American Association for the Study of Liver Diseases Expert Panel Consensus Statement: Vaccines to Prevent Coronavirus Disease 2019 Infection in Patients With Liver Disease.

The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.

Safety and Efficacy of Segmental Yttrium-90 Radioembolization for Hepatocellular Carcinoma after Transjugular Intrahepatic Portosystemic Shunt Creation.

PURPOSE: To evaluate safety and efficacy of segmental yttrium-90 (Y90) radioembolization for hepatocellular carcinoma (HCC) after transjugular intrahepatic portosystemic shunt (TIPS) placement. The hypothesis was liver sparing segmental Y90 for HCC after TIPS would provide high antitumor response with a tolerable safety profile. MATERIALS AND METHODS: This single-arm retrospective study included 39 patients (16 women, 23 men) with ages 49-81 years old who were treated with Y90. Child-Pugh A/B liver dysfunction was present in 72% (28/39) with a median Model for End-stage Liver Disease score of 18 (95% confidence interval, 16.4-19.4). Primary outcomes were clinical and biochemical toxicities and antitumor imaging response by World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. Secondary outcomes were orthotopic liver transplantation (OLT), time to progression (TTP), and overall survival (OS) estimates by the Kaplan-Meier method. RESULTS: The 30-day mortality was 0%. Grade 3+ clinical adverse events and grade 3+ hyperbilirubinemia occurred in 5% (2/39) and 0% (0/39), respectively. Imaging response was achieved in 58% (22/38, WHO criteria) and 74% (28/38, EASL criteria), respectively. Median TTP was 16.1 months for any cause and 27.5 months for primary index lesions. OLT was completed in 88% (21/24) of listed patients at a median time of 6.1 months (range, 0.9-11.7 months). Median OS was 31.6 months and 62.9 months censored and uncensored to OLT, respectively. CONCLUSIONS: Segmental Y90 for HCC appears safe and efficacious in patients after TIPS. Preserved transplant eligibility suggests that Y90 is a useful tool for bridging these patients to liver transplantation.

Role of locoregional therapies in the wake of systemic therapy.

Multiple systemic agents have recently been approved in the first- and second-line setting for hepatocellular carcinoma (HCC), increasing the therapeutic options for patients and treating physicians. The randomised controlled trials that led to these approvals were predominantly conducted in a population comprised of patients with advanced HCC. However, these trials also included a subset of patients who had progressed after locoregional therapies (LRTs), mostly transarterial chemoembolisation. With a greater number of systemic agents available, the role of LRTs has become a topic of debate, specifically regarding when to transition to systemic therapy in unresectable HCC and the potential opportunities for combining locoregional and systemic therapies. Trials of immuno-oncology agents (notably T cell checkpoint inhibitors) are ongoing in the advanced disease setting and these agents also present opportunities for combination therapies, both with other systemic agents and with LRTs in earlier stage disease. This article will review strategies to guide patient selection for LRT as well as the development of locoregional-systemic combinations based on scientific rationale and the challenges of clinical trial design in this setting.

Immuno-oncology and Its Opportunities for Interventional Radiologists: Immune Checkpoint Inhibition and Potential Synergies with Interventional Oncology Procedures.

Immunotherapy, specifically the use of immune checkpoint inhibitors, offers a new approach to fighting cancer. Although the results of treatment with immune checkpoint inhibition alone have been remarkable for certain cancers, these results are not universal. Preclinical and early clinical studies indicate the potential for synergistic effects when immune checkpoint inhibition is combined with immunogenic local therapies such as ablation and embolization. This review offers an overview of immunology as it relates to immune checkpoint inhibition and the possibilities for synergy when combined with interventional radiology treatments.

Hepatitis C disease severity in living versus deceased donor liver transplant recipients: an extended observation study.

UNLABELLED: Donor factors influence hepatitis C virus (HCV) disease severity in liver transplant (LT) recipients. Living donors, because they are typically young and have short cold ischemic times, may be advantageous for HCV-infected patients. Among HCV-infected patients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) surviving >90 days and followed for a median 4.7 years, advanced fibrosis (Ishak stage ≥3) and graft loss were determined. The 5-year cumulative risk of advanced fibrosis was 44% and 37% in living donor LT (LDLT) and deceased donor LT (DDLT) patients (P = 0.16), respectively. Aspartate aminotransferase (AST) activity at LT (hazard ratio [HR] = 1.38 for doubling of AST, P = 0.005) and biliary strictures (HR = 2.68, P = 0.0001) were associated with advanced fibrosis, but LDLT was not (HR = 1.11, 95% confidence interval [CI] 0.73-1.69, P = 0.63). The 5-year unadjusted patient and graft survival probabilities were 79% and 78% in LDLT, and 77% and 75% in DDLT (P = 0.43 and 0.32), with 27% and 20% of LDLT and DDLT graft losses due to HCV (P = 0.45). Biliary strictures (HR = 2.25, P = 0.0006), creatinine at LT (HR = 1.74 for doubling of creatinine, P = 0.0004), and AST at LT (HR = 1.36 for doubling of AST, P = 0.004) were associated with graft loss, but LDLT was not (HR = 0.76, 95% CI: 0.49-1.18, P = 0.23). CONCLUSION: Donor type does not affect the probability of advanced fibrosis or patient and graft survival in HCV-infected recipients. Thus, while LDLT offers the advantage of shorter wait times, there is no apparent benefit for HCV disease progression. Biliary strictures have a negative effect on HCV fibrosis severity and graft survival, and a high AST at LT may be an important predictor of fibrosis risk post-LT.

Perfusion reduction at transcatheter intraarterial perfusion MR imaging: a promising intraprocedural biomarker to predict transplant-free survival during chemoembolization of hepatocellular carcinoma.

PURPOSE: To investigate the predictive value of transcatheter intraarterial perfusion (TRIP) magnetic resonance (MR) imaging-measured tumor perfusion changes during transarterial chemoembolization on transplant-free survival (TFS) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This HIPAA-compliant prospective study was approved by the institutional review board. Written informed consent was obtained from all patients. Fifty-one consecutive adult patients with surgically unresectable single or multifocal measurable HCC and adequate laboratory parameters who underwent chemoembolization in a combined MR imaging-interventional radiology suite between February 2006 and June 2010 were studied. Tumor perfusion changes during chemoembolization were measured by using TRIP MR imaging with area under the time-signal intensity curve calculation. The end point of the study was TFS. The authors assessed the correlation between the percentage perfusion reduction in the tumor during chemoembolization and TFS by using univariate and multivariate analyses. RESULTS: Fifty patients (mean age, 61 years; 39 men aged 42-87 years [mean age, 61 years] and 11 women aged 49-83 years [mean age, 62 years]) were eligible for the analysis. Patients with 35%-85% intraprocedural tumor area under the time-signal intensity curve reduction (n = 32) showed significantly improved median TFS compared with patients with an area under the time-signal intensity curve reduction outside this range (n = 18) (16.6 months [95% confidence interval: 11.2, 22.0 months] vs 9.3 months [95% confidence interval: 6.6, 12.0 months], respectively; P = .046; hazard ratio: 0.46; 95% confidence interval: 0.21, 1.00). The cumulative TFS rates in the 35%-85% and less than 35% or more than 85% perfusion reduction groups at 1, 2, and 5 years after chemoembolization were 66.4%, 42.2%, and 28.2% versus 33.8%, 16.9%, and 0%, respectively. CONCLUSION: The study shows evidence of an association between intraprocedural tumor perfusion reduction during chemoembolization and TFS and suggests the utility of TRIP MR imaging- measured tumor perfusion reduction as an intraprocedural imaging biomarker during chemoembolization.

A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation.

UNLABELLED: Hepatitis C virus (HCV) infection recurs in liver recipients who are viremic at transplantation. We conducted a randomized, controlled trial to test the efficacy and safety of pretransplant pegylated interferon alpha-2b plus ribavirin (Peg-IFN-α2b/RBV) for prevention of post-transplant HCV recurrence. Enrollees had HCV and were listed for liver transplantation, with either potential living donors or Model for End-Stage Liver Disease upgrade for hepatocellular carcinoma. Patients with HCV genotypes (G) 1/4/6 (n = 44/2/1) were randomized 2:1 to treatment (n = 31) or untreated control (n = 16); HCV G2/3 (n=32) were assigned to treatment. Overall, 59 were treated and 20 were not. Peg-IFN-α2b, starting at 0.75 µg/kg/week, and RBV, starting at 600 mg/day, were escalated as tolerated. Patients assigned to treatment versus control had similar baseline characteristics. Combined virologic response (CVR) included pretransplant sustained virologic response and post-transplant virologic response (pTVR), defined as undetectable HCV RNA 12 weeks after end of treatment or transplant, respectively. In intent-to-treat analyses, 12 (19%) assigned to treatment and 1 (6%) assigned to control achieved CVR (P = 0.29); per-protocol values were 13 (22%) and 0 (0%) (P = 0.03). Among treated G1/4/6 patients, 23 of 30 received transplant, of whom 22% had pTVR; among treated G2/3 patients 21 of 29 received transplant, of whom 29% had pTVR. pTVR was 0%, 18%, and 50% in patients treated for <8, 8-16, and >16 weeks, respectively (P = 0.01). Serious adverse events (SAEs) occurred with similar frequency in treated versus untreated patients (68% versus 55%; P = 0.30), but the number of SAEs per patient was higher in the treated group (2.7 versus 1.3; P = 0.003). CONCLUSION: Pretransplant treatment with Peg-IFN-α2b/RBV prevents post-transplant recurrence of HCV in selected patients. Efficacy is higher with >16 weeks of treatment, but treatment is associated with increased risk of potentially serious complications.

The role of bridge therapy prior to orthotopic liver transplantation.

Orthotopic liver transplantation (OLT) offers the best chance for cure in the setting of unresectable hepatocellular carcinoma (HCC). A consensus statement recommends locoregional therapy (LRT) be considered in patients with HCC who are expected to wait more than 6 months for OLT to diminish dropout from the waiting list because of tumor progression. This article reviews LRT as a bridge to OLT in patients with HCC.

Comparative study of staging systems for hepatocellular carcinoma in 428 patients treated with radioembolization.

PURPOSE: To compare the utility of different staging systems and analyze independent predictors of survival in patients with hepatocellular carcinoma (HCC) treated with yttrium-90 ((90)Y) radioembolization. MATERIALS AND METHODS: During the period 2004-2011, 428 patients with HCC were treated with (90)Y radioembolization. All patients were staged prospectively by the following staging systems: Child-Turcotte-Pugh (CTP), United Network for Organ Sharing, Barcelona Clinic Liver Cancer (BCLC), Okuda classification, Cancer of the Liver Italian Program (CLIP), Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire, Chinese University Prognostic Index, and Japan Integrated Staging. The ability of the staging systems to predict survival was assessed. The staging systems were compared using Cox proportional hazards regression model, linear regression, Akaike information criterion (AIC), and concordance index (C-index). Univariate and multivariate analyses were employed to assess independent predictors of survival. RESULTS: When tested independently, all staging systems exhibited significant ability to discriminate early (long survival) from advanced (worse survival) disease. CLIP provided the most accurate information in predicting survival outcomes (AIC = 2,993, C-index = 0.8503); CTP was least informative (AIC = 3,074, C-index = 0.6445). Independent predictors of survival included Eastern Cooperative Oncology Group performance status grade 0 (hazard ration [HR], 0.56; confidence interval [CI], 0.34-0.93), noninfiltrative tumors (HR, 0.62; CI, 0.44-0.89), absence of portal venous thrombosis (HR, 0.60; CI, 0.40-0.89), absence of ascites (HR, 0.56; CI, 0.40-0.76), albumin ≥ 2.8 g/dL (HR, 0.72; CI, 0.55-0.94), alkaline phosphatase ≤ 200 U/L (HR, 0.68; CI, 0.50-0.92), and α-fetoprotein ≤ 200 ng/mL (HR, 0.67; CI, 0.51-0.86). CONCLUSIONS: CLIP was most accurate in predicting survival in patients with HCC. Given that not all patients receive the recommended BCLC treatment strategy, this information is relevant for clinical trial design and predicting long-term outcomes after (90)Y radioembolization.

Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers.

BACKGROUND & AIMS: Excellent single-center outcomes of neoadjuvant chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma caused the United Network of Organ Sharing to offer a standardized model of end-stage liver disease (MELD) exception for this disease. We analyzed data from multiple centers to determine the effectiveness of this treatment and the appropriateness of the MELD exception. METHODS: We collected and analyzed data from 12 large-volume transplant centers in the United States. These centers met the inclusion criteria of treating 3 or more patients with perihilar cholangiocarcinoma using neoadjuvant therapy, followed by liver transplantation, from 1993 to 2010 (n = 287 total patients). Center-specific protocols and medical charts were reviewed on-site. RESULTS: The patients completed external radiation (99%), brachytherapy (75%), radiosensitizing therapy (98%), and/or maintenance chemotherapy (65%). Seventy-one patients dropped out before liver transplantation (rate, 11.5% in 3 months). Intent-to-treat survival rates were 68% and 53%, 2 and 5 years after therapy, respectively; post-transplant, recurrence-free survival rates were 78% and 65%, respectively. Patients outside the United Network of Organ Sharing criteria (those with tumor mass >3 cm, transperitoneal tumor biopsy, or metastatic disease) or with a prior malignancy had significantly shorter survival times (P < .001). There were no differences in outcomes among patients based on differences in surgical staging or brachytherapy. Although most patients came from 1 center (n = 193), the other 11 centers had similar survival times after therapy. CONCLUSIONS: Patients with perihilar cholangiocarcinoma who were treated with neoadjuvant therapy followed up by liver transplantation at 12 US centers had a 65% rate of recurrence-free survival after 5 years, showing this therapy to be highly effective. An 11.5% drop-out rate after 3.5 months of therapy indicates the appropriateness of the MELD exception. Rigorous selection is important for the continued success of this treatment.

Hepatocellular Carcinoma: New Developments.

This is a review of current practices and upcoming developments regarding hepatocellular carcinoma (HCC). This includes a contemporary review of the diagnosis, staging, and treatment of HCC. Furthermore, the authors provide a review of certain ongoing trials and future directions of various treatment modalities for HCC.

Preclinical Development and Validation of Translational Temperature Sensitive Iodized Oil Emulsion Mediated Transcatheter Arterial Chemo-Immuno-Embolization for the Treatment of Hepatocellular Carcinoma.

Herein a practical strategy for augmenting immune activation in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is presented. Pluronic F127 (PF127) is incorporated with Lipiodol (LPD) to achieve safe and effective delivery of therapeutic agents during transcatheter intra-arterial (IA) local delivery. Enhanced emulsion stability, IA infusion, embolic effect, safety, pharmacokinetics, and tumor response of Doxorubicin loaded PF127-LPD (Dox-PF127-LPD) for TACE in both in vitro and in vivo preclinical VX2 liver cancer rabbit model and N1S1 HCC rat model are demonstrated. Then, transcatheter arterial chemo-immuno-embolization (TACIE) combining TACE and local delivery of immune adjuvant (TLR9 agonist CpG oligodeoxynucleotide) is successfully performed using CpG-loaded Dox-PF127-LPD. Concurrent and safe local delivery of CpG and TACE during TACIE demonstrate leveraged TACE-induced immunogenic tumor microenvironment and augment systemic anti-tumor immunity in syngeneic N1S1 HCC rat model. Finally, the broad utility and enhanced therapeutic efficacy of TACIE are validated in the diethylnitrosamine-induced rat HCC model. TACIE using clinically established protocols and materials shall be a convenient and powerful therapeutic approach that can be translated to patients with HCC. The robust anti-cancer immunity and tumor regression of TACIE, along with its favorable safety profile, indicate its potential as a novel localized combination immunotherapy for HCC treatment.

Role of the EASL, RECIST, and WHO response guidelines alone or in combination for hepatocellular carcinoma: radiologic-pathologic correlation.

BACKGROUND & AIMS: We sought to study receiver-operating characteristics (ROC) of the European Association for the Study of the Liver (EASL), Response Evaluation Criteria in Solid Tumors (RECIST), and World Health Organization (WHO) guidelines for assessing response following locoregional therapies individually and in various combinations. METHODS: Eighty-one patients with hepatocellular carcinoma underwent liver explantation following locoregional therapies. Response was assessed using EASL, RECIST, and WHO. Kappa statistics were used to determine inter-method agreement. Uni/multivariate logistic regression analyses were performed to determine the variables predicting complete pathologic necrosis. Numerical values were assigned to the response classes: complete response=0, partial response=1, stable disease=2, and progressive disease=3. Various mathematical combinations of EASL and WHO were tested to calculate scores and their ROCs were studied using pathological examination of the explant as the gold standard. RESULTS: Median times (95% CI) to the WHO, RECIST, and EASL responses were 5.3 (4-11.5), 5.6 (4-11.5), and 1.3months (1.2-1.5), respectively. Kappa coefficients for WHO/RECIST, WHO/EASL, and RECIST/EASL were 0.78, 0.28, and 0.31, respectively. EASL response demonstrated significant odds ratios for predicting complete pathologic necrosis on uni/multivariate analyses. Calculated areas under the ROC curves were: RECIST: 0.63, WHO: 0.68, EASL: 0.82, EASL+WHO: 0.82, EASL×WHO: 0.85, EASL+(2×WHO): 0.79 and (2×EASL)+WHO: 0.85. An EASL×WHO Score of ⩽1 had 90.2% sensitivity for predicting complete pathologic necrosis. CONCLUSIONS: The product of WHO and EASL demonstrated better ROC than the individual guidelines for assessment of tumor response. EASL×WHO scoring system provides a simple and clinically applicable method of response assessment following locoregional therapies for hepatocellular carcinoma.

Phase II Trial of the Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma with Tumor Mutation Profiling.

BACKGROUND: The mammalian target of rapamycin (mTOR) pathway is upregulated in nearly half of hepatocellular carcinoma (HCC) tumors and is associated with poor prognosis. In preclinical models of HCC, the combination of mTOR pathway inhibition with the multikinase inhibitor sorafenib improves treatment efficacy. A prior phase I study of the allosteric mTOR inhibitor temsirolimus combined with sorafenib demonstrated acceptable safety at the recommended phase II dose. METHODS: We conducted a single-arm, multicenter phase II trial of the combination of temsirolimus 10 mg intravenously weekly plus sorafenib 200 mg b.i.d. The primary endpoint was time to progression (TTP) with efficacy target of median TTP of at least 6 months; secondary endpoints included overall survival (OS), objective response rate, safety, and alpha-fetoprotein (AFP) tumor marker response. Next-generation tumor sequencing was performed as an exploratory endpoint. RESULTS: Twenty-nine patients were enrolled, including 48% with hepatitis C virus infection and 28% with hepatitis B virus; 86% had Barcelona clinic liver cancer stage C disease. Among 28 patients evaluable for efficacy, the median TTP was 3.7 (95% confidence interval [CI]: 2.2, 5.3) months, with 14% of patients achieving TTP of at least 6 months. The median OS was 8.8 (95% CI: 6.8, 14.8) months. There were no complete or partial responses; 75% of patients had stable disease as best response. AFP decline by at least 50% was associated with prolonged TTP and OS. Serious adverse events occurred in 21%; the most common treatment-related adverse events of CTCAE grade 3 or higher were hypophosphatemia (36%), thrombocytopenia (14%), and rash (11%). There were no grade 5 events attributed to sorafenib or temsirolimus. Tumor next-generation sequencing (NGS) was performed in a subgroup of 24 patients with adequate tumor samples. Tumor mTOR pathway mutations were identified in 42%. There was no association between tumor mutation profile and OS or TTP. CONCLUSIONS: The combination of temsirolimus and sorafenib demonstrated acceptable safety but did not achieve the target threshold for efficacy in this phase II study. Tumor NGS including the presence of mTOR pathway mutations was not associated with treatment response in an exploratory subgroup analysis.

Chemoembolization for hepatocellular carcinoma: comprehensive imaging and survival analysis in a 172-patient cohort.

PURPOSE: To determine comprehensive imaging and long-term survival outcome following chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One hundred seventy-two patients with HCC treated with chemoembolization were studied retrospectively in an institutional review board approved protocol; this study was HIPAA compliant. Baseline laboratory and imaging characteristics were obtained. Clinical and laboratory toxicities following treatment were assessed. Imaging characteristics following chemoembolization were evaluated to determine response rates (size and necrosis) and time to progression (TTP). Survival from the time of first chemoembolization treatment was calculated. Subanalyses were performed by stratifying the population according to Child-Pugh, United Network for Organ Sharing, and Barcelona Clinic for Liver Cancer (BCLC) staging systems. RESULTS: Cirrhosis was present in 157 patients (91%); portal hypertension was present in 139 patients (81%). Eleven patients (6%) had metastases at baseline. Portal vein thrombosis was present in 11 patients (6%). Fifty-five percent of patients experienced some form of toxicity following treatment; 21% developed grade 3 or 4 bilirubin toxicity. Post-chemoembolization response was seen in 31% and 64% of patients according to size and necrosis criteria, respectively. Median TTP was 7.9 months (95% confidence interval: 7.1, 9.4) but varied widely by stage. Median survival was significantly different between patients with BCLC stages A, B, and C disease (stage A, 40.0 months; B, 17.4 months; C, 6.3 months; P < .0001). CONCLUSION: The determination of TTP and survival in patients with HCC is confounded by tumor biology and background cirrhosis; chemoembolization was shown to be a safe and effective therapy in patients with HCC.

Quantitative 4D transcatheter intraarterial perfusion MRI for monitoring chemoembolization of hepatocellular carcinoma.

PURPOSE: To develop a fully quantitative 4D transcatheter intraarterial perfusion (TRIP) magnetic resonance imaging (MRI) technique and prospectively test the hypothesis that quantitative 4D TRIP-MRI can be used clinically to monitor intraprocedural liver tumor perfusion reductions during transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: TACE was performed within an x-ray digital subtraction angiography (DSA)-MRI procedure suite in 16 patients with hepatocellular carcinoma. Quantitative 4D TRIP-MRI with targeted radiofrequency field mapping and dynamic longitudinal relaxation rate mapping was used to monitor changes in tumor perfusion during TACE. First-pass perfusion analysis was performed to produce intraprocedural blood flow (Frho) maps. Mean liver tumor perfusions before and after TACE were compared with a paired t-test (alpha = 0.05). RESULTS: Perfusion reductions were successfully measured with quantitative 4D TRIP-MRI in 22 separate tumors during 18 treatment sessions. Mean tumor perfusion Frho decreased from 16.3 (95% confidence interval [CI]: 10.7-21.9) before TACE to 5.0 (95% CI: 3.5-6.5) (mL/min/100 mL) after TACE. Tumor perfusion reductions were statistically significant (P < 0.0005), with a mean absolute perfusion change of 11.4 (95% CI: 5.6-17.1) (mL/min/100 mL) and a mean percentage reduction of 61.0% (95% CI: 48.3%-73.6%). CONCLUSION: Quantitative 4D TRIP-MRI can be successfully performed within clinical interventional settings to monitor intraprocedural changes in liver tumor perfusion during TACE.

Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma.

CONTEXT: Response Evaluation Criteria in Solid Tumors (RECIST) (unidimensional), World Health Organization (WHO) (bidimensional), and European Association for Study of the Liver (EASL) (necrosis) guidelines are commonly used to assess response following therapy for hepatocellular carcinoma (HCC). No universally accepted standard exists. OBJECTIVES: To evaluate intermethod agreement between these 3 imaging guidelines and to introduce the concept of the "primary index lesion" as a biomarker for response. DESIGN, SETTING, AND PARTICIPANTS: Single-center comprehensive imaging analysis including 245 consecutive patients with HCC who were treated with chemoembolization or radioembolization between January 2000 and December 2008. Computed tomography and magnetic resonance imaging scans (N = 1065) were reviewed to assess response in the "primary index lesion," defined as the largest tumor targeted during first treatment. MAIN OUTCOME MEASURES: Intermethod agreement (kappa statistics) between RECIST, WHO, and EASL guidelines response; correlation of WHO and EASL response in the primary index lesion with time to progression and survival. RESULTS: Kappa coefficients were 0.86 (95% confidence interval [CI], 0.80-0.92) between the WHO and RECIST guidelines, 0.24 (95% CI, 0.16-0.33) between RECIST and EASL, and 0.28 (95% CI, 0.19-0.36) between WHO and EASL. Disease progressed in 96 patients; 113 died. The hazard ratio for time to progression in responders compared with nonresponders was 0.36 (95% CI, 0.23-0.57) for WHO, 0.38 (95% CI, 0.24-0.58) for RECIST, and 0.38 (95% CI, 0.22-0.64) for EASL. Hazard ratios for survival in responders compared with nonresponders in univariate and multivariate analyses were 0.46 (95% CI, 0.32-0.67) and 0.55 (95% CI, 0.35-0.84) for WHO and 0.36 (95% CI, 0.22-0.57) and 0.54 (95% CI, 0.34-0.85) for EASL. Hazard ratios for survival in responders vs nonresponders in patients with solitary and multifocal HCC were 0.39 (95% CI, 0.19-0.77) and 0.51 (95% CI, 0.32-0.82) for WHO and 0.26 (95% CI, 0.10-0.67) and 0.47 (95% CI, 0.28-0.79) for EASL. CONCLUSIONS: Among a group of patients with HCC, agreement for classification of therapeutic response was high between the RECIST and WHO guidelines but low between each of these and EASL. Application of these methods to measure response in a primary index lesion resulted in statistically significant correlations with disease progression and survival.