Nadine Abouchaleh

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)

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.

Y90 Radioembolization for Locally Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Long-Term Outcomes in a 185-Patient Cohort

We report survival outcomes for patients with advanced-stage hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) treated with 90Y radioembolization. Methods: With institutional review board approval, we searched our prospectively acquired database for 90Y patients treated between 2003 and 2017. Inclusion criteria were patients who had HCC with tumor PVT. Patients with metastases were excluded. Laboratory data were collected at baseline and 1 mo after 90Y radioembolization. Toxicity grades were reported according to the Common Terminology Criteria for Adverse Events, version 4.0, and long-term survival outcomes were reported and stratified by Child–Pugh class (CP). Overall survival was calculated using the Kaplan–Meier method. Multivariate analysis was performed using Cox proportional hazards regression. A subanalysis for patients with a high level of α-fetoprotein (AFP) (>100 ng/dL) was conducted. Results: In total, 185 patients with HCC PVT underwent 90Y radioembolization. Seventy-four (40%) were CP-A, 51 (28%) were CP-B7, and 60 (32%) were ≥CP-B8. New albumin, bilirubin, and alkaline phosphatase grade 3/4 toxicities were, respectively, 3%, 10%, and 0% for CP-A; 14%, 12%, and 6% for CP-B7; and 23%, 32%, and 3% for ≥CP-B8. Median overall survival for CP-A patients was 13.3 mo (95% confidence interval [CI], 8.7–15.7 mo). CP-B7 and ≥CP-B8 patients exhibited median overall survival of 6.9 mo (95% CI, 5.3–10.1 mo) and 3.9 mo (95% CI, 2.9–5.0 mo), respectively. Significant overall survival prognosticators on univariate analysis were albumin, bilirubin, ascites, tumor size 5 cm or smaller, focality, distribution, infiltration, Eastern Cooperative Oncology Group status, AFP level, and PVT extent. Multivariate analysis showed the prognosticators of overall survival to be bilirubin, no ascites, tumor size 5 cm or smaller, solitary lesion, baseline AFP level lower than 100 ng/dL, and Eastern Cooperative Oncology Group status. Of 123 patients with a high AFP level (>100 ng/dL), 12 patients achieved restored normal AFP levels (<13 ng/dL) and exhibited median overall survival of 23.9 mo (95% CI, 20.1–124.1 mo). AFP responders at 1 mo had better overall survival than nonresponders, at 8.5 mo versus 4.8 mo (P = 0.018); AFP responders at 3 mo had overall survival of 13.3 mo, versus 6.9 mo for nonresponders (P = 0.021). Conclusion: 90Y radioembolization can serve as a safe and effective treatment for advanced-stage HCC patients with tumor PVT. Overall survival outcomes are affected by baseline liver function, tumor size, and AFP level.

Radiation Segmentectomy: Potential Curative Therapy for Early Hepatocellular Carcinoma

Purpose To report long-term outcomes of radiation segmentectomy (RS) for early hepatocellular carcinoma (HCC). The authors hypothesized that outcomes are comparable to curative treatments for patients with solitary HCC less than or equal to 5 cm and preserved liver function. Materials and Methods This retrospective study included 70 patients (median age, 71 years; range, 22-96 years) with solitary HCC less than or equal to 5 cm not amenable to percutaneous ablation who underwent RS (dose of >190 Gy) between 2003 and 2016. Patients who underwent subsequent curative liver transplantation were excluded to eliminate this confounding variable affecting survival. Radiologic response of time to progression and median overall survival were estimated by using the Kaplan-Meier method per the guidelines of the European Association for the Study of the Liver (EASL) and the World Health Organization (WHO). Results Seventy patients were treated with RS over 14 years. Sixty-three patients (90%) showed response by using EASL criteria, of which 41 (59%) showed complete response. Fifty patients (71%) achieved response by using WHO criteria, of which 11 (16%) achieved complete response. Response rates at 6 months were 86% and 49% by using EASL and WHO criteria, respectively. Median time to progression was 2.4 years (95% confidence interval: 2.1, 5.7), with 72% of patients having no target lesion progression at 5 years. Median overall survival was 6.7 years (95% confidence interval: 3.1, 6.7); survival probability at 1, 3, and 5 years was 98%, 66%, and 57%, respectively. Overall survival probability at 1, 3, and 5 years was 100%, 82%, and 75%, respectively, in patients with baseline tumor size less than or equal to 3 cm (n = 45) and was significantly longer than in patients with tumors greater than 3 cm (P = .026). Conclusion RS provides response rates, tumor control, and survival outcomes comparable to curative-intent treatments for selected patients with early-stage HCC who have preserved liver function.