Novel fiducial marker has optimal characteristics for image-guided radiotherapy of abdominal tumours

Introduction
Most solid tumours originate from and amidst soft tissues and are localised in direct proximity of radiation sensitive organs at risk. That is why, e.g., in pancreatic cancer, the full potential of radio(chemo)therapy has not been exploited yet. In the era of highly conformal radiation techniques and hypofractionated treatment schedules, it is of increasing importance to accurately and precisely localise the tumour, both at treatment planning and delivery. Solid fiducial markers to be implanted in (the proximity of) the tumour have been available for some time, but have been shown to be suboptimal for particle therapy [1]. A novel liquid fiducial marker, BioXmark® (Nanovi A/S, Kgs. Lyngby, Denmark), was found to visible on x-ray, (conebeam)CT, and MRI, and to hardly interfere with particle beam irradiation [1-3]. The aim of this study was to assess the visibility and severity of imaging artefacts of BioXmark® in a tissue-equivalent phantom of the upper abdomen.

Material and Methods
In a dedicated phantom of the upper abdomen (CIRS, Norfolk, VA), including liver, vertebrae and soft tissue mimicking material, different radiopaque component concentrations (67%, 100%, 133%, 167% in relation to the currently available product), and quantities (25µl, 50µl, 100µl, 150µl) of BioXmark® were deposited at equi-distance in a gelatine-filled vial and inserted at the putative site of the pancreas. These vials were subjected to kV-X-ray (80; 100), single- and dual-energy computed tomography (SECT/DECT; Somatom Definition AS, Siemens Healthineers, Erlangen, Germany) and conebeam-CT (CBCT; VARIAN, Palo Alto, CA). The significant visibility of the markers on kV-imaging was assessed in coronal and sagittal projection using a contrast-to-noise-ratio (CNR) of at least 2.0 [4]. Moreover, a radiation oncologist, a medical physicist and two radiotherapy technicians scored the marker visibility using a four-point scale (0=not visible; 3=visible, suitable for clinical use). The degree of artefacts was determined calculating the Streaking Index (SI; [4]).

Results
Except for small marker quantities of low radiopaque component concentration, all BioXmark® passed the CNR-threshold (Fig. 1). Even though the experts scored the visibility of BioXmark® with a 2.5, only the 25µl with 67% radiopaque component concentration was deemed invisible (score: 1; Fig. 1). The artefacts seen on CBCT, SECT and DECT were small, with SI-values ranging from 8.2-52.2, 9.1-44.2, and 4.4-50.1, respectively (Fig. 2).

Conclusion
For targets in the upper abdomen, the trade-off between visibility and imaging artefacts is optimal using 50µl or 100µl of the BioXmark® at 100% or 133% radiopaque component concentrations. Monte-Carlo simulations on the interference of the different concentrations of BioXmark® with proton beam irradiation are ongoing.

References
[1] Rydhög JS et al. Radiother Oncol 2017;122:393-399
[2] Schneider S et al. Med Phys 2018;45:37-47
[3] De Roover R et al. Med Phys 2018;2205-2217
[4] Rydhög JS et al. Med Phys 2015;42:2818-2826