Sonia Sahu

Validation of the Hong Kong Liver Cancer Staging System in Determining Prognosis of the North American Patients Following Intra-arterial Therapy

Background & Aims There is debate over the best way to stage hepatocellular carcinoma (HCC). We attempted to validate the prognostic and clinical utility of the recently developed Hong Kong Liver Cancer (HKLC) staging system, a hepatitis B–based model, and compared data with that from the Barcelona Clinic Liver Cancer (BCLC) staging system in a North American population that underwent intra‐arterial therapy (IAT). Methods We performed a retrospective analysis of data from 1009 patients with HCC who underwent IAT from 2000 through 2014. Most patients had hepatitis C or unresectable tumors; all patients underwent IAT, with or without resection, transplantation, and/or systemic chemotherapy. We calculated HCC stage for each patient using 5‐stage HKLC (HKLC‐5) and 9‐stage HKLC (HKLC‐9) system classifications, and the BCLC system. Survival information was collected up until the end of 2014 at which point living or unconfirmed patients were censored. We compared performance of the BCLC, HKLC‐5, and HKLC‐9 systems in predicting patient outcomes using Kaplan‐Meier estimates, calibration plots, C statistic, Akaike information criterion, and the likelihood ratio test. Results Median overall survival time, calculated from first IAT until date of death or censorship, for the entire cohort (all stages) was 9.8 months. The BCLC and HKLC staging systems predicted patient survival times with significance (P < .001). HKLC‐5 and HKLC‐9 each demonstrated good calibration. The HKLC‐5 system outperformed the BCLC system in predicting patient survival times (HKLC C = 0.71, Akaike information criterion = 6242; BCLC C = 0.64, Akaike information criterion = 6320), reducing error in predicting survival time (HKLC reduced error by 14%, BCLC reduced error by 12%), and homogeneity (HKLC chi‐square = 201, P < .001; BCLC chi‐square = 119, P < .001) and monotonicity (HKLC linear trend chi‐square = 193, P < .001; BCLC linear trend chi‐square = 111, P < .001). Small proportions of patients with HCC of stages IV or V, according to the HKLC system, survived for 6 months and 4 months, respectively. Conclusions In a retrospective analysis of patients who underwent IAT for unresectable HCC, we found the HKLC‐5 staging system to have the best combination of performances in survival separation, calibration, and discrimination; it consistently outperformed the BCLC system in predicting survival times of patients. The HKLC system identified patients with HCC of stages IV and V who are unlikely to benefit from IAT.

Feasibility of a Modified Cone-Beam CT Rotation Trajectory to Improve Liver Periphery Visualization during Transarterial Chemoembolization

PURPOSE To compare liver coverage and tumor detectability by using preprocedural magnetic resonance (MR) images as a reference, as well as radiation exposure of cone-beam computed tomography (CT) with different rotational trajectories. MATERIALS AND METHODS Fifteen patients (nine men and six women; mean age ± standard deviation, 65 years ± 5) with primary or secondary liver cancer were retrospectively included in this institutional review board-approved study. A modified cone-beam CT protocol was used in which the C-arm rotates from +55° to -185° (open arc cone-beam CT) instead of -120° to +120° (closed arc cone-beam CT). Each patient underwent two sessions of transarterial chemoembolization between February 2013 and March 2014 with closed arc and open arc cone-beam CT (during the first and second transarterial chemoembolization sessions, respectively, as part of the institutional transarterial chemoembolization protocol). For each cone-beam CT examination, liver volume and tumor detectability were assessed by using MR images as the reference. Radiation exposure was compared by means of a phantom study. For statistical analysis, paired t tests and a Wilcoxon signed rank test were performed. RESULTS Mean liver volume imaged was 1695 cm(3) ± 542 and 1857 cm(3) ± 571 at closed arc and open arc cone-beam CT, respectively. The coverage of open arc cone-beam CT was significantly higher compared with closed arc cone-beam CT (97% vs 86% of the MR imaging liver volume, P = .002). In eight patients (53%), tumors were partially or completely outside the closed arc cone-beam CT field of view. All tumors were within the open arc cone-beam CT field of view. The open arc cone-beam CT radiation exposure by means of weighted CT index was slightly lower compared with that of closed arc cone-beam CT (-5.1%). CONCLUSION Open arc cone-beam CT allowed for a significantly improved intraprocedural depiction of peripheral hepatic tumors while achieving a slight radiation exposure reduction.

Imaging Biomarkers of Tumor Response in Neuroendocrine Liver Metastases Treated with Transarterial Chemoembolization: Can Enhancing Tumor Burden of the Whole Liver Help Predict Patient Survival?

Purpose To investigate whether whole-liver enhancing tumor burden [ETB] can serve as an imaging biomarker and help predict survival better than World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) methods in patients with multifocal, bilobar neuroendocrine liver metastases (NELM) after the first transarterial chemoembolization (TACE) procedure. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 51 patients (mean age, 57.8 years ± 13.2; range, 13.5-85.8 years) with multifocal, bilobar NELM treated with TACE. The largest area (WHO), longest diameter (RECIST), longest enhancing diameter (mRECIST), largest enhancing area (EASL), and largest enhancing volume (ETB) were measured at baseline and after the first TACE on contrast material-enhanced magnetic resonance images. With three-dimensional software, ETB was measured as more than 2 standard deviations the signal intensity of a region of interest in normal liver. Response was assessed with WHO, RECIST, mRECIST, and EASL methods according to their respective criteria. For ETB response, a decrease in enhancement of at least 30%, 50%, and 65% was analyzed by using the Akaike information criterion. Survival analysis included Kaplan-Meier curves and Cox regressions. Results Treatment response occurred in 5.9% (WHO criteria), 2.0% (RECIST), 25.5% (mRECIST), and 23.5% (EASL criteria) of patients. With 30%, 50%, and 65% cutoffs, ETB response was seen in 60.8%, 39.2%, and 21.6% of patients, respectively, and was the only biomarker associated with a survival difference between responders and nonresponders (45.0 months vs 10.0 months, 84.3 months vs 16.7 months, and 85.2 months vs 21.2 months, respectively; P < .01 for all). The 50% cutoff provided the best survival model (hazard ratio [HR]: 0.2; 95% confidence interval [CI]: 0.1, 0.4). At multivariate analysis, ETB response was an independent predictor of survival (HR: 0.2; 95% CI: 0.1, 0.6). Conclusion Volumetric ETB is an early treatment response biomarker and surrogate for survival in patients with multifocal, bilobar NELM after the first TACE procedure.

Renal Cell Carcinoma Metastatic to the Liver: Early Response Assessment after Intraarterial Therapy Using 3D Quantitative Tumor Enhancement Analysis

PURPOSE Liver metastases from renal cell carcinoma (RCC) are not uncommon in the course of disease. However, data about tumor response to intraarterial therapy (IAT) are scarce. This study assessed whether changes of enhancing tumor volume using quantitative European Association for the Study of the Liver (qEASL) on magnetic resonance imaging (MRI) and computed tomography (CT) can evaluate tumor response and predict overall survival (OS) early after therapy. METHODS AND MATERIALS Fourteen patients with liver metastatic RCC treated with IAT (transarterial chemoembolization: n= 9 and yttrium-90: n= 5) were retrospectively included. All patients underwent contrast-enhanced imaging (MRI: n= 10 and CT: n= 4) 3 to 4 weeks pre- and posttreatment. Response to treatment was evaluated on the arterial phase using Response Evaluation Criteria in Solid Tumors (RECIST), World Health Organization, modified RECIST, EASL, tumor volume, and qEASL. Paired t test was used to compare measurements pre- and post-IAT. Patients were stratified into responders (≥65% decrease in qEASL) and nonresponders (<65% decrease in qEASL). OS was evaluated using Kaplan-Meier curves with log-rank test and the Cox proportional hazard model. RESULTS Mean qEASL (cm3) decreased from 93.5 to 67.2 cm3 (P= .004) and mean qEASL (%) from 63.1% to 35.6% (P= .001). No significant changes were observed using other response criteria. qEASL was the only significant predictor of OS when used to stratify patients into responders and nonresponders with median OS of 31.9 versus 11.1 months (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.19-0.97; P= .042) for qEASL (cm3) and 29.9 versus 10.2 months (HR, 0.09; 95% CI, 0.01-0.74; P= .025) for qEASL (%). CONCLUSION Three-dimensional (3D) quantitative tumor analysis is a reliable predictor of OS when assessing treatment response after IAT in patients with RCC metastatic to the liver. qEASL outperforms conventional non-3D methods and can be used as a surrogate marker for OS early after therapy.