BioXmark liquid fiducial markers for image guided radiotherapy in bladder cancer, a safety and performance trial

Radical chemoradiotherapy for patients with muscle-invasive bladder cancer is
becoming accepted as a viable treatment option with good long-term outcomes.
However, a high dose radiation exposure can damage normal tissue and cause
radiotherapy related toxicity. In order to increase precision of the treatment,
image guided radiotherapy aided by fiducial markers will be a major benefit, on
one hand by sparing small bowel and uninvolved bladder and on the other hand by
increased accuracy of the gross tumor radiation. Traditional gold fiducial
markers are safe and feasible to apply, however, the procedure is time
consuming and literature showed that up to 40% of the gold seeds are lost in
verification imaging (mostly kV cone beam CT (CBCT). Liquid markers, such as
hydrogel and Lipiodol, are also shown to be safe and feasible to apply.
However, the biggest disadvantage of these liquid markers is fading (hydrogel)
or blurring (Lipiodol) of the liquid marker spots in the perivesical fatty
tissue, leading to inaccurate delineation of the tumor borders and impaired
usage of the spots during daily positioning verification on the treatment
machine. Furthermore, for accurate Lipiodol implantation (not too much and not
too less), fluoroscopy is needed during the endoscopical implantation. This
study will evaluate a novel liquid marker, BioXmark, which has the potential
benefit of stable visibility without blurring properties combined with simple
application.

This study will evaluate usability, safety and performance of a cystoscopic
guided injection of a marker (BioXmark) at the tumor site in patients with
bladder cancer on planning CT and CBCT during the irradiation period.

This study is a prospective non-randomized open label trial.

Injection of at least 3 liquid fiducial markers (BioXmark) in the bladder wall
cranial, lateral and caudal (optional) of the macroscopic tumor during
cystoscopy.

The patient will directly benefit from participation in the study. The markers
will be used for tumor delineation and positional verification in each patient.

For this study extra risks compared to the standard procedure are not to be
expected. Like all other endoscopic procedures a bleeding or perforation could
occur (overall risk < 1%). The infection risk is estimated low, comparable as
the bleeding risk, which is also estimated low and the same or lower than the
risk related to biopsy procedures. Should bleeding occur it is assumed to be
small and self-limiting. The liquid marker used has been demonstrated to be
biocompatible in accordance with regulatory requirements for medical devices
(EN ISO10993).