CT-based radiomics to predict development of macrovascular invasion in hepatocellular carcinoma: A multicenter study.

BACKGROUND: Macrovascular invasion (MaVI) occurs in nearly half of hepatocellular carcinoma (HCC) patients at diagnosis or during follow-up, which causes severe disease deterioration, and limits the possibility of surgical approaches. This study aimed to investigate whether computed tomography (CT)-based radiomics analysis could help predict development of MaVI in HCC. METHODS: A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups. CT-based radiomics signature was built via multi-strategy machine learning methods. Afterwards, MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model (CRIM, clinical-radiomics integrated model) via random forest modeling. Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development. Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development, progression-free survival (PFS), and overall survival (OS) based on the selected risk factors. RESULTS: The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors (P < 0.001). CRIM could predict MaVI with satisfactory areas under the curve (AUC) of 0.986 and 0.979 in the training (n = 154) and external validation (n = 72) datasets, respectively. CRIM presented with excellent generalization with AUC of 0.956, 1.000, and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory. Peel9_fos_InterquartileRange [hazard ratio (HR) = 1.98; P < 0.001] was selected as the independent risk factor. The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development (P < 0.001), PFS (P < 0.001) and OS (P = 0.002). CONCLUSIONS: The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.

Engineering the Properties of Transparent Hybrid Coating toward High Hardness, Excellent Flexibility, and Multifunction.

Transparent functional coatings with glass-like hardness and polymer-like flexibility are highly desirable for flexible and foldable displays. Although several coatings have been developed toward this goal, achieving a functional coating with 9H pencil hardness and extremely low bending radius of curvature (rc) remains a great challenge due to the inherent conflict between hardness and flexibility. To overcome this trade-off, a facile strategy is developed herein. The coating is an organic-inorganic hybrid nanocomposite that is prepared from thiol-acrylate polymerization of acrylo polyhedral oligomeric silsesquioxane and multifunctional thiols. The former provides the desired hardness, while the latter affords high flexibility and the maximum level of chemical bonding for organic-inorganic phases. Because of the good miscibility and varied functionality of monomers, we are able to manipulate the composition and internal structure of coating systematically, endowing it with high transparency (98%, 550 nm), super hardness (9H), excellent low modulus (1.85 GPa, the most flexible one to date), and the ability to withstand steel wool's abrasion and repeated bending (rc = 0.8 mm) 10 000 times on PET film. On the final coating, both antifouling and antibacterial abilities are integrated without sacrificing its other properties after postfunctionalizing a zwitterionic layer. This work balances the hardness-flexibility conflict effectively and provides some useful protective coatings for next-generation displays.

Combination of the neutrophil to lymphocyte ratio and the platelet to lymphocyte ratio as a useful predictor for recurrence following radiofrequency ablation of hepatocellular carcinoma.

The aim of the present study was to investigate the prognostic potential of a novel inflammation-based system, the combination of the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) (CNP), for predicting the survival time of patients with hepatocellular carcinoma (HCC) who had received radiofrequency ablation (RFA). A total of 287 HCC patients treated with RFA were enrolled in the study. Patients with an elevated NLR (>2.58) and an elevated PLR (>131.78) were allocated a score of 2, and patients exhibiting one or neither of these characteristics were allocated a score of 1 or 0, respectively. The association between the CNP and various HCC clinicopathological factors, patterns of recurrence and prognoses were analyzed. The CNP was associated with liver cirrhosis (P=0.015), Child-Pugh class (P=0.024), total bilirubin level (P=0.028), neutrophil count (P<0.001), lymphocyte count (P<0.001) and platelet count (P<0.001). Compared with their low-CNP counterparts, patients with an elevated CNP were more likely to develop distant intrahepatic recurrence [52.3% (CNP 2) vs. 33.9% (CNP 0) and 34.6% (CNP 1), P=0.015; CNP 0 vs. CNP 1, P=0.922; CNP 1 vs. CNP 2, P=0.020] and extrahepatic metastasis [25.0% (CNP 2) vs. 7.6% (CNP 0) and 18.5% (CNP 1), P=0.003; CNP 0 vs. CNP 1, P=0.020; CNP 1 vs. CNP 2, P=0.309], and had shorter overall survival (OS) time (CNP 0 vs. CNP 1, P<0.001; CNP 1 vs. CNP 2, P<0.001) and recurrence-free survival (RFS; CNP 0 vs. CNP 1, P=0.012; CNP 1 vs. CNP 2, P=0.004). Moreover, multivariate analysis revealed that the CNP was superior to the NLR and the PLR as an independent prognostic marker of OS and RFS. Therefore, it was concluded that the CNP may represent a useful predictor for recurrence and prognosis in patients with HCC treated with RFA.

Sorafenib continuation after first disease progression could reduce disease flares and provide survival benefits in patients with hepatocellular carcinoma: a pilot retrospective study.

BACKGROUND: Sorafenib is a promising drug for advanced hepatocellular carcinoma (HCC); however, treatment may be discontinued for multiple reasons, such as progressive disease, adverse events, or the cost of treatment. The consequences of sorafenib discontinuation and continuation are uncertain. MATERIALS AND METHODS: We retrospectively analyzed 88 HCC patients treated with sorafenib from July 2007 to January 2013. Overall survival (OS), post-disease progression overall survival (pOS), and time to disease progression (TTP) were compared for survival analysis. Cox proportional hazard regression was performed to assess the effect of important factors on OS in the overall patient population and on pOS in patients who continued sorafenib treatment. RESULTS: Sorafenib was discontinued and continued in 24 and 64 patients, respectively. The median OS (355 vs 517 days respectively; p=0.015) and median post-PD OS (260 vs 317 days, respectively; p=0.020) were statistically different between the discontinuation and continuation groups. Neither the median time to first PD nor the time to second PD were significantly different between the 2 groups. In the discontinuation group, 3 of the 24 patients (12.5%) suffered disease outbreaks. In Cox proportional hazard regression analysis after correction for confounding factors, BCLC stage (p=0.002) and PD site (p=0.024) were significantly correlated with pOS in patients who continued sorafenib treatment. CONCLUSIONS: Sorafenib discontinuation may cause HCC flares or outbreaks. It is advisable to continue sorafenib treatment after first PD, particularly in patients with Barcelona Clinic Liver Cancer stage B disease or only intrahepatic PD.

The relationship of kinase insert domain receptor gene polymorphisms and clinical outcome in advanced hepatocellular carcinoma patients treated with sorafenib.

Kinase insert domain receptor (KDR) is the principal receptor that promotes the pro-angiogenic action of vascular endothelial growth factor and has been the principal target of anti-angiogenic therapies. Our aim was to determine whether single-nucleotide polymorphisms (SNPs) in KDR gene are associated with clinical outcomes after first-line sorafenib therapy in advanced hepatocellular carcinoma (HCC). The SNPs in KDR were tested in 78 advanced HCC patients receiving first-line sorafenib. Correlations with clinicopathological features and survival were analyzed. Patients with AA genotype of rs1870377 and AA genotype of rs2305948 were significantly associated with a better response and longer time to progression (TTP) (5.8 vs 4.0 months, P=0.001; 5.8 vs 4.5 months, P=0.016, respectively). Patients harboring AA genotype in rs1870377 and TT/TC genotype in rs2071559 had a longer overall survival (OS) (15.0 vs 9.6 months, P=0.001; 13.0 vs 9.0 months, P=0.007, respectively). At multivariate analysis, major vascular invasion and rs1870377 were independent factors in TTP and performance status, rs1870377, and rs2071559 were independent factors in OS. Our results suggest that SNPs in KDR gene can predict clinical outcome in advanced HCC patients receiving first-line sorafenib.