Fiducial markers: can the urologist do better?
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Radiotherapy to the bladder has a risk of toxicity to pelvic structures, which can be reduced by using fiducial markers for targeting. Injectable contrast offers an alternative marker to gold seeds, which may fall out or exacerbate scarring. Combining contrast agents with tissue glue can minimize dispersion through tissue, enhancing its utility. We evaluated combinations of contrast agents and tissue glue using porcine bladder, for feasibility and utility as fiducial markers to aid image-guided radiotherapy.
Different contrast agents (Lipiodol ultra or Urografin) were combined with different tissue glues (Histoacryl, Tisseal or Glubran2). The mixtures were endoscopically injected into porcine bladder submucosa to identify the area of interest with multiple fiducial markers. The porcine bladders were imaged within a phantom porcine pelvis using standard radiation therapy imaging modalities. The feasibility as an injectable fiducial marker and visibility of each fiducial marker on imaging were scored as binary outcomes by two proceduralists and two radiation therapists, respectively.
Lipiodol–glue combinations were successfully administered as multiple fiducials that were evident on CT and CBCT. Lipiodol with Histoacryl or Glubran2 was visible on kV imaging. The Lipiodol Glubran2 combination was deemed subjectively easiest to use at delivery, and a better fiducial on KV imaging.
This study demonstrates the feasibility of mixing contrast medium Lipiodol with Histoacryl or Glubran2 tissue glue, which, injected endoscopically, provides discrete and visible fiducial markers to aid image-guided radiotherapy. Although promising, further study is required to assess the durability of these markers through a course of radiotherapy.
KeywordsFiducial markers Prostate cancer Bladder cancer Endoscopy Image-guided radiotherapy Cone beam computed tomography Iodized oil Tissue glue
CB: data collection or management. KB: data collection or management. MC: protocol/project development. CD: Data analysis, manuscript writing/editing. FF: protocol/project development, data analysis. TJ: protocol/project development. DLJ: protocol/project development, data analysis, manuscript writing/editing. VK: manuscript writing/editing. ML: data collection or management. NL: protocol/project development, manuscript writing/editing. RO: data collection or management. SS: protocol/project development, manuscript writing/editing. AV: data collection or management. MW: protocol/project development.
This study was not funded. The Lipiodol Ultra, Histoacryl, Tisseal, and Glubran2 were donated by Aspen, B Braun, Baxter and Matrix Surgical supplies, respectively, for the purpose of this comparison study.
Compliance with ethical standards
Conflict of interest
All of the authors declare that they have no conflict of interest.
This article does not contain any experimental studies with human participants or live animals performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Ethics approval was sought from the institutional ethics committee but deemed redundant by the ethics committee, as porcine bladders were used in isolation.
No patient data were included in this article.
- 1.Mottet N, Bellmunt J, Briers E, Bolla M, Bourke L, Cornford P, De Santis M, Henry A, Joniau S, Lam T, Mason MD, Van den Poel H, Van den Kwast TH, Rouvière O. Wiegel T (2017) EAU–ESTRO–SIOG guidelines on prostate cancer. European Association of Urology. https://uroweb.org/guidelines/. Accessed 28 Feb 2018
- 2.Witjes JAC, Compérat E, Cowan NC, Gakis G, Hernández V, Lebret T, Lorch A, van der Heijden AG, Ribal MJ, Guidelines Associates: Bruins M, Linares Espinós E, Rouanne M, Neuzillet Y, Veskimäe E (2017) Muscle Invasive and Metastatic Bladder Cancer. European Assocation of Urology. https://uroweb.org/guidelines/. Accessed 28 Feb 2018
- 5.O’Neill AGM, Jain S, Hounsell AR, O’Sullivan J (2016) Fiducial marker guided prostate radiotherapy: a review. Br J Radiol 89Google Scholar
- 6.Zelefsky MJ, Kollmeier M, Cox B, Fidaleo A, Sperling D, Pei X, Carver B, Coleman J, Lovelock M, Hunt M (2012) Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 84(1):125–129. https://doi.org/10.1016/j.ijrobp.2011.11.047 CrossRefPubMedGoogle Scholar
- 7.Fortin I, Carrier J-F, Beauchemin MC, Béliveau-Nadeau D, Delouya B, Taussky D (2014) Using fiducial markers in the prostate bed in postprostatectomy external beam radiation therapy improves accuracy over surgical clips. Strahlentherapie Onkologie 190:467–471. https://doi.org/10.1007/s00066-014-0631-3 CrossRefGoogle Scholar
- 9.Song Y, Yan M, Mueller B, Mychalczak B (2018) Investigation of fiducial marker migration during the treatment of bladder cancer with image-guided radiation therapy. Clin Oncol (R Coll Radiol) 3:1481Google Scholar
- 10.Kliton J, Polgar C, Tenke P, Kovacs G, Major T, Stelczer G, Agoston P (2017) Image-guided radiotherapy for muscle invasive bladder cancer with intravesical lipiodol injection. A new option for bladder sparing treatment. Orvosi hetilap 158(51):2041–2047. https://doi.org/10.1556/650.2017.30904 CrossRefPubMedGoogle Scholar
- 12.Committee AT, Bhat YM, Banerjee S, Barth BA, Chauhan SS, Gottlieb KT, Konda V, Maple JT, Murad FM, Pfau PR, Pleskow DK, Siddiqui UD, Tokar JL, Wang A, Rodriguez SA (2013) Tissue adhesives: cyanoacrylate glue and fibrin sealant. Gastrointest Endosc 78(2):209–215. https://doi.org/10.1016/j.gie.2013.04.166 CrossRefGoogle Scholar
- 13.Chandran S, Vaughan R, Jacob A, Hamilton C, Joon DL, Lim K, Tog C, Bhatia K, Aly A, Sweeney T, Efthymiou M (2016) A novel endoscopic marker for radiological localization and image-guided radiotherapy in esophageal and gastric cancers (with video). Gastrointest Endosc 83(2):309–317. https://doi.org/10.1016/j.gie.2015.06.042 CrossRefPubMedGoogle Scholar
- 14.Freilich JM, Spiess PE, Biagioli MC, Fernandez DC, Shi EJ, Hunt DC, Gupta S, Wilder RB (2014) Lipiodol as a fiducial marker for image-guided radiation therapy for bladder cancer. Int Braz J Urol 40(2):190–197. https://doi.org/10.1590/s1677-5538.Ibju.2014.02.08 CrossRefPubMedGoogle Scholar
- 16.Chai X, van Herk M, van de Kamer JB, Remeijer P, Bex A, Betgen A, De Reijke TM, Hulshof MC, Pos FJ, Bel A (2010) Behavior of lipiodol markers during image guided radiotherapy of bladder cancer. Int J Radiat Oncol Biol Phys 77(1):309–314. https://doi.org/10.1016/j.ijrobp.2009.08.019 CrossRefPubMedGoogle Scholar
- 17.Meijer GJ, van der Toorn PP, Bal M, Schuring D, Weterings J, de Wildt M (2012) High precision bladder cancer irradiation by integrating a library planning procedure of 6 prospectively generated SIB IMRT plans with image guidance using lipiodol markers. Radiother Oncol 105(2):174–179. https://doi.org/10.1016/j.radonc.2012.08.011 CrossRefPubMedGoogle Scholar
- 20.Lim JH, You D, Jeong IG, Park HK, Ahn H, Kim C (2013) Cystoscopic injection of N-butyl-2-cyanoacrylate followed by fibrin glue for the treatment of persistent or massive vesicourethral anastomotic urine leak after radical prostatectomy. Int J Urol 20:980–985. https://doi.org/10.1111/iju.12094 CrossRefPubMedGoogle Scholar
- 21.Chao M, Ho H, Chan Y, Tan A, Pham T, Bolton D, Troy A, Temelcos C, Sengupta S, McMillan K, Cham CW, Liu M, Ding W, Subramanian B, Wasiak J, Lim Joon D, Spencer S, Lawrentschuk N (2018) Prospective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy. BJU Int. https://doi.org/10.1111/bju.14192 CrossRefPubMedGoogle Scholar
- 22.Garcia MM, Gottschalk AR, Brajtbord J, Konety B, Meng M, Roach M, Carroll P (2014) Endoscopic gold fiducial marker placement into the bladder wall to optimize radiotherapy targeting for bladder-preserving management of muscle-invasive bladder cancer: feasibility and initial outcome. PLoS One 9(3):1–10. https://doi.org/10.1371/journal.pone.0089754 CrossRefGoogle Scholar