Yan Zhao

Intraprocedural 3D Quantification of Lipiodol Deposition on Cone-Beam CT Predicts Tumor Response After Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma

AbstractPurposenTo evaluate whether intraprocedural 3D quantification of Lipiodol deposition on cone-beam computed tomography (CBCT) can predict tumor response on follow-up contrast-enhanced magnetic resonance imaging (CE-MRI) in patients with hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization (cTACE).Materials and MethodsThis IRB approved, retrospective analysis included 36 patients with 51 HCC target lesions, who underwent cTACE with CBCT. CE-MRI was acquired at baseline and 1xa0month after cTACE. Overall tumor volumes as well as intratumoral Lipiodol volumes on CBCT were measured and compared with the overall and necrotic (non-enhancing) tumor volumes on CE-MRI using the paired student’s t test. Tumor response on CE-MRI was assessed using modified response evaluation criteria in solid tumors (mRECIST). A linear regression model was used to correlate tumor volumes, Lipiodol volumes, and the percentage of Lipiodol deposition on CBCT with the corresponding parameters on CE-MRI. Nonparametric spearman rank-order correlation and trend test were used to correlate the percentage of Lipiodol deposition in the tumor with tumor response.ResultA strong correlation between overall tumor volumes on CBCT and CE-MRI was observed (R2xa0=xa00.986). In addition, a strong correlation was obtained between the volume of Lipiodol deposition on CBCT and tumor necrosis (in cm3) on CE-MRI (R2xa0=xa00.960), and between the percentage of Lipiodol deposition and tumor necrosis (R2xa0=xa00.979). Importantly, the extent of Lipiodol deposition (in percentage of total tumor volume) correlated strongly with tumor response on CE-MRI (Spearman rhoxa0=xa00.84, pxa0<xa00.001).ConclusionsIntraprocedural 3D quantification of Lipiodol deposition on CBCT can be used to predict tumor response on follow-up CE-MRI.

Transarterial Chemoembolization for the Treatment of Advanced-Stage Hepatocellular Carcinoma

It remains controversial whether transarterial chemoembolization (TACE) should be performed in patients with advanced-stage hepatocellular carcinoma (HCC). The present large retrospective cohort study aimed to define the survival outcome following TACE of advanced HCC and to identify the prognostic factors. Five hundred eight patients with Barcelona Clinic Liver Cancer (BCLC) C-stage HCC, Child-Pugh A/B who were treated with TACE between November 1998 and December 2013 were identified. There was no significant difference in overall survival (OS) between patients with Eastern Cooperative Oncology Group (ECOG) 0 and those with ECOG ≥1 (10.5xa0months vs. 11.9xa0months, Pu2009=u20090.87). The median OS of patients without portal vein tumor thrombosis (PVTT) was longer than that of patients with PVTT (16.9 vs. 6.1xa0months, Pu2009<u20090.001). Child-Pugh B class, PVTT, extrahepatic metastasis, tumor size ≥5xa0cm, number of tumors ≥3, and alpha-fetoprotein ≥400xa0ng/dL were significantly associated with decreased survival and were used for determining the risk scores. All patients were divided into two groups (low-risk and high-risk groups) according to the cutoff value of 6.5 for risk scores. The patients with a value <6.5 (low-risk group) had significantly longer survival than those with >6.5 (high-risk group) (24.1 vs. 7.5xa0months, respectively; Pu2009<u20090.001). TACE is an effective therapy for select patients with advanced stage HCC and may provide equal or improved survival as compared with reported outcomes with sorafenib. The results highlight the need for a differentiated approach to therapeutic recommendations for patients with BCLC C.

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.

mRECIST response combined with sorafenib-related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib

The mRECIST and dermatologic adverse events (AEs) can be used to assess the patient response to transarterial chemoembolization (TACE) and/or sorafenib for hepatocellular carcinoma (HCC). Here, we aimed to combine the two criteria to stratify the prognosis in patients with unresectable HCC receiving TACE plus sorafenib (TACE‐S). In total, 176 consecutive HCC patients treated with TACE‐S were enrolled. CT scans and laboratory tests were conducted pretreatment (at baseline, 5–7 days before the TACE‐S) and post‐treatment (at 1, 2 and 3 months). The radiological response was assessed according to mRECIST. Sorafenib‐related AEs were recorded every 2 weeks after oral administration, and patients with dermatologic AEs of Grade 2 or more were defined as dermatologic responders. The earliest time at which mRECIST and dermatologic responses correlated with survival was 2 months after therapy. The mRECIST‐dermatologic AE combination assessment stratified patients into three different prognoses; responders on both assessments exhibited the longest median overall survival (OS), followed by responders on one assessment and non‐responders on both assessments (30.5, 17.4 and 8.3 months, respectively; pu2009<u20090.001). Achieving the highest C‐index, the mRECIST‐dermatologic AE combination showed better performance in predicting survival than either mRECIST or dermatologic AEs alone. Furthermore, the mRECIST‐dermatologic AE combination remained a significant predictor of OS, even when the patients were stratified according to the BCLC stage, ECOG score or alpha‐fetoprotein (AFP) value. This study showed that the combination of mRECIST response and dermatologic AEs is superior to either criterion used alone for predicting the survival of HCC patients treated with TACE‐S.

Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients.

The purpose of our study was to test the hypothesis that sorafenib‐related dermatologic adverse events (AEs) as an early biomarker can predict the long‐term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE‐S). The intermediate‐stage hepatocellular carcinoma patients who received either TACE‐S or TACE‐alone treatment were consecutively included into analysis. In the TACE‐S group, patients withu2009≥u2009grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those withu2009<u2009grade 2 were defined as nonresponders. In the TACE‐S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; pu2009=u20090.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HRu2009=u20091.9; 95% confidence Interval‐CI: 1.3–2.7; pu2009=u20090.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0–30.8) among responders treated with TACE‐S vs.18.3 months (95% CI: 14.5–22.1) among those who received TACE‐alone (pu2009=u20090.046). The median time to progression was 13.1 months (95% CI: 4.4–21.8) in the TACE‐S group, a duration that was significantly longer than that in the TACE‐alone group [5 months (95% CI: 6.4–13.3), pu2009=u20090.014]. This study demonstrated that sorafenib‐related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE‐S therapy. Sorafenib‐related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE‐S in future randomized controlled trials.

3D Quantitative tumour burden analysis in patients with hepatocellular carcinoma before TACE: comparing single-lesion vs. multi-lesion imaging biomarkers as predictors of patient survival

ObjectivesTo compare the ability of single- vs. multi-lesion assessment on baseline MRI using 1D- and 3D-based measurements to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) before transarterial chemoembolization (TACE).MethodsThis retrospective analysis included 122 patients. A quantitative 3D analysis was performed on baseline MRI to calculate enhancing tumour volume (ETV [cm3]) and enhancing tumour burden (ETB [%]) (ratio between ETV [cm3] and liver volume). Furthermore, enhancing and overall tumour diameters were measured. Patients were stratified into two groups using thresholds derived from the BCLC staging system. Statistical analysis included Kaplan–Meier plots, uni- and multivariate cox proportional hazard ratios (HR) and concordances.ResultsAll methods achieved good separation of the survival curves (pu2009<u20090.05). Multivariate analysis showed an HR of 5.2 (95xa0% CI 3.1–8.8, pu2009<u20090.001) for ETV [cm3] and HR 6.6 (95xa0% CI 3.7–11.5, pu2009<u20090.001) for ETB [%] vs. HR 2.6 (95xa0% CI 1.2–5.6, pu2009=u20090.012) for overall diameter and HR 3.0 (95xa0% CI 1.5–6.3, pu2009=u20090.003) for enhancing diameter. Concordances were highest for ETB [%], with no added predictive power for multi-lesion assessment (difference between concordances not significant).Conclusion3D quantitative assessment is a stronger predictor of survival as compared to diameter-based measurements. Assessing multiple lesions provides no substantial improvement in predicting OS than evaluating the dominant lesion alone.Key Points• 3D quantitative tumour assessment on baseline MRI predicts survival in HCC patients.• 3D quantitative tumour assessment predicts survival better than any current radiological method.• Multiple lesion assessment provides no improvement than evaluating the dominant lesion alone.• Measuring enhancing tumour volume in proportion to liver volume reflects tumour burden.

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.

Improved Visibility of Metastatic Disease in the Liver During Intra-Arterial Therapy Using Delayed Arterial Phase Cone-Beam CT

PurposeTo compare the visibility of liver metastases on dual-phase cone-beam CT (DP-CBCT) and digital subtraction angiography (DSA), with reference to preinterventional contrast-enhanced magnetic resonance imaging (CE-MRI) of the liver.MethodsThis IRB-approved, retrospective study included 28 patients with neuroendocrine (NELM), colorectal (CRCLM), or sarcoma (SLM) liver metastases who underwent DP-CBCT during intra-arterial therapy (IAT) between 01/2010 and 10/2014. DP-CBCT was acquired after a single contrast agent injection in the tumor-feeding arteries at early and delayed arterial phases (EAP and DAP). The visibility of each lesion was graded by two radiologists in consensus on a three-rank scale (complete, partial, none) on DP-CBCT and DSA images using CE-MRI as reference.Results47 NELM, 43 CRCLM, and 16 SLM were included. On DSA 85.1, 44.1, and 37.5xa0% of NELM, CRCLM, and SLM, were at least partially depicted, respectively. EAP-CBCT yielded significantly higher sensitivities of 88.3 and 87.5xa0% for CRCLM and SLM, respectively (pxa0<xa00.01), but not for NELM (89.4xa0%; pxa0=xa01.0). On DAP-CBCT all NELM, CRCLM, and SLM were visible (pxa0<xa00.001). Complete depiction was achieved on DSA for 59.6, 16.3, and 18.8xa0% of NELM, CRCLM, and SLM, respectively. The complete depiction rate on EAP-CBCT was significantly higher for CRCLM (46.5xa0%; pxa0<xa00.001), lower for NELM (40.4xa0%; pxa0=xa00.592), and similar for SLM (25xa0%, pxa0=xa00.399). On DAP-CBCT however, the highest rates of complete depiction were found—NELM (97.8xa0%; pxa0=xa00.008), CRCLM (95.3xa0%; pxa0=xa00.008), and SLM (100xa0%; pxa0<xa00.001).ConclusionDAP-CBCT substantially improved the visibility of liver metastases during IAT. Future studies need to evaluate the clinical impact.

Characteristics of a New X-Ray Imaging System for Interventional Procedures: Improved Image Quality and Reduced Radiation Dose

PurposeTo compare image quality and radiation exposure between a new angiographic imaging system and the preceding generation system during uterine artery embolization (UAE).Materials and MethodsIn this retrospective, IRB-approved two-arm study, 54 patients with symptomatic uterine fibroids were treated with UAE on two different angiographic imaging systems. The new system includes optimized acquisition parameters and real-time image processing algorithms. Air kerma (AK), dose area product (DAP) and acquisition time for digital fluoroscopy (DF) and digital subtraction angiography (DSA) were recorded. Body mass index was noted as well. DF image quality was assessed objectively by image noise measurements. DSA image quality was rated by two blinded, independent readers on a four-rank scale. Statistical differences were assessed with unpaired t tests and Wilcoxon rank-sum tests.ResultsThere was no significant difference between the patients treated on the new (nxa0=xa036) and the old system (nxa0=xa018) regarding age (pxa0=xa00.10), BMI (pxa0=xa00.18), DF time (pxa0=xa00.35) and DSA time (pxa0=xa00.17). The new system significantly reduced the cumulative AK and DAP by 64 and 72%, respectively (median 0.58xa0Gy and 145.9xa0Gy*cm2 vs. 1.62xa0Gy and 526.8xa0Gy*cm2, pxa0<xa00.01 for both). Specifically, DAP for DF and DSA decreased by 59% (75.3 vs. 181.9xa0Gy*cm2, pxa0<xa00.01) and 78% (67.6 vs. 312.2xa0Gy*cm2, pxa0<xa00.01), respectively. The new system achieved a significant decrease in DF image noise (pxa0<xa00.01) and a significantly better DSA image quality (pxa0<xa00.01).ConclusionsThe new angiographic imaging system significantly improved image quality and reduced radiation exposure during UAE procedures.

Which Criteria Applied in Multi-Phasic CT Can Predict Early Tumor Response in Patients with Hepatocellular Carcinoma Treated Using Conventional TACE: RECIST, mRECIST, EASL or qEASL?

PurposeOur study aimed to evaluate quantitative tumor response assessment (quantitative EASL-[qEASL]) on computed tomography (CT) images in patients with hepatocellular carcinoma (HCC) treated using conventional transarterial chemoembolization (cTACE), compared to existing 1-dimensional and 2-dimensional methods (RECIST, mRECIST, EASL).Materials and MethodsIn this IRB-approved, single-institution retrospective cohort study, 52 consecutive patients with intermediate-stage HCC were consecutively included. All patients underwent contrast-enhanced CT scan at baseline and 4xa0weeks after cTACE.ResultsMedian follow-up period was 13.5xa0months (range 1.2–54.1). RECIST, mRECIST and EASL identified progression in 2 (4%), 1 (2%) and 1 (2%) patients, respectively, whereas qEASL identified 10 (19%) patients. qEASL was the only tumor response method able to predict survival among different tumor response groups (Pxa0<xa00.05), whereas RECIST, mRECIST and EASL did not (Pxa0>xa00.05). Both EASL and qEASL were able to identify responders and non-responders and were predictive of survival (Pxa0<xa00.05). Multivariate analysis showed that progression was an independent predictor of overall survival with hazard ratio of 1.9 (Pxa0=xa00.025). Patients who demonstrated progression with qEASL had significantly shorter survival than those with non-progression (7.6 vs. 20.4xa0months, Pxa0=xa00.012). Similar multivariate analysis using RECIST, mRECIST and EASL could not be performed because too few patients were categorized as progressive disease.ConclusionqEASL could be applied on CT images to assess tumor response following cTACE and is a more sensitive biomarker to predict survival and identify tumor progression than RECIST, mRECIST and EASL at an early time point.Level of EvidenceLevel 2a, retrospective cohort study.