein. When compared with patients who underwent surgery alone (n = 50), neoadjuvant radiotherapy significantly decreased the rates of HCC recurrence and HCC-related death, with hazard ratios of 0.36 (95% CI, 0.19-0.70) and 0.32 (95% CI, 0.18-0.57), respectively.ConclusionFor patients with HCC with mPVTT, neoadjuvant radiotherapy before partial hepatectomy provided better postoperative survival outcomes than partial hepatectomy alone.
| S-EPMC4913143 | biostudies-literature
Project description: Not available
| S-EPMC10035715 | biostudies-literature
Project description:Rationale: Hepatocellular carcinoma (HCC) is primarily characterized by a high incidence of vascular invasion. However, the specific mechanism underlying portal vein tumor thrombus (PVTT) in HCC remains unclear. As a consequence of myeloid cell developmental arrest, CD71+ erythroid progenitor cells (EPCs) and myeloid-derived suppressor cells play important roles in HCC; however, their roles in PVTT remain unclear. Methods: The role of CD71+ EPCs in the HCC tumor microenvironment (TME) was evaluated via morphological, RNA-sequencing, enzyme-linked immunosorbent assay, and flow cytometric analyses. Co-culture techniques were employed to assess the CD45+ EPCs and their vascular compromising effect. Additionally, the PVTT-promoting function of CD45+ EPCs was explored in vivo in a murine model. Results: The CD45+EPCs in HCC tissues exhibited increased myeloid cell features, including morphology, surface markers, transforming growth factor (TGF)-β generation, and gene expression, compared with those in circulation. Hence, a large proportion of CD45+EPCs, particularly those in TMEs, comprise erythroid-transdifferentiated myeloid cells (EDMCs). Additionally, the expression of C-C chemokine receptor type 2 (CCR2) mRNA was upregulated in CD45+EPCs within the TME. Tumor macrophages from HCC tissues induced substantial migration of CD45+EPCs in a dose-dependent manner. Meanwhile, results from immunofluorescence analyses revealed that these two cell types are positively associated in the TME and circulation. That is, EDMCs are chemoattracted by HCC macrophages mainly via CCR2 from CD45+ EPCs in the circulation. Additionally, the expressions of FX, FVII, FGB, C4b, CFB, and CFH were elevated in CD45+EPCs within the TME compared with those in the spleen. The CD45+EPCs from the HCC TME promoted vessel endothelial cell migration and compromised tube formation through TGF-β and FGB, respectively. Additionally, CD45+EPCs from the TME induced HCC cell migration. HCC macrophage-induced CD45+EPCs to exhibit higher levels of FX, FVII, FGB, and TGF-β. Meanwhile, upregulation of CCAAT/enhancer binding protein beta expression induced FGB and TGF-β generation in CD45+EPCs in the TME. WTAP, a major RNA m6A writer, stabilized FX and FVII mRNA and enhanced their nuclear export in CD45+EPCs from the TME. CD45+EPCs from the TME were positively associated with PVTT and poor prognosis. Splenectomy reduced the level of CD45+EPCs in the circulation and TME, as well as the incidence of microvascular invasion. The incidence of microvascular invasion increased following the transfer of HCC tissue CD45+EPCs to splenectomized HCC-bearing mice. Conclusions: The CD45+EPCs enriched in the HCC microenvironment are EDMCs, which are induced by HCC macrophages to migrate from the circulation to the TME. Subsequently, EDMCs promote PVTT by compromising the blood vessel endothelium, aggravating coagulation, and promoting HCC cell migration.
| S-EPMC10465220 | biostudies-literature
Project description:ObjectivesTo compare the efficacy, overall survival (OS) and safety of drug-eluting beads-TACE (DEB-TACE) and C-TACE as initial treatment in advanced hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (mPVTT).MethodsThe medical records of consecutive advanced HCC patients with mPVTT who underwent initial DEB-TACE or C-TACE from September 2015 to October 2021 were retrospectively evaluated. Treatment crossover was allowed in this retrospective research. The adverse events, disease control rate (DCR), time to tumor progression (TTP) and OS of patients who underwent DEB-TACE were compared with those of patients who underwent C-TACE.ResultsEighty-three patients were included: 42 patients in DEB-TACE group and 41 patients in C-TACE group. DEB-TACE could be safely performed in HCC patients with mPVTT, and they gained a better DCR than those submitted to the C-TACE (76.2% vs. 53.7%, P = 0.031), which might have resulted in longer TTP (median TTP: 9.0 months vs. 3.0 months, P < 0.001). Furthermore, DEB-TACE showed significant OS benefits compared with C-TACE (median OS: 12.0 months vs. 5.0 months, P < 0.001). DEB-TACE, absence of arterioportal shunts (APS), leisons with capsular non-infiltration were found to be independent prognostic factors for better OS. Furthermore, subgroup analysis proved that patients with good DCR gained longer OS in DEB-TACE group.ConclusionsDEB-TACE could be safely performed and improve the DCR of HCC patients with mPVTT, which resulting in longer TTP and OS, compared with C-TACE.
| S-EPMC10362718 | biostudies-literature