BACKGROUND: The objective of this study was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) as a local salvage treatment after incomplete transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC). METHODS: The main eligibility criteria were a greatest tumor dimension (LD sum) <10 cm, inoperable HCC, and incomplete response after TACE. Prescribed SBRT doses were up to 60 gray (Gy) in 3 fractions, but doses were reduced until normal tissue constraints were allowed. RESULTS: Between May 2008 and February 2011, 50 patients were enrolled in this phase 2 trial, of which 47 patients were evaluable. Forty‐one patients had Child‐Pugh class A disease (A5/A6 were 32/9), 6 patients had class B7 disease, and 5 patients had portal vein tumor thrombosis. All patients underwent TACE 1 to 5 times before SBRT. SBRT doses ranged from 42 to 60 Gy in 3 fractions (median dose, 57 Gy), and the median LD sum was 29 mm (range, 13‐78 mm). Eighteen patients (38.3%) achieved complete remission within 6 months of completing of SBRT, and 18 patients (38.3%) had a partial response. The 2‐year local control rate was 94.6%, the overall survival rate was 68.7%, and the progression‐free survival rate was 33.8%. Three patients (6.4%) experienced grade 3 gastrointestinal toxicity, and 2 patients (4.3%) experienced grade 4 gastric ulcer perforation. CONCLUSIONS: This trial demonstrated that SBRT after incomplete TACE for inoperable HCC achieves promising rates of response and local control. On the basis of these study results, a modified, multi‐institutional, phase 2 trial to reduce gastrointestinal toxicity is recommended. Cancer 2012. © 2012 American Cancer Society.

Endothelial progenitor cells (EPCs) are a promising cell source for the treatment of several ischemic diseases for their potentials in neovascularization. However, the application of EPCs in cell-based therapy has shown low therapeutic efficacy due to hostile tissue conditions after ischemia. In this study, a bio-blood-vessel (BBV) is developed, which is produced using a novel hybrid bioink (a mixture of vascular-tissue-derived decellularized extracellular matrix (VdECM) and alginate) and a versatile 3D coaxial cell printing method for delivering EPC and proangiogenic drugs (atorvastatin) to the ischemic injury sites. The hybrid bioink not only provides a favorable environment to promote the proliferation, differentiation, and neovascularization of EPCs but also enables a direct fabrication of tubular BBV. By controlling the printing parameters, the printing method allows to construct BBVs in desired dimensions, carrying both EPCs and atorvastatin-loaded poly(lactic-co-glycolic) acid microspheres. The therapeutic efficacy of cell/drug-laden BBVs is evaluated in an ischemia model at nude mouse hind limb, which exhibits enhanced survival and differentiation of EPCs, increased rate of neovascularization, and remarkable salvage of ischemic limbs. These outcomes suggest that the 3D-printed ECM-mediated cell/drug implantation can be a new therapeutic approach for the treatment of various ischemic diseases.

BackgroundRecent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC.MethodsBetween 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0–7.0 cm), and the median dose was 51 Gy (range, 33–60 Gy).ResultsLC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45–54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT.ConclusionsThis study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.

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Twelve strains of a rapidly growing Mycobacterium species were isolated from an outbreak associated with intramuscular injections of an antimicrobial agent and were identified by comparative sequence analysis of rpoB and hsp65 . These isolates were identified as Mycobacterium massiliense (100% similarity).