Rectum cancer

• Worldwide in 2018, including both sexes and all ages, the number of new rectal cancer cases was 704,376 with 310,394 deaths from the disease. 1

• The current treatment paradigm for patients with stage II or III rectal cancers is concurrent chemotherapy and radiation therapy followed by surgical resection. 3

• Surgical resection of the rectum can cause long-term morbidity and impact negatively on quality of life for the patients (permanent colostomy).3

• Still, nonsurgical management with a close monitoring protocol is not a standard of care approach for rectal cancer. Lack of data from randomized trials, definition of clinical complete response and monitoring protocol is a significant challenge for wider implementation of a non-surgical treatment approach.3

BioXmark® is under development and not yet CE marked

BioXmark® for rectal cancer radiation therapy

At some clinics, rather than applying the current treatment paradigm, a “wait and see” approach has been established as standard of care for rectal cancer patients who achieve a complete response after neo-adjuvant chemo-radiotherapy.3

Directing a higher radiation dose to rectal tumors during neo-adjuvant chemo-radiotherapy increases the chance of complete response and thereby enables omission of surgery. In order to introduce tumor dose escalation, it is crucial to develop a technique that allows for high-precision image-guided radiation therapy (IGRT) with adequate set-up margins. A prerequisite for high-precision IGRT is good tumor target visibility on clinical images or the application of tumor surrogates such as fiducial markers.3

There is a high unmet need for a stable fiducial marker in rectal cancer, which does not migrate through the intestinal wall and has a low level of artefacts during imaging. Our liquid fiducial marker, BioXmark®, may provide for accurate determination of both inter- and intrafraction tumor location to effective guide for high-precision radiation treatment of rectal cancers with safe dose-escalation for higher efficacy and better outcomes.

BioXmark® – Clinical study for use in rectal cancer IGRT

The clinical study “BioXmark® liquid fiducials to enable radiotherapy tumor boosting in rectal cancer, a feasibility trial” has recently been completed in Maastricht UMC. Principal investigator is Dr. Maaike Berbée, dept. of Radiation Oncology, MAASTRO clinic, Maastricht UMC. ClinicalTrials.gov Identifier: NCT03265418.

For the patients in the study, BioXmark® markers were injected into the rectal wall after proper enema preparation using a sigmoidoscopy via thin needles (<25 Gauge) by two experienced gastroenterologists. A two-step marker method was used to minimize the risk of extra-luminal injection of the marker. First, a saline solution was injected into the submucosal space to create a bleb, where after the marker was injected into the bleb. A total of four marker spots with a volume of 80uL were injected into the rectal wall an approximately one-centimeter lateral from the tumor, two in caudal and two in cranial direction (see figure below). One-centimeter margins were chosen in agreement with the gastroenterologist. The markers were injected with an angle of approximately 45 degrees to limit perforation risk.

 

Figure: Schematic view of the location of BioXmark® markers relative to the tumor.

 

The preliminary conclusions of the study have been presented in a master thesis.4
Researchers provide evidence of the feasibility of BioXmark® fiducial marker for image-guided radiotherapy on daily cone beam CT for rectal cancer patients. BioXmark® may provide a tool for accurate determination of the day-to-day tumor location and thereby safe dose-escalation. BioXmark® did not migrate in 95.8% out of 72 analyzed markers and was clearly visible on planning CT scan and day-to-day cone beam CT. Additionally, marker injection had no major technical difficulties and was well tolerated by patients. Based on these results, BioXmark® seems to be superior over other markers such as gold or Visicoil. Thereby, this stable fiducial marker may open a window of opportunity for high precision image guided radiotherapy in other tumor sites.

The results from the study are not published yet.

For information about BioXmark®, see Bioxmark®

References

1. World Health Organization http://gco.iarc.fr/today/fact-sheets-cancers

2. The American Cancer Society http://www.cancer.org/cancer.html

3. Akce M., El-Rayes B. F. Nonsurgical Management of Rectal Cancer. Clinical review. J Oncol Pract. 2019; Volume 15, Issue 3 123

4. Opbroek T.J.S., BSc. BioXmark liquid fiducials to enable radiotherapy tumor boosting in rectal cancer, a feasibility trial. Master of Science Thesis. Maastricht University 2019 – Not publicly available