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Hepatocellular carcinoma (HCC) is a disease with a poor prognosis, often diagnosed at an advanced stage. Therapeutic options have developed considerably in recent years, particularly with trans-arterial treatments. Systemic treatments have also evolved significantly, with the rise of immune checkpoint inhibitors (ICI) as first-line treatment for advanced HCC. The combination of loco-regional treatments and ICI is opening up new prospects and is the subject of numerous clinical trials. Recently, two global phase 3 trials investigating ICI-based adjuvant combinations have demonstrated improvements in recurrence-free survival or progression-free survival in patients treated with resection, ablation, or trans-arterial chemoembolization. However, mature data and overall survival results are still awaited but will be difficult to interpret. We are at the start of a new era of combinations of loco-regional treatments and immunotherapy. The identification of the best therapeutic strategies and predictive biomarkers is a crucial issue for future standards in clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Background Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. Materials We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. Results In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. Conclusion The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

Backgrounds: It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC. Methods: This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM). Results: A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median followup of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)= 1.471, 95% CI: 1.199-1.803, P< 0.001). On multivariate analysis, alpha-fetoprotein = 5.0 ng/ml (aHR =0.202), ALBI grade =2 (aHR =0.709), tumor number =3 (aHR =0.404), and maximal tumor size =5 cm (aHR =0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR = 5.834; validation: aHR =5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR =3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR =0.816). Conclusions: Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score. [ABSTRACT FROM AUTHOR]

Purpose: To explore the safety and efficacy of lenvatinib in combination with trans-arterial chemoembolization (TACE) and programmed death receptor 1 (PD-1) antibody in the treatment of unresectable recurrent hepatocellular carcinoma (urHCC). Patients and methods: The clinical data of 16 patients with unresectable recurrent hepatocellular carcinoma admitted to the Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, and received the conversion therapy of lenvatinib + TACE + PD-1 antibody between January 2019 and January 2022 were retrospectively analyzed. Results: There were 25% (4/16) patients suffering from grade 3 adverse events and no patients suffering from grade 4 or higher adverse events. After 4 months of treatment of 16 patients, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), two, five, three, and six cases were in complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, and the objective response rate (ORR) was 43.8% (7/16). The 1-year overall survival (OS) rate and 1-year progressionfree survival (PFS) rate were 86.2% and 46.9%, respectively. In our subgroup analysis, the ORR of patients with multiple lesions reached up to 60%, which was higher than that of patients with single lesions. Conclusions: Lenvatinib in combination with TACE and PD-1 antibody is safe and effective in the treatment of unresectable recurrent hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Abstract Background Heterogeneity of liver function and tumor burden in intermediate-stage hepatocellular carcinoma (HCC) results in different outcomes after transarterial chemoembolization (TACE). Easy albumin-bilirubin (EZ-ALBI), a simplified albumin-bilirubin (ALBI) score, has recently been proposed as a new prognostic score for HCC. This study aimed to validate the EZ-ALBI score and evaluate the impact of dynamic changes in patients with intermediate-stage HCC undergoing TACE. Methods All patients with HCC treated with TACE at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between January 2015 and December 2019 were prospectively enrolled. Intermediate-stage HCC was defined as Barcelona Clinic Liver Cancer (BCLC) stage B or unresectable single HCC with size > 5 cm in BCLC stage A. EZ-ALBI and ALBI scores were calculated and stratified into three different grades. Overall survival (OS) and prognostic factors were assessed using the Kaplan–Meier curve and Cox proportional hazard model. Decision analysis curves were used to evaluate the clinical utility of the predictive scores. Results Among 672 patients with HCC treated with TACE, 166 patients with intermediate-stage HCC who met the eligibility criteria were enrolled. The median OS of all patients in the cohort was 21 months. A good correlation between the EZ-ALBI and ALBI scores was observed (correlation coefficient 1.000, p 20 ng/ml were significantly associated with OS [hazard ratio (HR) 2.20 (95% confidence interval [CI] 1.24–3.88, p = 0.007), 3.26 (95% CI 1.24–8.57, p = 0.016), and 1.77 (95% CI 1.10–2.84, p = 0.018), respectively]. Following TACE, 42 (29.6%) patients had a worsening EZ-ALBI grade. However, the EZ-ALBI grade migration was not significantly correlated with OS. EZ-ALBI and ALBI score provided improved discriminatory ability (Harrell’s concordance index 0.599 and 0.602, respectively) and better net benefit compared with Child-Turcotte-Pugh and Model for End-stage Liver Disease scores. Conclusions The baseline EZ-ALBI score demonstrated good predictive performance for survival and a strong correlation with conventional ALBI scores. Both the EZ-ALBI and ALBI scores outperformed other prognostic models in patients with intermediate-stage HCC receiving TACE. However, the dynamic change in the EZ-ALBI grade after TACE was not associated with postprocedural survival.

Simple Summary: Hepatocellular carcinoma (HCC) is one of the most prevalent and devastating malignancies worldwide. An ongoing phase-II clinical trial assesses the efficacy of a novel sequential trans-arterial chemoembolization (TACE) plus stereotactic body radiotherapy (SBRT) plus immunotherapy strategy as an induction therapy for unresectable HCC patients. This study aims to investigate the potential association between radiomic features extracted from pre-treatment multi-phasic MR images and treatment response following the novel intervention strategy. In this study, Four DeltaP-derived radiomics that characterize the temporal change in intratumoral randomness and uniformity were identified as the contributors to the treatment response for a 3-month timepoint. Additional arterial phase (AP)-derived radiomic features and tumor morphology were also shown to have strong associations with treatment response for a 6-month timepoint. The success of this study would demonstrate the feasibility of pre-treatment identification of responsive HCC patients, paving the way toward effective and personalized oncology for HCC management. This study aims to investigate the association of pre-treatment multi-phasic MR-based radiomics and dosimetric features with treatment response to a novel sequential trans-arterial chemoembolization (TACE) plus stereotactic body radiotherapy (SBRT) plus immunotherapy regimen in unresectable Hepatocellular Carcinoma (HCC) sub-population. Twenty-six patients with unresectable HCC were retrospectively analyzed. Radiomic features were extracted from 42 lesions on arterial phase (AP) and portal-venous phase (PVP) MR images. Delta-phase (DeltaP) radiomic features were calculated as AP-to-PVP ratio. Dosimetric data of the tumor was extracted from dose-volume-histograms. A two-sided independent Mann–Whitney U test was used to assess the clinical association of each feature, and the classification performance of each significant independent feature was assessed using logistic regression. For the 3-month timepoint, four DeltaP-derived radiomics that characterize the temporal change in intratumoral randomness and uniformity were the only contributors to the treatment response association (p-value = 0.038–0.063, AUC = 0.690–0.766). For the 6-month timepoint, DeltaP-derived radiomic features (n = 4) maintained strong clinical associations with the treatment response (p-value = 0.047–0.070, AUC = 0.699–0.788), additional AP-derived radiomic features (n = 4) that reflect baseline tumoral arterial-enhanced signal pattern and tumor morphology (n = 1) that denotes initial tumor burden were shown to have strong associations with treatment response (p-value = 0.028–0.074, AUC = 0.719–0.773). This pilot study successfully demonstrated associations of pre-treatment multi-phasic MR-based radiomics with tumor response to the novel treatment regimen. [ABSTRACT FROM AUTHOR]

Sihang Cheng,1,2 Xiang Yu,2 Siyun Liu,3 Zhengyu Jin,1 Huadan Xue,1 Zhiwei Wang,1 Ping Xie2 1Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Radiology, Sichuan Provincial People’s Hospital, Sichuan Academy of Medical Sciences, Chengdu, People’s Republic of China; 3Pharmaceutical Diagnostics, GE Healthcare, Beijing, People’s Republic of ChinaCorrespondence: Zhiwei Wang; Ping Xie Tel +8610 69159562; +8628 87393976Email zhiweiwang1981@sina.com; haoyanx@163.comObjective: To develop and validate a prognostic nomogram in eastern patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) receiving trans-arterial chemoembolization with drug-eluting beads (DEB-TACE).Methods: This retrospective study included 200 patients with training cohort (n = 118) from institution 1 and test cohort (n = 82) from institution 2. All these patients received first-line DEB-TACE between October 2016 and October 2018. Multivariate Cox proportional hazard regression analysis was performed on the training cohort to reveal the independent prognostic factors, and then prognostic nomograms were developed. In order to evaluate the performance of the nomogram comprehensively in both the training and test cohorts, C-index, Kaplan–Meier curve with Log rank test, receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA) were performed.Results: Tumor number, serum γ-glutamyl transferase (GGT) level, and level of PVTT were independent risk factors of prognosis. A nomogram was constructed to predict 6-, 12- and 18-month overall survival (OS) based on these identified prognostic factors. C-indexes of the nomogram were 0.88 (95% confidence interval [CI], 0.79– 0.97) in the training cohort and 0.87 (95% CI, 0.75– 0.99) in the test cohort. The Kaplan–Meier curve analysis showed that the nomogram was able to separate patients into low- and high-risk subgroups. ROC curves for the nomogram at 6-, 12- and 18-month showed satisfied discrimination, with an AUC of 0.765, 0.803 and 0.809 in the training cohort, respectively, and 0.772, 0.724 and 0.746 in the test cohort, respectively. The calibration curve demonstrated good agreement between predicted and actual survival rates in the training and test cohorts. The decision curve showed good performance of the nomogram in terms of clinical application.Conclusion: We developed and validated a nomogram that was accurate and clinically useful in eastern patients with HBV-associated HCC with PVTT who underwent DEB-TACE.Keywords: hepatocellular carcinoma, portal vein tumor thrombus, trans-arterial chemoembolization, drug-eluting beads, nomogram

Background: Heterogeneity of liver function and tumor burden in intermediate-stage hepatocellular carcinoma (HCC) results in different outcomes after transarterial chemoembolization (TACE). Easy albumin-bilirubin (EZ-ALBI), a simplified albumin-bilirubin (ALBI) score, has recently been proposed as a new prognostic score for HCC. This study aimed to validate the EZ-ALBI score and evaluate the impact of dynamic changes in patients with intermediate-stage HCC undergoing TACE.Methods: All patients with HCC treated with TACE at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between January 2015 and December 2019 were prospectively enrolled. Intermediate-stage HCC was defined as Barcelona Clinic Liver Cancer (BCLC) stage B or unresectable single HCC with size > 5 cm in BCLC stage A. EZ-ALBI and ALBI scores were calculated and stratified into three different grades. Overall survival (OS) and prognostic factors were assessed using the Kaplan-Meier curve and Cox proportional hazard model. Decision analysis curves were used to evaluate the clinical utility of the predictive scores.Results: Among 672 patients with HCC treated with TACE, 166 patients with intermediate-stage HCC who met the eligibility criteria were enrolled. The median OS of all patients in the cohort was 21 months. A good correlation between the EZ-ALBI and ALBI scores was observed (correlation coefficient 1.000, p < 0.001). The baseline EZ-ALBI grades 1, 2, and 3 were 24.5%, 70%, and 5.5%, respectively. EZ-ALBI grade can stratify patients with significantly different prognoses (p = 0.002). Baseline EZ-ALBI grade 2, 3, and serum alpha-fetoprotein > 20 ng/ml were significantly associated with OS [hazard ratio (HR) 2.20 (95% confidence interval [CI] 1.24-3.88, p = 0.007), 3.26 (95% CI 1.24-8.57, p = 0.016), and 1.77 (95% CI 1.10-2.84, p = 0.018), respectively]. Following TACE, 42 (29.6%) patients had a worsening EZ-ALBI grade. However, the EZ-ALBI grade migration was not significantly correlated with OS. EZ-ALBI and ALBI score provided improved discriminatory ability (Harrell's concordance index 0.599 and 0.602, respectively) and better net benefit compared with Child-Turcotte-Pugh and Model for End-stage Liver Disease scores.Conclusions: The baseline EZ-ALBI score demonstrated good predictive performance for survival and a strong correlation with conventional ALBI scores. Both the EZ-ALBI and ALBI scores outperformed other prognostic models in patients with intermediate-stage HCC receiving TACE. However, the dynamic change in the EZ-ALBI grade after TACE was not associated with postprocedural survival. [ABSTRACT FROM AUTHOR]

Multiphase MRI liver is the gold-standard imaging modality for staging hepatocellular carcinoma (HCC) in patients with cirrhosis. Often, small HCCs diagnosed on multiphase MRI are occult on B-mode ultrasound and multiphase CT (MPCT) and thus pose a challenge for loco-regional therapy. We adapted the technique of lipiodol CT in treating two such patients of small HCC. Lipiodol-CT involved an intra-arterial lipiodol injection through the hepatic artery followed by a noncontrast CT liver. CT delineated small, hyperdense, lipiodol-laden hepatic nodules, which served as a target for executing ablation of the nodule and also revealed the true disease stage by depicting the additional number of tumors in the liver. Case one was a 51-year female, known case of chronic hepatitis C who presented with ascites for two months. She was diagnosed with a small HCC (LI-RADS-4) in a cirrhotic liver on multiphase MRI. Percutaneous radiofrequency ablation was planned, but the mass was not located on ultrasound or multiphase CT. Lipiodol-CT was undertaken, which delineated the lipiodol-laden small HCC, which served as a target for executing ablation. Case 2 was a 55-year male, Child-Pugh A cirrhotic, who had undergone right extended hepatectomy for hepatitis B-related HCC. Follow-up MRI revealed a 5 mm segment III nodule, which had increased in size on repeat MRI at 3 months (LI-RADS-4). This nodule, too, was occult on both ultrasound and MPCT. Lipiodol CT revealed additional multiple, variable-sized lipiodol-laden nodules in the liver remnant. Treatment of trans-arterial chemoembolization was performed at one month. Both patients showed complete response to treatment. Conclusion: Lipiodol CT can be safely used in a new role of facilitating treatment of small HCCs diagnosed on MRI but occult on ultrasonography and MPCT. [ABSTRACT FROM AUTHOR]

Abstract Background Transarterial chemoembolization (TACE) is the recommended treatment modality for non-resectable intermediate-stage hepatocellular carcinoma; however, this stage has wide variable levels of liver functions and tumor burden making a challenge as regards the tolerability of the functioning residual liver to this type of therapy. Further stratification of this intermediate stage may help the clinical decision for the suitability of TACE, so we tried to derive a clinical decision support tool to predict the tolerability of the functioning residual liver to TACE using pre-intervention liver reserve function and liver residual volume as well as tumor burden. Results Two hundred and fifty-two patients with non-resectable intermediate-stage hepatocellular carcinoma (HCC) were consecutively included in this cohort study; all patients were blindly followed up for 6 weeks after TACE for manifestation of liver decompensation. For univariate logistic regression analysis, the significant predictors were age, s.albumin, s.bilirubin, prothrombin concentration (PC), tumor volume (TV), residual liver volume (RLV), and residual to liver volumetric ratio (RLVR) (sig, 0.007, 0.000, 0.000, 0.000, 0.000, 0.002, and 0.000, respectively). Multivariate logistic regression analysis illustrated that s.albumin, s.bilirubin, PC, and RLVR were the most independent significant predictors (sig, 0.000 for all with adjusted OR 0.002, 22.692, 0.827, and 0.000, respectively). The discriminatory performance of our proposed decision support score (liver tolerability score) was evaluated using the receiver operating characteristics that identified two cutoff points (≤ 0.30 and ≥ 0.83) to rule out or rule in the possibility of liver decompensation after TACE, respectively (AUC, 0.942 and sig. 0.000). Liver tolerability score stratified the intermediate stage of HCC to 3 risk grades (low, medium, and high) with significant difference as regards hazard distribution. Conclusion Computed tomography image-based assessment of RLVR may have a possible role in predicting future tolerability of the functioning residual tissue to TACE of HCC. Liver tolerability score (LTS) could stratify the intermediate stage HCC to 3 risk grades, so LTS may have a role in clinical decision for the suitability of TACE for intermediate stage HCC.

Aim: Trans-arterial chemoembolization (TACE) in combination with tyrosine kinase inhibitor (TKI) has been evidenced to improve outcomes in a portion of patients with hepatocellular carcinoma (HCC). Developing biomarkers to identify patients who might benefit from the combined treatment is needed. This study aims to investigate the efficacy of radiomics/deep learning features-based models in predicting short-term disease control and overall survival (OS) in HCC patients who received the combined treatment.Materials and Methods: A total of 103 HCC patients who received the combined treatment from Sep. 2015 to Dec. 2019 were enrolled in the study. We exacted radiomics features and deep learning features of six pre-trained convolutional neural networks (CNNs) from pretreatment computed tomography (CT) images. The robustness of features was evaluated, and those with excellent stability were used to construct predictive models by combining each of the seven feature exactors, 13 feature selection methods and 12 classifiers. The models were evaluated for predicting short-term disease by using the area under the receiver operating characteristics curve (AUC) and relative standard deviation (RSD). The optimal models were further analyzed for predictive performance on overall survival.Results: A total of the 1,092 models (156 with radiomics features and 936 with deep learning features) were constructed. Radiomics_GINI_Nearest Neighbors (RGNN) and Resnet50_MIM_Nearest Neighbors (RMNN) were identified as optimal models, with the AUC of 0.87 and 0.94, accuracy of 0.89 and 0.92, sensitivity of 0.88 and 0.97, specificity of 0.90 and 0.90, precision of 0.87 and 0.83, F1 score of 0.89 and 0.92, and RSD of 1.30 and 0.26, respectively. Kaplan-Meier survival analysis showed that RGNN and RMNN were associated with better OS (p = 0.006 for RGNN and p = 0.033 for RMNN).Conclusion: Pretreatment CT-based radiomics/deep learning models could non-invasively and efficiently predict outcomes in HCC patients who received combined therapy of TACE and TKI.

Background and Aims: Trans-arterial chemoembolization (TACE) has become a widely accepted treatment in unresectable hepatocellular carcinoma (HCC). We aimed at comparing the efficacy of Degradable Starch Microspheres (DSMs)-TACE with 50 ± 7µmversus 300–500 μm Drug Eluting Beads (DEB)-TACE in terms of initial clinical and radiological treatment response parameters. Material and Methods: A total of 54 patients with unresectable HCC who underwent DEB-TACE (n = 25) or DSMs-TACE (n = 29) were included in this retrospective study. Baseline demographic and clinical characteristics, duration of follow-up, local recurrence and survival status, as well as treatment outcome including treatment response via modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, viable and total tumor diameter and serum alpha-fetoprotein (AFP) levels were analyzed in both study groups. Results: No significant difference was noted between the two groups in terms of local recurrence (31.6 vs. 16.7%) or mortality (73.9 vs. 85.7%) rates after 36-month and 12-month follow-up, respectively. DSMs-TACE vs. DEB-TACE was associated with significantly higher complete response rate (27.6 vs. 0.0%, p = 0.011) and significant decrease in serum AFP levels (p = 0.013). Conclusion: Both DSMs-TACE with 50 ± 7µmmicrospheres and 300–500 μm DEB-TACE are effective for local control of unresectable HCC. Our findings revealed superiority of DSMs-TACE over DEB-TACEnin terms of initial clinical and radiological tumor response; though no significant difference was noted between the two patient groups in terms of local recurrence or mortality during follow up.

Despite careful selection for liver transplantation (LT) of patients with hepatocellular carcinoma (HCC), HCC may still recur after LT and is frequently associated with dismal outcome. Tumor factors, including serum alpha-fetoprotein (AFP), the presence of microvascular invasion, tumor grade/differentiation, and largest tumor size are amongst the most important predictors of recurrence after transplantation. The nature of recurrence can be highly variable, but often presents with extra-hepatic involvement. As such, management of patients with HCC can be challenging, and consensus guidelines are lacking. Curative options, with surgery or ablation, which may be applicable in patients with isolated intra-or extrahepatic metastases, offer the best chance for improved long-term outcome in patients with HCC recurrence after transplantation. Most patients with recurrence have unresectable disease, and may benefit from palliative treatments, including intra-arterial therapies and/or systemic therapy.

Background and Aims: Trans-arterial chemoembolization (TACE) has become a widely accepted treatment in unresectable hepatocellular carcinoma (HCC). We aimed at comparing the efficacy of Degradable Starch Microspheres (DSMs)-TACE with 50 ± 7 µm versus 300-500 µm Drug Eluting Beads (DEB)-TACE in terms of initial clinical and radiological treatment response parameters. Material and Methods: A total of 54 patients with unresectable HCC who underwent DEB-TACE (n = 25) or DSMs-TACE (n = 29) were included in this retrospective study. Baseline demographic and clinical characteristics, duration of follow-up, local recurrence and survival status, as well as treatment outcome including treatment response via modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, viable and total tumor diameter and serum alpha-fetoprotein (AFP) levels were analyzed in both study groups. Results: No significant difference was noted between the two groups in terms of local recurrence (31.6 vs. 16.7%) or mortality (73.9 vs. 85.7%) rates after 36-month and 12-month follow-up, respectively. DSMs-TACE vs. DEB-TACE was associated with significantly higher complete response rate (27.6 vs. 0.0%, p = 0.011) and significant decrease in serum AFP levels (p = 0.013). Conclusion: Both DSMs-TACE with 50 ± 7 µm microspheres and 300-500 µm DEB-TACE are effective for local control of unresectable HCC. Our findings revealed superiority of DSMs-TACE over DEB-TACEnin terms of initial clinical and radiological tumor response; though no significant difference was noted between the two patient groups in terms of local recurrence or mortality during follow up. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to investigate the effectiveness and safety of the combination of immune checkpoint inhibitor, local interventional therapy, and anti-angiogenic therapy in patients with metastatic soft-tissue sarcoma (mSTS).Settings and Design: We retrospectively evaluated the medical records of patients with mSTS who started treatment between September 2018 and June 2020 at our hospital.Materials and Methods: Overall, 33 patients with different subtypes of mSTS were included. Most primary tumors originated from the lungs, and the rest were scattered throughout the body. All patients were treated with camrelizumab combined with apatinib within 5 days of local interventional therapy using transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). Primary end point was progression-free survival (PFS), and secondary end points were objective response rate (ORR), disease control rate (DCR), and patient safety.Results: The median PFS, median overall survival (OS), ORR, and DCR were 8.8 months, 18.5 months, 36.4%, and 75.8%, respectively. Patients (n = 20) treated with RFA combined with TACE showed better responses than those treated with RFA alone (n = 13), with mPFS of 9.3 and 7.9 months (P = 0.044) and mOS of 19.0 and 16.2 months (P = 0.043), respectively. Patients (n = 8) with alveolar soft part sarcomas showed excellent efficacy, with ORR, DCR, mPFS, and mOS of 62.5%, 87.5%, 11.5 months, and 22.5 months, respectively. Grades 3 or 4 treatment-related adverse events occurred in 12 of 33 patients.Conclusions: Local intervention therapy combined with camrelizumab and apatinib is effective and safe for patients with mSTS and should be investigated in future clinical trials. [ABSTRACT FROM AUTHOR]

Background: The combination therapy of trans-arterial chemoembolization (TACE) and sorafenib were proved to be one of the effective methods for intermediate and advanced hepatocellular carcinoma (HCC). Although it has been confirmed that the combination therapy can prolong survival for advanced HCC effectively, the therapeutic efficacy and safety are still controversial and the clinical value has not been determined. This meta-analysis aims to evaluate the efficacy and safety of combination therapy and discuss the optimal timing of combination for better clinical benefits. Data sources: PubMed, EMBASE, the Cochrane Library, MEDLINE, and Web of Science were systematically reviewed to search for relevant studies published before May 15, 2021. Studies comparing the efficacy and safety of TACE + sorafenib with TACE + placebo / alone were adopted. Two reviewers independently extracted study outcomes. The data were analyzed through fixed/random-effect meta-analysis models with Review Manager (Version 5. 3) software. Results: 7 randomized controlled trials (RCTs) were included with 1464 patients with unresectable HCC (734 in TACE + sorafenib group and 730 in TACE + placebo or alone group). Meta-analysis showed that objective response rate (ORR) and disease control rate (DCR) were slightly improved in TACE + sorafenib group (ORR: risk ratio = 1.24; 95% confidence interval: 1.08–1.42; P = 0.002; DCR: risk ratio = 1.09; 95% confidence interval: 1.01–1.18; P = 0.02). The combination therapy obviously improved time to progression (TTP) (hazard ratio: 0.73; 95% confidence interval: 0.55–0.96; P = 0.03) and progression-free survival (PFS) (hazard ratio 0.62; 95% confidence interval: 0.52–0.73, P

Abstract Background The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE. Methods From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT. Results Eighty nine TACE procedures (1.35 ± 0.67; 1–4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), “typical tumor enhancement” (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis. Conclusions The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation.

Abstract Background Hepatoma arterial-embolization prognostic (HAP) score and its modifications (modified HAP [mHAP] and mHAP-II), consisting of some or all of the following factors of tumor size, number, alpha-fetoprotein, bilirubin, and serum albumin, have been found to predict outcomes after trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We investigated the feasibility of using HAP-related risk scores for dynamic risk assessment during repeated TACE. Methods A total of 619 HCC patients treated with TACE from two institutions between 2003 and 2010 were included. Results Patients with A-B class risk scores showed significantly better survival than those with C-D class risk scores at the first (median 43.7 vs. 21.5 months for mHAP-II, 35.2 vs. 10.2 months for mHAP, and 39.8 vs. 18.6 months for HAP; all P

PurposeThis study aimed to evaluate the efficacy and safety of trans-arterial chemoembolization (TACE) followed by stereotactic body radiation therapy (SBRT) in treating Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) not amenable to resection and radiofrequency ablation (RFA).MethodsFrom February 2012 to January 2017, a total of 57 BCLC stage B HCC patients who were unsuitable candidates for resection and RFA treated with TACE combined with CyberKnife SBRT were included in this retrospective study. Patients underwent TACE for a median of two times (1–5 times) before SBRT. SBRT prescription doses ranged from 30 Gy to 50 Gy in 3–5 fractions.ResultsThe median follow-up time was 42 months. The objective response rate (CR + PR) was 85.9%, and the disease control rate (CR + PR + SD) was 96.5%. The local control (LC) rates were 91.1% and 84.3% at 1 and 2 years, respectively. The 1-, 2-, 3-year overall survival (OS) and the median survival time were 73.2%, 51.4%, 32.4% and 26.6 months, respectively. The 1-, 2-, and 3-year progression-free survival (PFS) were 34.2%, 21.6%, and 9%, respectively, with a median PFS time of 9.7 months. A subgroup analysis was conducted in 32 patients with AFP ≥ 200 ng/ml before TACE. OS was significantly prolonged in those with AFP that decreased by more than 75% than those with AFP that decreased by less than 75% (P = 0.018) after SBRT. The treatment was well tolerated with only one patient (1.8%) developed grade 3 gastrointestinal toxicity, and another patient developed non-classical RILD. In multivariate analysis, tumor length ≥ 10 cm and AFP ≥ 200 ng/ml were independent poor prognostic factors for OS.ConclusionThe combination of TACE and Cyberknife SBRT showed optimal efficacy with acceptable toxicity for BCLC stage B HCC.

Purpose: This study aimed to evaluate the efficacy and safety of trans-arterial chemoembolization (TACE) followed by stereotactic body radiation therapy (SBRT) in treating Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) not amenable to resection and radiofrequency ablation (RFA). Methods: From February 2012 to January 2017, a total of 57 BCLC stage B HCC patients who were unsuitable candidates for resection and RFA treated with TACE combined with CyberKnife SBRT were included in this retrospective study. Patients underwent TACE for a median of two times (1–5 times) before SBRT. SBRT prescription doses ranged from 30 Gy to 50 Gy in 3–5 fractions. Results: The median follow-up time was 42 months. The objective response rate (CR + PR) was 85.9%, and the disease control rate (CR + PR + SD) was 96.5%. The local control (LC) rates were 91.1% and 84.3% at 1 and 2 years, respectively. The 1-, 2-, 3-year overall survival (OS) and the median survival time were 73.2%, 51.4%, 32.4% and 26.6 months, respectively. The 1-, 2-, and 3-year progression-free survival (PFS) were 34.2%, 21.6%, and 9%, respectively, with a median PFS time of 9.7 months. A subgroup analysis was conducted in 32 patients with AFP ≥ 200 ng/ml before TACE. OS was significantly prolonged in those with AFP that decreased by more than 75% than those with AFP that decreased by less than 75% (P = 0.018) after SBRT. The treatment was well tolerated with only one patient (1.8%) developed grade 3 gastrointestinal toxicity, and another patient developed non-classical RILD. In multivariate analysis, tumor length ≥ 10 cm and AFP ≥ 200 ng/ml were independent poor prognostic factors for OS. Conclusion: The combination of TACE and Cyberknife SBRT showed optimal efficacy with acceptable toxicity for BCLC stage B HCC. [ABSTRACT FROM AUTHOR]

Background: Transarterial chemoembolization (TACE) is the recommended treatment modality for non-resectable intermediate-stage hepatocellular carcinoma; however, this stage has wide variable levels of liver functions and tumor burden making a challenge as regards the tolerability of the functioning residual liver to this type of therapy. Further stratification of this intermediate stage may help the clinical decision for the suitability of TACE, so we tried to derive a clinical decision support tool to predict the tolerability of the functioning residual liver to TACE using pre-intervention liver reserve function and liver residual volume as well as tumor burden. Results: Two hundred and fifty-two patients with non-resectable intermediate-stage hepatocellular carcinoma (HCC) were consecutively included in this cohort study; all patients were blindly followed up for 6 weeks after TACE for manifestation of liver decompensation. For univariate logistic regression analysis, the significant predictors were age, s.albumin, s.bilirubin, prothrombin concentration (PC), tumor volume (TV), residual liver volume (RLV), and residual to liver volumetric ratio (RLVR) (sig, 0.007, 0.000, 0.000, 0.000, 0.000, 0.002, and 0.000, respectively). Multivariate logistic regression analysis illustrated that s.albumin, s.bilirubin, PC, and RLVR were the most independent significant predictors (sig, 0.000 for all with adjusted OR 0.002, 22.692, 0.827, and 0.000, respectively). The discriminatory performance of our proposed decision support score (liver tolerability score) was evaluated using the receiver operating characteristics that identified two cutoff points (≤ 0.30 and ≥ 0.83) to rule out or rule in the possibility of liver decompensation after TACE, respectively (AUC, 0.942 and sig. 0.000). Liver tolerability score stratified the intermediate stage of HCC to 3 risk grades (low, medium, and high) with significant difference as regards hazard distribution. Conclusion: Computed tomography image-based assessment of RLVR may have a possible role in predicting future tolerability of the functioning residual tissue to TACE of HCC. Liver tolerability score (LTS) could stratify the intermediate stage HCC to 3 risk grades, so LTS may have a role in clinical decision for the suitability of TACE for intermediate stage HCC. [ABSTRACT FROM AUTHOR]

Despite careful selection for liver transplantation (LT) of patients with hepatocellular carcinoma (HCC), HCC may still recur after LT and is frequently associated with dismal outcome. Tumor factors, including serum alpha-fetoprotein (AFP), the presence of microvascular invasion, tumor grade/differentiation, and largest tumor size are amongst the most important predictors of recurrence after transplantation. The nature of recurrence can be highly variable, but often presents with extra-hepatic involvement. As such, management of patients with HCC can be challenging, and consensus guidelines are lacking. Curative options, with surgery or ablation, which may be applicable in patients with isolated intra-or extrahepatic metastases, offer the best chance for improved long-term outcome in patients with HCC recurrence after transplantation. Most patients with recurrence have unresectable disease, and may benefit from palliative treatments, including intra-arterial therapies and/or systemic therapy. [ABSTRACT FROM AUTHOR]

Background: The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE.Methods: From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT.Results: Eighty nine TACE procedures (1.35 ± 0.67; 1-4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), "typical tumor enhancement" (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis.Conclusions: The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation. [ABSTRACT FROM AUTHOR]

Although different treatment methods have been introduced to treat advanced pancreatic carcinoma, the median overall survival rate remains unsatisfactory. Theoretically, combining different treatment methods should work in synergy to enhance locoregional disease control and improve survival. Therefore, the aim of the present retrospective study was to analyze the effectiveness of combined interventional therapy compared with trans-arterial chemoembolization (TACE) or chemotherapy alone for the treatment of unresectable pancreatic carcinoma. A total of 266 patients who were undergoing treatment for unresectable pancreatic carcinoma between July 2012 and November 2015 were included in the current study. The tumor responses and 3-year overall survival rates of patients treated with combined interventional therapy (TACE combined with iodine-125 seed implantation and/or radiofrequency ablation; CIT group; n=84) were compared with those of patients treated with TACE alone (TACE group; n=59), as well as patients treated with systemic chemotherapy alone (control group; n=123). Patients in the CIT group exhibited significantly improved tumor responses compared with patients in the TACE group (51.89 vs. 30.61%; P=0.028) or control group (51.89 vs. 17.20%; P<0.001). The 3-year overall survival rate of the CIT group was also significantly higher compared with that of the TACE and control groups (P=0.0116 and P=0.0001, respectively). Furthermore, the CIT group exhibited a significantly higher overall survival rate for patients with unresectable metastatic pancreatic cancer compared with the TACE and control groups (P=0.0088 and P<0.0001, respectively), which suggests that a combination of different interventional techniques increases the survival of patients with unresectable pancreatic cancer. No life-threatening complications were observed in any treatment group. In conclusion, combined interventional therapy exhibits a good efficacy and an improved survival rate for unresectable pancreatic cancer compared with TACE alone. [ABSTRACT FROM AUTHOR]

Background: Hepatoma arterial-embolization prognostic (HAP) score and its modifications (modified HAP [mHAP] and mHAP-II), consisting of some or all of the following factors of tumor size, number, alpha-fetoprotein, bilirubin, and serum albumin, have been found to predict outcomes after trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We investigated the feasibility of using HAP-related risk scores for dynamic risk assessment during repeated TACE.Methods: A total of 619 HCC patients treated with TACE from two institutions between 2003 and 2010 were included.Results: Patients with A-B class risk scores showed significantly better survival than those with C-D class risk scores at the first (median 43.7 vs. 21.5 months for mHAP-II, 35.2 vs. 10.2 months for mHAP, and 39.8 vs. 18.6 months for HAP; all P < 0.001) and the second rounds of TACE (38.6 vs. 17.2 months for mHAP-II, 30.0 vs. 8.5 months for mHAP, and 32.6 vs. 17.3 months for HAP; all P < 0.001). Sequential assessment of risk scores at the second TACE round was applied for patients with A-B class risk scores at the first TACE round, which further identified two subgroups of A-B and C-D class risk scores with different outcomes (median survival 40.6 vs. 19.6 months for mHAP-II, 31.2 vs. 16.9 months for mHAP, and 35.8 vs. 21.0 months for HAP; all P < 0.001). Compared with mHAP and HAP, mHAP-II showed the highest likelihood ratio (22.61 vs. 14.67 and 13.97, respectively), highest linear trend (24.43 vs. 19.67 and 14.19, respectively), and lowest Akaike information criteria value (1432.51 vs. 3412.29 and 2296.98, respectively).Conclusions: All HAP-related risk scores dynamically predicted outcomes during repeated TACE. Sequential risk assessment using mHAP-II best identified optimal candidates for repeated TACE. [ABSTRACT FROM AUTHOR]

Objective: To evaluate MDCT perfusion role in HCC local therapy response. Patients and methods: Post radiofrequency ablation and trans-arterial chemoembolization 14 (88%) male and 2 (12%) female HCC patients; with the mean age, 55.75 ± 10.6 years underwent follow-up hepatic CT perfusion. The hepatic arterial and portal venous perfusions (HAP and HPP, ml/min/100 ml) and hepatic perfusion index (HPI%) were indicated using the color coded maps to assess the effects of local therapy on hepatic perfusion values. Results: The post local treatment CTP of the recurrent tumor confirmed relative increased HAP and HPI and reduced PVP relative to the background values of the cirrhotic hepatic parenchyma. The recurrent HCC post-treatment CTP including HAP is 71 ± 12.19, the PVP is 25.5 ± 8.66 and HPI is 52.5 ± 11.9. The post local-treatment CTP of the necrosis confirmed relative decreased HAP and HPI and increased PVP. The post-treatment necrosis CTP including HAP is 23 ± 10.39, the PVP is 34.75 ± 11.5 and HPI is 29 ± 16.51. The CTP sensitivity is 75%, specificity 50% and P-value

Aim: To identify the role of serum MicroRNA-335 (miR-335) in determining the treatment response to Trans-arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and their prognosis after TACE. Methods: A total of 125 HCC patients were enrolled in this study. All these patients underwent TACE and the treatment response was evaluated. All patients were followed for prognosis analyses. Serum miR-335 levels immediate before and 30 days after TACE were determined. Results: HCC patients had significantly lower miR-335 levels than hepatitis patients and healthy controls. Lower serum miR-335 levels were closely associated with more progressive clinical features, including a higher mean serum AFP level, more vascular invasion, cirrhosis and larger tumor size. Response rates were higher in patients with high miR-335 compared to those with low miR-335 level. Patients with lower serum miR-335 levels had significantly poorer prognosis than patients with higher serum miR-335 levels. Conclusion: Our data suggest that serum miR-335 can be used as a molecular marker to predict the treatment response and clinical outcome in HCC patients receiving TACE.

The majority of patients with unresectable hepatocellular carcinoma (HCC) undergo trans-arterial chemoembolization (TACE). However, the prognosis of HCC remains poor. In the present study, five staging systems were compared to predict the survival rate of patients with HCC undergoing TACE treatment. A total of 220 patients with HCC were examined according to the model to estimate survival for hepatocellular carcinoma (MESH), hepatoma arterial embolization prognostic score (HAP), modified HAP (mHAP), performance status combined Japan Integrated Staging system (PSJIS) and tumor-node-metastasis (TNM) staging systems. The endpoints of the study were 3-month survival, 6-month survival, 1-year survival and overall survival (OS) rates. Receiver operating characteristic curve analysis indicated that the area under the curve of MESH, HAP, mHAP, PSJIS and TNM was 0.858, 0.728, 0.690, 0.688 and 0.699, respectively, in predicting 3-month survival rates; 0.822, 0.747, 0.720, 0.722 and 0.715, respectively, in predicting 6-month survival rates and 0.725, 0.664, 0.672, 0.645 and 0.654, respectively, in predicting 1-year survival rates. Discriminatory ability, homogeneity, monotonicity and prognostic stratification ability was evaluated using a likelihood ratio test and Akaike information criterion values among the five staging systems, and revealed that the MESH system was the optimal prognostic staging system for HCC. In conclusion, the results of the present study suggest that the MESH system is the most accurate prognostic staging system of 3-month survival, 6-month survival, 1-year survival and OS rates among the five systems analyzed in patients with HCC who have received TACE treatment. [ABSTRACT FROM AUTHOR]

In patients with AFP-negative hepatocellular carcinoma (HCC), des-γ-carboxyprothrombin (DCP) is an important prognostic indicator for the preoperative assessment of transarterial chemoembolization (TACE). However, the association between the serum DCP levels and the degree of progression and prognosis of patients with AFP-negative HCC treated with TACE has not been thoroughly investigated to date, and the molecular mechanism is also unclear. The present study retrospectively analyzed the clinical data of 107 patients with AFP-negative HCC treated with TACE and divided them into two groups based on the median serum DCP levels. The association between DCP and the clinical characteristics of the patients was analyzed, and the survival data were analyzed using Kaplan-Meier curves and Cox regression models. The results demonstrated that the median follow-up time was 755 days (range, 64–1,556 days), and patients in the low-DCP group (n=11; 20.8%) had a lower mortality rate than those in the high-DCP group (n=20; 37.0%). Cox multivariate regression analysis suggested that preoperative lymph node metastasis [hazard ratio (HR), 3.903; 95% CI, 1.778-8.519; P=0.001] and DCP group (HR, 2.465; 95% CI, 1.038-5.854; P=0.041) were independent risk factors. Furthermore, the Gene Expression Omnibus database was utilized to screen differentially expressed mRNAs. Enrichment analyses were then performed, and a protein-protein interaction (PPI) network was constructed to identify hub genes. A total of 169 differentially expressed genes were screened. Enrichment analyses revealed that cancer-related and ribosomal pathways were significantly enriched. Furthermore, 10 hub genes were identified in the PPI network by counting the number of gene interactions, the majority of which belonged to the ribosomal protein (RPS) family, and the top three significant genes were RPS23, RPS11 and RPS3A. In patients with AFP-negative HCC, higher serum DCP levels were associated with poor prognosis after TACE. This may be associated with genes such as those belonging to the RPS family, which may contribute to future personalized therapy for this disease. [ABSTRACT FROM AUTHOR]

Aim: To identify the role of serum MicroRNA-335 (miR-335) in determining the treatment response to Trans-arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and their prognosis after TACE. Methods: A total of 125 HCC patients were enrolled in this study. All these patients underwent TACE and the treatment response was evaluated. All patients were followed for prognosis analyses. Serum miR-335 levels immediate before and 30 days after TACE were determined. Results: HCC patients had significantly lower miR-335 levels than hepatitis patients and healthy controls. Lower serum miR-335 levels were closely associated with more progressive clinical features, including a higher mean serum AFP level, more vascular invasion, cirrhosis and larger tumor size. Response rates were higher in patients with high miR-335 compared to those with low miR-335 level. Patients with lower serum miR-335 levels had significantly poorer prognosis than patients with higher serum miR-335 levels. Conclusion: Our data suggest that serum miR-335 can be used as a molecular marker to predict the treatment response and clinical outcome in HCC patients receiving TACE. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In patients with AFP-negative hepatocellular carcinoma (HCC), des-γ-carboxyprothrombin (DCP) is an important prognostic indicator for the preoperative assessment of transarterial chemoembolization (TACE). However, the association between the serum DCP levels and the degree of progression and prognosis of patients with AFP-negative HCC treated with TACE has not been thoroughly investigated to date, and the molecular mechanism is also unclear. The present study retrospectively analyzed the clinical data of 107 patients with AFP-negative HCC treated with TACE and divided them into two groups based on the median serum DCP levels. The association between DCP and the clinical characteristics of the patients was analyzed, and the survival data were analyzed using Kaplan-Meier curves and Cox regression models. The results demonstrated that the median follow-up time was 755 days (range, 64-1,556 days), and patients in the low-DCP group (n=11; 20.8%) had a lower mortality rate than those in the high-DCP group (n=20; 37.0%). Cox multivariate regression analysis suggested that preoperative lymph node metastasis [hazard ratio (HR), 3.903; 95% CI, 1.778-8.519; P=0.001] and DCP group (HR, 2.465; 95% CI, 1.038-5.854; P=0.041) were independent risk factors. Furthermore, the Gene Expression Omnibus database was utilized to screen differentially expressed mRNAs. Enrichment analyses were then performed, and a protein-protein interaction (PPI) network was constructed to identify hub genes. A total of 169 differentially expressed genes were screened. Enrichment analyses revealed that cancer-related and ribosomal pathways were significantly enriched. Furthermore, 10 hub genes were identified in the PPI network by counting the number of gene interactions, the majority of which belonged to the ribosomal protein (RPS) family, and the top three significant genes were RPS23, RPS11 and RPS3A. In patients with AFP-negative HCC, higher serum DCP levels were associated with poor prognosis after TACE. This may be associated with genes such as those belonging to the RPS family, which may contribute to future personalized therapy for this disease., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Sun et al.)

Background: Hepatocellular carcinoma (HCC) is a common tumour often diagnosed with a multifocal presentation. Patients with multifocal HCC represent a heterogeneous group. Although Trans-Arterial ChemoEmbolization (TACE) is the most frequently employed treatment for these patients, previous data suggested that liver resection (LR) could be a safe and effective procedure., Aim: To compare LR and TACE in patients with multifocal HCC in terms of procedure-related morbidity and oncologic outcomes., Methods: All patients with multifocal HCC who underwent LR or TACE as the first procedure between May 2011 and March 2021 were enrolled. The decision to perform surgery or TACE was made after a multidisciplinary team evaluation. Only patients in Child-Pugh class A or B7 and stage B (according to the Barcelona Clinic Liver Cancer staging system, without severe portal hypertension, vascular invasion, or extrahepatic spread) were included in the final analysis. Propensity score matching was used to adjust the baseline differences between patients undergoing LR and the TACE group [number and diameter of lesions, presence of cirrhosis, alpha-fetoprotein (AFP) levels, and Model for End-Stage Liver Disease score]. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). The outcomes of LR and TACE were compared using the log-rank test., Results: After matching, 30 patients were eligible for the final analysis, 15 in each group. Morbidity rates were 42.9% and 40% for LR and TACE, respectively ( P = 0.876). Median OS was not different in the LR and TACE groups (53 mo vs 18 mo, P = 0.312), while DFS was significantly longer with LR (19 mo vs 0 mo, P = 0.0001). Subgroup analysis showed that patients in the Italian Liver Cancer (ITA.LI.CA) B2 stage, with AFP levels lower than 400 ng/mL, less than 3 lesions, and lesions bigger than 41 mm, benefited more from LR in terms of DFS. Patients classified as ITA.LI.CA B3, with AFP levels higher than 400 ng/mL and with more than 3 lesions, appeared to receive more benefit from TACE in terms of OS., Conclusion: In a small cohort of patients with multifocal HCC, LR confers longer DFS compared with TACE, with similar OS and post-procedural morbidity., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Simple Summary: Colorectal cancer liver metastasis occurs in more than 50% of patients with colorectal cancer and is thought to be the most common cause of death from this cancer. The mainstay of treatment for inoperable liver metastasis has been combination systemic chemotherapy with or without the addition of biological targeted therapy with a goal for disease downstaging, for potential curative resection, or more frequently, for disease control. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies including hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are alternative treatment strategies that have shown promising results, most commonly in the salvage setting in patients with chemo-refractory disease. In recent years, their role in the first-line setting in conjunction with concurrent systemic chemotherapy has also been explored. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies such as hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are treatment strategies which are increasingly being considered to improve local tumor response and to reduce systemic side effects. Currently, these therapies are mostly used in the salvage setting in patients with chemo-refractory disease. However, their use in the first-line setting in conjunction with systemic chemotherapy as well as to a lesser degree, in a neoadjuvant setting, for downstaging to resection have also been investigated. Furthermore, some clinicians have considered these therapies as a temporizing tool for local disease control in patients undergoing a chemotherapy 'holiday' or acting as a bridge in patients between different lines of systemic treatment. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, efficacy and safety of embolization alone and trans-arterial chemoembolization were compared in 265 patients with intermediate stage hepatocellular carcinoma. Trans-arterial chemoembolization was associated with a significant increase of complete radiological response, but without significant impact on overall response, and survival outcomes after propensity score matching. Both techniques showed similar safety profiles. To this day, embolization alone and trans-arterial chemoembolization are two available options in the treatment of intermediate stage hepatocellular carcinoma. No definitive conclusion could be reached about the role of chemotherapy in adjunction of embolization in the treatment of hepatocellular carcinoma (HCC). We aim to compare radiological response, toxicity and long-term outcomes of patients with hepatocellular carcinoma (HCC) treated by trans-arterial bland embolization (TAE) versus trans-arterial chemoembolization (TACE). We retrospectively included 265 patients with HCC treated by a first session of TACE or TAE in two centers. Clinical and biological features were recorded before the treatment and radiological response was assessed after the first treatment using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Correlation between the treatment and overall, progression-free and transplantation-free survival was performed after adjustment using a propensity score matching: 86 patients were treated by bland embolization and 179 patients by TACE, including 44 patients with drug-eluting beads and 135 with lipiodol TACE, 89.8% of patients were male with a median age of 65 years old. Cirrhosis was present in 90.9% of patients with a Child Pugh score A in 84% of cases. After adjustment, no difference in the rate of AE, including liver failure, was observed between the two treatments. TACE was associated with a significant increase in complete radiological response (odds ratio (OR) = 8.5 (95% confidence interval (CI): 2.8–25.4)) but not in the overall response rate (OR = 2.2 (95% CI = 0.8–5.8)). No difference in terms of overall survival (p = 0.3905), progression-free survival (p = 0.4478) and transplantation-free survival (p = 0.9020) was observed between TACE and TAE. TACE was associated with a higher rate of complete radiological response but without any impact on overall radiological response, progression-free survival and overall survival compared to TAE. [ABSTRACT FROM AUTHOR]