New Research Explores the Tumor Microenvironment Post-Embolization

Recent research from investigators at the NIH (1) has attempted to quantify changes in the tumor microvascular (<1 mm) perfusion as compared to normal, standard angiographic endpoints. As per usual, this manuscript accurately portrays how little we know about what chemoembolization actually does on the microscopic level. Johnson et al. used a rabbit Vx2 liver tumor and embolized with 100-300-µm LC Bead particles to endpoints of substasis or complete stasis. A novel method of evaluation was used to define microvascular perfusion by delivering two different fluorophore-conjugated perfusion markers through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was then labeled with an anti-CD31 antibody and analyzed with fluoroscene microscopy for perfusion marker overlap/mismatch. Embolization to substasis eliminated perfusion in 37% +/-9 of perfused microvessels while embolization to stasis eliminated perfusion in 56%+/- 8 of perfused microvessels. Further, embolization to substasis resulted in 8% newly perfused microvasculature. This amount is not statistically significant from control (12%) and likely reflects intermittent fluctuations in perfusion often found in solid tumors. Embolization to stasis resulted in <1% newly perfused microvasculature. The authors concluded that these findings suggest that angiography is not capable of detecting residual tumor microvascular perfusion. Further, while embolization to both substasis and stasis permitted persistent microvascular perfusion, embolization to stasis eliminated newly perfused microvasculature and this may significantly impact tumor microenvironment.

Comment:

While this research may not have immediate implications on your current practice, it is a valuable manuscript for identifying the fallacies of both the intervention we perform and the method we use to monitor that treatment. The research community has long attempted to explore and define the tumor microenvironment and the effect of embolization. Even from the work by Yumoto et al. (2) in 1985 on detecting HCC by iodized oil we have attempted to understand the therapy delivered and its effect on the microvasculature. However, our knowledge on this topic remains woefully incomplete. The current manuscript is noteworthy because it attempts to define what happens to the microvasculature with LC Bead embolization. More specifically, this manuscript demonstrated the dynamic changes that occur in tumor microvascular perfusion following embolization. While there are limitations in the present study, the authors developed a novel method for quantification that yielded interesting results and will hopefully spur additional research on the topic leading to better and more effective therapy.



Microvascular perfusion analysis with embolization to angiographic stasis. Representative perfusion maps generated from MATLAB processed data (CD31+ microvessels and lectin perfusion markers;  from a Vx2 tumor illustrate localization of the microvasculature. The perfusion map legend indicates the color that represents the perfusion status of the microvasculature after substasis embolization. The box in the perfusion map of the entire tumor cross section indicates the region of magnification for the perfusion map zoom.

Click Here for Abstract

1. Johnson GC, et al. Microvascular perfusion changes following transarterial hepatic tumor embolization. Journal of Vascular and Interventional Radiology 2015. DOI: 10.1016/j.jvir.2015.06.036

2. Yumoto, Y., et al. Hepatocellular carcinoma detected by iodized oil. Radiology 1985;154:19-24.

Post Author:
Luke R. Wilkins, MD