Goodemunksgaard0296
Targeted therapies like vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are the first-choice treatment in several types of cancers. We aim to determine the comparative risk of bleeding events associated with the VEGFR-TKIs through a network meta-analysis.
Published data search up to November 2018 reporting bleeding in cancer patients treated with VEGFR-TKIs was performed. The primary outcome was presence of hemorrhagic events at the end of the trial. Bleeding as a side-effect profile was examined for eleven VEGFR-TKIs (Apatinib, Brivanib, Cabozantinib, Lenvatinib, Motesanib, Nintedanib, Pazopanib, Regorafenib, Sorafenib, Sunitinib and Vandetanib). Network meta-analysis based on random effects model estimating Odds Ratio (OR) with 95 % confidence interval (CI), compared the risk of bleeding events among the VEGFR-TKIs with respect to placebo control conditions.
Fifty Randomized Clinical Trials (RCTs) including 16,753 cancer patients were included in this analysis. Twenty studies compared VEGFR-TKIs with placebo, the remaining studies compared VEGFR-TKIs with the standard chemotherapeutic regimen. VEGFR-TKIs were associated with increased incidence of all-grade hemorrhagic events in comparison to control (standard chemotherapy and/or placebo) (OR = 1.79; 95 % CI 1.50-2.13, p-value <0.0001) and placebo (OR = 1.50; 95 % CI 1.16-1.93, p-value = 0.1). However, there was no difference in high-grade bleeding in patients treated with VEGFR-TKI in comparison to control (OR = 1.22; 95 % CI 0.87-1.71, p-value 0.74) or placebo alone (OR = 1.05; 95 % CI 0.65-1.70, p-value 0.73). Among individual VEGFR-TKIs, Sunitinib (OR = 3.31, 95 % CI 2.34-4.69) and Regorafenib (OR = 2.92, 95 % CI 1.50-5.71) were associated with higher risk of hemorrhagic events in comparison to placebo.
VEGR-TKIs, particularly Sunitinib and Regorafenib appear to be associated with increased risk of bleeding incidence.
PROSPERO CRD42017056406.
PROSPERO CRD42017056406.
Tumor microenvironmentplays an essential role during the progression of hepatocellular carcinoma (HCC). Tumor infiltrating immune cells (TILs)was an important component of tumor microenvironment. However, whether TIL features are correlated with the prognosis of HCC patients remains unclear.
Cancer tissue and paired paracancerous tissues from 220 stage II∼III HBV-related HCCpatients were collected. TILs were analyzed using a tyramide signal amplification system combined with immunohistochemistry.Kaplan-Meier survival analysis was conducted to investigate the associations between the prognosis and the infiltrating pattern of TILs.
The patients were classified into three distinct subgroups (Clusters (C)1-3) with different overall survival (OS) and disease-free survival (DFS) according to the distribution pattern of TILs. The CD68/CD8 ratio in the cancer SA was correlated with the prognosis. Patients with a higher CD68/CD8 ratio exhibited poorer OS and DFS than those with a lower ratio. The CD68/CD8 ratio in the cancer SA was an independent factor for OS prediction but not DFS.
CD68+ macrophages and CD8+ T-cells are essential immunological determinants for HBV-related HCC prognosis, and the CD68/CD8 ratio in cancer SA is a novel, prognostic factor for OS prediction in HBV-related HCC patients.
CD68+ macrophages and CD8+ T-cells are essential immunological determinants for HBV-related HCC prognosis, and the CD68/CD8 ratio in cancer SA is a novel, prognostic factor for OS prediction in HBV-related HCC patients.
Several treatment strategies for early stage hepatocellular cancers (HCC) have been evaluated in randomised controlled trials (RCTs). This network meta-analysis (NMA) aimed to explore the relative effectiveness of these different approaches on their impact on overall (OS) and recurrence-free survival (RFS).
A systematic review was conducted to identify RCT's reported up to 23rd January 2020. Indirect comparisons of all regimens were simultaneously compared using random-effects NMA.
Twenty-eight RCT's, involving 3,618 patients, reporting 13 different treatment strategies for early stage HCC were identified. Median follow-up, reported in 22 studies, ranged from 12-93 months. In this NMA, RFA in combination with iodine-125 was ranked first for both RFS (HR 0.50, 95% CI 0.19-1.31) and OS (HR 0.41, 95% CI 0.19-0.94). In subgroup with solitary HCC, lack of studies reporting RFS precluded reliable analysis. However, RFA in combination with iodine-125 was associated with markedly better OS (HR 0.21, 95% CI 0.05-0.93).
This NMA identified RFA in combination with iodine-125 as a treatment delivering better RFS and OS, in patients with early stage HCC, especially for those with solitary HCC. This technique warrants further evaluation in both Asia and Western regions.
This NMA identified RFA in combination with iodine-125 as a treatment delivering better RFS and OS, in patients with early stage HCC, especially for those with solitary HCC. selleck This technique warrants further evaluation in both Asia and Western regions.
The prevalence of non-alcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC) has increased parallelly with that of metabolic syndrome. This study aimed to compare the clinical and survival outcomes of NAFLD-HCC and HBV-related HCC(HBV-HCC).
The medical records of patients who underwent hepatectomy for HCC at Severance Hospital between 2005 and 2015 were retrospectively reviewed. Occult HBV infection was identified by nested PCR. Propensity score matching (PSM) was conducted to minimize lead-time bias caused by the lack of surveillance in NAFLD patients. Surgical and oncologic outcomes were compared between the two groups.
There were 32 patients (7%) with NAFLD-HCC, 200 (46%) with HBV-HCC, and 194 (44%) with HBV/NAFLD-HCC (HBV and NAFLD). Before PSM, cirrhosis was more frequently detected in HBV-HCC patients (55% vs 15%,p<0.001) and the average tumor size was larger in the NAFLD-HCC group than in the HBV-HCC group (4.4±3.3cm vs 3.4±1.8cm,p=0.014). After a median follow-up of 74 monients with metabolic syndrome for the early detection of HCC.
