No abstract

Liver metastases are a major cause of death from colorectal cancer. Intraarterial therapy options for colorectal liver metastases include chemoinfusion via a hepatic arterial pump or port, irinotecan-loaded drug-eluting beads, and radioembolization using Y microspheres. Intraarterial therapy allows the delivery of a high dose of chemotherapy or radiation into liver tumors while minimizing the impact on liver parenchyma and avoiding systemic effects. Specificity in intraarterial therapy can be achieved both through preferential arterial flow to the tumor and through selective catheter positioning. In this review, we discuss indications, contraindications, preprocedure evaluation, activity prescription, follow-up, outcomes, and complications of radioembolization of colorectal liver metastases. Methods for preventing off-target embolization, increasing the specificity of microsphere delivery, and reducing the lung-shunt fraction are discussed. There are 2 types ofY microspheres: resin and glass. Because glass microspheres have a higher activity per particle, they can deliver a particular radiation dose with fewer particles, likely reducing embolic effects. Glass microspheres thus may be more suitable when early stasis or reflux is a concern, in the setting of hepatocellular carcinoma with portal vein invasion, and for radiation segmentectomy. Because resin microspheres have a lower activity per particle, more particles are needed to deliver a particular radiation dose. Resin microspheres thus may be preferable for larger tumors and those with high arterial flow. In addition, resin microspheres have been approved by the U.S. Food and Drug Administration for colorectal liver metastases, whereas institutional review board approval is required before glass microspheres can be used under a compassionate-use or research protocol. Finally, radiation segmentectomy involves delivering a calculated lobar activity of Y microspheres selectively to treat a tumor involving 1 or 2 liver segments. This technique administers a very high radiation dose and effectively causes the ablation of tumors that are too large or are in a location considered unsafe for thermal ablation. The selective delivery spares surrounding normal liver, reducing the risk of liver failure.

Objectives-To identify predictors of overall (OS) and liver progression-free survival (LPFS) following 90 Y radioembolization (RAE) of heavily pretreated patients with colorectal cancer liver metastases (CLM). Create and validate a predictive nomogram for OS.Materials and Methods-Metabolic, anatomic, laboratory, pathologic, genetic, primary-disease and procedure-related factors, as well as pre-and post-RAE therapies in 103 CLM patients treated with RAE from 9/15/2009 to 3/21/2017 were analyzed. LPFS was defined by RECIST 1.1 and EORTC criteria. Prognosticators of OS and LPFS were selected using univariate Cox regression, adjusted for clustering and competing risk analysis (for LPFS) and subsequently tested in

OBJECTIVE. The purpose of this study was to assess the mechanism by which aspirin therapy improves survival when combined with transarterial chemoembolization or transarterial embolization (TAE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS. A retrospective review included 304 patients with HCC who were treated with TAE. The patients were divided into two groups on the basis of whether the patient took aspirin (n = 42) or did not take aspirin (n = 262) at the time of initial TAE. For each patient, response of embolized tumors, time to progression, initial site of progression, survival time, and liver function test results before and after embolization were evaluated. RESULTS. Patients taking aspirin and those not taking aspirin at the time of initial TAE for HCC had no difference in initial response rate (88% vs 90% complete response or partial response, p = 0.59), median time to progression (6.2 vs 5.2 months, p = 0.42), initial site of progression (p = 0.77), or fraction of patients dying with disease progression (88% vs 89%, p = 1.00). Before embolization, there was no difference in mean bilirubin level (0.8 vs 0.9 mg/dL, p = 0.11) for patients taking versus not taking aspirin. Among patients taking aspirin, bilirubin level was significantly lower 1 day (0.9 vs 1.3, p < 0.001), 1 month (0.9 vs 1.2, p = 0.048), and 1 year (0.8 vs 1.0, p = 0.021) after embolization. The median overall survival period after initial embolization was longer for patients taking aspirin (57 vs 23 months, p = 0.008). CONCLUSION. Aspirin use is associated with improved liver function test results and survival after TAE for HCC. It is not associated with differences in response or time to progression.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. New animal models that faithfully recapitulate human HCC phenotypes are required to address unmet clinical needs and advance standard-of-care therapeutics. This study utilized the Oncopig Cancer Model to develop a translational porcine HCC model which can serve as a bridge between murine studies and human clinical practice. Reliable development of Oncopig HCC cell lines was demonstrated through hepatocyte isolation and Cre recombinase exposure across 15 Oncopigs. Oncopig and human HCC cell lines displayed similar cell cycle lengths, alpha-fetoprotein production, arginase-1 staining, chemosusceptibility, and drug metabolizing enzyme expression. The ability of Oncopig HCC cells to consistently produce tumors in vivo was confirmed via subcutaneous (SQ) injection into immunodeficient mice and Oncopigs. Reproducible development of intrahepatic tumors in an alcohol-induced fibrotic microenvironment was achieved via engraftment of SQ tumors into fibrotic Oncopig livers. Whole-genome sequencing demontrated intrahepatic tumor tissue resembled human HCC at the genomic level. Finally, Oncopig HCC cells are amenable to gene editing for development of personalized HCC tumors. This study provides a novel, clinically-relevant porcine HCC model which holds great promise for improving HCC outcomes through testing of novel therapeutic approaches to accelerate and enhance clinical trials.