Esophagus cancer

• Worldwide, the number of new cases in 2018, both sexes, all ages is 572,034 and 508,585 deaths from esophageal cancer 1

• In the EU, the highest age-standardized incidence rates for esophageal cancer are in the Netherlands for men and the UK for women 3

• Esophageal cancer has as a high degree recurrence after primary surgical resection and poor 5-year overall survival that rarely exceeds 40% 3

• Evidence suggests that neoadjuvant chemoradiotherapy (CRT) followed by surgery and definitive CRT are equally effective with regard to overall survival. For patients not willing to undergo esophageal surgery or who are medically unfit for major surgery, or with a very proximal/cervical cancer location, definitive chemoradiotherapy should be preferred 3,4

BioXmark® is under development and not yet CE marked

BioXmark® use for esophageal cancer

Endoscopic/EUS (Endoscopic ultrasonography)-guided insertion of fiducial markers at the esophageal tumor borders was shown feasible and safe.5,6 However, during EUS procedure, the caudal border of the tumor cannot be reached in about half of the patients because of stenosis.6 A thinner endoscope often still can, but without EUS-guidance, accurate determination of the definitive marker position is more difficult and less safe in case of gold markers, since the gold marker continues 5mm in the tissue after release from the needle tip. Also, each gold marker needs to be pre-loaded by hand and fixed by bone wax which requires experienced personnel and is time consuming. Furthermore, markers can be lost prior to insertion. Last, gold markers cannot be recognized easily on MRI. 5,6

With a liquid marker, the complete needle system can be primed at once and several markers injections can be consecutively performed in the esophagus, thus without need for removal of the system.5,6 Previously, another type of liquid marker (a hydrogel) was analyzed in patients with esophageal cancer, but not found suitable for IGRT because of its blurring and poor visibility on cone beam CT (CBCT) scan during the radiotherapy course.5

Moreover, with several studies investigating dose escalation to the esophageal tumor and studies exploring preoperative CRT in stomach cancer, an increase of fiducial marker indications, as well as a higher number of fiducials per patient (i.e., markers in all directions instead of only in craniocaudal direction (e.g., in stomach cancer, cardiac involved esophageal cancer) is expected. Markers can facilitate target definition, make it more accurate and will audit target coverage during CRT. This makes an easy applicable marker with good visibility on different imaging modalities, more vital.

A novel liquid fiducial marker BioXmark® is therefore promising for use in image-guided radiotherapy as was demonstrated in following clinical studies:

A clinical study performed in 4 patients (Rigshospitalet, Copenhagen Denmark) have demonstrated that BioXmark® placement proved safe and clinically feasible.7

A newly published prospective study from AMC, Amsterdam, the Netherlands, have evaluated the technical feasibility and clinical performance (visibility on different imaging modalities, continuous clear visibility on CBCT, and positional stability on CBCT) of BioXmark® fiducials in a small cohort (10 patients) of esophageal cancer patients.6 It was concluded that endoscopy/EUS-guided injection of a novel liquid fiducial marker is technical feasible for esophageal tumors.

Volumes of > 0.05 ml have an appropriate visualization both on CT and over the treatment course on CBCT. Further, for MR-based treatment preparation and delivery this liquid fiducial marker shows potential. The largest advantage of the liquid marker BioXmark® is not the clinical performance during IGRT, since this is also good with gold markers, but might be the easier and faster endoscopic injection procedure especially when multiple markers are needed.

For information about BioXmark®, see BioXmark®.


1. World Health Organization

2. The American Cancer Society

3. Shapiro J. at al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 2015; 16: 1090–98

4. Lordick al. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2016; 2 (Supplement 5): v50–v57

5. Machiels M. et al. Endoscopy/EUS-guided fiducial marker placement in patients with esophageal cancer: a comparative analysis of 3 types of markers. Gastrointest Endosc. 2015;82(4):641-9

6. Machiels M. et al. A novel liquid fiducial marker in esophageal cancer image-guided radiotherapy: technical feasibility and visibility on imaging. Pract Radiat Oncol. 2019 Jul 4. [Epub ahead of print]

7. S.Riisgaard de Blanck et al. Feasibility of a novel liquid fiducial marker for use in image guided radiotherapy of oesophageal cancer. Br J Radiol 2018; 91: 20180236