ABSTRACT
BACKGROUND AND OBJECTIVE: In recent years, combination therapies for hepatocellular carcinoma (HCC) have been increasingly used with superior treatment responses compared to monotherapies. However, the safety and efficacy of the transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) combinations for HCC patients have not been investigated in the literature. In this study, our aim was to evaluate the safety and outcomes of TACE after TARE in HCC patients. MATERIALS AND METHODS: All TARE procedures performed on HCC patients at a single institution between January 2008 and November 2016 were retrospectively reviewed. Seventy-three patients who did not receive any additional transarterial therapy in the areas targeted by TARE were assigned to the "TARE group," while 27 patients who received TACE after TARE to the same target area were assigned to the "Combo group." Post-procedural liver toxicity, tumor response, overall survival (OS), and time to progression (TTP) were evaluated. RESULTS: Fewer patients in the Combo group had worsening liver function than the TARE group based on the change in bilirubin levels (19% vs. 40%; p=0.029) and Child-Pugh score increase (28% vs. 51%; p=0.056). The median OS time of all patients was 11.04 months. The Combo group had a significantly longer median OS of 36.8 months (vs. 10.6, p=0.003) and median TTP of 14.4 months (vs. 5.5, p=0.018). After accounting for selection bias, OS and TTP were still in favor of the Combo group, with hazard ratios of 0.651 (p<0.05) and 0.63 (p<0.05), respectively. CONCLUSION: The addition of TACE to TARE is a safe and effective treatment in unresectable HCC patients and can be considered in select patients with a lack of complete response or disease progression.
ABSTRACT
PURPOSE: To compare the prognostic accuracy of nine staging systems, some of which are well-known and some of which have only been more recently described, for patients with unresectable HCC treated with radioembolization (RE). MATERIALS AND METHODS: Individual scores or classes for the following staging systems were recorded or calculated for patients (n = 89) with unresectable HCC who underwent RE at a single tertiary care center from January 2008 to October 2016: Eastern Cooperative Oncology Group, Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, Okuda, Cancer of the Liver Italian Program (CLIP), Model for End Stage Liver Disease, Child-Pugh (CP) Categorical and Numeric, and Albumin-Bilirubin. For each staging system, a cox proportional hazards regression model was fit to the data and log-rank test statistics, concordance indices, Akaike Information Criteria (AIC) and other diagnostic statistics were calculated. RESULTS: Of the nine staging systems analyzed, the basic discriminatory ability assessed with the log-rank test (rejected at the α = .05-level) was significant for two of the systems: CP Numeric (p < .001) and CLIP (p < .05). Out of these two systems, CP Numeric system had a higher prognostic accuracy than CLIP with the lowest AIC (464.90), the highest optimism-corrected pseudo R2 (0.16), and the highest estimated concordance index (0.64). CONCLUSION: As applied to our patient population, the CP Numeric system contained the most predictive prognostic information for patients with HCC undergoing radioembolization. However, all evaluated staging systems performed suboptimally, and the relative superiority of any of the systems remains unclear when ranking them according to common practice. Further evaluation of current ranking methodologies is recommended.
ABSTRACT
Sigma (σ) receptors are unique non-opioid binding sites that are associated with a broad range of disease states. Sigma-2 receptors provide a promising target for diagnostic imaging and pharmacological interventions to curb tumor progression. Most recently, the progesterone receptor (PGRMC1, 25 kDa) has been shown to have σ2 receptor-like binding properties, thus highlighting the need to understand the biological function of an 18 kDa protein that exhibits σ2-like photoaffinity labeling (denoted here as σ2-18k) but the amino acid sequence of which is not known. In order to provide new tools for the study of the σ2-18k protein, we have developed bifunctional σ receptor ligands each bearing a benzophenone photo-crosslinking moiety and an alkyne group to which an azide-containing biotin affinity tag can be covalently attached through click chemistry after photo-crosslinking. Although several compounds showed favorable σ2 binding properties, the highest affinity (2 nM) and the greatest potency in blocking photolabeling of σ2-18k by a radioactive photoaffinity ligand was shown by compound 22. These benzophenone-alkyne σ receptor ligands might therefore be amenable for studying the σ2-18k protein through chemical biology approaches. To the best of our knowledge, these compounds represent the first reported benzophenone-containing clickable σ receptor ligands, which might potentially have broad applications based on the "plugging in" of various tags.
