Chemoembolization Research Articles

Creation of a Prediction Model of Local Tumor Recurrence After a Successful Conventional Transcatheter Arterial Chemoembolization Using Cone-Beam Computed Tomography Based-Radiomics.

To create and evaluate prediction models of local tumor recurrence after successful conventional transcatheter arterial chemoembolization (c-TACE) via radiomics analysis of lipiodol deposition using cone-beam computed tomography (CBCT) images obtained at the completion of TACE. A total of 103 hepatocellular carcinoma nodules in 71 patients, who achieved a complete response (CR) based on the modified Response Evaluation Criteria in Solid Tumors 1month after TACE, were categorized into two groups: prolonged CR and recurrence groups. Three types of areas were segmented on CBCT: whole segment (WS), tumor segment (TS), and peritumor segment (PS). From each segment, 105 radiomic features were extracted. The nodules were randomly divided into training and test datasets at a ratio of 7:3. Following feature reduction for each segment, three models (clinical, radiomics, and clinical-radiomics models) were developed to predict recurrence based on logistic regression. The clinical-radiomics model of WS showed the best performance, with the area under the curve values of 0.853 (95% confidence interval: 0.765-0.941) in training and 0.752 (0.580-0.924) in test dataset. In the analysis of radiomic feature importance of all models, among all radiomic features, glcm_MaximumProbability, shape_MeshVolume and shape_MajorAxisLength had negative coefficients. In contrast, shape_SurfaceVolumeRatio, shape_Elongation, glszm_SizeZoneNonUniformityNormalized, and gldm_GrayLevelNonUniformity had positive coefficients. In this study, a machine-learning model based on cone-beam CT images obtained at the completion of c-TACE was able to predict local tumor recurrence after successful c-TACE. Nonuniform lipiodol deposition and irregular shapes may increase the likelihood of recurrence.

6799 RZ358 Therapy. A Novel Approach to Hyperinsulinemia in Metastatic Neuroendocrine Tumor Patients

Abstract Disclosure: J. Noreña: None. T. Akcan: None. S. Patel: None. W. Madeleine: None. S. Shaheen: None. M. Tan: None. RZ358, an intravenously administered monoclonal antibody, targets a unique allosteric site on the insulin receptor. It is under investigation for hypoglycemia due to congenital hyperinsulinism. We present a case of its efficacy in treating refractory hyperinsulinemic-hypoglycemia (HH) due to a metastatic pancreatic neuroendocrine tumor (pNET). Clinical Case: A 50-year-old woman with a 6-year history of HH initially presented in 2016 with epigastric pain and was diagnosed with gastrin secreting pNET pT3N1. After Whipple surgery and cholecystectomy. A well-differentiated, WHO grade 2 NET, positive in immunohistochemistry for AE1/3, synaptophysin and Ki-67 index of 9.2% was confirmed. She presented recurrent disease with liver metastasis requiring somatostatin analogue Lanreotide. Subsequently despite Lanreotide, hypoglycemia persisted, and 72-hour fast confirmed HH. DOTATATE scan showed progression to new liver lesions. Everolimus was started and subsequently peptide receptor radionuclide therapy (PRRT) with fair hypoglycemia control. Unfortunately, her disease progressed. Oral glucose, cornstarch, and diazoxide failed. After a left hepatectomy and transarterial chemoembolization, her severe hypoglycemia improved briefly. Despite high-dose dexamethasone (up to 4 mg daily), octreotide 400 mcg every 8 hours, and high-calorie total parenteral nutrition (TPN) (over 800 grams of carbohydrates daily), she required multiple hospitalizations for persistent symptomatic hypoglycemia. Moreover, these therapies led to significant side effects, including recurrent episodes of volume overload, 240 pounds weight gain over a year, and Cushingoid features. Given RZ358's reports in reversing HH in rodents, humans, and a recent report of successful use in a malignant insulinoma case, we aimed to start RZ358 in our patient. We obtained, emergency use authorization from the FDA, IRB of Stanford University School of Medicine approval, and patient written informed consent. RZ358 was started at 6 mg/kg biweekly, along with octreotide, dexamethasone, and TPN. RZ358 dosage was later increased to 9 mg/kg weekly, allowing a substantial reduction in dexamethasone to physiological doses and a 50% reduction in TPN carbohydrate requirements. She achieved normoglycemia and returned home, but missing a single weekly RZ358 dose caused recurrent severe hypoglycemia until the next dose administration.As her disease progressed, the patient opted for comfort care, discontinuing TPN and RZ358. Conclusion: RZ358 represents a novel and unique treatment option for refractory HH in patients with metastatic NETs and can improve clinical outcomes when standard interventions fail. This case underscores the potential of RZ358, a monoclonal antibody, to treat HH beyond its approved use for congenital cases, suggesting its applicability to cases of hyperinsulinemia secondary to NETs in adults. Presentation: 6/2/2024

9286 RZ358 Therapy. A Novel Approach To Hyperinsulinemia In Metastatic Neuroendocrine Tumor Patients

Abstract Disclosure: J. Noreña: None. T. Akcan: None. S. Patel: None. M. Welsh: None. S. Shaheen: None. M. Tan: None. RZ358, an intravenously administered monoclonal antibody, targets a unique allosteric site on the insulin receptor. It is under investigation for hypoglycemia due to congenital hyperinsulinism. We present a case of its efficacy in treating refractory hyperinsulinemic-hypoglycemia (HH) due to a metastatic pancreatic neuroendocrine tumor (pNET). Clinical Case: A 50-year-old woman with a 6-year history of HH initially presented in 2016 with epigastric pain and was diagnosed with gastrin secreting pNET pT3N1. After Whipple surgery and cholecystectomy. A well-differentiated, WHO grade 2 NET, positive in immunohistochemistry for AE1/3, synaptophysin and Ki-67 index of 9.2% was confirmed. She presented recurrent disease with liver metastasis requiring somatostatin analogue Lanreotide. Subsequently despite Lanreotide, hypoglycemia persisted, and 72-hour fast confirmed HH. DOTATATE scan showed progression to new liver lesions. Everolimus was started and subsequently peptide receptor radionuclide therapy (PRRT) with fair hypoglycemia control. Unfortunately, her disease progressed. Oral glucose, cornstarch, and diazoxide failed. After a left hepatectomy and transarterial chemoembolization, her severe hypoglycemia improved briefly. Despite high-dose dexamethasone (up to 4 mg daily), octreotide 400 mcg every 8 hours, and high-calorie total parenteral nutrition (TPN) (over 800 grams of carbohydrates daily), she required multiple hospitalizations for persistent symptomatic hypoglycemia. Moreover, these therapies led to significant side effects, including recurrent episodes of volume overload, 240 pounds weight gain over a year, and Cushingoid features. Given RZ358's reports in reversing HH in rodents, humans, and a recent report of successful use in a malignant insulinoma case, we aimed to start RZ358 in our patient. We obtained, emergency use authorization from the FDA, IRB of Stanford University School of Medicine approval, and patient written informed consent. RZ358 was started at 6 mg/kg biweekly, along with octreotide, dexamethasone, and TPN. RZ358 dosage was later increased to 9 mg/kg weekly, allowing a substantial reduction in dexamethasone to physiological doses and a 50% reduction in TPN carbohydrate requirements. She achieved normoglycemia and returned home, but missing a single weekly RZ358 dose caused recurrent severe hypoglycemia until the next dose administration.As her disease progressed, the patient opted for comfort care, discontinuing TPN and RZ358. Conclusion: RZ358 represents a novel and unique treatment option for refractory HH in patients with metastatic NETs and can improve clinical outcomes when standard interventions fail. This case underscores the potential of RZ358, a monoclonal antibody, to treat HH beyond its approved use for congenital cases, suggesting its applicability to cases of hyperinsulinemia secondary to NETs in adults. Presentation: 6/2/2024

6799 RZ358 Therapy. A Novel Approach To Hyperinsulinemia In Metastatic Neuroendocrine Tumor Patients

Abstract Disclosure: J. Noreña: None. T. Akcan: None. S. Patel: None. W. Madeleine: None. S. Shaheen: None. M. Tan: None. RZ358, an intravenously administered monoclonal antibody, targets a unique allosteric site on the insulin receptor. It is under investigation for hypoglycemia due to congenital hyperinsulinism. We present a case of its efficacy in treating refractory hyperinsulinemic-hypoglycemia (HH) due to a metastatic pancreatic neuroendocrine tumor (pNET). Clinical Case: A 50-year-old woman with a 6-year history of HH initially presented in 2016 with epigastric pain and was diagnosed with gastrin secreting pNET pT3N1. After Whipple surgery and cholecystectomy. A well-differentiated, WHO grade 2 NET, positive in immunohistochemistry for AE1/3, synaptophysin and Ki-67 index of 9.2% was confirmed. She presented recurrent disease with liver metastasis requiring somatostatin analogue Lanreotide. Subsequently despite Lanreotide, hypoglycemia persisted, and 72-hour fast confirmed HH. DOTATATE scan showed progression to new liver lesions. Everolimus was started and subsequently peptide receptor radionuclide therapy (PRRT) with fair hypoglycemia control. Unfortunately, her disease progressed. Oral glucose, cornstarch, and diazoxide failed. After a left hepatectomy and transarterial chemoembolization, her severe hypoglycemia improved briefly. Despite high-dose dexamethasone (up to 4 mg daily), octreotide 400 mcg every 8 hours, and high-calorie total parenteral nutrition (TPN) (over 800 grams of carbohydrates daily), she required multiple hospitalizations for persistent symptomatic hypoglycemia. Moreover, these therapies led to significant side effects, including recurrent episodes of volume overload, 240 pounds weight gain over a year, and Cushingoid features. Given RZ358's reports in reversing HH in rodents, humans, and a recent report of successful use in a malignant insulinoma case, we aimed to start RZ358 in our patient. We obtained, emergency use authorization from the FDA, IRB of Stanford University School of Medicine approval, and patient written informed consent. RZ358 was started at 6 mg/kg biweekly, along with octreotide, dexamethasone, and TPN. RZ358 dosage was later increased to 9 mg/kg weekly, allowing a substantial reduction in dexamethasone to physiological doses and a 50% reduction in TPN carbohydrate requirements. She achieved normoglycemia and returned home, but missing a single weekly RZ358 dose caused recurrent severe hypoglycemia until the next dose administration.As her disease progressed, the patient opted for comfort care, discontinuing TPN and RZ358. Conclusion: RZ358 represents a novel and unique treatment option for refractory HH in patients with metastatic NETs and can improve clinical outcomes when standard interventions fail. This case underscores the potential of RZ358, a monoclonal antibody, to treat HH beyond its approved use for congenital cases, suggesting its applicability to cases of hyperinsulinemia secondary to NETs in adults. Presentation: 6/2/2024

9286 RZ358 Therapy. A Novel Approach to Hyperinsulinemia in Metastatic Neuroendocrine Tumor Patients

Abstract Disclosure: J. Noreña: None. T. Akcan: None. S. Patel: None. M. Welsh: None. S. Shaheen: None. M. Tan: None. RZ358, an intravenously administered monoclonal antibody, targets a unique allosteric site on the insulin receptor. It is under investigation for hypoglycemia due to congenital hyperinsulinism. We present a case of its efficacy in treating refractory hyperinsulinemic-hypoglycemia (HH) due to a metastatic pancreatic neuroendocrine tumor (pNET). Clinical Case: A 50-year-old woman with a 6-year history of HH initially presented in 2016 with epigastric pain and was diagnosed with gastrin secreting pNET pT3N1. After Whipple surgery and cholecystectomy. A well-differentiated, WHO grade 2 NET, positive in immunohistochemistry for AE1/3, synaptophysin and Ki-67 index of 9.2% was confirmed. She presented recurrent disease with liver metastasis requiring somatostatin analogue Lanreotide. Subsequently despite Lanreotide, hypoglycemia persisted, and 72-hour fast confirmed HH. DOTATATE scan showed progression to new liver lesions. Everolimus was started and subsequently peptide receptor radionuclide therapy (PRRT) with fair hypoglycemia control. Unfortunately, her disease progressed. Oral glucose, cornstarch, and diazoxide failed. After a left hepatectomy and transarterial chemoembolization, her severe hypoglycemia improved briefly. Despite high-dose dexamethasone (up to 4 mg daily), octreotide 400 mcg every 8 hours, and high-calorie total parenteral nutrition (TPN) (over 800 grams of carbohydrates daily), she required multiple hospitalizations for persistent symptomatic hypoglycemia. Moreover, these therapies led to significant side effects, including recurrent episodes of volume overload, 240 pounds weight gain over a year, and Cushingoid features. Given RZ358's reports in reversing HH in rodents, humans, and a recent report of successful use in a malignant insulinoma case, we aimed to start RZ358 in our patient. We obtained, emergency use authorization from the FDA, IRB of Stanford University School of Medicine approval, and patient written informed consent. RZ358 was started at 6 mg/kg biweekly, along with octreotide, dexamethasone, and TPN. RZ358 dosage was later increased to 9 mg/kg weekly, allowing a substantial reduction in dexamethasone to physiological doses and a 50% reduction in TPN carbohydrate requirements. She achieved normoglycemia and returned home, but missing a single weekly RZ358 dose caused recurrent severe hypoglycemia until the next dose administration.As her disease progressed, the patient opted for comfort care, discontinuing TPN and RZ358. Conclusion: RZ358 represents a novel and unique treatment option for refractory HH in patients with metastatic NETs and can improve clinical outcomes when standard interventions fail. This case underscores the potential of RZ358, a monoclonal antibody, to treat HH beyond its approved use for congenital cases, suggesting its applicability to cases of hyperinsulinemia secondary to NETs in adults. Presentation: 6/2/2024

Idarubicin-loaded drug-eluting microspheres transarterial chemoembolization for intermediate stage hepatocellular carcinoma: safety, efficacy, and pharmacokinetics.

Transarterial chemoembolization (TACE) is the treatment of choice for the intermediate stage hepatocellular carcinoma (HCC). Doxorubicin remains the most used chemotherapeutic agent in TACE, although in vitro screening has demonstrated that idarubicin exhibits greater cytotoxicity against HCC. This study aimed to evaluate safety, efficacy, and pharmacokinetics of idarubicin-loaded drug-eluting microspheres TACE (DEMIDA-TACE) in intermediate stage HCC patients. Between September 2019 and December 2021, 31 consecutive intermediate stage HCC patients (96.8% cirrhotic) were included to this study. 2 mL of LifePearl™ microspheres (100 μm) loaded with 10 mg of 1 mg/mL idarubicin were used for treatment. The adverse events, objective response rate (ORR), progression free survival (PFS), time to TACE untreatable progression (TTUP), median overall survival (mOS), and pharmacokinetics were evaluated. There were 68 TACE procedures performed. Adverse events grade ≥ 3 were noted after 29.4% procedures. The ORR was 83.9%, median PFS and TTUP were 10.5 months (95% CI: 6.8-14.3 months) and 24.6 months (95% CI: 11.6-37.6 months), respectively. Median OS was 36.0 months (95% CI: 21.1-50.9 months). Significant differences between patients achieving objective response (OR) and those with progressive disease were observed regarding idarubicinol and combined idarubicin-idarubicinol plasma concentrations at 72 hours post-procedure, higher plasma concentrations were observed in patients achieving OR (p = 0.014 and 0.014; cut-off values 1.2 and 1.29 ng/mL, respectively). DEMIDA-TACE emerges as a safe and effective method of treatment for the intermediate stage HCC with low rates of adverse events alongside high tumor response, favourable disease control and overall survival. Idarubicinol and combined idarubicin-idarubicinol plasma concentrations at 72 hours post-procedure may serve as prognostic factors for achieving OR.

Long-Term Outcome of a Multicenter Prospective Study on Efficacy and Safety of High-Dose Stereotactic Body Radiation Therapy ≥48-h Interfraction Interval for ≤5 cm Hepatocellular Carcinoma

Introduction: The goal of this study was to evaluate the efficacy and safety of high-dose stereotactic body radiation therapy (SBRT) with an extended (48 h or more) interfraction interval for hepatocellular carcinoma (HCC) ≤5 cm in size after incomplete response to transarterial chemoembolization (TACE). Methods: This multicenter prospective study included 54 patients with inoperable HCC of ≤5 cm size between July 2012 and June 2015. A total SBRT dose of 60 Gy in 3 fractions was administered within 14 days with ≥48-h interfraction interval to patients who showed an incomplete response after 1–5 sessions of TACE. Treatment responses were defined according to the modified Response Evaluation Criteria for Solid Tumors. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results: Forty-eight patients were evaluated with a median follow-up period of 66 months (range, 2–126 months). The median tumor size was 2.0 cm (range, 1.0–4.5 cm), and most patients (87.5%) had a single lesion. The 1-, 2-, and 5-year local control (LC) rates were 100%, 94.8%, and 90.7%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates were 63.4%, 56.9%, and 24.9%, respectively. The 1-, 2-, and 5-year overall survival (OS) rates were 95.6%, 90.9%, and 76.5%, respectively. None of the patients experienced grade 3+ gastrointestinal toxicity, while 1 patient developed non-classic radiation-induced liver disease 2 months after SBRT. Conclusion: High-dose SBRT with a ≥48-h interfraction interval after incomplete response to TACE is effective for HCC ≤5 cm in size as evidenced by the high rates of LC and OS and acceptable treatment-related toxicity.

Prognostic implications of CK19 positivity in patients with early recurrent hepatocellular carcinoma after hepatic resection undergoing transarterial chemoembolization

BackgroundThis study aimed to compare the survival outcomes of transarterial chemoembolization (TACE) between patients with early recurrent hepatocellular carcinoma (rHCC) after hepatic resection, stratified by cytokeratin (CK) 19 expression.MethodsA retrospective analysis was conducted on 63 patients with early rHCC after hepatic resection who underwent TACE between January 2017 and December 2021. Patients were divided into two groups based on CK19 expression: CK19-negative (n=31) and CK19-positive (n=32). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to identify independent risk factors for OS and PFS.ResultsThe CK19-negative group demonstrated a significantly longer median OS compared to the CK19-positive group (635 days vs. 432 days, p=0.013). Similarly, the CK19-negative group had a longer median PFS than the CK19-positive group (291 days vs. 117 days, p=0.014). Multivariate Cox analysis identified Child-Pugh A grade, CK19-negative expression, and increased TACE sessions as protective factors for OS. No severe TACE-related adverse events were observed.ConclusionIn patients with early rHCC after hepatic resection, those with CK19-positive expression had poorer survival outcomes following TACE compared to CK19-negative patients. These findings suggest the need for additional therapies to improve survival in CK19-positive individuals.

Is DEB-TACE as locoregional therapy before liver transplantation for hepatocellular carcinoma effective?

BackgroundThe objectives were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) as locoregional therapy (LRT) in hepatocellular carcinoma (HCC) before liver transplantation (LT) beyond Hangzhou criteria (HC) and to analyze the prognostic factors.MethodsForty patients with HCC beyond HC who received DEB-TACE only before LT were retrospectively analyzed between January 2017 and December 2022. Data on patient demographics, disease characteristics, treatment response, and adverse events (AE) were collected. Overall survival (OS) and recurrence-free survival (RFS) were evaluated with Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to identify factors independently associated with RFS and OS.ResultsAll patients successfully underwent LT following DEB-TACE with a mean interval of 2.3 months. The objective response rates (ORRs) for these patients following DEB-TACE was 82.5%. The primary AE was post-embolization syndrome (PES), with affected patients experiencing grades I and II. The median RFS and OS were 12.0 months (95%CI: 0.0-30.1) and 52.0 months (95%CI: 11.8–92.2) over the follow-up period until December 2022. The 2-year RFS and OS rates were 42.5%, and 67.5%. Multivariate analyses revealed Child-Pugh classification (HR = 6.24; 95%CI,1.83–21.24; P = 0.01) and macrovascular invasion (MAV) (HR = 3.89; 95%CI,1.07–14.15; P = 0.04) were both significant independent predictors of OS.ConclusionsDEB-TACE can serve as a safe and effective LRT in HCC patients beyond HC before LT, and can improve the prognosis of patients, especially without MAV. The higher Child–Pugh classification and MAV are independent prognostic factors after LT.

Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE.

Transarterial chemoembolization (TACE) is the first-line treatment for patients with advanced HCC, but there are limited studies on the microenvironment alterations caused by TACE. Six fresh HBV-related HCC specimens with or without TACE intervention were used to perform single-cell RNA sequencing. The 757 bulk samples from 3 large-scale multicenter cohorts were applied for comprehensive analysis. The biological functions of the biomarkers were further validated by phenotypic experiments. Using single-cell RNA sequencing analysis, we delineated the global cell atlas of post-TACE and demonstrated elevated tumor heterogeneity and an enhanced proinflammatory microenvironment induced by TACE. Cell-cell communication analysis revealed that markedly elevated interactions between NABP1+ malignant hepatocytes, neutrophils, and CD8+ T cells after TACE might accelerate the shift from CD8+ effector memory T cells to CD8+ effector T cells. This result was substantiated by the developmental trajectory between the 2 and dramatically decreased resident scores along the pseudotemporal trajectory. Integrating bulk data, we further found that the increased estimated proportion of NABP1+ malignant hepatocytes was related to poor TACE response and dismal prognosis, and its biomarker role could be replaced by NABP1. In vitro, multiple biological experiments consistently verified that NABP1 knockdown significantly inhibited the proliferation and migration of HCC cells. Based on our depicted global map of post-TACE, we confirmed that the enhanced interactions within the microenvironment after TACE may be the culprits for postoperative progression. NABP1 may become an attractive tool for the early identification of patients sensitive to first-line TACE in clinical practice.

Prognosis of Patients with Hepatocellular Carcinoma Treated with TACE: A New Score Combining Alpha-Fetoprotein and Des-γ-Carboxy Prothrombin.

Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE). This was a retrospective study that included 295HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification. The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set. For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE.

Tumor Growth Pattern and Intra- and Peritumoral Radiomics Combined for Prediction of Initial TACE Outcome in Patients with Primary Hepatocellular Carcinoma.

Non-invasive methods are urgently needed to assess the efficacy of transarterial chemoembolization (TACE) and to identify patients with hepatocellular carcinoma (HCC) who may benefit from this procedure. This study, therefore, aimed to investigate the predictive ability of tumor growth patterns and radiomics features from contrast-enhanced magnetic resonance imaging (CE-MRI) in predicting tumor response to TACE among patients with HCC. A retrospective study was conducted on 133 patients with HCC who underwent TACE at three centers between January 2015 and April 2023. Enrolled patients were divided into training, testing, and validation cohorts. Rim arterial phase hyperenhancement (Rim APHE), tumor growth patterns, nonperipheral washout, markedly low apparent diffusion coefficient (ADC) value, intratumoral arteries, and clinical baseline features were documented for all patients. Radiomics features were extracted from the intratumoral and peritumoral regions across the three phases of CE-MRI. Seven prediction models were developed, and their performances were evaluated using receiver operating characteristic (ROC) and decision curve analysis (DCA). Tumor growth patterns and albumin-bilirubin (ALBI) score were significantly correlated with tumor response. Tumor growth patterns also showed a positive correlation with tumor burden (r = 0.634, P = 0.000). The Peritumor (AUC = 0.85, 0.71, and 0.77), Clinics_Peritumor (AUC = 0.86, 0.77, and 0.81), and Tumor_Peritumor (AUC = 0.87, 0.77, and 0.80) models significantly outperformed the Clinics and Tumor models (P < 0.05), while the Clinics_Tumor_Peritumor model (AUC = 0.88, 0.81, and 0.81) outperformed the Clinics (AUC = 0.67, 0.77, and 0.75), Tumor (AUC = 0.78, 0.72, and 0.68), and Clinics_Tumor (AUC = 0.82, 0.83, and 0.78) models (P < 0.05 or 0.053, respectively). The DCA curve demonstrated better predictive performance within a specific threshold probability range for Clinics_Tumor_Peritumor. Combining tumor growth patterns, intra- and peri-tumoral radiomics features, and ALBI score could be a robust tool for non-invasive and personalized prediction of treatment response to TACE in patients with HCC.

Efficacy of Atezolizumab Plus Bevacizumab Combined with Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Real-World Study.

Transarterial chemoembolization (TACE), when used in combination with immunotherapy and antiangiogenic therapy, has been shown to have synergistic anticancer effects. The aim of this study was to further assess the efficacy and safety of TACE combined with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC) in the real world. Between August 2021 and September 2023, clinical information was collected from consecutive HCC patients who received treatment via TACE-Atezo/Bev at four tertiary institutions. This study evaluated the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) as outcomes. Predictors for OS and PFS were also analyzed. Treatment-related adverse events (TRAEs) were recorded and assessed. Ninety-two patients were enrolled in this study, with a median follow-up duration of 14.1 months. The ORRs based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) and RECIST 1.1 criteria were 54.3% and 41.3%, respectively. The median OS and PFS of the patients were 15.9 months [95% confidence interval (CI), 14.5-17.2 months] and 9.1 months (95% CI, 7.4-10.8 months), respectively. Multivariate analyses revealed that the Eastern Cooperative Oncology Group score and neutrophil‒lymphocyte ratio were independent risk factors for OS, whereas tumor size and extrahepatic metastasis were independent risk factors for PFS. Grade 3/4 TRAEs occurred in 16.3% (15/92) of the patients and were controlled conservatively. The combination of Atezo/Bev with TACE demonstrated acceptable synergistic therapeutic effects and manageable safety profiles in patients with unresectable HCC.

Determining the gross tumor volume for hepatocellular carcinoma radiotherapy based on multi-phase contrast-enhanced magnetic resonance imaging

PurposeThe aim of this study was to quantitatively analyze of the differences in determining the gross tumor volume (GTV) for hepatocellular carcinoma (HCC) radiotherapy using multi-phase contrast-enhanced magnetic resonance imaging (CE-MRI) and provide a reference for determining the GTV for radiotherapy of HCC. MethodsThis retrospective study analyzed 99 HCC patients (145 lesions) who underwent MR simulation. T1-weighted imaging (T1WI), contrast-enhanced T1WI (CE-T1WI) at 15 s, 45 s, 75 s, 150 s, and 20 min after contrast agent injection were performed, comprising a total of six imaging sequences. The GTVs identified on different sequences were grouped and fused in various combinations. The internal GTV (IGTV), which was the reference structure, was obtained by the fusion of all six sequences. Mean signal intensity (SI), volume, shape, and fibrous capsule (FC) thickness among GTVs were compared. Results(1) The mean SI value of GTV-T1WI, GTV-15s-GTV-20min in patients with transarterial chemoembolization (TACE) was lower by 14.09 % (GTV-T1WI) to 31.31 % (GTV-15s) compared with that in patients without TACE. Except for GTV-T1WI, the differences in SI values between the two groups for other GTVs were statistically significant (p < 0.05). (2) The volumes of GTV-T1WI, GTV-15s-GTV-20min ranged from 32.66-34.99 cm3. The volume differences between GTV-45s and the other GTVs were statistically significant (p < 0.05), excluding the GTV-T1WI. (3) Compared with the IGTV, the change trend of GTV volume reduction rate is consistent with that of dice similarity coefficients (DSC). (4) In the CE-T1WI sequences (except for CE-T1WI-15s), FC measurement was possible in 39.31 % of lesions (57/145), with the largest mean thickness observed at 75 s. ConclusionAlthough single-phase CE-MRI introduces uncertainty in HCC GTV determination, combining different phases CE-MRI can enhance accuracy. The CE-T1WI-45s should be routinely included as a necessary scanning sequence

Prognostic Efficacy of the Albumin Grade in Patients with Hepatocellular Carcinoma.

We previously found that "albumin grade", formerly called the "ALBS grade," demonstrated significant capability for prognostic stratification in hepatocellular carcinoma (HCC) patients treated with lenvatinib. The purpose of the present study was to compare the performance of the albumin grade with that of the modified albumin-bilirubin (mALBI) grade in predicting overall survival of HCC patients with different BCLC stages and treatment types. We enrolled 7,645 Japanese patients newly diagnosed with HCC using the Akaike information criteria (AIC), likelihood ratio, and C-index in different Barcelona Clinic Liver Cancer (BCLC) stages and treatments. The albumin grade showed similar and slightly better performance than the mALBI grade for BCLC stage 0 and A and especially for patients who underwent curative surgery and ablation. In patients treated with transcatheter arterial chemoembolization, molecular targeted agents, and the best supportive care, the mALBI grade had better performance than the albumin grade. However, the differences of the indices were very small in all scenarios. Overall, the albumin grade was comparable in efficacy to the mALBI grade, showing particular benefit for patients with early-stage HCC.

Network Pharmacology to Reveal the Mechanism of Fufang Banmao Capsule for Treating Unresectable Primary Liver Cancer and Clinical Data Validation.

Fufang Banmao capsule (FFBM), a traditional Chinese medicine, has been used to treat primary liver cancer (PLC) for several years. However, the bioactive ingredients, and mechanism of FFBM for treating PLC remains unclear. Our objective is to utilize network pharmacology to investigate these aspects and subsequently validate their effectiveness through clinical data. The FFBM ingredients were obtained from the HERB database and screened for bioactive ingredients using the SwissTargetPrediction database. The PharmMapper and GEO database were used to acquire targets and differentially expressed genes (DEGs) for FFBM and PLC, respectively. Common targets were identified using Venn diagrams, followed by enrichment and protein-protein interaction (PPI) analysis. Furthermore, the Cytoscape software was utilized to identify Hub genes and construct the ingredienttarget- pathway network. Subsequently, patients diagnosed with unresectable PLC who underwent transcatheter arterial chemoembolization (TACE) at our hospital between January 2008 and December 2019 were retrospectively collected. Finally, Cox analysis was conducted to reveal the role of FFBM in the treatment of unresectable PLC. FFBM had 232 targets, and PLC had 1582 DEGs. HSP90AA1 and SRC were identified as crucial targets. Alpha-santalol, glycyrrhizin, and morroniside were identified as the top three bioactive ingredients. Enrichment analysis revealed a significant connection between FFBM utilization for treating PLC and multiple pathways, such as chemical carcinogenesis, PI3K-AKT, Rap1, FoxO, MAPK, and VEGF pathway. Clinical data revealed that consuming FFBM significantly improved the prognosis of unresectable PLC with a hazard ratio of 0.69. Our study identified the bioactive ingredients of FFBM and its potential mechanisms for treating PLC. Additionally, we validated the effectiveness through clinical data.

S5150 Gastric Ulceration Induced by Transarterial Chemoembolization in a Patient with Hepatocellular Carcinoma

S5150 Gastric Ulceration Induced by Transarterial Chemoembolization in a Patient with Hepatocellular Carcinoma

Transarterial chemoembolization combined with lenvatinib plus tislelizumab for unresectable hepatocellular carcinoma: a multicenter cohort study.

Comparing the efficacy of transarterial chemoembolization (TACE) combined with lenvatinib plus tislelizumab (TLT) with TACE combined with lenvatinib (TL) for unresectable hepatocellular carcinoma, particularly in determining which patients can benefit more from the TLT treatment. From March 2021 to September 2023, a total of 169 patients from three centers were included in this study, with 103 patients receiving TLT and 66 patients receiving TL. The Kaplan-Meier method was utilized to evaluate the cumulative overall survival (OS) and progression-free survival (PFS) between the two groups and were assessed using the log-rank test. Subgroup analysis on tumor number, maximum tumor diameter, presence of portal vein thrombosis, AFP level, and Child-Pugh class were conducted. The median OS was 26 months in the TLT group, and 20 months in the TL group. The median PFS was 14 months in the TLT group and 9 months in the TL group. The Kaplan-Meier curve demonstrated a significantly superior OS and PFS in the TLT group compared to the TL group. Subgroup analysis showed that for patients with a maximum tumor diameter greater than 7 cm, AFP > 400 ng/ml and accompanied by portal vein tumor thrombus, and Child-Pugh class A, there was a statistically significant difference in OS between TLT and TL groups. OS and PFS were significantly improved in patients who received TLT compared to those who received TL, patients with a largest tumor diameter greater than 7 cm, AFP > 400 ng/ml, Child-Pugh class A and PVTT appeared to derive more benefit.

Aberrant activation of a miR-101–UBE2D1 axis contributes to the advanced progression and chemotherapy sensitivity in human hepatocellular carcinoma

AbstractChemotherapeutic drugs, such as cisplatin (cis-dichlorodiamineplatinum [II], cDDP) and 5-fluorouracil (5Fu), are widely used in transarterial chemoembolization (TACE), which is a standard therapy for patients with hepatocellular carcinoma (HCC). Chemoresistance is a major cause of TACE treatment failure in HCC patients. Our previous studies have identified the expression levels of miR-101 responsive genes, such as EED, EZH2, STMN1 and JUNB, exhibit significant correlation with the occurrence and progression of HCC, while the role of miR-101 responsive gene signatures in the chemoresistance of HCC treatment remains unclear. In this study, we identified ubiquitin-coupled enzyme E2D1 (UBE2D1) as a crucial regulatory factor in the chemoresistance of HCC, which is a direct target of miR-101 and exhibits significant correlation with miR-101-responsive gene signatures. The bioinformatics analysis showed the expression of UBE2D1 was significantly increased in HCC tissues and was closely correlated with the poor prognosis. In addition, we analyzed the role of miR-101/UBE2D1 axis in regulating chemo-sensitive of HCC cells. Our results showed that miR-101 increases the DNA damage and apoptosis of HCC cells by inhibiting the expression of UBE2D1, which in turn increases the sensitivity of HCC cells to cDDP and 5Fu both in vitro and in vivo. Therefore, simultaneous assessment of miR-101 and UBE2D1 expression levels might provide an effective approach in preselecting HCC patients with survival benefit from TACE treatment. Moreover, further elucidation of the underlying molecular mechanisms of the miR-101/UBE2D1 axis could provide novel insight for targeted therapy of HCC.

FOLFOX-Based Hepatic Arterial Infusion Chemotherapy with Sequential Drug-Eluting Bead Transarterial Chemoembolization for Unresectable Large Hepatocellular Carcinoma: A Single-Center Retrospective Cohort Study.

For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (TACE) remains suboptimal, which necessitates the administration of substantial volumes of chemotherapy drugs and lipiodol, thereby increasing the risk of liver failure and other chemotherapy-related complications. Therefore, we devised a strategy of initial hepatic arterial infusion chemotherapy (HAIC) followed by sequential drug-eluting bead TACE (DEB-TACE). In our treatment design, a lower tumor burden after HAIC facilitated complete embolization of tumor vasculature, and the use of less amount of embolic agents reduced the incidence of liver failure and embolization syndromes. This retrospective study evaluated consecutive patients with unresectable large HCC with a maximum tumor diameter of ≥7 cm who received FOLFOX-HAIC combined with sequential DEB-TACE from April 2019 to February 2024. Efficacy was evaluated using the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS); and safety was assessed using the frequency of key adverse events (AEs). Among the 76 patients included, the median maximum tumor diameter was 12.4 cm (range, 7.0-23.4 cm). The overall ORRs based on mRECIST and RECIST 1.1 criteria were 94.1% and 51.5%, respectively. The median OS was 28.1 months (95% CI, 22.7-33.4), and the median PFS was 11.7 months (95% CI, 7.7-15.8). All patients experienced AEs, but only 18.4% experienced grade 3 or 4 AEs, there was no treatment-related mortality. In this single-center, retrospective study, our results suggested that FOLFOX-HAIC with sequential DEB-TACE demonstrated promising efficacy and safety for patients with unresectable HCC with a maximum tumor diameter of ≥7 cm.