Yttrium-90 radioembolization (Y90RE) is a novel approach to radiation therapy for hepatocellular carcinoma (HCC), never tested in phase 2 studies. Fifty-two patients with intermediate (n.17) to advanced (n.35) HCC were prospectively recruited to assess, as the primary endpoint, efficacy of Y90RE on time-to-progression (TTP). Secondary endpoints were tumor response, safety, and overall survival (OS). All patients were Eastern Cooperative Oncology Group (ECOG) score 0-1, Child-Pugh class A-B7. Y90RE treatments aimed at a lobar delivery of 120 Gy. Retrospective dosimetric correlations were conducted and related to response. Fifty-eight treatments were performed on 52 patients. The median follow-up was 36 months. The median TTP was 11 months with no significant difference between portal vein thrombosis (PVT) versus no PVT (7 versus 13 months). The median OS was 15 months (95% confidence interval [CI], 12-18 months) with a nonsignificant trend in favor of non-PVT versus PVT patients (18 versus 13 months). Five complete responses occurred (9.6%), and the 2 year-progression rate was 62%. Objective response was 40.4%, whereas the disease control rate (78.8%) significantly affected survival (responders versus nonresponders: 18.4% versus 9.1%; P = 0.009). Tumor response significantly correlated with absorbed dose in target lesions ( r = 0.60, 95% CI, 0.41-0.74, P < 0.001) and a threshold of 500 Gy predicted response (area under the curve, 0.78). Mortality at 30-90 days was 0%-3.8%. Various grades of reduction in liver function occurred within 6 months in 36.5% of patients, with no differences among stages. On multivariate analysis, tumor response was the sole variable affecting TTP ( P < 0.001) and the second affecting survival (after Child-Pugh class). Conclusion: Y90RE is an effective treatment in intermediate to advanced HCC, particularly in the case of PVT. Further prospective evaluations comparing Y90RE with conventional treatments are warranted.

Asian series have shown a 5-year survival rate of ≈70% after resection of hepatocellular carcinoma (HCC) ≤2 cm. Western outcomes with resection have not been as good. In addition, ablation of HCC ≤2 cm has been shown to achieve competitive results, leaving the role of resection in these patients unclear. Records of patients undergoing resection at two Western centers between January 1990 and December 2009 were reviewed. Patients with a single HCC ≤2 cm on pathologic analysis were included. Thirty clinical variables including demographics, liver function, tumor characteristics, nature of the surgery, and the surrounding liver were examined. An exploratory statistical analysis was conducted to determine variables associated with recurrence and survival. The study included 132 patients with a median follow-up of 37.5 months. There was one (<1%) 90-day mortality. There were 32 deaths with a median survival of 74.5 months and a 5-year survival rate of 70% (63% in patients with cirrhosis). The median time to recurrence was 31.6 months and the 5-year recurrence rate was 68%. Presence of satellites (hazard ratio [HR], 2.46; P = 0.031) and platelet count <150,000/μL (HR, 2.37; P = 0.026) were independently associated with survival. Presence of satellites (HR, 2.79; P = 0.003), cirrhosis (HR, 2.3; P = 0.010), and nonanatomic resection (HR, 1.79; P = 0.031) were independently associated with recurrence. Patients with a single HCC ≤2 cm and platelet count ≥150,000/μL achieved a median survival of 138 months and a 5-year survival rate of 81%, respectively. Conclusion: Resection of HCC ≤2 cm is safe and achieves excellent results in Western centers. Recurrence continues to be a significant problem. Presence of satellites, platelet count, anatomic resection, and cirrhosis are associated with outcomes after resection, even among such early tumors. Resection should continue to be considered a primary treatment modality in patients with small HCC and well-preserved liver function.

The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that “very early” iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with “very early” iCCA and those with “advanced” disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the “very early” iCCA group and 33/48 (69%) the “advanced” group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the “advanced” group (3.1 [2.5‐4.4] versus 1.6 [1.5‐1.8]). After a median follow‐up of 35 (13.5‐76.4) months, the 1‐year, 3‐year, and 5‐year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1‐year, 3‐year, and 5‐year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. Conclusion: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178‐1188)

Objective: The aim of this study was to estimate probabilities of achieving the statistical cure from hepatocellular carcinoma (HCC) with hepatic resection (HR) and liver transplantation (LT). Background: Statistical cure occurs when the mortality of a specific population returns to values of that of general population. Resection and transplantation are considered potentially curative therapies for HCC, but their effect on the residual entire life-expectancy has never been investigated. Methods: Data from 3286 HCC patients treated with LT (n = 1218) or HR (n = 2068) were used to estimate statistical cure. Disease-free survival (DFS) was the primary survival measure to estimate cure fractions through a nonmixture model. Overall survival (OS) was a secondary measure. In both, patients were matched with general population by age, sex, year, and race/ethnicity. Cure variations after LT were also adjusted for different waiting-list drop-outs. Results: Considering DFS, the cure fraction after LT was 74.1% and after HR was 24.1% (effect size >0.8). LT outperformed HR within all transplant criteria considered (effect size >0.8), especially for multiple tumors (>0.9) and even in presence of a drop-out up to 20% (>0.5). Considering OS, the cure fraction after LT marginally increased to 75.8%, and after that HR increased to 40.5%. The effect size of LT over HR in terms of cure decreased for oligonodular tumors (<0.5), became small for drop-out up to ∼20% (<0.2), and negligible for single tumors <5 cm (∼0.1). Conclusion: As other malignancies, statistical cure can occur for HCC, primarily with LT and secondarily with HR, depending on waiting-list capabilities and efficacy of tumor recurrence therapies after resection.