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Friday, December 10, 2021

Yttrium-90 Radioembolization to the Prostate Gland: Proof of Concept in a Canine Model and Clinical Translation

Yttrium-90 Radioembolization to the Prostate Gland: Proof of Concept in a Canine Model and Clinical Translation


Clinical question
To investigate the feasibility, safety, and absorbed-dose distribution of prostatic artery radioembolization (RE) in a canine model

Take-away point
Prostate Y90 RE is safe and feasible in a canine model, with focal dose-dependent prostate changes, without unwanted extraprostatic effects.

Reference
Mouli SK, et al. Yttrium-90 Radioembolization to the Prostate Gland: Proof of Concept in a Canine Model and Clinical Translation. J Vasc Interv Radiol. 2021 Aug;32(8):1103-1112.e12.

Study Design
Preclinical animal study

Funding Source
Research grants from Boston Scientific provided to Northwestern University Department of Radiology, Section of Interventional Radiology.

Setting
Single-center.

Summary


Prostate cancer is the most common non-cutaneous cancer in men. Currently, nonoperative candidates are managed with brachytherapy (BT) or external-beam radiotherapy (EBRT), however biochemical recurrence and radiation induced toxicity to adjacent structures range from 10% to 60%. Prostatic artery (PA) embolization already has an established safety and efficacy profile for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). However, both bland and chemoembolization for prostate cancer have not shown efficacious outcomes in small studies. Y90 radioembolization has proven efficacy and safety as HCC locoregional therapy and may be replicated for prostate cancer treatment.

14 castrated canines were assigned to Y90 treatment groups: low (60-70Gy), medium (80-120Gy), and high dose (150-200Gy). Doses were delivered to 1 hemi-gland of each subject. After 60 days, gross pathologic and histologic analysis of the prostate, bladder, penis, rectum, urethra, and the left and right neurovascular bundles was performed.

Y90 administration was technically successful in all subjects, with dose delivered to target hemigland without significant non-target exposure by imaging. Serial MRI follow up demonstrated hemigland volume significantly and progressively decreased with noticeable signal changes on T2 weighted, ADC map, and DCE (dynamic contrast enhanced imaging) sequences. The high-dose group demonstrated higher volume loss (60%) compared to the low-dose group.



Gross pathological examination demonstrated radiation-induced glandular changes in a dose-dependent fashion, with the high-dose group demonstrating increased degeneration, inflammation, and atrophy of the prostatic gland sand glandular epithelial metaplasia. The majority of the contralateral control hemiglands were histologically unremarkable. No adverse events were noted on clinical, pathologic, or histologic analysis including: cavitary necrosis, hemorrhage, urinary retention, incontinence, hematuria, diarrhea, or rectal bleeding. No significant radioactivity was detected in the animals’ urine and feces during follow up. No gross pathological or histological abnormalities were seen in the surrounding tissues upon necropsy including perianal inflammation or necrosis, urethral strictures, radiation cystitis or proctitis. In 1 high-dose subject, there were isolated microspheres in the periprostatic tissues (bladder, rectum, neurovascular bundle) but no evidence of tissue damage. Particularly, the neurovascular bundle (NVB) appears to be relatively spared in radioembolization.

Commentary


The authors noted that EBRT or brachytherapy have better homogeneity, but at the expense of more normal tissue exposure. The beta particle penetration of Y90 has limited range which provides more accurate locoregional target tissue coverage with limited risk to surrounding structures. Even with high theoretical absorbed doses delivered to the treated prostate hemigland (155–502 Gy), the most conservative QUANTEC limits were not exceeded for surrounding organs.

Some drawbacks noted during this study were that each animal served as its own control with the contralateral untreated prostate hemigland, which may have received some inadvertent dose due to intraprostatic collaterals. Furthermore, compared to similar canine models for prostate bland embolization, the volume changes with radioembolization in this study were not as profound and were dose dependent. However, the level of atrophy was still greater than those seen following EBRT in preclinical and clinical studies. The author also noted a few limitations of the study, namely (1) a canine prostatic hyperplasia model was used and (2) microdosimetry provided a range of dose distributions from ideal to conservative due to limitations gland segmentation on micro-CT.

This study proves the technical success of Y90 prostate radioembolization in a canine hyperplasia model, demonstrating pathologic and histologic evidence of significant dose-dependent glandular atrophy without evidence of radiation induced side effects. Perhaps most notably, neurovascular bundle sparring is an attractive opportunity if similar treatment effects can be proven. This is a very promising first step and we look forward to the ensuing clinical safety and efficacy trials.

Post Author
Vaishak Amblee, MD
Rush University Medical Center
Integrated Vascular & Interventional Radiology Residency, Class of 2023

David M. Tabriz, MD
Program Director, Vascular & Interventional Radiology (Integrated)Program Director, Vascular & Interventional Radiology (Independent)
Rush University Medical Center
@DrDaveTabriz

Edited and formatted by @NingchengLi
Interventional Radiology Resident
Dotter Institute, Oregon Health and Science University

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