Ahmed Gabr

Independent Analysis of Albumin-Bilirubin Grade in a 765-Patient Cohort Treated with Transarterial Locoregional Therapy for Hepatocellular Carcinoma.

PURPOSE To assess validity of albumin-bilirubin (ALBI) grade as a predictor of survival in patients undergoing transarterial embolization for hepatocellular carcinoma. MATERIALS AND METHODS Baseline albumin and bilirubin values of 765 consecutive patients treated with conventional transarterial chemoembolization or yttrium-90 ((90)Y) radioembolization at a single institution were used to determine liver function according to ALBI grade. Survival outcomes were stratified by ALBI grade using Kaplan-Meier and stratified by Child-Pugh (C-P) class and Barcelona Clinic Liver Cancer (BCLC) stage. Discriminatory ability was assessed by C-index. RESULTS For 428 patients receiving (90)Y radioembolization, ALBI grade yielded distinct survival curves (P < .001). When stratified by C-P class and BCLC stage, ALBI grade revealed different survival outcomes for C-P B (P = .001), BCLC A (P < .001), BCLC B (P = .001), and BCLC C (P < .001). When substratified by BCLC stage, ALBI grade was a better discriminator of survival than C-P class (C-index 0.792, 0.763, respectively). For 337 patients receiving transarterial chemoembolization, ALBI grade yielded distinct survival curves (P < .001). When stratified by C-P class and BCLC stage, ALBI grade provided distinct survival curves for C-P B (P = .02), BCLC B (P = .001), and BCLC C (P = .02). When substratified by BCLC stage, ALBI grade was a better discriminator of survival than C-P class (C-index 0.739, 0.735, respectively). CONCLUSIONS ALBI grade outperforms C-P class at discriminating survival in patients receiving transarterial chemoembolization or (90)Y radioembolization. ALBI grade is also valuable in patients with moderate liver dysfunction and BCLC B disease.

90Y Radioembolization of Colorectal Hepatic Metastases Using Glass Microspheres: Safety and Survival Outcomes from a 531-Patient Multicenter Study

Hepatic metastases of colorectal carcinoma are a leading cause of cancer-related mortality. Most colorectal liver metastases become refractory to chemotherapy and biologic agents, at which point the median overall survival declines to 4–5 mo. Radioembolization with 90Y has been used in the salvage setting with favorable outcomes. This study reports the survival and safety outcomes of 531 patients treated with glass-based 90Y microspheres at 8 institutions, making it the largest 90Y study for patients with colorectal liver metastases. Methods: Data were retrospectively compiled from 8 institutions for all 90Y glass microsphere treatments for colorectal liver metastases. Exposure to chemotherapeutic or biologic agents, prior liver therapies, biochemical parameters before and after treatment, radiation dosimetry, and complications were recorded. Uni- and multivariate analyses for predictors of survival were performed. Survival outcomes and clinical or biochemical adverse events were recorded. Results: In total, 531 patients received 90Y radioembolization for colorectal liver metastases. The most common clinical adverse events were fatigue (55%), abdominal pain (34%), and nausea (19%). Grade 3 or 4 hyperbilirubinemia occurred in 13% of patients at any time. The median overall survival from the first 90Y treatment was 10.6 mo (95% confidence interval, 8.8–12.4). Performance status, no more than 25% tumor burden, no extrahepatic metastases, albumin greater than 3 g/dL, and receipt of no more than 2 chemotherapeutic agents independently predicted better survival outcomes. Conclusion: This multiinstitutional review of a large cohort of patients with colorectal liver metastases treated with 90Y radioembolization using glass microspheres has demonstrated promising survival outcomes with low toxicity and low side effects. The outcomes were reproducible and consistent with prior reports of radioembolization.

Hepatic imaging following intra-arterial embolotherapy

PurposeTo discuss guidelines and salient imaging findings of solid tumors treated with common intra-arterial procedures used in interventional oncology.MethodsA meticulous literature search of PubMed-indexed articles was conducted. Key words included “imaging + embolization,” “imaging + TACE,” “imaging + radioembolization,” “imaging + Y90,” “mRECIST,” and “EASL.” Representative post-treatment cross-sectional images were obtained from past cases in this institution.ResultsIntra-arterial therapy (IAT) in interventional oncology includes bland embolization, chemoembolization, and radioembolization. Solid tumors of the liver are the primary focus of these procedures. Cross-sectional CT and/or MR are the main modalities used to image tumors after treatment. Traditional size-based response criteria (WHO and RECIST) alone are of limited utility in determining response to IAT; tumoral necrosis and enhancement must be considered. Specifically for HCC, the EASL and mRECIST guidelines are becoming widely adopted response criteria to assess these factors. DWI, FDG-PET, and CEUS are modalities that play an adjunctive but controversial role.ConclusionsRadiologists must be aware that the different forms of intra-arterial therapy yield characteristic findings on cross-sectional imaging. Knowledge of these findings is integral to accurate assessment of tumor response and progression.

Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience

Yttrium‐90 transarterial radioembolization (TARE) is a locoregional therapy (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall survival (OS) outcomes in a 1,000‐patient cohort acquired over a 15‐year period. Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated with TARE as part of a prospective cohort study. A comprehensive review of toxicity and survival outcomes was performed. Outcomes were stratified by baseline Child‐Pugh (CP) class, United Network for Organ Sharing (UNOS), and Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin laboratory toxicities were compared to baseline. OS outcomes were reported using censoring and intention‐to‐treat methodologies. All treatments were outpatient, with a median one treatment per patient. Five hundred six (51%) were CP A, 450 (45%) CP B, and 44 (4%) CP C. Two hundred sixty‐three (26%) patients were BCLC A, 152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty‐eight (37%) were UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5‐80.3) months, BCLC B 25.0 (CI, 17.3‐30.5) months, and BCLC C 15.0 (CI, 13.8‐17.7) months. In CP B patients, censored OS for BCLC A was 27 (CI, 21‐30.2) months, BCLC B 15.0 (CI, 12.3‐19.0) months, and BCLC C 8.0 (CI, 6.8‐9.5) months. Forty‐nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin toxicities, respectively. Conclusion: Based on our experience with 1,000 patients over 15 years, we have made a decision to adopt TARE as the first‐line transarterial LRT for patients with HCC. Our decision was informed by prospective data and incrementally reported demonstrating outcomes stratified by BCLC, applied as either neoadjuvant or definitive treatment. (Hepatology 2017).

Radioembolization for hepatocellular carcinoma: Statistical confirmation of improved survival in responders by landmark analyses

Does imaging response predict survival in hepatocellular carcinoma (HCC)? We studied the ability of posttherapeutic imaging response to predict overall survival. Over 14 years, 948 patients with HCC were treated with radioembolization. Patients with baseline metastases, vascular invasion, multifocal disease, Child‐Pugh > B7, and transplanted/resected were excluded. This created our homogeneous study cohort of 134 patients with Child‐Pugh ≤ B7 and solitary HCC. Response (using European Association for Study of the Liver [EASL] and Response Evaluation Criteria in Solid Tumors 1.1 [RECIST 1.1] criteria) was associated with survival using Landmark and risk‐of‐death methodologies after reviewing 960 scans. In a subanalysis, survival times of responders were compared to those of patients with stable disease (SD) and progressive disease (PD). Uni/multivariate survival analyses were performed at each Landmark. At the 3‐month Landmark, responders survived longer than nonresponders by EASL (hazard ratio [HR], 0.46; confidence interval [CI], 0.26‐0.82; P = 0.002) but not RECIST 1.1 criteria (HR, 0.70; CI, 0.37‐1.32; P = 0.32). At the 6‐month Landmark, responders survived longer than nonresponders by EASL (HR, 0.32; CI, 0.15‐0.77; P < 0.001) and RECIST 1.1 criteria (HR, 0.50; CI, 0.29‐0.87; P = 0.021). At the 12‐month Landmark, responders survived longer than nonresponders by EASL (HR, 0.34; CI, 0.15‐0.77; P <  0.001) and RECIST 1.1 criteria (HR, 0.52; CI 0.27‐0.98; P = 0.049). At 6 months, risk of death was lower for responders by EASL (P <  0.001) and RECIST 1.1 (P = 0.0445). In subanalyses, responders lived longer than patients with SD or PD. EASL response was a significant predictor of survival at 3‐, 6‐, and 12‐month Landmarks on uni/multivariate analyses. Conclusion: Response to radioembolization in patients with solitary HCC can prognosticate improved survival. EASL necrosis criteria outperformed RECIST 1.1 size criteria in predicting survival. The therapeutic objective of radioembolization should be radiologic response and not solely to prevent progression. (Hepatology 2018;67:873–883)

Single- versus Triple-Drug Chemoembolization for Hepatocellular Carcinoma: Comparing Outcomes by Toxicity, Imaging Response, and Survival

PURPOSE To determine the efficacy of single- versus triple-drug chemoembolization for the treatment of hepatocellular carcinoma, as measured by toxicity, tumor response, time to progression (TTP), and overall survival (OS). MATERIALS AND METHODS A single-center retrospective review was performed on 337 patients who underwent chemoembolization over a 14-year period; 172 patients underwent triple-drug conventional transarterial chemoembolization, and 165 patients underwent single-agent doxorubicin chemoembolization. Imaging characteristics and clinical follow-up after conventional transarterial chemoembolization were evaluated to determine TTP. Imaging response was determined per World Health Organization and European Association for the Study of Liver criteria. OS from time of first chemoembolization was calculated. RESULTS Median TTP was similar between groups: 7.9 months (95% confidence interval [CI], 7.1-9.4) and 6.8 months (95% CI, 4.6-8.6) for triple- and single-drug regimens, respectively (P > .05). For single-agent conventional transarterial chemoembolization, median OS varied significantly by Barcelona Clinic for Liver Cancer (BCLC) stage: A, 40.8 months; B, 36.4 months; C, 10.9 months (P < .01). Median OS for triple-drug therapy also varied significantly by BCLC: A, 28.9 months; B, 18.1 months; C, 9.0 months (P < .01). Single-drug conventional transarterial chemoembolization demonstrated longer median OS compared with triple-drug therapy (P < .05) for BCLC A/B patients. CONCLUSIONS Single-agent chemoembolization with doxorubicin and ethiodized oil demonstrates acceptable efficacy as measured by TTP and OS. Results compare favorably with traditional triple-drug therapy.

Angiogenic Response following Radioembolization: Results from a Randomized Pilot Study of Yttrium-90 with or without Sorafenib

PURPOSE To compare the regulation of serum angiogenic factors in patients with unresectable early hepatocellular carcinoma (HCC) treated with yttrium-90 ((90)Y) radioembolization alone vs with sorafenib. MATERIALS AND METHODS In a single-center pilot study, 23 patients with unresectable HCC awaiting orthotopic liver transplantation were prospectively randomized to receive radioembolization alone (n = 12) or radioembolization with sorafenib (n = 11). Serum angiogenic markers (angiopoietin-2 [Ang-2], hepatocyte growth factor, interleukin [IL]-6, IL-8, c-reactive protein, platelet-derived growth factor [PDGF], and vascular endothelial growth factor [VEGF]) were assayed at baseline and at 2 and 4 weeks after radioembolization ((90)Y alone, n = 6; (90)Y plus sorafenib, n = 7). RESULTS In the (90)Y-alone group, all growth factors were elevated above baseline levels at 2 and 4 weeks: VEGF increased 36% vs baseline at 2 weeks and 22% at 4 weeks, and PDGF increased 24% at 2 weeks and 3% at 4 weeks. In the (90)Y/sorafenib arm, Ang-2 and PDGF decreased at 2 weeks and the remainder increased. By 4 weeks, only PDGF remained below baseline levels. VEGF increased 49% at 2 weeks and 28% at 4 weeks, and PDGF decreased 31% at 2 weeks and 39% at 4 weeks. Differences were statistically significant for hepatocyte growth factor (P = .03) and PDGF (P = .02) at 2 weeks and for IL-6 (P = .05) at 4 weeks. CONCLUSIONS Radioembolization is associated with a mild increase in angiogenic markers. The addition of sorafenib blunts PDGF response; other factors such as VEGF remain unaffected. The predominant effect of sorafenib may be through downregulation of PDGF and not VEGF.

New Developments in Interventional Oncology: Liver Metastases from Colorectal Cancer

AbstractColorectal cancer is the third leading cause of cancer death in the United States. Although hepatic excision is the first-line treatment for colorectal liver metastasis (CRLM), few patients are candidates. Locoregional therapy (LRT) encompasses minimally invasive techniques practiced by interventional radiology. These include ablative treatments (radiofrequency ablation, microwave ablation, and cryosurgical ablation) and transcatheter intra-arterial therapy (hepatic arterial infusion chemotherapy, transarterial “bland” embolization, transarterial chemoembolization, and radioembolization with yttrium 90). The National Comprehensive Cancer Network recommends LRT for unresectable CRLM refractory to chemotherapy. The following is a review of LRT in CRLM, including salient features, advantages, limitations, current roles, and future considerations.

Comparative study of post-transplant outcomes in hepatocellular carcinoma patients treated with chemoembolization or radioembolization

PURPOSE To analyze long-term outcomes in patients bridged/downstaged to orthotopic liver transplantation (OLT) by transarterial chemoembolization (TACE) or yttrium-90 radioembolization (Y90) for hepatocellular carcinoma (HCC). METHODS 172 HCC patients who underwent OLT after being treated with transarterial liver-directed therapies (LDTs) (Y90: 93; TACE: 79) were identified. Pre-LDT and pre-OLT clinical/imaging/laboratory characteristics including United Network for Organ Sharing (UNOS) staging and alpha-fetoprotein values (AFP) were tabulated. Post-OLT HCC recurrence was assessed by imaging follow-up per standard of care. Recurrence-free (RFS) and overall survival (OS) were calculated. Uni/multivariate and sub-stratification analyses were performed. RESULTS Time-to-OLT was longer in the Y90 group (Y90: 6.5 months; TACE: 4.8 months; p=0.02). With a median post-OLT follow-up of 26.1 months (IQR: 11.1-49.7), tumor recurrence was found in 6/79 (8%) TACE and 8/93 (9%) Y90 patients. Time-to-recurrence was 26.6 (CI: 7.0-49.5) and 15.9 months (CI: 7.8-46.8) for TACE and Y90, respectively (p=0.48). RFS (Y90: 79 months; TACE: 77 months; p=0.84) and OS (Y90: 57% alive at 100 months; TACE: 84.2 months; p=0.57) were similar. 54/155 patients (Y90: 29; TACE: 25) were downstaged to UNOS T2 or less. RFS hazard ratios for patients downstaged to ≤T2 versus those that were not were 0.6 (CI: 0.33-1.1) and 1.7 (CI: 0.9-3.1) respectively (p=0.13). 17/155 patients (Y90: 8; TACE: 9) that were >T2 were downstaged to UNOS T2 or less (within transplant criteria). Distribution (unilobar/bilobar), AFP, and pre-transplant UNOS stage affected RFS on univariate analyses. CONCLUSION Despite longer time-to-OLT for Y90 patients, post-OLT outcomes were similar between patients bridged or downstaged by TACE or Y90. A trend towards improved RFS for downstaged patients was identified.

Comparison of the Adverse Event Profile of TheraSphere® with SIR-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review

To compare the safety profiles of TheraSphere® (glass) and SIR-Spheres® (resin) Y90 microspheres for the treatment of hepatocellular carcinoma. A systematic review was conducted using the databases MEDLINE, Embase, and Cochrane Trials Register to identify all relevant studies. Baseline characteristics and adverse events of all grades related to gastrointestinal, hepatobiliary, and respiratory systems were collected along with commonly reported outcomes related to post-embolization syndrome. For all outcomes, data from each study were tabulated for each intervention. Adverse events and patients were summed across studies on TheraSphere® and SIR-Spheres®, respectively, and the resulting proportion of patients experiencing an outcome for both interventions was calculated. Thirty-one observational studies were included in the review. In the adverse events of all grades, more patients treated with resin microspheres reported gastric ulcers, hepatic encephalopathy, cholecystitis, hepatic failure, and pleural effusion. Patients treated with resin microspheres also had more hepatobiliary adverse events of grade 3 or higher. In the events related to post-embolization syndrome, glass microspheres exhibited a similar safety profile compared to resin microspheres. Ascites and nausea grade 3 or higher were recorded more frequently with glass microsphere treatment. Based on this review of the published literature, glass microspheres exhibit a safety profile with fewer gastrointestinal and pulmonary adverse events compared to resin microspheres in the treatment of hepatocellular carcinoma.