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.

Systemic Inflammation Response Index is a Prognostic Risk Factor in Patients with Hepatocellular Carcinoma Undergoing TACE.

BACKGROUND: Mounting evidence has shown that systemic inflammation response index (SIRI), a novel prognostic biomarker based on peripheral lymphocyte, neutrophil and monocyte counts, is associated with poor prognosis for several tumors. However, the prognostic value of SIRI in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is elusive. Herein, we aimed to evaluate the correlation between SIRI and clinical outcomes in these patients. METHODS: A total of 194 consecutive patients who underwent TACE were included in this study. Patients were stratified into high and low SIRI groups based on the cut-off value using receiver operating characteristic (ROC) analysis. Independent risk factors for tumor response were analyzed using forward stepwise logistic regression. A one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) and overall survival (OS) between low and high SIRI patients. The discriminatory power of the combination of number of tumors and SIRI in predicting initial TACE response was evaluated by ROC analysis. RESULTS: Patients were divided into high SIRI (> 0.88) and low SIRI (≤ 0.88) groups. High SIRI (p = 0.003) and more than three tumors (p = 0.002) were significantly related to poorer tumor response. Moreover, the low SIRI group had longer PFS and OS than the high SIRI group (both P < 0.05) before and after PSM. Combination of SIRI and number of tumors can improve the predictive ability to predict initial TACE response with an area under the curve (AUC) of 0.678. CONCLUSION: Pretreatment peripheral blood SIRI was found to be an independent predictor of tumor response and clinical outcomes in patients with HCC undergoing TACE. Patients with high SIRI may have a poor prognosis.

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.

Tumor enhancement ratio with unenhanced imaging is an independent prognostic factor for patients with hepatocellular carcinoma after transarterial chemoembolization.

OBJECTIVE: To investigative whether the odds tumor enhancement ratio (OTER) on cross-sectional imaging is a prognostic factor for hepatocellular carcinoma after transarterial chemoembolization (TACE). METHODS: This study involved 126 patients who underwent TACE from May 2015 to March 2019. The signal intensity/Hounsfield units (HU) was measured by placing regions of interest on the tumor and surrounding liver in unenhanced and arterial-phase contrast-enhanced cross-sectional images. The OTER was calculated as follows: OTER = (HUTUMORart - HUTUMORun)/ (HULIVERart - HULIVERun). Univariate analysis was performed to determine the factors associated with overall survival (OS). Variables with a P value of <0.10 were included in the multivariate Cox regression analysis. RESULTS: The median OS was 757 days. Tumors with a peripheral location, small size, and low OTER had better OS than those with a central location, large size, and high OTER. OS did not differ according to the extent of tumor involvement or tumor enhancement pattern. The OTER, tumor location, and size were included in the multivariate Cox regression analysis. A low OTER was the predictor of better OS. CONCLUSION: A high OTER is a risk factor for poor OS in patients undergoing TACE. This should be taken into consideration before the procedure.

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.

15-hydroxy-6α,12-epoxy-7ß,10αH,11ßH-spiroax-4-ene-12-one exerts anti-tumor effects against osteosarcoma through apoptosis induction.

Osteosarcoma is the most common type of malignant bone tumor, which has an overall survival rate of only 15-30%. The present study aimed to investigate the effects of 15-hydroxy-6α,12-epoxy-7ß,10αH,11ßH-spiroax-4-ene-12-one (HESEO), a compound extracted from the endophytic fungus Penicillium sp. FJ-1 isolated from Avicennia marina, on the proliferation of osteosarcoma cells and to explore its underlying mechanisms of action. Cell number was counted to measure the cell proliferation. JC-1 reagent was used to measure mitochondrial membrane potential. ELISA was used to measure the cytochrome c level and caspase activities. Apoptosis was detected by Annexin V-Propidium Iodide staining. Gene and protein expression were measured by reverse-transcription-PCR and western blot analysis, respectively. Additionally, the anti-tumor effects of HESEO were explored within a syngeneic osteosarcoma tumor model. The results suggested that HESEO significantly inhibited the proliferation of osteosarcoma cells and induced apoptosis of MG-63 cells, evidenced by their decreased mitochondrial membrane potential, and increased cytochrome c release, caspase activities and percentage of apoptotic cells. In addition, HESEO increased the expression of pro-apoptotic genes and proteins compared with control cells. The results indicated that HESEO may act through increasing p53 upregulated modulator of apoptosis expression. Furthermore, HESEO treatment significantly increased the survival time and decreased the tumor burden of osteosarcoma tumor-bearing mice compared with vehicle treatment. Furthermore, combined treatment with HESEO enhanced the effects of the chemotherapeutic agent methotrexate on a lung metastasis osteosarcoma model. These data suggested that HESEO could be developed as a potential anti-tumor agent against osteosarcoma.