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Background: This study aimed to assess the effectiveness and safety of vascular intervention combined with lenvatinib versus vascular intervention alone in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to identify prognostic factors associated with the treatment outcomes. Methods: We conducted a retrospective analysis of data from 92 patients with advanced HCC and PVTT who were treated between February 2016 and February 2023. Among them, 56 patients underwent vascular intervention alone (transarterial chemoembolization, TACE), while 36 patients received vascular intervention (TACE or hepatic arterial infusion chemotherapy [HAIC]) combined with lenvatinib. The primary outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Survival rates were estimated by the Kaplan-Meier method, and confounders were adjusted using inverse probability of treatment weighting (IPTW). Prognostic factors were determined through the Cox regression model. Results: The median follow-up duration was 20.07 months (interquartile range: 6.41-25.36). The combination therapy group had a significantly longer median PFS (11.00 vs. 5.00 months, P<0.05) and OS (12.91 vs. 6.83 months, P<0.05) in comparison to the monotherapy group, and these findings remained consistent after IPTW matching. Moreover, the combination therapy group showed a higher ORR (55.56% vs. 26.79%, P<0.05) based on mRECIST criteria. Cox multivariate analysis identified extrahepatic metastasis and maximum tumor diameter as risk factors for PFS, while age, tumor number, and maximum tumor diameter influenced OS. Combined treatment emerged as a protective factor for OS. In the combination therapy group, hypertension was the most frequent adverse event, with grade 3 or 4 adverse events occurring rarely. Conclusion: The combination of vascular intervention with lenvatinib has demonstrated improved PFS and OS in advanced HCC patients with PVTT, and its safety profile appears to be acceptable. Adoption of this combined treatment strategy at an earlier stage may enhance patient outcomes.
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Background: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide. Less than 30% of patients are suitable candidates for surgery. Transarterial chemoembolization (TACE) is considered as a first-line treatment for patients with unresectable advanced liver cancer. In the routine diagnosis and treatment pathway for unresectable HCC, a biopsy is usually performed firstly, followed by hepatic artery angiography and TACE. However, hepatic artery angiography data reveals that the risk of arteriovenous shunt (AVS) is significantly increased following biopsy, which negatively affects the outcomes of TACE. Aim: To investigate the feasibility of delayed biopsy following TACE in patients with HCC. Methods: Data from 112 patients with a definitive diagnosis of HCC were retrospectively analyzed. Patients who underwent biopsy immediately after TACE formed the experimental group (n = 55) and those who underwent biopsy before TACE formed the control group (n = 57). Positive pathological diagnosis rate, incidence of AVS, and rates of TACE-related complications were compared between the two groups. In addition, factors affecting the occurrence of AVS were assessed. Results: There was no significant difference in positive pathological diagnosis rate between the experimental and control groups (81.8% vs. 77.2%, respectively; P = 0.545). The incidence of AVS in the experimental group was lower than that in the control group (3.6% vs. 22.8%, respectively; P = 0.003), and embolization results were better in the experimental group. There was no difference in the incidence of TACE-related complications between the two groups. Late tumor stage (P = 0.04) and pre-TACE biopsy puncture (P = 0.003) are associated with the occurrence of AVS. Conclusion: In patients with HCC, delayed biopsy following completion of TACE did not affect pathological diagnosis results and yielded better embolization outcomes. Therefore, delayed biopsy following completion of TACE in patients with HCC is worth popularizing for clinical use. However, with the development of precision medicine, the diagnosis and treatment of tumor will certainly advance to the molecular level, whether the ischemic and oxygen-deficient tumor microenvironment caused by TACE treatment will have an impact on tumor tissue at molecular level remains unknown.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Biopsia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/terapia , Oxígeno , Estudios Retrospectivos , Resultado del Tratamiento , Microambiente TumoralRESUMEN
Purpose: To retrospectively evaluate the safety and efficacy of percutaneous computed tomography (CT)-guided microwave ablation (MWA) in colorectal cancer (CRC) lung metastases, and to analyze prognostic factors. Materials and methods: Data were collected from 31 patients with CRC lung metastases from May 2013 to September 2017. They had removed the CRC, no extrapulmonary metastases, no more than three metastases in the lung, the maximum diameter of the lesions was ≤3 cm, and all the lung metastases could be completely ablated. The ablation procedures were performed using a KY-2000 microwave multifunctional therapeutic apparatus. Efficacy is assessed two to four weeks after ablation, and follow-up are performed every three months for two years. The primary outcome was overall survival (OS). The secondary outcomes were progression-free survival (PFS), and complications. Cox regression analysis was used for the evaluation of the statistical significance of factors affecting the end result of MWA therapy. The Kaplan-Meier method was used for estimation of survival rates. Results: A total of 45 metastatic lung lesions from CRC in 31 patients were treated with CT-guided MWA procedures. The median OS was 76 months. The one, two, three, and five-year survival rates were 93.5%, 80.6%, 61.3%, and 51.6%, respectively. Multivariate analysis showed that the primary tumor from the rectum (P = 0.009) and liver metastases at the diagnosis of lung metastases (P = 0.043) were risk factors affecting OS, while PFS was a protective factor. The median PFS was 13 months. The maximum diameter of lung metastases lesions (P = 0.004) was a risk factor. The interval between pulmonary metastases and MWA (P=0.031) was the protective factor. Pneumothorax was observed in 13 out of 36 procedures. Four patients developed pneumothorax requiring drainage tube insertion. No patient deaths occurred within 30 days of ablation. Three out of 31 patients (9.67%) were found to have local recurrence of the original lung metastatic ablation foci. Conclusion: MWA therapy may be safely and effectively used as a therapeutic tool for the treatment of selected CRC pulmonary metastases, and the prognosis is better in patients without liver metastases at the diagnosis of lung metastases.
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BACKGROUND: The benefits and tolerability of transarterial chemoembolization (TACE) combined with regorafenib as a second-line therapy has not been reported for unresectable hepatocellular carcinoma (HCC). This study aimed to explore the benefits and tolerability of TACE combined with second-line regorafenib in patients with unresectable advanced HCC and failure to first-line treatment. METHODS: This was a multicenter retrospective study of patients with progression after first-line sorafenib and/or lenvatinib between 01/2019 and 04/2020 at four tertiary hospitals in China. The patients were treated with TACE. Then, 5-7 days after the first TACE, the patients started taking regorafenib for 3 weeks every 4-week cycle. The overall survival (OS), time to progression (TTP), progression-free survival (PFS), and adverse events (AEs) were observed. RESULTS: The median follow-up was 5.6 (range 0.7, 17.0) months. The median age was 60 (range 35, 79) years. There were 32 (84.2%) males. The patients underwent a median of three TACE sessions (range 1-13). The initial doses of regorafenib were 20 mg/d (n = 1, 2.6%), 80 mg/d (n = 10, 26.3%), 120 mg/d (n = 15, 39.5%), and 160 mg/d (n = 11, 28.9%). The incidence of grade 3/4 AEs was 15.8%. Two patients stopped regorafenib due to AEs. The median OS was 14.3 months. The median PFS and TTP were 9.1 (95% CI 4.0, 14.2) and 9.1 (95% CI 5.5, 12.8) months, respectively. CONCLUSIONS: The present study provides real-world evidence indicating that regorafenib combined with TACE was beneficial and tolerable in patients with unresectable HCC. Additional prospective large-scale studies are required for confirmation.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Adulto , Anciano , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Niacinamida , Compuestos de Fenilurea , Estudios Prospectivos , Piridinas , Estudios RetrospectivosRESUMEN
BACKGROUND: The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma (HCC) used placebo or sorafenib as comparators, and there are limited data providing a cross comparison of treatments in this setting, especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination treatments. AIM: To systematically review and compare response rates, survival outcomes, and safety of first-line systemic therapies for advanced hepatocellular carcinoma. METHODS: We searched PubMed, Science Direct, the Cochrane Database, Excerpta Medica Database, and abstracts from the American Society of Clinical Oncology 2020 annual congress. Eligible studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable HCC. Risk of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials. A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments. P value, a frequentist analog to the surface under the cumulative ranking curve, was used to rank treatments. RESULTS: In total, 1398 articles were screened and 27 included. Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and three other combination therapies. For overall response rate, lenvatinib ranked 1/19, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival (PFS), atezolizumab + bevacizumab was ranked 1/15, followed by lenvatinib. With the exception of atezolizumab + bevacizumab [hazard ratios (HR)PFS = 0.90; 95% confidence interval (CI): 0.64-1.25], the estimated HRs for PFS for all included treatments vs lenvatinib were > 1; however, the associated 95%CI passed through unity for bevacizumab plus erlotinib, linifanib, and FOLFOX4. For overall survival, atezolizumab plus bevacizumab was ranked 1/25, followed by vandetanib 100 mg/d and donafinib, with lenvatinib ranked 6/25. Atezolizumab + bevacizumab was associated with a lower risk of death vs lenvatinib (HRos = 0.63; 95%CI: 0.44-0.89), while the HR for overall survival for most other treatments vs lenvatinib had associated 95%CIs that passed through unity. Vandetanib 300 mg/d and 100 mg/d were ranked 1/13 and 2/13, respectively, for the lowest incidence of treatment terminations due to adverse events, followed by sorafenib (5/13), lenvatinib (10/13), and atezolizumab + bevacizumab (13/13). CONCLUSION: There is not one single first-line treatment for advanced HCC associated with superior outcomes across all outcome measurements. Therefore, first-line systemic treatment should be selected based on individualized treatment goals.