Dataset Information

Hepatocellular carcinoma with main portal vein tumor thrombus: a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy.

ABSTRACT:

Background

Hepatocellular 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.

Methods

A 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.

Results

95 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.

Conclusion

For patients with HCC with mPVTT, neoadjuvant radiotherapy before partial hepatectomy provided better postoperative survival outcomes than partial hepatectomy alone.

SUBMITTER: Li N

PROVIDER: S-EPMC4913143 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

Hepatocellular carcinoma with main portal vein tumor thrombus: a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy.

Li Nan N Feng Shuang S Xue Jie J Wei Xu-Biao XB Shi Jie J Guo Wei-Xing WX Lau Wan-Yee WY Wu Meng-Chao MC Cheng Shu-Qun SQ Meng Yan Y

HPB : the official journal of the International Hepato Pancreato Biliary Association 20160507 6

<h4>Background</h4>Hepatocellular 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.<h4>Methods</h4>A non-randomized comparative study was performed. For patients in the neoadjuvant radiothera ...[more]

PMID: 27317960

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Project description:BackgroundThe prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is extremely poor. The clinical outcome of preoperative radiotherapy (RT) is still controversial. This study aimed to compare the clinical outcomes of combined neoadjuvant RT and hepatectomy with hepatectomy alone for HCC with PVTT.MethodsComprehensive database searches were performed in PubMed, the Cochrane Library, EMBASE, and the Web of Science to retrieve studies published from the database creation to July 1, 2020. Only comparative studies that measured survival between neoadjuvant RT followed by hepatectomy and hepatectomy alone were included. The characteristics of the included studies and patients were extracted, and the included data are presented as relative ratio (RR) estimates with 95% confidence intervals (CIs) for all outcomes. The RRs of each study were pooled using a fixed or random effects model with Review Manager (the Cochrane Collaboration, Oxford, UK) version 5.3. The response rate to RT and the overall survival (OS) rate in neoadjuvant RT followed by hepatectomy and hepatectomy alone were measured.ResultsOne randomized and two non-randomized controlled trials with 302 patients were included. Most patients were classified as Child-Pugh A, and Type II and III PVTT were the most common types. After RT, 29 (22.8%) patients were evaluated as partial response (PR) and had a positive RT response, but nine (7.1%) had progressive disease (PD). Neoadjuvant RT followed by hepatectomy was received by 127 (42.1%) patients after excluding 15 (5.0%) patients with severe complications or PD after RT, and 160 (53.0%) patients received hepatectomy alone. In the randomized controlled trial (RCT), the 1-year OS rate in the neoadjuvant RT group and the surgery alone group was 75.2% and 43.1%, respectively (P<0.001). In the two non-randomized studies, a meta-analysis with a fixed effects model showed a longer OS in patients undergoing neoadjuvant RT followed by hepatectomy compared with hepatectomy alone at 1-year follow-up (RR =2.02; 95% CI: 1.45-2.80; P<0.0001).ConclusionsThis systematic review showed that neoadjuvant RT followed by hepatectomy in patients with resectable HCC and PVTT was associated with a longer OS than patients who received hepatectomy alone.

Project description:Background and aimsPortal vein tumor thrombus (PVTT) occurs frequently in hepatocellular carcinoma (HCC) patients. However, there is currently no satisfactory treatment. Radiotherapy (RT) and tyrosine kinase inhibitors (TKI) are currently commonly used. However, whether their combined use provides a survival benefit is debatable. This retrospective study compared the efficacy and safety between radiotherapy plus lenvatinib (RT + L) and radiotherapy plus sorafenib (RT + S) in the treatment of hepatocellular carcinoma with portal vein tumor thrombus (PVTT).MethodsAmong patients with PVTT who received RT + L or RT + S between March 2017 and September 2022, the primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse effects. The prognostic factors were also assessed.ResultsThe analysis included 152 patients (RT + L: 48; RL: 25; RT + S: 55; S: 24). Compared with the RT + S group, the RT + L group had a longer OS and PFS. Among patients with type I/II PVTT, the median OS times were 19.8 months and 13.5 months (p = 0.047) and the median PFS was 12.3 months and 7.3 months (p = 0.042), respectively. And the median OS of the patients with type I/II PVTT were 14.4 months and 8.3 months (p = 0.030) and the median PFS was 8.3 months and 6.2 months (p = 0.026). ORR and DCR in RT + L group (25.0% and 75.0%) were also little higher than those in RT + S group (20.0% and 70.9%), but not statistically significant. In univariate analysis, etiology, Type of PVTT, alpha-fetoprotein (AFP) level, Child-Pugh score, and treatment method influenced OS. Multivariate analysis confirmed that treatment method, etiology, alpha-fetoprotein (AFP) level, and Child-Pugh score were independent prognostic factors for OS. Similar safety profiles were observed in the RT + L and RT + S groups. The most common adverse events were myelosuppression, decreased liver function, fatigue, diarrhea, nausea, and vomiting. Most adverse reactions were grade 1-2.ConclusionThe side effects of radiotherapy plus lenvatinib were acceptable. Compared to RT + S, RT + L had good efficacy in the treatment of hepatocellular carcinoma with PVTT. Validation is needed in prospective studies with larger sample sizes.

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.

Dataset Information

Hepatocellular carcinoma with main portal vein tumor thrombus: a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy.

Background

Methods

Results

Conclusion

Publications

Hepatocellular carcinoma with main portal vein tumor thrombus: a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy.

Similar Datasets

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