Prior Transarterial Chemoembolization Research Articles

Y90 Radiation Segmentectomy versus Microwave Ablation for Hepatocellular Carcinoma in Locations Suboptimal for Percutaneous Ablation

Abstract Purpose The purpose of our study was to evaluate outcomes following percutaneous microwave ablation (MWA) versus yttrium-90 (Y90) radiation segmentectomy (RS) for tumors in suboptimal locations for ablation. Materials and Methods Retrospective review (January 2014–July 2019) was performed on patients who underwent Y90-RS or MWA (with or without prior transarterial chemoembolization [TACE]) with curative intent for early-stage hepatocellular carcinoma (HCC) lesions in suboptimal locations for percutaneous ablation, defined as locations in which needle placement is within 5 mm of critical structures (liver dome, liver capsule, gallbladder, and hilum). The primary endpoints were treatment response as per the modified Response Evaluation Criteria in Solid Tumors criteria and complications. Statistical Analysis Fischer's exact test was performed for categorical variables, and Student's t-tests for nominal variables. Results Twenty-three lesions in 20 patients (13 male, 67 ± 8.8 years) and 30 lesions in 30 patients (18 male, 62.5 ± 10.6 years) were treated with Y90-RS and MWA (19 with prior TACE), respectively. There were no differences in demographics (p > 0.05). Mean tumor diameter was 2.9 ± 1.0 in those treated with Y90-RS and 2.3 ± 0.9 for MWA (p < 0.05). Lesions were located adjacent to the following structures: dome (n = 22), capsule (n = 16), hilum (n = 9), and gallbladder (n = 6). All patients were Eastern Cooperative Oncology Group performance status 0 to 1. Of the MWA cohort, 19 were Child-Pugh class A, 5 were B, and 6 were C and the mean pretreatment laboratory values were as follows: Model for End-stage Liver Disease sodium (MELD-Na) 12.7 ± 4.6, alpha-fetoprotein (AFP) 848 ± 3168.0, aspartate aminotransferase (AST) 71.9 ± 49.1, alanine aminotransferase (ALT) 48.0 ± 32.4, and total bilirubin 2.4 ± 2.7. Of the Y90-RS cohort, 15 were Child-Pugh class A, 4 were B, and 1 was C and pretreatment laboratory values were as follows: MELD-Na 10.5 ± 3.3 (Y90-RS), AFP 762.2 ± 1793.8 (Y90), AST 50.3 ± 30.5 (Y90), ALT 30.1 ± 16.9 (Y90), and total bilirubin 1.6 ± 1.1 (Y90). Complete response rate following Y90 was 96 versus 76% for MWA, with no disease progression after Y90-RS within the follow-up period. Three (13%) lesions demonstrated progression of disease (time to progression 6.3 months) after MWA. No grade > 2 toxicities or procedure-related complications were noted following Y90-RS. There were 7 major (arterioportal fistula with hemoperitoneum, pneumothorax, liver infarction, and capsular burn) and 3 minor complications following MWA. Conclusion Y90-RS is a valuable alternative to percutaneous MWA as a first-line therapy for early-stage HCC for tumors in suboptimal locations for ablation, offering a favorable treatment response and safety profile.

Hepatic arterial infusion chemotherapy for hepatocellular carcinoma refractory to transarterial chemoembolization: exploring the influence of prior transarterial chemoembolization and additional transarterial chemoembolization on survival outcomes.

The selection of an efficacious treatment modality for patients with hepatocellular carcinoma (HCC) diagnosed as refractory to transarterial chemoembolization (TACE) presents numerous challenges. In addition to systemic therapies, hepatic arterial infusion chemotherapy (HAIC) may serve as an alternative option. However, it is imperative to identify patients who are appropriate candidates for HAIC to confer a survival benefit. Our study aimed to evaluate the impact of the number of TACE sessions prior to HAIC treatment and the addition of TACE during HAIC on the survival of HCC patient's refractory to TACE. This retrospective study included 82 patients with HCC refractory to TACE (mean age 60.5 years, 75 males). Survival analysis was conducted using the Kaplan-Meier method, with comparison between two groups via the log-rank test; the Cox regression model was utilized to identify factors influencing survival. The overall response rate (ORR) was observed to be 29.3%, with a disease control rate (DCR) of 56.1%. Patients receiving more than four TACE sessions prior to HAIC exhibited a significantly poorer survival prognosis compared to those receiving fewer than four TACE sessions, with a hazard ratio (HR) of 0.151 (P=0.02). The median overall survival (OS) was markedly different, being 3.4 (range, 0.5-13.6) months for the former group and 14 (range, 8.5-19.5) months for the latter (P=0.01). Furthermore, patients undergoing additional TACE while receiving HAIC treatment demonstrated improved survival outcomes compared to those who did not, with an HR of 0.491 (P=0.02); the respective OS for these groups was 14 (range, 3.6-14.4) and 6.7 (range, 2.8-11) months (P=0.02). HAIC can be a suitable alternative treatment for HCC patient's refractory to TACE. For those with a history of more than 4 TACE sessions, other alternative treatments should be considered. The addition of TACE during HAIC treatment may extend patient OS time, provided it is balanced with maintaining safe liver function.

Outcome of transarterial radioembolization in patients with hepatocellular carcinoma as a first-line interventional therapy and after a previous transarterial chemoembolization.

Due to a lack of data, there is an ongoing debate regarding the optimal frontline interventional therapy for unresectable hepatocellular carcinoma (HCC). The aim of the study is to compare the results of transarterial radioembolization (TARE) as the first-line therapy and as a subsequent therapy following prior transarterial chemoembolization (TACE) in these patients. A total of 83 patients were evaluated, with 38 patients having undergone at least one TACE session prior to TARE [27 male; mean age 67.2 years; 68.4% stage Barcelona clinic liver cancer (BCLC) B, 31.6% BCLC C]; 45 patients underwent primary TARE (33 male; mean age 69.9 years; 40% BCLC B, 58% BCLC C). Clinical [age, gender, BCLC stage, activity in gigabecquerel (GBq), Child-Pugh status, portal vein thrombosis, tumor volume] and procedural [overall survival (OS), local tumor control (LTC), and progression-free survival (PFS)] data were compared. A regression analysis was performed to evaluate OS, LTC, and PFS. No differences were found in OS (95% CI: 1.12, P = 0.289), LTC (95% CI: 0.003, P = 0.95), and PFS (95% CI: 0.4, P = 0.525). The regression analysis revealed a relationship between Child-Pugh score (P = 0.005), size of HCC lesions (>10 cm) (P = 0.022), and OS; neither prior TACE (Child-Pugh B patients; 95% CI: 0.120, P = 0.729) nor number of lesions (>10; 95% CI: 2.930, P = 0.087) correlated with OS. Prior TACE does not affect the outcome of TARE in unresectable HCC.

Predictive Value of Tumor Volume on Local Control in Hepatocellular Carcinoma Treated with Image Guided Hypofractionated Radiation Treatment

External beam radiation treatment (EBRT) is an important local treatment in liver-confined hepatocellular carcinoma (HCC) patients who are not candidates for curative therapy. EBRT dose, technique and prognostic factors are evolving. We hypothesized that tumor volume to liver volume ratio can be a predictor of local control (LC) in patients treated with hypo-fractionated radiation (HFRT) in HCC MATERIALS/METHODS: We retrospectively reviewed 50 patients of HCC treated with HFRT at our institution. HFRT schedule was chosen such that the radiation dose to the remaining liver and other organs at risk (OAR) met the standard dosimetric constraints. Image guided techniques were used for motion management, internal target volume (ITV) and planning target volume (PTV) delineation. Tumor to Liver Ratio (TLR) was defined as ratio of PTV volume to whole liver volume. TLR ≤ 0.3 was considered as low volume disease and TLR > 0.3 was considered as high-volume disease. The radiation dose ranged from 45 Gy to 67.5 Gy in 5 - 15 fractions. The biologically equivalent dose (BED) for tumor ranged from 58.5 Gy10 to 100 Gy10. Local control (LC) was evaluated by Kaplan-Meier analysis, with log-rank test for groups stratified as per TLR. Multivariate Cox regression analysis was performed to identify additional prognostic factors. The mean duration of follow-up was 24 months. The median age was 69 years (range 50 - 90) and 76% were males. 32 patients had CP-A class cirrhosis while 17 had CP-B and 1 had CP-C class. BCLC stage A, B, C and D was seen in 2, 14, 33 and 2 patients, respectively. Portal vein thrombosis was present in 9 patients and prior trans-arterial chemo embolization (TACE) was done in 23 patients. The median volume of PTV was 551 cc (range 52 - 1990 cc). The TLR ranged from 0.04 - 0.67 with a median of 0.29. The median BED radiation dose was 78.4 Gy10 (range - 58.5 Gy10 to 100 Gy10). Nine patients had local recurrence with overall LC rate of 82%. The LC was better in low volume tumors, with the TLR cut-off of 0.3 as a significant factor associated with LC (p = 0.007). The 1-year actuarial LC with TLR ≤ 0.3 was 88% as compared 61% in TLR of > 0.3 (p = 0.007). BED ≥60 Gy10 was associated with better 1 year LC as compared to BED < 60 Gy10 (89% vs 62%; p = 0.11). ALBI grade 1 was associated with better 1 year LC as compared to ALBI grade 2 (80% versus 75%; p = 0.40). On multivariate analysis, high volume disease and TLR >0.3 were significant prognostic factor for LC. HFRT has good 1-year local control of 82% in carefully selected unresectable HCC. Radiation with BED greater than 60 Gy10 and ALBI grade 1 showed a trend towards better LC. Smaller tumors had better LC with a PTV to liver ratio (TLR) of < 0.3. This information can help in identifying the poor responders, intensifying the radiation treatment and adding additional therapy to improve the oncological outcomes.

Predicting Infectious Complications after Percutaneous Thermal Ablation of Liver Malignancies: A 12-year Single-Center Experience.

Background Infectious complications after percutaneous thermal ablation are seldom discussed, but better understanding of risk factors and early prediction is critical. Purpose To estimate the incidence of infectious complications after percutaneous thermal ablation of liver malignancies and to develop prediction models. Materials and Methods This single-center retrospective study reviewed the data of 3167 patients who underwent 7545 percutaneous US-guided thermal ablation procedures of liver malignancies between January 2010 and January 2022. All procedures with infectious complications were included as the case group. For each case, one treatment date-matched control subject without infection was randomly selected following a nested case-control design. Independent factors of overall and hepatobiliary infection were investigated with multivariable logistic regression. Results A total of 80 patients (median age, 59 years; IQR, 51-68 years; 64 men, 16 women) developed infectious complications after 80 ablation procedures; the incidence was 1.1% (80 of 7545 procedures). Of those with infection, 18% (14 of 80 patients) were severe, and 10% (eight of 80 patients) died as a result. Independent risk factors for overall infectious complication included prior biliary intervention (odds ratio [OR], 18.6; 95% CI: 4, 86; P < .001), prior transarterial chemoembolization (TACE) (OR, 2.4; 95% CI: 1.0, 5.8; P = .045), and the largest tumor size (OR, 1.9; 95% CI: 1.3, 2.8; P = .002); on this basis, subcapsular location was an additional risk factor of hepatobiliary infection. Prediction models for overall and hepatobiliary infection had an area under the receiver operating characteristics curve (AUC) of 0.77 and 0.82, respectively, both of which showed better AUC compared with the models, including prior biliary intervention alone (AUC = 0.63 and 0.65, respectively; P = .01 and P = .005, respectively). Conclusion Infectious complications after percutaneous thermal ablation of liver malignancies were uncommon but potentially fatal. Independent predictors were prior biliary intervention, prior transarterial chemoembolization, and the largest tumor size. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ben-Arie and Sosna in this issue.

A Phase 2, Prospective, Multicenter, Single-Arm Trial of Transarterial Chemoembolization Therapy in Combination Strategy with Lenvatinib in Patients with Unresectable Intermediate-Stage Hepatocellular Carcinoma: TACTICS-L Trial

Introduction: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC), but recurrence after TACE is common. The present phase 2, prospective, multicenter, single-arm trial, the TACTICS-L trial, investigated the efficacy and safety of TACE plus lenvatinib (LEN), a drug that more strongly promotes vascular normalization and has a better objective response rate (ORR) than sorafenib (jRCTs031180074). Methods: Participants were patients with HCC who had not previously received systemic therapy, hepatic arterial infusion chemotherapy, or immunotherapy and who were ineligible for resection or percutaneous ablation therapy. LEN was to be administered 14–21 days before the first TACE, stopped 2 days before TACE, and resumed 3 days after TACE. Key inclusion criteria were unresectable HCC, Child-Pugh A liver function, 0–2 prior TACE sessions, tumor size ≤10 cm, number of tumors ≤10, and ECOG performance status 0–1. Key exclusion criteria were vascular invasion and extrahepatic spread. The primary endpoint was progression-free survival (PFS) by RECICL, and secondary endpoints were time to untreatable progression, ORR, overall survival (OS), and safety. Results: A total of 62 HCC patients were enrolled in this trial. The median age was 72 years, 77.4% of patients were men, and 95.2% had PS 0. The primary endpoint of median PFS was 28.0 months (90% confidence interval [CI] 25.1–31.0) after a minimum 24 months of follow-up. The secondary endpoint of median OS was not reached (90% CI 35.5 months–NR). LEN-TACE achieved a high response rate and high complete response (CR) rate (4 weeks after the first TACE: ORR 79.0%, CR rate 53.2%; best response: ORR 88.7%, CR rate 67.7%) by RECICL. Exploratory subgroup analyses showed that the characteristics of responders/nonresponders (ORR and CR rate) were similar and that LEN-TACE would be effective in all subgroups, including the population in whom TACE alone would be less likely to be curative (e.g., patients with the non-simple nodular type or a high tumor burden). The relative dose intensity of LEN before the first TACE was important for achieving higher CR rate/ORR by LEN-TACE. No new safety concerns were observed. Conclusion: The results of this trial provide encouraging evidence, supporting the efficacy and favorable safety profile of LEN-TACE in patients who are ineligible for locoregional therapy.

Development of a Multivariate Prognostic Model for Lenvatinib Treatment in Hepatocellular Carcinoma.

Lenvatinib is a first-line agent for advanced hepatocellular carcinoma (HCC), but individual responses to treatment are highly heterogeneous. The aim of this study was to investigate the clinical parameters that influence the efficacy of Lenvatinib and to develop a prognostic model. We retrospectively enrolled 333 Lenvatinib-treated patients with HCC with a median age of 57 years. Two hundred nd sixty-three of these patients had BCLC (2022) stage C. The median overall survival (mOS) time within the cohort was 12.1 months, and the median progression-free survival (mPFS) time was 4.7 months. Univariate Cox regression, best subset regression, and Lasso regression were used to screen primary variables for possible contribution to OS, multivariate Cox analysis was used to fit selected models, and the final model was selected using the maximum area under the curve (AUC) and minimum AIC. Receiver operating curves (ROC), calibration curves, and decision curve analysis were plotted to assess model performance, and 5-fold cross-validation was performed for internal validation. X-tile software was used to select the best cutoff points and to divide the study cohort into 3 different risk groups. Seven variables were included in the final model: BCLC stage, prior transarterial chemoembolization and immunotherapy history, tumor number, prognostic nutritional index, log (alpha-fetoprotein), and log (platelet-to-lymphocyte ratio). We named this final model the "multivariate prognostic model for Lenvatinib" (MPML), and a nomogram was constructed to predict the probability of survival at 6, 9, and 12 months. The MPML had good discrimination, calibration, and applicability. Cross-validation showed mean AUC values of 0.7779, 0.7738, and 0.7871 at 6, 9, and 12 months, respectively. According to nomogram points, mOS time was 21.57, 8.70, and 5.37 months in the low, medium, and high-risk groups, respectively (P < .001), and these differences were also observed in the PFS survival curve (P < .001). The MPML stratified patients according to baseline clinical characteristics had a strong performance in predicting Lenvatinib efficacy and has the potential for use as an auxiliary clinical tool for individualized decision-making.

Improving Adjuvant Liver-Directed Treatment Recommendations for Unresectable Hepatocellular Carcinoma: An Artificial Intelligence-Based Decision-Making Tool

<h3>Purpose/Objective(s)</h3> Liver-directed therapy (LDT) following transarterial chemoembolization (TACE) can lead to improvement in survival for selected patients with unresectable hepatocellular carcinoma (HCC). However, there is uncertainty in the appropriate application and modality of therapy in current clinical practice guidelines. The aim of this study was to develop a proof-of-concept, machine-learning (ML) tool for treatment recommendation in patients previously treated with TACE and identify patients who may benefit from additional treatment with combination stereotactic body radiotherapy (SBRT) or radiofrequency ablation (RFA). <h3>Materials/Methods</h3> This retrospective, observational study was based on data from an urban, academic hospital system selecting for patients diagnosed with stage I-III HCC from January 1, 2008 to December 31, 2018, treated with TACE, followed by adjuvant RFA, SBRT, or no additional liver-directed modality. The dataset was divided in half into training and testing groups. A feed-forward ML ensemble model based on the DeepSurv algorithm, provided a treatment recommendation using pair-wise assessments between each potential treatment option and an estimated benefit in survival. Final ensemble model treatment recommendation was selected based on the treatment yielding the best hazard rate among all pairwise models on an individual patient basis. <h3>Results</h3> Two hundred thirty-seven patients met inclusion criteria, of whom 54 (23%) and 49 (21%) received combination TACE and SBRT or TACE and RFA respectively. The ML model recommended a different consolidative modality in 33% of cases among patients who had previously received combination treatment. Patients treated in concordance with model recommendations had a numerical improvement in overall survival (HR 0.63; p=0.160) and significant improvement in progression free survival (HR 0.50; p=0.007). The most critical features for model treatment recommendation were cause of cirrhosis, stage of cancer, and ALBI grade (a measure of liver function). <h3>Conclusion</h3> In this proof-of-concept study, we developed an ensemble ML model which was able to provide treatment recommendations for HCC who had undergone prior TACE therapy. Our data suggest additional treatment in-line with model recommendations was associated with significant improvement in progression free survival suggesting a potential benefit for ML-guided medical decision making. In the future, this tool will provide the framework for a prospective study where treatment decisions for complex clinical cases may be enhanced through personalized, machine-learning recommendations.

Improving Adjuvant Liver-Directed Treatment Recommendations for Unresectable Hepatocellular Carcinoma: An Artificial Intelligence-Based Decision-Making Tool.

Liver-directed therapy after transarterial chemoembolization (TACE) can lead to improvement in survival for selected patients with unresectable hepatocellular carcinoma (HCC). However, there is uncertainty in the appropriate application and modality of therapy in current clinical practice guidelines. The aim of this study was to develop a proof-of-concept, machine learning (ML) model for treatment recommendation in patients previously treated with TACE and select patients who might benefit from additional treatment with combination stereotactic body radiotherapy (SBRT) or radiofrequency ablation (RFA). This retrospective observational study was based on data from an urban, academic hospital system selecting for patients diagnosed with stage I-III HCC from January 1, 2008, to December 31, 2018, treated with TACE, followed by adjuvant RFA, SBRT, or no additional liver-directed modality. A feedforward, ML ensemble model provided a treatment recommendation on the basis of pairwise assessments evaluating each potential treatment option and estimated benefit in survival. Two hundred thirty-seven patients met inclusion criteria, of whom 54 (23%) and 49 (21%) received combination of TACE and SBRT or TACE and RFA, respectively. The ML model suggested a different consolidative modality in 32.7% of cases among patients who had previously received combination treatment. Patients treated in concordance with model recommendations had significant improvement in progression-free survival (hazard ratio 0.5; P = .007). The most important features for model prediction were cause of cirrhosis, stage of disease, and albumin-bilirubin grade (a measure of liver function). In this proof-of-concept study, an ensemble ML model was able to provide treatment recommendations for HCC who had undergone prior TACE. Additional treatment in line with model recommendations was associated with significant improvement in progression-free survival, suggesting a potential benefit for ML-guided medical decision making.

Atezolizumab and bevacizumab with transarterial chemoembolization in hepatocellular carcinoma: The DEMAND randomized phase II clinical trial.

TPS492 Background: Atezolizumab and bevacizumab is the first approved immunotherapeutic regimen for first-line treatment of patients with advanced hepatocellular carcinoma (HCC). The efficacy and tolerability of this regimen suggests that its use could be extended to the treatment of patients with intermediate-stage HCC in combination with transarterial chemoembolization (TACE). The effect of TACE combined with atezolizumab and bevacizumab could improve response and tumor control as well as prevent disease progression in non-responders to TACE. Response to the early use of immunotherapy could also reduce the number and extent of TACE cycles needed to achieve tumor control, thereby contributing to the prevention of collateral damage to the liver parenchyma and preservation of liver function. Initiating immunotherapy first may also promote the access of circulating lymphocytes into tumor lesions. The DEMAND study investigates the efficacy and ideal sequence of TACE and immunotherapy in intermediate stage HCC. Methods: This investigator-initiated, multi-center, randomized, open-label phase 2 trial is the first study to evaluate the safety and efficacy of atezolizumab and bevacizumab prior to, or in combination with TACE in patients with unresectable HCC. 106 patients (Barcelona Clinic Liver Cancer Stage A not amenable to curative therapy or B, Child-Pugh A or B7, Eastern Cooperative Oncology Group performance status 0 or 1, no prior TACE) will be randomized in a 1:1 ratio to receive either up-front atezolizumab and bevacizumab followed by TACE selectively directed against progressive lesions (Arm A, 53 patients), or TACE and synchronous treatment with atezolizumab and bevacizumab (Arm B, 53 patients). Patients receive study treatment until loss of clinical benefit or unacceptable toxicity for up to 24 months. The use of local ablation is allowed for the treatment of lesions which cannot be targeted sufficiently selectively by TACE, or of de-novo lesions. The primary endpoint is the 24-month survival rate; secondary endpoints include objective response rate, progression-free survival, safety and quality of life. Translational analyses aim at identifying predictive biomarkers and focus on immune cell phenotyping in tumor and peripheral blood, circulating tumor DNA and changes in the diversity of the gut microbiome. Recruitment is ongoing in 15 German centers with 21 of 106 patients randomized. Clinical trial information: NCT04224636.

Abstract No. 33 Safety and efficacy of transarterial radioembolization after prior transarterial chemoembolization

Transarterial radioembolization (TARE) is a common technique to treat patients with hepatocellular carcinoma refractory to transarterial chemoembolization (TACE). TARE can cause liver toxicity. The degree of toxicity may be heightened due to previous liver injury from prior endovascular therapies. This study assessed the safety and changes in liver function after TARE for multifocal hepatocellular carcinoma refractory to previous embolization.

Hsa‑circRNA‑G004213 promotes cisplatin sensitivity by regulating miR‑513b‑5p/PRPF39 in liver cancer.

In recent years, increasing evidence has confirmed that exosomal circular RNAs (circRNAs) serve a crucial role in the prognostic prediction and diagnosis of liver cancer (LC). The present study compared the expression patterns of exosomal circRNAs during transarterial chemoembolization (TACE). CircRNA sequencing analysis identified 390 differentially expressed circRNAs between the prior TACE and following the first TACE operation groups and 489 differentially expressed circRNAs between the prior to TACE and following the second TACE operation groups. Gene Ontology analysis of the differentially expressed circRNAs demonstrated that they were associated with fatty acid metabolism, receptor binding and membrane protein complexes. Kyoto Encyclopedia of Genes and Genomes pathway analysis predicted that protein digestion and absorption pathways were activated following TACE. A novel gene was screened out; hsa-circRNA-G004213 (circ-G004213) was significantly upregulated following TACE (fold change >10, P<0.01). Further analysis found circ-G004213 significantly increased the cisplatin sensitivity of HepG2 cells and positively associated with the prognosis of tumor-bearing mice. Based on the potential downstream miRNAs and mRNAs, the circRNA-miRNA-mRNA network was constructed. It was demonstrated that circ-G004213 regulated cisplatin resistance via the miR-513b-5p/PRPF39 axis. Finally, the present study confirmed that circ-G004213 was positively associated with the prognosis of patients with LC following TACE. Therefore, circ-G004213 may be used as an indicator for predicting the efficacy of TACE.

3:54 PM Abstract No. 304 Hepatobiliary toxicity in nivolumab-treated hepatocellular carcinoma in the presence or absence of transarterial chemoembolization

To compare hepatobiliary toxicity in unresectable hepatocellular carcinoma (HCC) patients receiving nivolumab alone with those receiving nivolumab after transarterial chemoembolization (TACE). This single-institution retrospective study analyzed 28 patients who had received nivolumab therapy for treatment of HCC during 2018-2019. Patients that had undergone prior TACE (N = 11) had mean age of 68 years, with Child-Pugh Class A (64%), Class B (27%), and Class C (9%). Patients without prior TACE (N = 17) had a mean age of 64 years, with Child-Pugh Class A (59%), Class B (23%), Class C (18%). Hepatobiliary complications were graded using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0), with the exception of portal hypertension, as a majority of patients had portal venous involvement prior to treatment. Comparison was made between a patient’s initial oncology evaluation for nivolumab and the follow-up visit after their last known treatment with nivolumab (average 127 ± 118 days). Patients that had undergone prior TACE had an average of 2 TACE treatments and 4 cycles (range, 1 to 17) of nivolumab, with an average of 215 days between last TACE treatment to initiation of nivolumab. Patients without prior TACE had undergone an average of 5 cycles (range, 1 to 24) of nivolumab. Hepatobiliary complications occurred in 45% (5/11) of patients that had undergone prior TACE, which included of CTCAE v5.0 grade I (27%, N = 3) and grade 3 (18%, N = 2) complications. Hepatobiliary complications occurred in 47% (8/17) patients that had not undergone TACE, which included grade 1 (18%, N = 3), grade 2 (12%, N = 2) and grade 3 (18%, N = 3) complications. Prior treatment with TACE did not result in increased hepatobiliary toxicity in patients undergoing treatment with nivolumab.

749P - Prognostic and predictive factors from the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (aHCC)

749P - Prognostic and predictive factors from the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (aHCC)

Stereotactic body radiation therapy for early hepatocellular carcinoma: a retrospective analysis of the South Australian experience.

Stereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumours unsuitable for established curative treatment such as ablation or surgery. The aim of the study is to evaluate the efficacy and safety of SBRT in the treatment of small hepatocellular carcinoma (HCC) in South Australia. From 2014 to 2018, 13 HCC patients were treated with SBRT. Eligibility criteria for SBRT included: unsuitable for standard curative therapies (resection or percutaneous ablation), lack of complete response to prior transarterial chemoembolization, Child-Pugh classification ≤B7, tumours ≤5 cm and minimum of up to 6 months follow-up post-SBRT. The prescribed radiation dose was determined by liver function with doses ranging from 40 to 45 Gy in three or five fractions. Records for all patients were reviewed, and treatment response was scored according to the modified response evaluation criteria in solid tumours. Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up time was 22.7 months, and the median tumour size was 40 mm. The 1 year local control was 92.3%, recurrence-free survival was 67.7% and overall survival was 86.4% at end of study. Three patients underwent liver transplant. No grade ≥3 non-haematological toxicities were observed. One patient experienced acute grade ≥3 haematological toxicity. SBRT is a safe, effective and non-invasive alternative treatment option for patients with small HCCs, unsuitable for standard, evidence-based therapies and lacking complete response to transarterial chemoembolization. Randomized controlled trials are required to further investigate the role of SBRT in HCC.

Imaging findings of patients undergoing SBRT for HCC after prior TACE.

252 Background: Our purpose is to assess the treatment response using follow up MRI or CT in lesions treated with stereotactic body radiation therapy (SBRT) after transarterial chemoembolization (TACE). Methods: Twenty-six patients treated with liver SBRT at our institution in the period between 2015 and 2017. Of these we included patients who had lesions diagnosed as HCC (LR-5) or probable HCC (LR-4), and who had prior TACE with a residual/recurrent enhancing component on the pre SBRT images with adequate post SBRT imaging. One radiologist (5 year experience) evaluated all pre and post SBRT imaging and measured the lesion size and the size of the largest enhancing component. Lesion decrease or increased in size was assessed based on the mRECIST criteria. Explant pathology results were collected for patients who received transplant. Necrosis &gt; 90% on explant was considered full response to treatment. AFP (alpha-fetoprotien) values before and after SBRT were collected. Results: Eight patients with 9 lesions meet our inclusion criteria, 3 of which were LR-5 and 6 LR-4 prior to the TACE. At 3 month, 2 lesions had no residual enhancing component, 2 lesions decreased in size, 2 lesions increased in size, 3 lesions remain unchanged. After maximum available follow-up (ranging from 3 to 8 months), 3 lesions had no residual enhancing component, 2 decreased, 2 lesions increased in size, 2 lesions remain unchanged. Of the 3 lesions that were definitive HCC (LR-5): 1 lesion decreased in size, 2 lesions increased in size. 4 of 8 patients (4 lesions) underwent transplant, 3 of them showed only 50% necrosis on explant. 1 of 3 lesions showed no change in size by imaging, the other 2 lesions had no residual enhancing component. Only 1 lesion had full response on the transplant. This lesion was unchanged on 3 and 6 months follow up. The AFP was not helpful since the majority of the patient had low pre-treatment AFP. Conclusions: Patient with viable disease on imaging after TACE subsequently treated with SBRT demonstrated variable behavior on imaging. Close to half demonstrated resolution of the enhancing component, however, in the few that had explant follow up there was no correlation between imaging findings and pathology.

TACE prior to laparoscopic liver resection of hepatocarcinoma on cirrhotic liver. Propensity score matching with open surgery

Background: Laparoscopic liver resection in hepatocarcinoma is more difficult in cirrhotic liver because of a higher risk of hemorrhage. We indicated transarterial chemoembolization (TACE) prior to liver resection in these patients. The aim is to compare laparoscopic (LS) vs open surgery (OS) after TACE doing a propensity score matching (PSM). Methods: We have resected 52 patients with HCC on cirrhosis liver (22 by LS and 30 by OS). After PSM (age, gendre, preoperative comorbidity, etiology of cirrhosis, Child and BCLC classification, number of nodules, surgical technique), we included 22 patients in each arm. Results: There were not differences in number of Pringle maneuver. Laparoscopic group had a shorter surgical time than open surgery (120 vs 150 min, p=0.042) and less blood loss (100 vs 250 cc; p=0.042). There were no differences in postoperative morbidity (0% vs 19%; p=0.091) and mortality (0% vs 2.7%; p=0.549). Mean hospital stay in LS was lower than in OS (5 vs 8 days; p<0.001). There were not statistically significant differences between both groups in overall survival (p=0.453) and disease free survival (DFS) (p=0.105) at 3 and 5-years. Conclusion: LS with prior TACE get less surgical time, blood loss and hospital stay than OS, with similar DFS and overall survival.

Stereotactic Body Radiation Therapy (SBRT) for Hepatocellular Carcinoma: High Rates of Local Control With Low Toxicity.

Stereotactic body radiotherapy (SBRT) is potentially curative treatment for small hepatocellular carcinomas (HCC), but data are limited on its efficacy and toxicity. We hypothesized that SBRT can achieve excellent local control (LC) with acceptable toxicity treating HCC lesions, even in advanced cirrhosis. Thirty-seven nonmetastatic HCC patients received SBRT to 43 lesions between October 2012 and April 2016. Median dose was 50 Gy/5 fractions. All Child-Pugh (CP) ≥B patients underwent a planned 1-month break after the first 3 fractions to assess hepatic toxicity. Patients were treated without separately placed fiducial markers using Linac-based SBRT with breath-hold (67%) or 4D-computed tomography with compression belt (33%) to reduce motion. Patients underwent magnetic resonance imaging q3 months post-SBRT. Median age was 65 (range, 44 to 88). Pre-SBRT mean CP was 6.4 (range, A5 to C11). Nine (24%) had CP≥B8. Thirty-one of 33 patients (93%) had prior liver-directed therapy (median 2). Seventeen (40%) had solitary lesions. Median lesion diameter was 2.7 cm (range, 1.1 to 5.6). Median follow-up was 14 months (range, 2 to 45). There was 1 local failure (multifocal HCC with 3 prior transarterial chemoembolization). LC, freedom from liver progression, and overall survival at 12 months was 95%, 66%, 87% in the full cohort, and 100%, 76%, 93% for patients with solitary lesions. Four had grade 3 toxicity (ascites [n=2]/gastrointestinal bleed [n=1]/capsular pain [n=1]). Eight of 9 CP≥B8 patients had no grade ≥3 hepatic toxicity. SBRT for HCC is well-tolerated even in patients with advanced cirrhosis and prior liver-directed treatment and provides excellent LC even for larger lesions that cannot be controlled with radiofrequency ablation. LC with SBRT compares favorably to other liver-directed therapies. Prospective studies comparing SBRT with other liver-directed therapies are warranted.

704P - Outcomes by prior transarterial chemoembolization (TACE) in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC)

704P - Outcomes by prior transarterial chemoembolization (TACE) in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC)

Transarterial Radioembolization Following Chemoembolization for Unresectable Hepatocellular Carcinoma: Response Based on Apparent Diffusion Coefficient Change is an Independent Predictor for Survival.

To evaluate whether response based on contrast-enhanced magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) change at diffusion-weighted MRI after transarterial radioembolization (TARE) can predict survival, in patients with prior transarterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). We identified all patients who received DEB-TACE prior to TARE for HCC between 2007 and 2016. Response on MRI was determined by modified RECIST (mRECIST) and ADC change relative to pre-TARE imaging (ADCratio). Kaplan-Meier and log-rank tests were used to correlate the response/disease and treatment variables to overall survival. Multivariable Cox regression models were used to correct for confounders. A total of 29 consecutive patients were included. Univariable analysis showed that response determined by mRECIST was a nonsignificant predictor of survival (p = 0.057), and response determined by ADCratio was a significant predictor of survival (p = 0.011). Number of prior DEB-TACE procedures (p = 0.037), female gender (p < 0.001) and BCLC C (p = 0.03) were related to worse survival. The number of prior DEB-TACE procedure was significantly higher in non-responders determined by ADCratio (p = 0.028). Multivariable analyses showed that response based on ADCratio was an independent predictor of survival (p = 0.041). ADCratio following TARE is an independent predictor for survival in patients who previously underwent DEB-TACE for HCC.