Identifying Proliferative Hepatocellular Carcinoma at Pretreatment CT: Implications for Therapeutic Outcomes after Transarterial Chemoembolization.

Background Hepatocellular carcinomas (HCCs) can be divided into proliferative and nonproliferative types, which may have implications for outcomes after conventional transarterial chemoembolization (cTACE). Biopsy to identify proliferative HCC is not routinely performed before cTACE. Purpose To develop and validate a predictive model for identifying proliferative HCCs using CT imaging features and to compare therapeutic outcomes between predicted proliferative and nonproliferative HCCs after cTACE according to this model. Materials and Methods This retrospective multicenter study included adults with HCC who underwent liver resection or cTACE between August 2013 and December 2020. A CT-based predictive model for identifying proliferative HCCs was developed and externally validated in a cohort that underwent resection. Diagnostic performance was calculated for the model. Thereafter, patients in the cTACE cohort were stratified into groups with predicted proliferative or nonproliferative HCCs according to the model. The primary outcome was overall survival (OS), and the secondary outcomes were tumor response rate and progression-free survival (PFS). These were compared between the two groups with use of the χ2 test and the log-rank test. Results A total of 1194 patients (1021 men; mean age, 54 years ± 12 [SD]; median follow-up time, 29.1 months) were included. The predictive model, named the SMARS score, incorporated lobulated shape, mosaic architecture, α-fetoprotein levels, rim arterial phase hyperenhancement, and satellite lesions. The area under the receiver operating characteristic curve for the SMARS score was 0.83 for the training cohort and 0.80 for the validation cohort. According to the SMARS score, patients with predicted proliferative HCCs (n = 114) had lower tumor response rate (48% vs 71%; P < .001) and worse PFS (6.6 months vs 12.4 months; P < .001) and OS (14.4 months vs 38.7 months; P < .001) than those with nonproliferative HCCs (n = 263). Conclusion The predictive model demonstrated good performance for identifying proliferative HCCs. According to the SMARS score, patients with predicted proliferative HCCs have worse prognosis than those with predicted nonproliferative HCCs after cTACE. © RSNA, 2023 Supplemental material is available for this article.

An Integrated Liver Function, Systemic Inflammation, and Tumor Characteristic Score Predicts Prognosis in Hepatocellular Carcinoma After Curative Resection.

BACKGROUND: Several scoring systems are currently used to predict prognosis of hepatocellular carcinoma (HCC), but none of them integrates liver function, systemic inflammation, and tumor characteristics in a unified model. The current study aimed to develop and validate a novel prognostic score that integrates liver function, systemic inflammation, and tumor characteristics in a unified model to predict the prognosis of HCC after curative resection. METHODS: Patients with HCC who underwent curative liver resection were included in a training set (n = 1027). Multivariate Cox regression was performed to determine the risk factors for a poor prognosis. A prognostic score was developed by assigning points for risk factors in proportion to beta coefficients in a Cox multivariable model. Predictive performance and distinction ability of the prognostic score were further evaluated in two independent validation cohorts treated with either curative resection (n = 281) or transarterial chemoembolization (TACE) (n = 404) and compared with 16 other models. RESULTS: The prognostic predictive system, named the function-inflammation-burden-alpha-fetoprotein (FIBA) score, was derived by assigning points for six independent predictors including albumin, total bilirubin, lymphocyte count, diameter of the largest tumor, number of tumors, and alpha-fetoprotein (AFP). The FIBA score showed an outperformed predictive value compared with other systems in both training and validation cohorts by giving the highest C-index, likelihood ratio chi-square values, and Wald test values as well as the lowest Akaike information criterion. CONCLUSION: The FIBA score can be used to stratify HCC patients treated with curative resection. Meanwhile, the FIBA score performs well against other prognostic scoring systems and is potentially broadly applicable to a TACE-treated patient cohort.

Integrated Liver Inflammatory Score Predicts the Therapeutic Outcome of Patients with Hepatocellular Carcinoma after Transarterial Chemoembolization.

PURPOSE: To evaluate the performance of the integrated liver inflammatory score (ILIS) in predicting survival in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization, and to compare ILIS to other prognostic scoring systems and inflammatory indices. MATERIALS AND METHODS: This study included 192 patients with unresectable HCC who underwent transarterial chemoembolization from 3 medical centers. The potential risk factors of the patients' overall survival (OS) were determined by multivariate Cox regression analysis. The predictive performances of ILIS in 1-, 2-, 3-, 4-, and 5-year survival were evaluated using receiver operating characteristic curves. The discriminatory power in the OS of ILIS and the other known scoring systems or inflammatory indices was determined by C-statistic. RESULTS: Multivariate regression analysis showed that high ILIS (P = .047), low lymphocyte count (P = .034), beyond up-to-seven criteria (P = .021), and nonresponse to the first transarterial chemoembolization session (P = .039) were risk factors for poor prognosis after transarterial chemoembolization. The predictive performances of ILIS for 1-, 2-, 3-, 4-, and 5-year survival were good, with area under the curve values of 0.627, 0.631, 0.621, 0.577, and 0.681, respectively. ILIS outperformed other standard scoring systems and inflammatory indices in predicting OS, with a C-statistic of 0.625. CONCLUSIONS: ILIS is a powerful prognostic index for predicting the survival of patients with HCC after transarterial chemoembolization, which suggests that ILIS before treatment should be considered during the patient evaluation process.

Determination of risk factors for predicting the onset of symptoms in asymptomatic COVID-19 infected patients.

Background: The number of asymptomatic infected patients with coronavirus disease 2019 (COVID-2019) is rampaging around the world but limited information aimed on risk factors of asymptomatic infections. The purpose of this study is to investigate the risk factors of symptoms onset and clinical features in asymptomatic COVID-19 infected patients. Methods: A retrospective study was performed in 70 asymptomatic COVID-2019 infected patients confirmed by nucleic acid tests in Hunan province, China between 28 January 2020 and 18 February, 2020. The epidemiological, clinical features and laboratory data were reviewed and analyzed. Presence or absence at the onset of symptoms was taken as the outcome. A Cox regression model was performed to evaluate the potential predictors of the onset of symptoms. Results: The study included 36 males and 34 females with a mean age of 33.24±20.40 years (range, 0.5-84 years). There were 22 asymptomatic carriers developed symptoms during hospitalization isolated observation, and diagnosed as confirmed cases, while 48 cases remained asymptomatic throughout the course of disease. Of 70 asymptomatic patients, 14 (14/70, 20%) had underlying diseases, 3 (3/70, 4.3%) had drinking history, and 11 (11/70, 15.7%) had smoking history. 22 patients developed symptoms onset of fever (4/22, 18.2%), cough (13/22, 59.1%), chest discomfort (2/22, 9.1%), fatigue (1/22, 4.5%), pharyngalgia (1/22, 4.5%) during hospitalization; only one (1/22, 4.5%) patient developed signs of both cough and pharyngalgia. Abnormalities on chest CT were detected among 35 of the 69 patients (50.7%) after admission, except for one pregnant woman had not been examined. 4 (4/70, 5.7%) and 8 (8/70, 11.4%) cases showed leucopenia and lymphopenia. With the effective antiviral treatment, all the 70 asymptomatic infections had been discharged, none cases developed severe pneumonia, admission to intensive care unit, or died. The mean time from nucleic acid positive to negative was 13.2±6.84 days. Cox regression analysis showed that smoking history (P=0.028, hazard ratio=4.49, 95% CI 1.18-17.08) and existence of pulmonary disease (P=0.038, hazard ratio=7.09, 95% CI 1.12-44.90) were risk factors of the onset of symptoms in asymptomatic carries. Conclusion: The initially asymptomatic patients can develop mild symptoms and have a good prognosis. History of smoking and pulmonary disease was prone to illness onset in asymptomatic patients, and it is necessary to be highly vigilant to those patients.

Conventional versus drug-eluting beads chemoembolization for infiltrative hepatocellular carcinoma: a comparison of efficacy and safety.

BACKGROUND: To compare the efficacy and safety between conventional transarterial chemoembolization (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with infiltrative hepatocellular carcinoma (iHCC). METHODS: A total of 89 iHCC patients who were treated with either cTACE (n = 33) or DEB-TACE (n = 56) between April 2013 and September 2017 were included in this retrospective study. Patients with the situations that might have a poor outcome were defined as advanced disease including Child-Pugh class B, bilobar lesions, tumor size greater than 10 cm, ECOG 1-2, tumor burden of 50-70%, and the presence of ascites, arterioportal shunt (APS), and portal venous tumor thrombus (PVTT). The tumor response was measured 1-month and 3-month after the procedure. Progression-free survival (PFS) was calculated. Toxicity was graded by Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The differences in tumor response, PFS, and toxicity were compared between the DEB-TACE group and cTACE group. RESULTS: At 1-month and 3-month after the procedure, the objective response rate (ORR) in the overall study population was similar in DEB-TACE group and cTACE group. The disease control rate (DCR), at 1-month after the procedure, was significantly higher in the patients treated with DEB-TACE relative to those treated with cTACE (P = 0.034), while after 3 months, the difference did not differ between two groups. DEB-TACE showed a higher DCR than cTACE in patients with tumor size greater than 10 cm (P = 0.036) or associated with APS (P = 0.030) at 1-month after the procedure, while after 3 months, the difference was only noted in patients with APS (P = 0.036). The median PFS in DEB-TACE group was 96 days, while in cTACE group was 94 days, and there was no difference in PFS between two groups (P = 0.831). In the side effect analysis, abdominal pain (P = 0.034) and fever (P = 0.009) were more frequently present in the cTACE group than DEB-TACE group, but there was no difference in high grade liver toxicity between the two groups. CONCLUSIONS: Compared to cTACE, DEB-TACE offers slightly better DCR and tolerability for iHCC patients, particularly in patients associated with APS and large tumor size. However, DEB-TACE does not provide higher PFS than cTACE.

Cavographic vs. cross-sectional measurement of the inferior vena cava diameter before filter placement: are we routinely oversizing?

OBJECTIVE: A megacava (vena cava with a diameter of 28 mm or greater) requires a particular filter to avoid migration. However, caval morphologies are variable. As the inferior vena cava (IVC) usually adopts a circular geometry after a filter is inserted, this study aims (a) to classify caval geometry and orientation; (b) to compare discrepancy between anterioposterior projective diameter (PD) and circumference-based calculated diameter (CD) measurements on cross-sectional computed tomography (CT) images; (c) if a discrepancy exists, determine how often it can affect IVC filter selection. METHODS: A total of 1503 patients were retrospectively reviewed. Caval morphology was classified. PD and CD were measured at infrarenal IVC. Differences between the PD and CD were assessed by the Wilcoxon signed-rank test or paired t test (if appropriate). The scatterplot of PD vs. CD was used to show whether one is consistently larger than the other. RESULTS: The PD was significantly larger than the CD (22.3 ± 3.5 vs. 20.4 ± 2.8, p < 0.001). The caval morphologies were divided into five types. Type 1 was oval IVC oriented left-anterior-oblique to the horizontal line with an angle (n = 999, 66.5%), type 2 was round IVC (n = 49, 3.3%), type 3 was oval IVC with a vertical long axis (n = 8, 0.5%), type 4 was oval IVC with a horizontal long axis (n = 75, 5.0%), and type 5 was irregularly shaped IVC (n = 372, 24.7%). CONCLUSION: Patients with round IVC are rare. Measurement of CD may be better to assess maximum IVC diameter compared with PD for the purpose of IVC filter placement. KEY POINTS: • Five types of IVC orientation are described in this paper: type 1 (n = 999, 66.5%), type 2 (n = 49, 3.3%), type 3 (n = 8, 0.5%), type 4 (n = 75, 5.0%), and type 5 (n = 372, 24.7%). • The incidence of megacava (vena cava with a diameter of 28 mm or greater) measured on anterioposterior projective imaging may be overestimated. • As an IVC will adopt a circular geometry following filter placement, circumference-based calculated diameter may be an appropriate approach for caval size determination.

Does the Surgery-First Approach Produce Better Outcomes in Orthognathic Surgery? A Systematic Review and Meta-Analysis.

PURPOSE: The surgery-first approach (SFA) in orthognathic surgery, performed without presurgical orthodontic treatment, has gained attention, but the results remain controversial. The purpose of this study was to assess the current evidence on stability, efficacy, and surgical results of SFA versus conventional 3-stage method (CTM) orthognathic surgery. MATERIALS AND METHODS: A comprehensive search in PubMed and Web of Science was conducted. A systematic review and cumulative meta-analysis of all comparative studies were performed to assess the 2 strategies (SFA and CTM) using a random- or a fixed-effects model. Outcomes included treatment duration, postoperative stability, surgical movement, and postoperative occlusion. RESULTS: Ten nonrandomized controlled studies including 513 patients were identified. Compared with CTM, patients in the SFA group benefited from shorter total treatment duration (weighted mean difference [WMD], -5.25; 95% confidence interval [CI], -8.21 to -2.29; P = .0005), similar postoperative stability of the mandible (WMD, 0.35 mm; 95% CI, -0.24 to 0.94; P = .55) and maxilla (WMD, 0.13 mm; 95% CI, -0.35 to 0.60; P = .60), similar surgical movements, and other surgical results. CONCLUSIONS: SFA offers an efficient alternative to CTM with shorter total treatment duration, similar postoperative stability, and other surgical results but longer postoperative orthodontic time.

Prognostic Factors for Patients with Proliferative Hepatocellular Carcinoma After Liver Resection.

Purpose: There is a scarcity of predictive models currently accessible for prognosticating proliferative hepatocellular carcinoma (HCC), an integrated class of subtype, characterized by a dismal prognosis. Consequently, this study aimed to develop and validate a novel prognostic model capable of accurately predicting the prognosis of proliferative HCC after curative resection. Patients and Methods: This retrospective multicenter study included patients with solitary HCC who underwent curative liver resection from August 2014 to December 2020 (n = 816). Patients were stratified into either the proliferative HCC cohort (n = 259) or the nonproliferative HCC cohort (n = 557) based on histological criteria. Disease-free survival (DFS) was compared between the two groups before and after one-to-one propensity score matching (PSM). Of all the proliferative HCC patients, 203 patients were assigned to training cohort, and 56 patients were assigned to validation cohort. Univariate and multivariate analyses were performed in training cohort to identify risk factors associated with worse DFS. Thereafter, a predictive model was constructed, subsequently validated in the validation cohort. Results: The DFS of proliferative HCC was significantly worse than nonproliferative HCC before and after PSM. Meanwhile, multivariate regression analysis revealed that liver cirrhosis (P = 0.032) and larger tumor size (P = 0.000) were independent risk factors of worse DFS. Lastly, the discriminative abilities of the predictive model for 1, 3, 5-year DFS rates, as determined by receiver operating characteristic (ROC) curves, were 0.702, 0.720, and 0.809 in the training cohort and 0.752, 0.776, and 0.851 in the validation cohort, respectively. Conclusion: This study developed a predictive model with satisfactory accuracy to predict the worse DFS in proliferative HCCs after liver resection. Moreover, this predictive model may serve as a valuable tool for clinicians to predict postoperative HCC recurrence, thereby enabling them to implement early preventative strategies.

Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy.

To improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The mRNA levels of these genes were validated by qRT-PCR in 20 paired fresh HCC samples. The results demonstrated that the eight-gene model was effective in predicting the prognosis of HCC patients in the validation cohorts. Based on qRT-PCR results, NOX4 was selected to further explore biological functions within the model and 150 cases of paraffin-embedded HCC tissues were scored for NOX4 immunohistochemical staining. We found that the NOX4 expression was significantly upregulated in HCC and was associated with poor survival. In terms of function, the knockdown of NOX4 markedly inhibited the progression of HCC in vivo and in vitro. Mechanistic studies suggested that NOX4 promotes HCC progression through the activation of the epithelial-mesenchymal transition. In addition, the sensitivity of HCC cells to sorafenib treatment was obviously decreased after NOX4 overexpression. Taken together, this study reveals NOX4 as a potential therapeutic target for HCC and a biomarker for predicting the sorafenib treatment response.

Combined transarterial iodized oil injection and computed tomography-guided thermal ablation for hepatocellular carcinoma: utility of the iodized oil retention pattern.

PURPOSE: To investigate whether the iodized oil (Lipiodol, Guerbet Group, Villepinte, France) retention pattern influences the treatment efficacy of combined transarterial Lipiodol injection (TLI) and thermal ablation in patients with hepatocellular carcinoma (HCC). METHODS: Data of 198 patients (280 HCC lesions), who underwent TLI plus computed tomography (CT)-guided thermal ablation at three separate medical institutions between June 2014 and September 2020, were reviewed and analyzed. The Lipiodol retention pattern was classified as complete or incomplete based on non-enhanced CT at the time of ablation. The primary outcome was local recurrence-free survival (LRFS) for lesions; the secondary outcome was overall survival (OS) for patients. Propensity score matching (PSM) was performed using a caliper width of 0.1 between the two groups. Differences in LRFS and OS between the two groups were compared using the log-rank test. RESULTS: A total of 133 lesions exhibited a complete Lipiodol retention pattern, while 147 exhibited an incomplete pattern. After PSM analysis of baseline characteristics of the lesions, 121 pairs of lesions were matched. LRFS was significantly longer for lesions exhibiting complete retention than for those exhibiting incomplete retention (P = 0.030). After PSM analysis of patient baseline characteristics, 74 pairs of patients were matched. There was no significant difference in OS between the two groups (P = 0.456). CONCLUSION: Lipiodol retention patterns may influence the treatment efficacy of combined TLI and thermal ablation for HCC lesions. However, a survival benefit for the Lipiodol retention pattern among HCC patients was not observed and needs further confirmation.

Ideal patients for liver resection in Barcelona Clinic Liver Cancer or Hong Kong Liver clinic systems for hepatocellular carcinoma: Conservative or aggressive?

Background: Both the Barcelona Clinic Liver Cancer (BCLC) staging and the Hong Kong Liver Cancer (HKLC) staging have their own definitions of ideal patients for liver resection (IPLR) in hepatocellular carcinoma (HCC). This study aimed to compare the prognosis of IPLRs between the BCLC and HKLC staging systems, and to identify patients who may benefit from liver resection (LR) in the HKLC staging but beyond the BCLC staging. Methods: This retrospective study evaluated 1,296 consecutive patients with HCC who underwent LR between August 2013 and April 2021 (457 patients and 1,046 patients were IPLR according to the BCLC and HKLC staging systems, respectively). Overall survival (OS) was compared between the two groups. To assess potential benefit of LR for IPLR in the HKLC staging but beyond the BCLC staging, univariate and multivariate Cox regression analysis was performed to determine prognostic factors of OS, and prognostic stratification was performed based on the selected prognostic factors. The IPLRs in the HKLC staging but beyond the BCLC staging were divided into subgroups according to the prognostic stratification and separately compared with the IPLRs in the BCLC staging. Results: OS was different between the two staging systems (P = 0.011). All the 457 IPLRs in the BCLC staging were also the IPLRs in the HKLC staging. Diameter of the largest tumor5 cm (HR = 1.58; 95% CI: 1.18-2.10; P = 0.002) and liver cirrhosis (HR = 1.61; 95% CI: 1.19-2.20; P = 0.002) were risk factors for poor OS in IPLRs in the HKLC staging but beyond the BCLC staging; hence, patients were divided into the low-risk (n = 104), intermediate-risk (n = 369), and high-risk groups (n = 116) accordingly. There was no difference in OS between patients in the BCLC staging and patients in low-risk group (P = 0.996). However, OS was significantly different between patients in the BCLC staging and those in intermediate-risk (P = 0.003) and high-risk groups (P < 0.001). Conclusion: IPLRs in the BCLC staging system have better prognosis. However, IPLRs in the HKLC staging system but beyond the BCLC staging may have equivalent prognosis to IPLRs in the BCLC staging if the tumor size is ≤ 5 cm and liver cirrhosis is absent.

Liver resection versus microwave ablation for hepatocellular carcinoma in ideal candidates for ablation per Barcelona Clinic Liver Cancer staging: a propensity score matching and inverse probability of treatment weighting analysis.

BACKGROUND: Liver resection (LRE) and microwave ablation (MWA) for hepatocellular carcinoma (HCC) have been widely compared. AIMS: To compare the therapeutic outcomes of percutaneous MWA and LRE for HCC in ideal candidates for ablation according to Barcelona Clinic Liver Cancer (BCLC) staging METHODS: Between August 2013 and November 2020, 483 consecutive patients meeting criteria for "ideal candidates for ablation" per the BCLC staging initially treated with MWA (n = 168) or LRE (n = 315) were included. Patients were further divided into BCLC-0 (n = 116) and BCLC-A (n = 367) groups. Overall survival (OS), recurrence-free survival (RFS) and post-procedure-related complication rates were compared before and after propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) in the overall population and subgroups. Multivariate Cox regression analysis was performed to determine whether the treatment modality was an independent prognostic factor. RESULTS: LRE had a better RFS and similar OS and post-procedure-related complication rates compared to MWA in the overall population and in the BCLC-A subgroup both before and after PSM and IPTW. However, the OS, RFS and post-procedure-related complication rates were equivalent between the two groups before and after PSM and IPTW in patients with BCLC-0 disease. The multivariate Cox regression analysis showed that LRE was associated with better RFS over MWA in overall population (p = 0.003; HR = 0.67; 95% CI: 0.51-0.87) and BCLC-A disease (p = 0.046; HR = 0.74; 95% CI: 0.56-0.99), while it did not differ in OS. CONCLUSION: An 'ideal candidate for ablation' according to the BCLC staging system may not be an ideal candidate for MWA. However, patients with BCLC-0 may be the optimal population for MWA.

Current updates in machine learning in the prediction of therapeutic outcome of hepatocellular carcinoma: what should we know?

With the development of machine learning (ML) algorithms, a growing number of predictive models have been established for predicting the therapeutic outcome of patients with hepatocellular carcinoma (HCC) after various treatment modalities. By using the different combinations of clinical and radiological variables, ML algorithms can simulate human learning to detect hidden patterns within the data and play a critical role in artificial intelligence techniques. Compared to traditional statistical methods, ML methods have greater predictive effects. ML algorithms are widely applied in nearly all steps of model establishment, such as imaging feature extraction, predictive factor classification, and model development. Therefore, this review presents the literature pertaining to ML algorithms and aims to summarize the strengths and limitations of ML, as well as its potential value in prognostic prediction, after various treatment modalities for HCC.

Initial Incomplete Thermal Ablation Is Associated With a High Risk of Tumor Progression in Patients With Hepatocellular Carcinoma.

PURPOSE: To investigate whether incomplete thermal ablation is associated with a high risk of tumor progression in patients with hepatocellular carcinoma (HCC), and to compare the efficacy of repeated thermal ablation and transarterial chemoembolization (TACE) for residual tumor after incomplete ablation. METHODS: This retrospective study included 284 patients with unresectable HCC who underwent thermal ablation from June 2014 to September 2020. The response of the initially attempted ablation was classified into complete (n=236) and incomplete (n=48). The progression-free survival (PFS) and overall survival (OS) were compared between patients with complete and incomplete responses, before and after a one-to-one propensity score-matching (PSM), and between patients in whom repeated ablation or TACE was performed after a first attempt incomplete ablation. RESULTS: After PSM of the 284 patients, 46 pairs of patients were matched. The PFS was significantly higher in the complete response group than in the incomplete response group (P<0.001). No difference in OS was noted between two groups (P=0.181). After a first attempt incomplete ablation, 29 and 19 patients underwent repeated ablation and TACE, respectively. There were no significant differences in PFS (P=0.424) and OS (P=0.178) between patients who underwent repeated ablation and TACE. In multivariate Cox regression analysis, incomplete response (P<0.001) and Child-Pugh class B (P=0.017) were independent risk factors for tumor progression, while higher AFP level (P=0.011) and Child-Pugh class B (P=0.026) were independent risk factors for poor OS. CONCLUSION: Although patients with incomplete ablation are associated with tumor progression compared with those with complete ablation, their OS is not affected by incomplete ablation. When patients present with residual tumors, TACE may be an alternative if repeated ablation is infeasible.

Development and Validation of a Predictive Model for Early Refractoriness of Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma.

Objectives: To develop and validate a predictive model for early refractoriness of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: In this multicenter retrospective study, a total of 204 consecutive patients who initially underwent TACE were included. Early TACE refractoriness was defined as patients presented with TACE refractoriness after initial two consecutive TACE procedures. Of all patients, 147 patients (approximately 70%) were assigned to a training set, and the remaining 57 patients (approximately 30%) were assigned to a validation set. Predictive model was established using forward stepwise logistic regression and nomogram. Based on factors selected by logistic regression, a one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) between patients who were present or absent of early TACE refractoriness. PFS curve was estimated by Kaplan-Meier method and compared by log-rank test. Results: Logistic regression revealed that bilobar tumor distribution (p = 0.002), more than three tumors (p = 0.005) and beyond up-to-seven criteria (p = 0.001) were significantly related to early TACE refractoriness. The discriminative abilities, as determined by the area under the receiver operating characteristic (ROC) curve, were 0.788 in the training cohort and 0.706 in the validation cohort. After PSM, the result showed that patients who were absent of early TACE refractoriness had a significantly higher PFS rate than those of patients who were present (p < 0.001). Conclusion: This study presents a predictive model with moderate accuracy to identify patients with high risk of early TACE refractoriness, and patients with early TACE refractoriness may have a poor prognosis.

A predictive model of incomplete response after transarterial chemoembolization for early or intermediate stage of hepatocellular carcinoma: consideration of hepatic angiographic and cross-sectional imaging.

OBJECTIVES: The purpose of the present study is to develop a predictive model for incomplete response (IR) after conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) based on hepatic angiographic and cross-sectional imaging. METHODS: Sixty patients with 139 target HCC lesions who underwent cTACE from February 2013 to March 2019 were included in this retrospective study. Hepatic angiographic features were identified: the number of feeding arteries, vascularity of the tumor, tumor staining on angiography, vascular lake phenomenon, and hepatic arterio-portal shunt. Cross-sectional imaging features were also identified: tumor extent, location, size, and enhancement pattern. Treatment response was assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Logistic regression analysis was performed to determine the potential predictive factors for treatment response. To validate the predictive value of potential factors, the means of a decision tree were also calculated by Classification and Regression Tree (CART). P < 0.05 was considered statistically significant. RESULTS: The IR rate was 43.2% (60/139) in the entire study population. Logistic regression analysis showed that a tumor size > 50 mm (P = 0.005; odds ratio, 7.25; 95% CI 1.79-29.33), central location (P = 0.007; odds ratio, 0.14; 95% CI 0.03-0.59), and nondense tumor staining (P < 0.001; odds ratio, 0.08; 95% CI 0.02-0.28) were predictors of IR after cTACE. Decision tree analysis showed a good ability to classify treatment response with an accuracy of 78.4%. CONCLUSION: Tumor size > 50 mm, central tumor location, and nondense tumor staining were predictors of IR after cTACE. These factors should be taken into consideration when performing cTACE.

Predicting early refractoriness of transarterial chemoembolization in patients with hepatocellular carcinoma using a random forest algorithm: A pilot study.

Purpose: To develop and validate a random forest (RF) based predictive model of early refractoriness to transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). Methods: A total of 227 patients with unresectable HCC who initially treated with TACE from three independent institutions were retrospectively included. Following a random split, 158 patients (70%) were assigned to a training cohort and the remaining 69 patients (30%) were assigned to a validation cohort. The process of variables selection was based on the importance variable scores generated by RF algorithm. A RF predictive model incorporating the selected variables was developed, and five-fold cross-validation was performed. The discrimination and calibration of the RF model were measured by a receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test. Results: The potential variables selected by RF algorithm for developing predictive model of early TACE refractoriness included patients' age, number of tumors, tumor distribution, platelet count (PLT), and neutrophil-to-lymphocyte ratio (NLR). The results showed that the RF predictive model had good discrimination ability, with an area under curve (AUC) of 0.863 in the training cohort and 0.767 in the validation cohort, respectively. In Hosmer-Lemeshow test, the RF model had a satisfactory calibration with P values of 0.538 and 0.068 in training cohort and validation cohort, respectively. Conclusion: The RF algorithm-based model has a good predictive performance in the prediction of early TACE refractoriness, which may easily be deployed in clinical routine and help to determine the optimal patient of care.

Chemoembolization Plus Microwave Ablation vs Chemoembolization Alone in Unresectable Hepatocellular Carcinoma Beyond the Milan Criteria: A Propensity Scoring Matching Study.

PURPOSE: Transarterial chemoembolization (TACE) is recommended in patients with unresectable HCC beyond the Milan criteria (MC). However, the long-term efficacy of TACE remains unsatisfactory. Percutaneous microwave ablation (MWA) is a curative therapy for early-stage HCC that provides better local tumor control than TACE; however, MWA is limited for large or multifocal lesions. We aimed to compare treatment efficacy and downstaging rate following combined TACE-MWA and TACE alone in patients with unresectable HCC beyond the MC. PATIENTS AND METHODS: Patients with unresectable HCC beyond the MC who underwent either TACE-MWA (n=91) or TACE alone (n=140) at four medical institutions were included. Potential influencing factors on overall survival (OS) and progression-free survival (PFS) were included in the Cox regression analysis. Propensity-score matching of patients treated with TACE-MWA and TACE alone was performed. Differences in OS and PFS were compared with the Log rank test. Patients who met the University of California, San Francisco criteria were eligible for assessment of the probability of downstaging within the MC. Downstaging rate was compared between the two groups. RESULTS: In multivariate analysis, treatment with TACE alone was an independent predictor of poor PFS (P=0.011) and OS (P<0.001). Both PFS (P=0.043) and OS (P=0.002) were significantly higher in patients treated with TACE-MWA than those treated with TACE alone. The downstaging rate was higher in patients treated with TACE-MWA than those treated with TACE alone (P=0.039). CONCLUSION: Compared with TACE alone, TACE-MWA may offer a survival benefit in terms of OS and PFS in HCC patients beyond the MC. Additionally, TACE-MWA may provide higher probability of downstaging within the MC than TACE alone, thereby increasing the possibility of liver transplantation.