MR Imaging Biomarkers for the Prediction of Outcome after Radiofrequency Ablation of Hepatocellular Carcinoma: Qualitative and Quantitative Assessments of the Liver Imaging Reporting and Data System and Radiomic Features

PurposeTo assess the Liver Imaging Reporting and Data System (LI-RADS) and radiomic features in pretreatment magnetic resonance (MR) imaging for predicting progression-free survival (PFS) in patients with nodular hepatocellular carcinoma (HCC) treated with radiofrequency (RF) ablation.Material and MethodsSixty-five therapy-naïve patients with 85 nodular HCC tumors <5 cm in size were included in this Health Insurance Portability and Accountability Act–compliant, institutional review board–approved, retrospective study. All patients underwent RF ablation as first-line treatment and demonstrated complete response on the first follow-up imaging. Gadolinium-enhanced MR imaging biomarkers were analyzed for LI-RADS features by 2 board-certified radiologists or by analysis of nodular and perinodular radiomic features from 3-dimensional segmentations. A radiomic signature was calculated with the most informative features of a least absolute shrinkage and selection operator Cox regression model using leave-one-out cross-validation. The association between both LI-RADS features and radiomic signatures with PFS was assessed via the Kaplan-Meier analysis and a weighted log-rank test.ResultsThe median PFS was 19 months (95% confidence interval, 16.1–19.4) for a follow-up period of 24 months. Multifocality (P = .033); the appearance of capsular continuity, compared with an absent or discontinuous capsule (P = .012); and a higher radiomic signature based on nodular and perinodular features (P = .030) were associated with poorer PFS in early-stage HCC. The observation size, presence of arterial hyperenhancement, nonperipheral washout, and appearance of an enhancing “capsule” were not associated with PFS (P > .05).ConclusionsAlthough multifocal HCC clearly indicates a more aggressive phenotype even in early-stage disease, the continuity of an enhancing capsule and a higher radiomic signature may add value as MR imaging biomarkers for poor PFS in HCC treated with RF ablation.     

Transarterial Radioembolization for Hepatic Metastases of Pancreatic Adenocarcinoma: A Systematic Review

PurposeTo assess the safety and effectiveness of transarterial radioembolization (TARE) in the treatment of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsA systematic search of the Embase and MEDLINE databases was conducted using keywords and Medical Subject Headings terms related to TARE and hepatic metastases from PDAC. Observational studies and clinical trials reporting overall survival (OS), hepatic progression-free survival (hPFS), or tumor response after TARE were included.ResultsEight studies, comprising 145 patients with metastatic PDAC, met the inclusion criteria. No randomized controlled trials were identified, and 4 studies were prospective. Forty-four (30.3%) patients underwent previous pancreatic resection, and 66 (45.5%) had extrahepatic metastases at the time of TARE. Most studies (n = 6) used resin microspheres for TARE. The pooled disease control rate was 69.4% at a median of 3 months. The median OS from the time of TARE ranged from 3.7 to 9 months. The median hPFS ranged from 2.4 to 5.2 months. There were 31 Grade 3–4 biochemical toxicities and 4 treatment-related deaths.ConclusionsThe role of TARE in patients with hepatic metastases from PDAC remains unclear owing to low patient numbers, limited prospective data, and heterogeneity in the study design. Further prospective studies are required to evaluate the role of TARE in carefully selected patients with liver-only metastatic disease.     

MR Imaging Volumetric Response after Yttrium-90 Radioembolization for Colorectal Liver Metastases: Predictability at Baseline and Correlation with Survival

PurposeTo prove the utility of magnetic resonance (MR) imaging response as a surrogate end point of treatment efficacy and survival after yttrium-90 transarterial radioembolization (TARE) for colorectal liver metastases (CRLMs), and to investigate whether outcomes can be predicted at baseline using MR imaging or clinical variables.Materials and MethodsA total of 50 (135) patients with TARE for CRLMs between August 2008 and January 2020 and peri-interventional MR imaging within defined timeframes were included for tumor segmentation. Pretreatment and posttreatment target tumor volumes were measured according to the volumetric Response Evaluation Criteria In Solid Tumors (vRECIST) and the quantitative European Association for the Study of the Liver (qEASL) criteria. Cox regression models were used to analyze the impact of MR morphologic response, vascularity at baseline, and clinical variables on patient survival. Logistic regression analyses were used to evaluate the predictors of MR morphologic response at baseline.ResultsThe median survival was 337 days (95% confidence interval [CI], 243–431). As opposed to the vRECIST, the application of the qEASL criteria 3 months after the treatment allowed for a significant (P < .05) separation of the survival curves for partial response, stable disease, and progressive disease with a median survival of 412 days (95% CI, 57–767) in responders. High tumor burden and technetium-99m lung shunt significantly decreased the probability of survival. MR morphologic response was not predictable at baseline using imaging or clinical data.ConclusionsMR response according to the qEASL criteria outperformed the vRECIST in measuring the biologic impact of TARE and predicting patient survival. Baseline contrast enhancement did not predict MR response to treatment, which may reflect elevated dose requirements in tumors with a high proportion of viable tumor volume.     

Transarterial Radioembolization for Hepatocellular Carcinoma with Major Vascular Invasion: A Nationwide Propensity Score–Matched Analysis with Target Trial Emulation

PurposeTo examine National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between patients undergoing transarterial radioembolization (TARE) and those undergoing systemic therapy for hepatocellular carcinoma with major vascular invasion (HCC-MVI).MethodsOne thousand five hundred fourteen patients with HCC-MVI undergoing first-line TARE or systemic therapy were identified from the NCDB. OS was compared using propensity score–matched Cox regression and landmark analysis. Efficacy was also compared within a target trial framework.ResultsTARE usage doubled between 2010 and 2015. Intervals before treatment were longer for TARE than for systemic therapy (mean [median], 66.5 [60] days vs 46.8 (35) days, respectively, P < .0001). In propensity-score–matched and landmark-time–adjusted analyses, TARE was found to be associated with a hazard ratio of 0.74 (95 % CI, 0.60–0.91; P = .005) and median OS of 7.1 months (95 % CI, 5.0–10.5) versus 4.9 months (95 % CI, 3.9–6.5) for systemically treated patients. In an emulated target trial involving 236 patients with unilobular HCC-MVI, a low number of comorbidities, creatinine levels <2.0 mg/dL, bilirubin levels <2.0 mg/dL, and international normalized ratio <1.7, TARE was found to be associated with a hazard ratio of 0.57 (95 % CI, 0.39–0.83; P = .004) and a median OS of 12.9 months (95 % CI, 7.6–19.2) versus 6.5 months (95 % CI, 3.6–11.1) for the systemic therapy arm.ConclusionsIn propensity-score–matched analyses involving pragmatic and target trial HCC-MVI cohorts, TARE was found to be associated with significant survival benefits compared with systemic therapy. Although not a substitute for prospective trials, these findings suggest that the increasing use of TARE for HCC-MVI is accompanied by improved OS. Further trials of TARE in patients with HCC-MVI are needed, especially to compare with newer systemic therapies.     

Radioembolization for Intermediate-Stage Hepatocellular Carcinoma Maintains Liver Function and Permits Systemic Therapy at Progression

PurposeTo assess the liver function trends in patients with intermediate-stage (Barcelona Clinic Liver Cancer [BCLC] Stage B) hepatocellular carcinoma (HCC) who underwent yttrium-90 transarterial radioembolization (TARE) in response to a growing concern that liver-directed therapies negatively affect liver function and prevent patients with HCC from systemic therapy candidacy.Materials and MethodsAn HCC/TARE database (2004–2017) was retrospectively reviewed. Patients with BCLC Stage B/Child–Pugh (CP)-A HCC with laboratory test and imaging data at baseline and for at least 1 month after TARE were included. Follow-ups were at 3-month intervals. CP stage was assessed at each time point. End points included time to persistent CP-B status, time to CP-C status, and median overall survival (OS). Time–to–end point analyses were performed using the Kaplan–Meier method.ResultsSeventy-four patients (80% men, with a mean age of 63 years) with mostly (62%) bilobar disease underwent 186 TARE treatments (median, 2; range, 1–8). The median time to second TARE was 2.3 months (range, 1.7–6.4 months), and the median times to third and fourth TAREs were 11.7 months (range, 7.5–15 months) and 17.3 months (range, 11.5–23.1 months), respectively. Forty-three (58%) patients developed persistent CP-B HCC at a median time of 15.4 months (95% CI, 9.2–25.3 months); 17 (23%) patients developed CP-C HCC at a median time of 87.2 months (95% CI, 39.8–136.1 months). The median OS censored to transplantation was 30.4 months (95% CI, 22.7–37.4 months). On univariate and multivariate analyses, baseline albumin was a significant prognosticator of OS, whereas baseline albumin and bilirubin were significant prognosticators of time to persistent CP-B HCC and time to CP-C HCC.ConclusionsIn patients with CP-A HCC who underwent TARE for BCLC Stage B HCC, the median time to persistent CP-B HCC was 15.4 months. These findings indicate that patients would be candidates for systemic therapy at progression if indicated.     

Chronic Hepatotoxicity in Patients with Metastatic Neuroendocrine Tumor: Transarterial Chemoembolization versus Transarterial Radioembolization

PurposeTo compare the manifestations of chronic liver injury following transarterial chemoembolization with those of transarterial radioembolization (TARE) in patients with neuroendocrine tumor (NET).Materials and MethodsThis study consisted of an Institutional Review Board-approved single-institution retrospective analysis of NET patients who received transarterial chemoembolization from 2006 to 2016 and TARE from 2005 to 2014 and survived at least 1 year from the initial treatment. Patients receiving only transarterial chemoembolization (n = 63) or TARE (n = 28) were evaluated for the presence or absence of durable hepatic toxicities occurring at least 6 months after initial treatment. The definitions and grades of liver injury were adapted from Common Terminology Criteria for Adverse Events version 4.0 and were characterized by the presence of laboratory or clinical toxicities of Grade 3 or above.ResultsChronic hepatic toxicity occurred in 14 of 63 transarterial chemoembolization patients (22%) with a total of 26 Grade 3-4 events, in whom elevation of bilirubin was the most common toxicity, compared to 8 of 28 TARE patients (29%) with a total of 16 Grade 3-4 and 2 Grade 5 events, in whom ascites were the most frequent toxicity. There were more laboratory toxicities in the transarterial chemoembolization group (65% vs 38%, P = .11) and fewer Grade 4–5 injuries (6% vs 27% of patients, P = .06). There was also a significantly higher number of patients who experienced intrahepatic progression of disease in the transarterial chemoembolization cohort than in the TARE patients (75% vs 43%, respectively; P = .005).ConclusionsDelayed hepatotoxicity from transarterial chemoembolization and TARE occurred in 22% and 29% of patients, respectively, from 6 months to several years following treatment. Transarterial chemoembolization-related toxicities on average were less severe and manifested primarily as laboratory derangements, compared to TARE toxicities which consisted of clinical hepatic decompensation.     

Machine learning to identify lymph node metastasis from thyroid cancer in patients undergoing contrast-enhanced CT studies

IntroductionWe compared the diagnostic performance of morphological methods such as the major axis, the minor axis, the volume and sphericity and of machine learning with texture analysis in the identification of lymph node metastasis in patients with thyroid cancer who had undergone contrast-enhanced CT studies.MethodsWe sampled 772 lymph nodes with histology defined tissue types (84 metastatic and 688 benign lymph nodes) that were visualised on CT images of 117 patients. A support vector machine (SVM), free programming software (Python), and the scikit-learn machine learning library were used to discriminate metastatic-from benign lymph nodes. We assessed 96 texture and 4 morphological features (major axis, minor axis, volume, sphericity) that were reported useful for the differentiation between metastatic and benign lymph nodes on CT images. The area under the curve (AUC) obtained by receiver operating characteristic analysis of univariate logistic regression and SVM classifiers were calculated for the training and testing datasets.ResultsThe AUC for all classifiers in training and testing datasets was 0.96 and 0.86, at the SVM for machine learning. When we applied conventional methods to the training and testing datasets, the AUCs were 0.63 and 0.48 for the major axis, 0.70 and 0.44 for the minor axis, 0.66 and 0.43 for the volume, and 0.69 and 0.54 for sphericity, respectively. The SVM using texture features yielded significantly higher AUCs than univariate logistic regression models using morphological features (p = 0.001).ConclusionFor the identification of metastatic lymph nodes from thyroid cancer on contrast-enhanced CT images, machine learning combined with texture analysis was superior to conventional diagnostic methods with the morphological parameters.Implications for practiceOur findings suggest that in patients with thyroid cancer and suspected lymph node metastasis who undergo contrast-enhanced CT studies, machine learning using texture analysis is high diagnostic value for the identification of metastatic lymph nodes.     

Transarterial Radioembolization Treatment of Pancreatic Cancer Patients with Liver-Dominant Metastatic Disease Using Yttrium-90 Glass Microspheres: A Single-Institution Retrospective Study

PurposeTo retrospectively evaluate the safety and efficacy of transarterial radioembolization (TARE) with yttrium-90 (⁹⁰Y)-labeled glass microspheres in pancreatic adenocarcinoma patients with liver-dominant metastatic disease.Materials and MethodsThis retrospective, single-center study evaluated 26 patients (12 men and 14 women; mean age, 65.5 ± 11.2 years) with liver-dominant metastatic pancreatic cancer who were treated with TARE from April 2010 to September 2017. All patients received systemic chemotherapy before TARE, and 19 received systemic therapy after embolization. Nineteen patients had extrahepatic disease at the time of TARE. Response to treatment was determined by Response Evaluation Criteria in Solid Tumors at 3 months.ResultsMedian overall survival (OS) from pancreatic cancer diagnosis was 33.0 months (range, 8.5–87.5 months); median OS from diagnosis of liver metastasis was 21.8 months (range, 2.0–86.2 months); and median OS from TARE treatment was 7.0 months (range, 1.0–84.1 months). Grade 1–2 clinical toxicities were noted in 21 patients (80.8%), and 24 patients (92.3%) had grade 1–2 biochemical toxicities. Four patients (15.4%) had grade 3 clinical toxicities, and 6 patients (23.1%) had grade 3 biochemical toxicities. Imaging was available in 22 patients (84.6%) and demonstrated partial response in 1 patient, stable disease in 9 patients, and progressive disease in 12 patients. Improved hepatic progression-free survival was associated in patients younger than 65 years and in those whose carbohydrate antigen 19-9 level decreased or remained stable after treatment.ConclusionsTARE with ⁹⁰Y-labeled glass microspheres is safe and led to promising OS in liver-dominant metastatic pancreatic cancer.     

Socioeconomic and Survival Analysis of Radioembolization in Patients with Intrahepatic Cholangiocarcinoma: A Propensity Score–Adjusted Study

PurposeTo determine whether transarterial radioembolization (TARE) is associated with longer survival of patients with intrahepatic cholangiocarcinoma (ICC) and whether access to TARE is influenced by socioeconomic factors.Materials and MethodsRetrospective review of patients with ICC in the National Cancer Database from 2004 to 2018 was performed with Cox regression analysis to identify predictors of survival. Overall survival (OS) was estimated using the Kaplan-Meier method. Socioeconomic factors were compared between 2 groups using the Wilcoxon rank-sum test and χ² test. Propensity score–matched cohorts were created between patients with ICC who did and did not undergo TARE.ResultsThe number of patients receiving TARE for ICC increased over time from 1 in 2004 to 210 in 2018. Patients in the TARE group were more likely to be White (87.9% vs 84.3%; P = .012) and less likely to be Hispanic/Latino (7.7% vs 11.0%; P = .009). Fewer patients who underwent TARE were uninsured (0.9% vs 2.8%; P = .012). Older age, male sex, non-White race, higher tumor grade size, and stage, earlier year of diagnosis, lack of treatment with surgery or systemic therapy, and presence of lymphatic or vascular invasion exhibited significant associations with decreased survival (P < .05 for all). Patients who underwent TARE had longer survival in both unadjusted and adjusted cohorts, with an OS of 17.5 months (vs 7.2 months in the non-TARE group) after propensity matching.ConclusionsPatients with ICC who had undergone TARE experienced significantly longer survival than that experienced by those who had not after adjusting for measurable confounders. Significant socioeconomic disparities in access to TARE remain.     

Machine Learning Offers Exciting Potential for Predicting Postprocedural Outcomes: A Framework for Developing Random Forest Models in IR

PurposeTo demonstrate that random forest models trained on a large national sample can accurately predict relevant outcomes and may ultimately contribute to future clinical decision support tools in IR.Materials and MethodsPatient data from years 2012–2014 of the National Inpatient Sample were used to develop random forest machine learning models to predict iatrogenic pneumothorax after computed tomography–guided transthoracic biopsy (TTB), in-hospital mortality after transjugular intrahepatic portosystemic shunt (TIPS), and length of stay > 3 days after uterine artery embolization (UAE). Model performance was evaluated with area under the receiver operating characteristic curve (AUROC) and maximum F1 score. The threshold for AUROC significance was set at 0.75.ResultsAUROC was 0.913 for the TTB model, 0.788 for the TIPS model, and 0.879 for the UAE model. Maximum F1 score was 0.532 for the TTB model, 0.357 for the TIPS model, and 0.700 for the UAE model. The TTB model had the highest AUROC, while the UAE model had the highest F1 score. All models met the criteria for AUROC significance.ConclusionsThis study demonstrates that machine learning models may suitably predict a variety of different clinically relevant outcomes, including procedure-specific complications, mortality, and length of stay. Performance of these models will improve as more high-quality IR data become available.     

Toxicity and Survival of Hepatocellular Carcinoma Patients with Hepatitis B Infection Treated with Yttrium-90 Radioembolization: An Updated 15-Year Study

PurposeTo evaluate the toxicity and survival of hepatocellular carcinoma (HCC) secondary to hepatitis B virus (HBV) infection treated with yttrium-90 transarterial radioembolization (TARE) over a 15-year period.Materials and MethodsThis study retrospectively analyzed 93 consecutive patients with HBV HCC—all derived from an original cohort of 1,000 patients—who were treated with TARE via standard radiation segmentectomy/lobectomy between December 2003 and December 2018. This group comprised 80 males and 13 females, with 79 having only HBV and 14 having additional liver comorbidities. Toxicity grades were determined by Common Terminology Criteria for Adverse Events, version 5.0. Overall survival (OS) was reported using intention-to-treat (ITT), censored, or competing risk. Univariate/multivariate analyses were used to evaluate predictors of OS.ResultsPosttreatment grade 3/4 toxicities included albumin (1.1%), bilirubin (4.3%), aspartate transaminase (6.5%), and alanine transaminase (3.2%). Median censored OS was 16.9 months (95% confidence interval [CI], 11.8–23.5): 17.5 months (95% CI, 11.5–86.9) for Child-Pugh (CP) A and 14.5 months (95% CI, 5.2–22.5) for CP B; not reached, 16.9 months (95% CI, 11.2–68.7), and 11.5 months (95% CI, 8.6–17.5) for Barcelona Clinic Liver Cancer (BCLC) A, B, and C, respectively. Multivariate analysis revealed albumin, alpha-fetoprotein, and portal vein thrombosis as independent predictors of ITT OS and albumin and tumor size as predictors when curative therapy was assigned as a competing risk.ConclusionsThis retrospective study showed that TARE therapy resulted in minimal toxicity in patients with HBV-derived HCC. Patients with CP A or BCLC A disease had superior survival outcomes compared to patients with CP B and BCLC B/C disease. These findings suggest that TARE is a viable treatment option for certain patient groups with HCC tumors secondary to HBV infection.     

Induction of Contralateral Hepatic Hypertrophy by Unilobar Yttrium-90 Transarterial Radioembolization versus Portal Vein Embolization: An Animal Study

PurposeTo compare hepatic hypertrophy in the contralateral lobe achieved by unilobar transarterial radioembolization (TARE) versus portal vein embolization (PVE) in a swine model.MethodsAfter an escalation study to determine the optimum dose to achieve hypertrophy after unilobar TARE in 4 animals, 16 pigs were treated by TARE (yttrium-90 resin microspheres) or PVE (lipiodol/n-butyl cyanoacrylate). Liver volume was calculated based on CT before treatment and during 6 months of follow-up. Independent t-test (P < .05) was used to compare hypertrophy. The relationship between hypertrophy after TARE and absorbed dose was calculated using the Pearson correlation.ResultsAt 2 and 4 weeks after treatment, a significantly higher degree of future liver remnant hypertrophy was observed in the PVE group versus the TARE group, with a median volume gain of 31% (interquartile range [IQR]: 16%–66%) for PVE versus 23% (IQR: 6%–36%) for TARE after 2 weeks and 51% (IQR: 47%–69%) for PVE versus 29% (IQR: 20%–50%) for TARE after 4 weeks. After 3 and 6 months, hypertrophy converged without a statistically significant difference, with a volume gain of 103% (IQR: 86%–119%) for PVE versus 82% (IQR: 70%–96%) for TARE after 3 months and 115% (IQR: 70%–46%) for PVE versus 86% (IQR: 58%–111%) for TARE after 6 months. A strong correlation was observed between radiation dose (median 162 Gy, IQR: 139–175) and hypertrophy.ConclusionsPVE resulted in rapid hypertrophy within 1 month of the procedure, followed by a plateau, whereas TARE resulted in comparable hypertrophy by 3–6 months. TARE-induced hypertrophy correlated with radiation absorbed dose.     

Effect of image reconstruction algorithms on volumetric and radiomic parameters of coronary plaques

BackgroundVolumetric and radiomic analysis of atherosclerotic plaques on coronary CT angiography have been shown to predict high-risk plaque morphology and to predict patient outcomes. However, there is limited information whether image reconstruction algorithms and preprocessing steps (type of binning, number of bins used for discretization) may influence parameter values.MethodsWe retrospectively identified 60 coronary lesions on coronary CT angiography (CTA). All images were reconstructed using filtered back projection (FBP), hybrid (HIR) and model-based (MIR) iterative reconstruction. Plaques were segmented manually on HIR images and copied to FBP and MIR images to ensure identical voxels were analyzed. Overall, 4 volumetric and 169 radiomic parameters were calculated. Intra-class correlation coefficient (ICC) was used to assess reproducibility between image reconstructions, while linear regression analysis was used to assess the effect of preprocessing steps done before calculating radiomic metrics.ResultsAll volumetric and radiomic metrics had ICC>0.90 except for first-order statistics: mode, harmonic mean, minimum (0.45, 0.76, 0.84; respectively) and gray level co-occurrence (GLCM) parameters: inverse difference sum and sum variance (0.01, 0.04; respectively). Among GLCM parameters 90% were significantly affected by the type of binning and 100% by the number of bins. In case of gray level run length matrix parameters 100% of metrics were affected by both preprocessing steps.ConclusionsVolumetric and radiomic statistics are robust to image reconstruction algorithms. However, all radiomic variables were affected by preprocessing steps therefore, showing the need for standardization before being implemented into everyday clinical practice.     

Safety and Efficacy of Arterially Directed Liver Therapies in the Treatment of Hepatic Metastatic Ovarian Cancer: A Retrospective Single-Institution Study

PurposeTo evaluate the safety and efficacy of 2 locoregional therapies (LRTs) including hepatic artery embolization (HAE) and transarterial radioembolization (TARE) in the treatment of patients with metastatic ovarian cancer to the liver.Material and MethodsFrom October 2010 to May 2019, the data of 15 consecutive patients (median age, 54 years ± 9.8; range, 35–78 years) with hepatic metastatic ovarian cancer who were treated with either HAE (n = 6; 40%) or TARE (n = 9; 60%) were reviewed. The most common histopathologic type was epithelial ovarian carcinoma (80%). The most common chemotherapy regimens used prior to embolization included carboplatin, paclitaxel, cisplatin, and bevacizumab. Patients received a mean of 4 lines ± 3 (range, 1–9) of chemotherapy. All patients with serous carcinoma were resistant to platinum at the time of embolization. Indications for embolization were progression of disease to the liver while receiving chemotherapy in 14 (93.3%) patients and palliative pain control in 1 patient.ResultsThe overall response rates at 1, 3, and 6 months were 92.4%, 85.6%, and 70%, respectively. Median overall survival from the time of LRT was 9 (95% confidence interval [CI], 4–14) months. Median local tumor progression was 6.4 months ± 5.03 (95% CI, 3.3–9.5). No grade 3–5 adverse events were detected in either group.ConclusionsHAE and TARE were well tolerated in patients with metastatic ovarian cancer to the liver and possibly ensured prolonged disease control in heavily treated, predominantly in patients resistant to platinum. Larger numbers are needed to verify these data.     

Transarterial Radioembolization versus Transarterial Chemoembolization Plus Percutaneous Ablation for Unresectable,Solitary Hepatocellular Carcinoma of ≥3 cm: A Propensity Score–Matched Study

PurposeTo compare the safety and effectiveness of transarterial radioembolization (TARE) and transarterial chemoembolization with drug-eluting embolic agents combined with percutaneous ablation (transarterial chemoembolization [TACE] + ablation) in the treatment of treatment-naïve, unresectable, solitary hepatocellular carcinoma (HCC) of ≥3 cm.Materials and MethodsTwenty-nine patients with treatment-naïve, unresectable, solitary HCC of ≥3 cm received combined TACE + ablation, and 40 patients received TARE at a single institution. Local tumor response, tumor progression-free survival (PFS), overall survival, need for reintervention, bridge to transplant, and major complications were compared. Clinical variables and outcomes were compared before and after propensity score matching (PSM).ResultsBefore PSM, patients who underwent TARE had a larger tumor size (3.7 vs 5.5 cm; P = .0005) and were older (61.5 vs 69.3 years; P = .0014). After PSM, there was no difference in baseline characteristics between the 2 groups, with the mean tumor sizes measuring 3.9 and 4.1 cm in the TACE + ablation and TARE cohorts, respectively. After PSM (n = 19 in each group), no statistically significant difference was observed in local radiological response (disease control rates, 100% vs 94.7%; P = .31), survival (subdistribution hazard ratio [SHR], 0.71; 95% confidence interval [CI], 0.28–1.80; P = .469), PFS (SHR, 0.61; 95% CI, 0.21–1.71; P = .342), bridge to transplant (21.1% vs 31.6%, P = .46), and major adverse event rates (15.8% vs 10.5%, P = .63) between the 2 groups. The mean total number of locoregional interventions was higher in the TACE + ablation cohort (1.9 vs 1.3 sessions, P = .02), with an earlier median reintervention trend (SHR, 0.61; 95% CI, 0.20–1.32; P = .167).ConclusionsThe present study showed that TARE and the combination of TACE and ablation are comparable in safety and effectiveness for treating treatment-naïve, unresectable, solitary HCC of ≥3 cm.     

Multicenter Evaluation of Survival and Toxicities of Hepatocellular Carcinoma following Radioembolization: Analysis of the RESiN Registry

PurposeTo determine overall survival (OS), progression-free survival (PFS), and toxicity in patients with hepatocellular carcinoma (HCC) in a multicenter, real-world data registry using transarterial radioembolization (TARE) with resin microspheres.Materials and MethodsA total of 448 patients with HCC were treated at 36 centers between 2015 and 2019. Treatment history, baseline laboratory and imaging, and treatment goal were assessed. OS and PFS were stratified using Barcelona Clinic Liver Cancer (BCLC) and Child-Pugh (CP) classifications. Kaplan-Meier analyses compared OS and PFS with 95% confidence intervals. Transplants were tracked. Toxicities were assessed using Common Terminology Criteria for Adverse Events v5. Cox proportional hazard of baseline demographics assessed factors affecting survival.ResultsPrior chemoembolization and systemic therapy were used in 107 (26%) and 68 (16%) patients, respectively. Using the BCLC staging system, 66 patients (19%) were BCLC A and 202, 51, and 26 were BCLC B, C, and D, respectively. Median OS for patients with BCLC A disease was not achieved at 30 months. Median OS for patients with BCLC B, C, and D disease were 19.5, 13.6, and 11.5 months, respectively (P = .0006). Median PFS for patients with BCLC A, B, C, and D were 19.8, 10.0, 6.3, and 5.9 months, respectively (P = .003). Twenty patients underwent transplantation, representing 14 of 43 (33%) and 6 of 28 (21%) patients who underwent bridging and downstaging therapy, respectively. Common Grade 3 toxicities were encephalopathy (11/448, 2.5%), hyperbilirubinemia (10/448, 2.2%), and ascites (9/448, 2.0%). Factors predicting longer survival included CP A (χ² = 4.2, P = .04) and BCLC A (χ² = 5.2, P = .02).ConclusionsIn a frequently pretreated patient cohort with disease burden in 81% beyond the Milan criteria, TARE with resin microspheres provided OS comparable to other studies in this multicenter registry.     

Evaluation of an Integrated Spectroscopy and Classification Platform for Point-of-Care Core Needle Biopsy Assessment: Performance Characteristics from Ex Vivo Renal Mass Biopsies

PurposeTo evaluate a transmission optical spectroscopy instrument for rapid ex vivo assessment of core needle cancer biopsies (CNBs) at the point of care.Materials and MethodsCNBs from surgically resected renal tumors and nontumor regions were scanned on their sampling trays with a custom spectroscopy instrument. After extracting principal spectral components, machine learning was used to train logistic regression, support vector machines, and random decision forest (RF) classifiers on 80% of randomized and stratified data. The algorithms were evaluated on the remaining 20% of the data set held out during training. Binary classification (tumor/nontumor) was performed based on a decision threshold. Multinomial classification was also performed to differentiate between the subtypes of renal cell carcinoma (RCC) and account for potential confounding effects from fat, blood, and necrotic tissue. Classifiers were compared based on sensitivity, specificity, and positive predictive value (PPV) relative to a histopathologic standard.ResultsA total of 545 CNBs from 102 patients were analyzed, yielding 5,583 spectra after outlier exclusion. At the individual spectra level, the best performing algorithm was RF with sensitivities of 96% and 92% and specificities of 90% and 89%, for the binary and multiclass analyses, respectively. At the full CNB level, RF algorithm also showed the highest sensitivity and specificity (93% and 91%, respectively). For RCC subtypes, the highest sensitivity and PPV were attained for clear cell (93.5%) and chromophobe (98.2%) subtypes, respectively.ConclusionsEx vivo spectroscopy imaging paired with machine learning can accurately characterize renal mass CNB at the time of tissue acquisition.     

Alpha-Fetoprotein,Des-Gamma-Carboxy Prothrombin,and Modified RECIST Response as Predictors of Survival after Transarterial Radioembolization for Hepatocellular Carcinoma

PurposeTo evaluate the prognostic role of alpha-fetoprotein (AFP), des-gamma-carboxy protein (DCP), and modified Response Evaluation Criteria in Solid Tumors (mRECIST) in patients with hepatocellular carcinoma after transarterial radioembolization (TARE).Materials and MethodsDuring 2009–2016, 63 patients with AFP >20 ng/mL, DCP >20 mAU/mL, and Child-Pugh class A who were treated with TARE were evaluated using landmark and risk-of-death method after TARE. Both resin microspheres (n = 46) and glass microspheres (n = 17) were used. AFP or DCP response was defined as more than 50% decrease from baseline. mRECIST response was defined as complete or partial response. Median age was 60 years, and the proportion of male sex was 77.8% (n = 49). The proportions of patients with Barcelona Clinic Liver Cancer stages A, B, and C were 7.9% (n = 5), 46.0% (n = 29), and 46.0% (n = 29), respectively.ResultsAt the 3-month landmark, AFP, DCP, and mRECIST responders lived longer than nonresponders (median overall survival, 75.8 vs 7.6 months for AFP; 75.8 vs 7.1 months for DCP; and 75.8 vs 10.0 months for mRECIST; all P < .05). The 6-month risk of death at the 3-month landmark was statistically different only between DCP responders and nonresponders (P = .002). In multivariate analysis, age less than 70 years (P = .024), absence of distant metastasis (P = .049), DCP response (P = .003), and mRECIST response (P = .003) were independent predictors for overall survival at the 3-month landmark after TARE.ConclusionsAFP, DCP, and mRECIST responders showed better prognosis than nonresponders after TARE, and DCP response was a more potent predictor than AFP response. Tumor marker response, as well as radiologic response, may be useful to predict post-TARE survival.     

Cost-Effectiveness Analysis of Interventional Liver-Directed Therapies for a Single,Small Hepatocellular Carcinoma in Liver Transplant Candidates

PurposeTo assess the cost effectiveness of 3 main locoregional therapies (LRTs) (transarterial chemoembolization [TACE], transarterial radioembolization [TARE], and percutaneous ablation) as bridging therapy.Materials and MethodsA cost-effectiveness analysis was performed comparing the 3 LRTs for patients with a single hepatocellular carcinoma (HCC) with a diameter of 3 cm or less over a 5-year time horizon from a payer’s perspective. The clinical courses, including transplantation, decompensation resulting in delisting, and the need for a second LRT, were based on data from the United Network for Organ Sharing (2016–2019). Costs and effectiveness were measured in U.S. dollars and quality-adjusted life-years, respectively. Probabilistic and deterministic sensitivity analyses were performed.ResultsA total of 2,594, 1,576, and 903 patients underwent TACE, ablation, and TARE, respectively. Ablation was the dominant strategy, with the lowest expected cost and highest effectiveness. The probabilistic sensitivity analysis demonstrated that ablation was the most cost-effective strategy in 93.9% of simulations. A subgroup analysis was performed for different wait times, with ablation remaining the most cost-effective strategy. The sensitivity analysis showed that ablation was most effective if the risk of waitlist dropout was less than 2.00% and the rate of transplantation was more than 15.1% quarterly. TARE was most effective if the risk of dropout was less than 1.19% and the rate of transplantation was more than 24.0%. TACE was most effective if the risk of dropout was less than 1.01% and the rate of transplantation was more than 45.7%. Ablation remained the most cost-effective modality until its procedural cost was more than $34,843.ConclusionsAblation is the most cost-effective bridging strategy for patients with a single, small (≤3 cm) HCC prior to liver transplantation. The conclusion remained robust in multiple sensitivity analyses.     

Yttrium-90 Radioembolization and Concomitant Systemic Gemcitabine,Cisplatin, and Capecitabine as the First-Line Therapy for Locally Advanced Intrahepatic Cholangiocarcinoma

PurposeTo determine the safety and effectiveness of yttrium-90 transarterial radioembolization (TARE) combined with systemic gemcitabine, cisplatin, and capecitabine for the first-line treatment of locally advanced intrahepatic cholangiocarcinoma (iCCA).Materials and MethodsData of 13 patients with treatment-naïve, locally advanced iCCA treated with a downstaging protocol using gemcitabine, cisplatin, TARE, and capecitabine were retrospectively reviewed. Overall survival (OS), local tumor response (modified Response Evaluation Criteria in Solid Tumors), progression-free survival (PFS), technical adverse events, and toxicity were measured.ResultsCalculated from the time of diagnosis, the median OS was 29 months (95% confidence interval [CI], 15 to not reached), with a 1-year OS of 84.6% (95% CI, 52.2%–95.9%) and 2-year OS of 52.9% (95% CI, 20.3%–77.5%). The median OS values were 24 months (95% CI, 8 to not reached) and 21 months (95% CI, 5 to not reached) from the time of initial cycle of chemotherapy and TARE, respectively. Patients who were downstaged to surgery (n = 7, 53.8%) had a more favorable OS (median OS, not reached vs 15 months; P = .0221). Complete and partial radiologic responses were achieved in 5 (38.5%) and 6 (46.2%) patients, respectively. The median PFS was 13 months (95% CI, 12 to not reached). Although no serum toxicity with Grade >2 occurred within 3 months after TARE, 1 patient was no longer a surgical candidate given suboptimal nutrition status despite successful downstage on imaging studies. Two patients required a reduced dose or delay of post-TARE chemotherapy.ConclusionsFirst-line combination therapy with TARE and systemic gemcitabine, cisplatin, and capecitabine is an effective treatment with an acceptable safety profile for iCCA with a high rate of downstaging to resection.