Sirius: Low Dose Rate (LDR) Brachytherapy

3D rendering of prostate

“Permanent prostate brachytherapy dosimetry based only on MRI using positive contrast MRI markers [Sirius] is feasible, accurate, and reduces the uncertainties arising from CT-MRI fusion abating the need for postimplant multimodality imaging.” 2

LDR brachytherapy, or permanent radioactive seed implantation, is a standard option for the curative treatment of prostate cancer. Brachytherapy involves implanting radioactive seeds directly into the prostate. Its popularity has increased due to its effectiveness, convenience, relatively low incidence of erectile dysfunction, and minimal invasiveness. 3 Radiation released from the seeds penetrates the surrounding prostate tissue at a distance of ~15 mm, with most of the radiation concentrated within the prostate. Outcomes after brachytherapy can be excellent but depend greatly on the quality of the implant: 8-year prostate-specific antigen (PSA) relapse-free survival rates of 93% for high-quality implants vs. 76% for low-quality ones have been reported. 4

The inability of standard imaging options (ultrasound, computed tomography [CT], fluoroscopy) to clearly visualize soft tissue complicates accurate assessment of the radiation dose delivered by implanted seeds. Prostate edge detection is very poor on CT images, which can result in a high degree of inter-observer variability in prostate contouring and hence in implant quality evaluation. A study estimating prostate gland volumes highlighted the significant inter-observer differences when using post-implant CT scans. 5

The efficacy of MRI for evaluating soft tissues after seed implantation has been well described. 6 The internal and external urinary sphincters in particular cannot be adequately identified with CT imaging, but they are well visualized with MRI. However, the use of MRI in LDR prostate brachytherapy has been limited by the inability to accurately identify the seeds. All implanted seeds have the radioactive element encased within a titanium shell, which appears under MRI as a signal void that often cannot be easily distinguished from other artifacts, such as needle tracks. In LDR brachytherapy, where mm-level precision is necessary to limit excessive radiation dose (“hotspots”) within normal tissue and to prevent poor radiation coverage (“cold spots”) of the prostate, 7 it is unlikely that adequate seed separation can be achieved with MRI detection of seed artifacts alone.

The development of a positive-signal MRI marker to aid in seed detection and localization is an advance for prostate brachytherapy, with the potential to improve the quality of implants. Clinicians could have more confidence in the quality of treatment delivered, with effective clinical management strategies immediately employed if regions are known to have inadvertently receive an excess dose. The superior image quality of MRI could improve the accuracy of prostate contouring, allow detailed appreciation of adjacent critical organs and reveal the true relationship of the implanted seeds to the prostate and critical dose-limiting structures.


Sirius MRI Marker

The Sirius™ MRI Marker has been demonstrated to be visible with MRI, positively identifying the location of radioactive sources. 8

The superior image quality of MRI could improve the accuracy of brachytherapy, revealing the true relationship of radiation dose to the targeted cancer and nearby critical dose-limiting anatomy.

MRI Marker in Brachytherapy Strand

Sirius™ consists of a sealed biocompatible, polymer capsule containing C4, a unique MRI agent. The length of each capsule is 5.5 mm and the diameter is 0.8 mm. Sirius™ is intended to be implanted as a brachytherapy seed spacer that facilitates the anatomical post-implant localization of seeds.

Anisotropy measurements taken when attached to Iodine 125 seeds were equivalent to the standard TG43U parameters. 9 A Monte Carlo study was performed to assess the impact on a simulated prostate implant. Sirius™ does not alter radiation treatment delivery when compared with a standard seed spacer. 9

References

  1. Martin GV, et al. Permanent prostate brachytherapy postimplant magnetic resonance imaging dosimetry using positive contrast magnetic resonance imaging markers. Brachytherapy. 2017;16:761–769.
  2. Frank SJ, et al. American College of Radiology Appropriateness Criteria: Permanent Source Brachytherapy for Prostate Cancer. Brachytherapy. 2011;10(5):357–362.
  3. Zelefsky MJ, et al. Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation. Int J Radiat Oncol Biol Phys. 2007;67(2):327–333.
  4. Lee WR, et al. Interobserver variability leads to significant differences in quantifiers of prostate implant adequacy. Int J Radiat Oncol Biol Phys. 2002;54(2):457–461.
  5. McLaughlin PW, et al. Functional anatomy of the prostate: implications for treatment planning. Int J Radiat Oncol Biol Phys. 2005;63(2):479–491.
  6. Dawson JE, et al. Dose effects of seeds placement deviations from pre-planned positions in ultrasound guided prostate implants. Radiother Oncol. 1994;32:268–270.
  7. Frank SJ, et al. Anisotropy characterization of I-125 seed with attached encapsulated cobalt chloride complex contrast agent markers for MRI-based prostate brachytherapy. Med Dosim. 2011 36(2): 200-205.
  8. Melhus C, et al. Dosimetric Influence of Brachytherapy Seed Spacers. Brachytherapy. 2011 10(1, Suppl): S94 - S95 (#PD71)