Updates on LI-RADS Treatment Response Criteria for Hepatocellular Carcinoma: Focusing on MRI.

As the incidence of hepatocellular carcinoma (HCC) and subsequent treatments with liver-directed therapies rise, the complexity of assessing lesion response has also increased. The Liver Imaging Reporting and Data Systems (LI-RADS) treatment response algorithm (LI-RADS TRA) was created to standardize the assessment of response after locoregional therapy (LRT) on contrast-enhanced CT or MRI. Originally created based on expert opinion, these guidelines are currently undergoing revision based on emerging evidence. While many studies support the use of LR-TRA for evaluation of HCC response after thermal ablation and intra-arterial embolic therapy, data suggest a need for refinements to improve assessment after radiation therapy. In this manuscript, we review expected MR imaging findings after different forms of LRT, clarify how to apply the current LI-RADS TRA by type of LRT, explore emerging literature on LI-RADS TRA, and highlight future updates to the algorithm. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

In vivo effects of the human type I insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent xenograft human prostate tumors.

PURPOSE: The type I insulin-like growth factor receptor (IGF-IR) and its ligands have been shown to play a critical role in prostate carcinoma development, growth, and metastasis. Targeting the IGF-IR may be a potential treatment for prostate cancer. A fully human monoclonal antibody, A12, specific to IGF-IR, has shown potent antitumor effects in breast, colon, and pancreatic cancers in vitro and in vivo. In this study, we tested the in vivo effects of A12 on androgen-dependent and androgen-independent prostate tumor growth. EXPERIMENTAL DESIGN: Androgen-dependent LuCaP 35 and androgen-independent LuCaP 35V prostate tumors were implanted s.c. into intact and castrated severe combined immunodeficient mice, respectively. When tumor volume reached about 150 to 200 mm(3), A12 was injected at 40 mg/kg body weight thrice a week for up to 5 weeks. RESULTS: We find that A12 significantly inhibits growth of androgen-dependent LuCaP 35 and androgen-independent LuCaP 35V prostate xenografts, however, by different mechanisms. In LuCaP 35 xenografts, A12 treatment induces tumor cell apoptosis or G(1) cycle arrest. In LuCaP 35V xenografts, A12 treatment induces tumor cell G(2)-M cycle arrest. Moreover, we find that blocking the function of IGF-IR down-regulates androgen-regulated gene expression in androgen-independent LuCaP 35V tumor cells. CONCLUSIONS: Our findings suggest that A12 is a therapeutic candidate for both androgen-dependent and androgen-independent prostate cancer. Our findings also suggest an IGF-IR-dependent activity of the androgen receptor in androgen-independent prostate cancer cells.

Prevalent expression of the immunostimulatory MHC class I chain-related molecule is counteracted by shedding in prostate cancer.

The MHC class I chain-related molecules (MICs) have previously been shown to be induced on most epithelial tumor cells. Engagement of MIC by the activating immune receptor NKG2D triggers NK cells and augments antigen-specific CTL anti-tumor immunity. The MIC-NKG2D system was proposed to participate in epithelial tumor immune surveillance. Paradoxically, studies suggest that tumors may evade MIC-NKG2D-mediated immunity by MIC shedding-induced impairment of effector cell function. Here we demonstrate the first evidence to our knowledge of a significant correlation of MIC shedding and deficiency in NK cell function with the grade of disease in prostate cancer. MIC is widely expressed in prostate carcinoma. The presence of surface target MIC, however, is counteracted by shedding. A significant increase in serum levels of soluble MIC (sMIC) and deficiency in NK cell function was shown in patients with advanced cancer. Finally, the deficiency in NK cell function can be overcome by treatment with IL-2 or IL-15 in vitro. Our results suggest that (a) deficiency in MIC-NKG2D immune surveillance may contribute to prostate cancer progression, (b) sMIC may be a novel biomarker for prostate cancer, and (c) using cytokines to restore MIC-NKG2D-mediated immunity may have clinical significance for prostate cancer in cell-based adaptive immunotherapy.