A novel EUS-guided liquid fiducial marker for image-guided radiotherapy in esophageal cancer: The safety and efficacy in vitro and vivo evaluations.

Abstract

e15573 Background: The true tumor extent of esophageal cancer is hard to visualize on current modalities during radiotherapy. In this study, we evaluated the safety and feasibility of the mixture of N-Butyl Cyanoacrylate and lipiodol to find the most optimal application as the fiducial marker to marking the true tumor extent in esophageal radiotherapy. Methods: Four types of injection matches (1:1-0.1ml, 1:1-0.15ml, 1:3-0.1ml, 1:30.15ml) were injected via syringes in subcutaneous tissue in rats model. Gross histopathological changes, weight, skin score, nodule volume, neutrophil counts and macrophage counts were observed to analyses the effect of different mixing ratios and injection volumes to find the best match. Evaluations following ISO standard criteria are further delivered to test the biocompatibility of the best applicable setting of this fiducial maker. Results: At 7th week, 42 markers (42/48, 87.5%) were still visualized on CT images. No serious adverse events or obvious artifacts were noted through the study. The overall review about the histopathological reaction of the NBCA/Lipiodol was considered to be a combination of acute inflammation, chronic inflammation, granulation tissue, foreign-body reaction and fibrous capsule formation in development. The quantitative analysis showed that when the density of NBCA was low (1:3), lower injection volume (0.1ml) brought the lower weights (p < 0.001). When the injection volume is high (0.15ml), the high NBCA (1:1) caused the lower weight (p < 0.001). At the most time points, the lower injection volume had the lower weights. High injection volume created a 0.079 cm3 increase in nodule size than low volume and high NBCA density also increased the nodule size. As for the inflammatory cells counts, the 3rd week was a key time point, before which the neutrophils decreased sharply and the macrophages keep almost steady, but after that the neutrophils stayed a low level and the macrophages started a rapid growth. On the comparisons of different index (Table), it is showed that the 1:3-0.15ml had an excellent performance as the fiducial marker and final biocompatibility test proved its safety. Conclusions: Overall, our results show that the mixture of NBCA/Lip as the fiducial marker is safe and feasible and the setting of 1:3-0.15ml was most optimal.[Table: see text]