Richard K. G. Do

Randomized Trial of Hepatic Artery Embolization for Hepatocellular Carcinoma Using Doxorubicin-Eluting Microspheres Compared With Embolization With Microspheres Alone

PURPOSE Transarterial chemoembolization is accepted therapy for hepatocellular carcinoma (HCC). No randomized trial has demonstrated superiority of chemoembolization compared with embolization, and the role of chemotherapy remains unclear. This randomized trial compares the outcome of embolization using microspheres alone with chemoembolization using doxorubicin-eluting microspheres. MATERIALS AND METHODS At a single tertiary referral center, patients with HCC were randomly assigned to embolization with microspheres alone (Bead Block [BB]) or loaded with doxorubicin 150 mg (LC Bead [LCB]). Random assignment was stratified by number of embolizations to complete treatment, and assignments were generated by permuted blocks in the institutional database. The primary end point was response according to RECIST 1.0 (Response Evaluation Criteria in Solid Tumors) using multiphase computed tomography 2 to 3 weeks post-treatment and then at quarterly intervals, with the reviewer blinded to treatment allocation. Secondary objectives included safety and tolerability, time to progression, progression-free survival, and overall survival. This trial is currently closed to accrual. RESULTS Between December 2007 and April 2012, 101 patients were randomly assigned: 51 to BB and 50 to LCB. Demographics were comparable: median age, 67 years; 77% male; and 22% Barcelona Clinic Liver Cancer stage A and 78% stage B or C. Adverse events occurred with similar frequency in both groups: BB, 19 of 51 patients (38%); LCB, 20 of 50 patients (40%; P = .48), with no difference in RECIST response: BB, 5.9% versus LCB, 6.0% (difference, -0.1%; 95% CI, -9% to 9%). Median PFS was 6.2 versus 2.8 months (hazard ratio, 1.36; 95% CI, 0.91 to 2.05; P = .11), and overall survival, 19.6 versus 20.8 months (hazard ratio, 1.11; 95% CI, 0.71 to 1.76; P = .64) for BB and LCB, respectively. CONCLUSION There was no apparent difference between the treatment arms. These results challenge the use of doxorubicin-eluting beads for chemoembolization of HCC.

Dynamic contrast-enhanced MR imaging of the liver: current status and future directions.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MR imaging) is emerging as a tool that can quantify changes in liver perfusion that occur in both diffuse and focal liver diseases. Recent data show promise for DCE-MR imaging of the liver in diagnosing fibrosis and cirrhosis before morphologic changes can be detected. It may also be valuable in the assessment of hepatocellular carcinoma and liver metastases. Acquisition parameters, postprocessing methods, applications, and recent results of DCE-MR imaging of the liver are also described. Finally, it reviews the limitations and future directions of DCE-MR imaging for liver applications.

Diffusion-weighted imaging for prediction of volumetric response of leiomyomas following uterine artery embolization: a preliminary study.

To determine if pretreatment apparent diffusion coefficient (ADC) of leiomyomas could predict volumetric response (VR) following uterine artery embolization (UAE).

Colorectal Cancer Liver Metastases: Biopsy of the Ablation Zone and Margins Can Be Used to Predict Oncologic Outcome

Purpose To establish the prognostic value of biopsy of the central and marginal ablation zones for time to local tumor progression (LTP) after radiofrequency (RF) ablation of colorectal cancer liver metastasis (CLM). Materials and Methods A total of 47 patients with 67 CLMs were enrolled in this prospective institutional review board-approved and HIPAA-compliant study between November 2009 and August 2012. Mean tumor size was 2.1 cm (range, 0.6-4.3 cm). Biopsy of the center and margin of the ablation zone was performed immediately after RF ablation (mean number of biopsy samples per ablation zone, 1.9) and was evaluated for the presence of viable tumor cells. Samples containing tumor cells at morphologic evaluation were further interrogated with immunohistochemistry and were classified as either positive, viable tumor (V) or negative, necrotic (N). Minimal ablation margin size was evaluated in the first postablation CT study performed 4-8 weeks after ablation. Variables were evaluated as predictors of time to LTP with the competing-risks model (uni- and multivariate analyses). Results Technical effectiveness was evident in 66 of 67 (98%) ablated lesions on the first contrast material-enhanced CT images at 4-8-week follow-up. The cumulative incidence of LTP at 12-month follow-up was 22% (95% confidence interval [CI]: 12, 32). Samples from 16 (24%) of 67 ablation zones were classified as viable tumor. At univariate analysis, tumor size, minimal margin size, and biopsy results were significant in predicting LTP. When these variables were subsequently entered in a multivariate model, margin size of less than 5 mm (P < .001; hazard ratio [HR], 6.7) and positive biopsy results (P = .008; HR, 3.4) were significant. LTP within 12 months after RF ablation was noted in 3% (95% CI: 0, 9) of necrotic CLMs with margins of at least 5 mm. Conclusion Biopsy proof of complete tumor ablation and minimal ablation margins of at least 5 mm are independent predictors of LTP and yield the best oncologic outcomes. (©) RSNA, 2016.

The effect of liver iron deposition on hepatic apparent diffusion coefficient values in cirrhosis.

OBJECTIVE The purpose of this study was to assess the effect of hepatic iron deposition on apparent diffusion coefficient (ADC) values measured with single-shot echo-planar imaging (EPI) diffusion-weighted MRI (DWI) in patients with liver cirrhosis and in vitro. MATERIALS AND METHODS Fifty-two patients with liver cirrhosis who underwent breath-hold single-shot EPI DWI at 1.5 T before liver transplantation were retrospectively assessed. Estimated signal-to-noise ratio (SNRest) and ADC were measured in the right hepatic lobe (for b values of 50 and 500 s/mm2). SNRest and ADC were compared between patients stratified by pathologic iron grade using the Mann-Whitney test. Hepatic ADC values were correlated to T2* values using the Spearman correlation test in a subset of patients. In addition, a phantom consisting of solutions of varying iron concentrations was imaged with single-shot EPI DWI and T2* imaging, and iron concentration was correlated with ADC and T2*. RESULTS In phantoms, there was a decrease in ADC and T2* with increasing iron concentration (r=-0.95 and -0.92, respectively; p<0.05). Patients with hepatic siderosis had significantly lower SNRest and ADC compared with patients without siderosis (p<0.0001). SNRest at b=50 s/mm2 and b=500 s/mm2 and ADC had a significant negative correlation with pathologic iron grade (r=-0.67 to 0.77, p<0.0001). There was a significant correlation between liver T2* and ADC (r=0.83, p<0.0001). CONCLUSION Hepatic siderosis lowers liver ADC and should be taken into account when using ADC for diagnosing liver cirrhosis.

Surrogate Imaging Biomarkers of Response of Colorectal Liver Metastases After Salvage Radioembolization Using 90Y-Loaded Resin Microspheres

OBJECTIVE The purpose of the present study is to evaluate Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, tumor attenuation criteria, Choi criteria, and European Organization for Research and Treatment of Cancer (EORTC) PET criteria as measures of response and subsequent predictors of liver progression-free survival (PFS) after radioembolization (RE) of colorectal liver metastases (CLM). The study also assesses interobserver variability for measuring tumor attenuation using a single 2D ROI on a simple PACS workstation. MATERIALS AND METHODS We performed a retrospective review of the clinical RE database at our institution, to identify patients treated in the salvage setting for CLM between December 2009 and March 2013. Response was evaluated on FDG PET scans, with the use of EORTC PET criteria, and on portal venous phase CT scans, with the use of RECIST 1.1, tumor attenuation criteria, and Choi criteria. Two independent blinded observers measured tumor attenuation using a single 2D ROI. The intraclass correlation coefficient (ICC) for interobserver variability was assessed. Kaplan-Meier methodology was used to calculate liver PFS, and the log-rank test was used to assess the response criteria as predictors of liver PFS. RESULTS A total of 25 patients with 46 target tumors were enrolled in the study. The ICC was 0.95 at baseline and 0.98 at response evaluation. Among the 25 patients, more responders (i.e., partial response) were identified on the basis of EORTC PET criteria (n = 14), Choi criteria (n = 15), and tumor attenuation criteria (n = 13) than on the basis of RECIST 1.1 (n = 2). The median liver PFS was 3.0 months (95% CI, 2.1-4.0 months). Response identified on the basis of EORTC PET criteria (p < 0.001), Choi criteria (p < 0.001), or tumor attenuation criteria (p = 0.01) predicted liver PFS; however, response identified by RECIST 1.1 did not (p = 0.1). CONCLUSION RECIST 1.1 has poor sensitivity for detecting metabolic responses classified by EORTC PET criteria. EORTC PET criteria, Choi criteria, and tumor attenuation criteria appear to be equally reliable surrogate imaging biomarkers of liver PFS after RE in patients with CLM.

O6-Methylguanine DNA Methyltransferase Status Does Not Predict Response or Resistance to Alkylating Agents in Well-Differentiated Pancreatic Neuroendocrine Tumors

OBJECTIVES Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. METHODS We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. RESULTS Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. CONCLUSIONS We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.Objectives Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O6-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. Methods We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. Results Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O6-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. Conclusions We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O6-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.

Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients

The Liver Imaging Reporting and Data System (LI-RADS) is composed of four individual algorithms intended to standardize the lexicon, as well as reporting and care, in patients with or at risk for hepatocellular carcinoma in the context of surveillance with US; diagnosis with CT, MRI, or contrast material-enhanced US; and assessment of treatment response with CT or MRI. This report provides a broad overview of LI-RADS, including its historic development, relationship to other imaging guidelines, composition, aims, and future directions. In addition, readers will understand the motivation for and key components of the 2018 update.

Quantitative CT analysis for the preoperative prediction of pathologic grade in pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) account for approximately 5% of all pancreatic tumors, affecting one individual per million each year.1 PanNETs are difficult to treat due to biological variability from benign to highly malignant, indolent to very aggressive. The World Health Organization classifies PanNETs into three categories based on cell proliferative rate, usually detected using the Ki67 index and cell morphology: low-grade (G1), intermediate-grade (G2) and high-grade (G3) tumors. Knowledge of grade prior to treatment would select patients for optimal therapy: G1/G2 tumors respond well to somatostatin analogs and targeted or cytotoxic drugs whereas G3 tumors would be targeted with platinum or alkylating agents.2, 3 Grade assessment is based on the pathologic examination of the surgical specimen, biopsy or ne-needle aspiration; however, heterogeneity in the proliferative index can lead to sampling errors.4 Based on studies relating qualitatively assessed shape and enhancement characteristics on CT imaging to tumor grade in PanNET,5 we propose objective classification of PanNET grade with quantitative analysis of CT images. Fifty-five patients were included in our retrospective analysis. A pathologist graded the tumors. Texture and shape-based features were extracted from CT. Random forest and naive Bayes classifiers were compared for the classification of G1/G2 and G3 PanNETs. The best area under the receiver operating characteristic curve (AUC) of 0:74 and accuracy of 71:64% was achieved with texture features. The shape-based features achieved an AUC of 0:70 and accuracy of 78:73%.

Quantitative imaging features of pretreatment CT predict volumetric response to chemotherapy in patients with colorectal liver metastases

ObjectivesThis study investigates whether quantitative image analysis of pretreatment CT scans can predict volumetric response to chemotherapy for patients with colorectal liver metastases (CRLM).MethodsPatients treated with chemotherapy for CRLM (hepatic artery infusion (HAI) combined with systemic or systemic alone) were included in the study. Patients were imaged at baseline and approximately 8 weeks after treatment. Response was measured as the percentage change in tumour volume from baseline. Quantitative imaging features were derived from the index hepatic tumour on pretreatment CT, and features statistically significant on univariate analysis were included in a linear regression model to predict volumetric response. The regression model was constructed from 70% of data, while 30% were reserved for testing. Test data were input into the trained model. Model performance was evaluated with mean absolute prediction error (MAPE) and R2. Clinicopatholologic factors were assessed for correlation with response.Results157 patients were included, split into training (n = 110) and validation (n = 47) sets. MAPE from the multivariate linear regression model was 16.5% (R2 = 0.774) and 21.5% in the training and validation sets, respectively. Stratified by HAI utilisation, MAPE in the validation set was 19.6% for HAI and 25.1% for systemic chemotherapy alone. Clinical factors associated with differences in median tumour response were treatment strategy, systemic chemotherapy regimen, age and KRAS mutation status (p < 0.05).ConclusionQuantitative imaging features extracted from pretreatment CT are promising predictors of volumetric response to chemotherapy in patients with CRLM. Pretreatment predictors of response have the potential to better select patients for specific therapies.Key Points• Colorectal liver metastases (CRLM) are downsized with chemotherapy but predicting the patients that will respond to chemotherapy is currently not possible.• Heterogeneity and enhancement patterns of CRLM can be measured with quantitative imaging.• Prediction model constructed that predicts volumetric response with 20% error suggesting that quantitative imaging holds promise to better select patients for specific treatments.