Assessment of Response to Transcatheter Arterial Chemoembolization with Doxorubicin-eluting Microspheres: Tumor Biology and Hepatocellular Carcinoma Recurrence in a 5-year Transplant Cohort.

Purpose To assess response to transcatheter arterial chemoembolization (TACE) based on immune markers and tumor biology in patients with hepatocellular carcinoma (HCC) who were bridged to liver transplantation, and to produce an optimized pretransplantation model for posttransplantation recurrence risk. Materials and Methods In this institutional review board-approved HIPAA-compliant retrospective analysis, 93 consecutive patients (73 male, 20 female; mean age, 59.6 years; age range, 23-72 years) underwent TACE with doxorubicin-eluting microspheres (DEB) (hereafter, DEB-TACE) and subsequently underwent transplantation over a 5-year period from July 7, 2011, to May 16, 2016. DEB-TACE response was based on modified Response Evaluation Criteria in Solid Tumors. Imaging responses and posttransplantation recurrence were compared with demographics, liver function, basic immune markers, treatment dose, and tumor morphology. Treatment response and recurrence were analyzed with uni- and multivariate statistics, as well as internal validation and propensity score matching of factors known to affect recurrence to assess independent effects of DEB-TACE response on recurrence. Results Low-grade tumors (grade 0, 1, or 2) demonstrated a favorable long-term treatment response in 87% of patients (complete response, 49%; partial response, 38%; stable disease [SD] or local disease progression [DP], 13%) versus 33% of high-grade tumors (grade 3 or 4) (complete response, 0%; partial response, 33%; SD or DP, 67%) (P < .001). Of the 93 patients who underwent treatment, 82 were followed-up after transplantation (mean duration, 757 days). Recurrence occurred in seven (9%) patients (mean time after transplantation, 635 days). Poor response to DEB-TACE (SD or DP) was present in 86% of cases and accounted for 35% of all patients with SD or DP (P < .001). By using only variables routinely available prior to liver transplantation, a validated model of posttransplantation recurrence risk was produced with a concordance statistic of 0.83. The validated model shows sensitivity of 83.6%, specificity of 82.6%, and negative predictive value of 98.4%, which are pessimistic estimates. Conclusion Response to DEB-TACE is correlated with tumor biology and patients at risk for posttransplantation recurrence, and it may be associated with HCC recurrence after liver transplantation. © RSNA, 2017 Online supplemental material is available for this article.

Intraarterial Liver-Directed Therapies: The Role of Interventional Oncology.

BACKGROUND: Since the early 1990s, the minimally invasive image-guided therapies used in interventional oncology to treat hepatocellular carcinoma have continued to evolve. Additionally, the range of applications has been expanded to the treatment of hepatic metastases from colorectal cancer, neuroendocrine tumors, cholangiocarcinoma, breast cancer, melanoma, and sarcoma. METHODS: We searched the literature to identify publications from 1990 to the present on various image-guided intraarterial therapies and their efficacy, as well as their role in the management of primary and secondary liver malignancies. RESULTS: Chemoembolization and radioembolization are considered a standard of care in treating, delaying progression of disease, and downstaging to bridge to liver transplantation. Progression-free survival and overall survival outcomes are promising in patients with colorectal cancer and neuroendocrine tumors with liver metastases. Applications in the treatment of hepatic metastases from cholangiocarcinoma, breast cancer, melanoma, and sarcoma also show potential. CONCLUSION: Interventional oncology and its image-guided intraarterial therapies continue to gain recognition as treatment options for primary and secondary liver cancers. Growing evidence supports their role as a standard of care alongside medical oncology, surgery, and radiation oncology.

Elevated Lung Shunt Fraction as a Prognostic Indicator for Disease Progression and Metastasis in Hepatocellular Carcinoma.

PURPOSE: To evaluate lung shunt fraction (LSF) as an early predictor for local disease progression or the development of metastatic disease. MATERIALS AND METHODS: Retrospective analysis was performed on 52 patients with hepatocellular carcinoma who underwent preradioembolization assessment, including the calculation of LSF. Comparison of preprocedural and postprocedural surveillance imaging was performed. Mean patient age was 67 years (range, 50-88 y), with a mean surveillance of 245 days (range, 24-871 d). Statistical analysis was conducted to assess the relationship between LSF and local disease progression or development of new metastatic disease. RESULTS: In patients in whom metastatic disease developed during routine surveillance, the mean LSF was almost double that in patients in whom no metastasis developed (18.3% vs 9.3%; P = .001). Patients with elevated LSFs were also more likely to show intrahepatic disease progression (15.6% vs 8.5%; P = .003). LSFs < 8% corresponded to negative predictive values of 74% for local disease progression and 95% for development of metastasis, signaling a better prognosis. Of pretreatment variables examined (age, sex, previous treatment with disease progression, lesion size, lesion number, LSF, α-fetoprotein level, and portal vein thrombus), only LSF was an independent predictor for new metastasis (odds ratio [OR] = 1.2; P = .01). LSF (OR = 1.2; P = .03) and progression after previous treatment (OR = 4.7; P = .04) were independent predictors for local progression. CONCLUSIONS: As local disease progression and metastatic disease were more likely to occur in patients with elevated LSFs, LSF may be the most sensitive predictor for local disease progression and new metastatic disease.

Improved method for calculating hepatic steatosis using the hepatorenal index.

OBJECTIVES: Marshall et al (AJR Am J Roentgenol 2012; 199:997-1002) initially demonstrated that the hepatorenal index is an effective and noninvasive tool to screen patients for hepatic steatosis. The aim of this study was to determine whether the hepatorenal index can be accurately calculated directly from a picture archiving and communication system (PACS) quickly and efficiently without the need for the multiple steps and specialized software used to calculate hepatorenal index in the study by Marshall et al. METHODS: We evaluated 99 of the 101 patients included in the study by Marshall et al: patients being followed by hepatologists with plans for liver biopsy. The hepatorenal index was calculated by using Digital Imaging and Communications in Medicine (DICOM) images from a PACS and a markup region-of-interest tool. We compared this value to the value that Marshall et al derived by using specialized software and to standard histologic estimates. We created similar subgroups: patients with steatosis based on histologically estimated intracellular fat exceeding 5% and patients without steatosis. RESULTS: The mean hepatorenal index ± SD for those with steatosis according to histologic findings was 1.87 ± 0.6, and for those without, it was 1.14 ± 0.2. A hepatorenal index of 1.34 or higher had 92% sensitivity for identifying fat exceeding 5%, 85% specificity, a 94% negative predictive value, and a 79% positive predictive value. Substantial agreement was found between the hepatorenal index calculated from DICOM images and macrovesicular fat categorized at the cut point of 1.34 or higher (κ = 0.76; 95% confidence interval, 0.62-0.88; P < .001). CONCLUSIONS: The hepatorenal index can be quickly and accurately calculated from DICOM images directly on a PACS without supplementary software.

Hepatorenal index as an accurate, simple, and effective tool in screening for steatosis.

OBJECTIVE: The hepatorenal index has been reported to be a sensitive and noninvasive test to quantify steatosis, but it is cumbersome and time-consuming and requires specialized software. The aim of this study was to improve and simplify the hepatorenal index calculation and determine whether it is an effective tool for differentiating patients with steatosis from those without steatosis, thereby eliminating the need for biopsy in a large number of patients. MATERIALS AND METHODS: One hundred one patients who had undergone ultrasound-guided percutaneous liver biopsy at our institution were selected from a patient database. Patients with renal disease, patients with liver masses, and patients whose liver and right kidney were not included on the same image were excluded. Images were acquired with high-resolution ultrasound, and the hepatorenal index was calculated using freeware based on comparison of hepatic and renal brightness. RESULTS: Of the 101 patients, 63 had 5% or less steatosis and 38 had more than 5% steatosis. Using freeware available online from the National Institutes of Health, we calculated hepatorenal index values for all patients. Our data showed a strong correlation between the hepatorenal index and percentage of fat (r = 0.71, p < 0.0001). A hepatorenal index of 1.28 or greater had a 100% sensitivity for identifying more than 5% fat, 54% specificity, 0.57 positive predictive value, and 1.0 negative predictive value. If this method had been used prospectively to select patients for biopsy in our sample, 34% of biopsies could have been avoided. CONCLUSION: The hepatorenal index is a simple, reliable, and cost-effective screening tool for identifying patients who should not undergo liver biopsy for evaluation of steatosis.