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BioXmark, Rectal Feasibility Trial

Not Applicable
Completed
Conditions
Rectal Cancer
Interventions
Device: BioXmark liquid fiducial markers
Other: Imaging
Procedure: surgery or wait-and-see
Registration Number
NCT03265418
Lead Sponsor
Maastricht Radiation Oncology
Brief Summary

To test the feasibility and accuracy of BioXmark fiducial markers for image guided radiotherapy (IGRT) based rectal tumor boosting in 20 patients referred for long course chemo-radiotherapy of the locally advanced rectal cancer.

Detailed Description

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

A total of 20 patients who will undergo neo-adjuvant chemo-radiotherapy for rectal cancer will be included in this study upon informed consent.

During an extra sigmoidoscopy after enema preparation, 4 liquid marker spots will be placed 1 cm from the tumor; two in the in the cranial and two in the caudal direction of the tumor (4 markers in total per patient).

Participants will undergo standard treatment for their rectal cancer.

As part of standard patient set-up directly before each radiotherapy treatment, kilovoltage (KV) cone-beam computed tomography (CBCT) will be acquired. Treatment positioning will be based on the regular clinical decision protocols for treatment of rectal cancer and not on the markers. During treatment potential fiducial movement will be assessed using an externally positioned ultra-sound probe (this probe will be positioned against the abdominal or perineal skin of the patients depending on de position of the tumor/fiducials in the rectum). Moreover, for patients in this study 2 orthogonal kV images will be made immediately after each radiation using the electronic portal imaging (EPI) device.

As part of standard clinical practice an Magnetic resonance imaging (MRI) of the rectum will be made for response evaluation 6-8 weeks after the end of neo-adjuvant chemo-radiotherapy.

As part of standard clinical practice patients whose tumor has not responded completely will be operated on 8-12 weeks after the end of neoadjuvant chemo-radiotherapy. Patients with a complete response will be follow-upped according to the "wait-and-see" protocol.

Cone-beam CT and MR images which are obtained as routine practice during treatment of the participants will be compared with images of 20 non-participating patients treated at our institute in the same period.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
Inclusion Criteria
  • Patients with histological or cytological proven adenocarcinoma of the rectum, treated with long course external beam radiotherapy
  • Age > 18 years
  • Have given written informed consent before patient registration
Exclusion Criteria
  • Patients using anticoagulants: platelet aggregation inhibitors or coumarines
  • Iodine allergy

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BioXmark liquid fiducial markersImagingPlacement of 4 BioXmark liquid fiducial markers, standard treatment (chemo-radiotherapy followed by surgery or wait-and-see) with extra imaging to evaluate the behaviour of the markers before, during and after the radiotherapy
BioXmark liquid fiducial markersBioXmark liquid fiducial markersPlacement of 4 BioXmark liquid fiducial markers, standard treatment (chemo-radiotherapy followed by surgery or wait-and-see) with extra imaging to evaluate the behaviour of the markers before, during and after the radiotherapy
BioXmark liquid fiducial markerssurgery or wait-and-seePlacement of 4 BioXmark liquid fiducial markers, standard treatment (chemo-radiotherapy followed by surgery or wait-and-see) with extra imaging to evaluate the behaviour of the markers before, during and after the radiotherapy
Primary Outcome Measures
NameTimeMethod
Positional stability of BioXmark liquid fiducial markers during the treatment coursewill be determined through the course of radiotherapy, an average of 5 weeks

Positional stability / potential marker migration will be assessed by calculating marker pair distances.

Secondary Outcome Measures
NameTimeMethod
Adverse events (AE) potentially associated with BioXmarkuntil rectal surgery, on average 11 weeks, or in case of omission of surgery, until 3 months after marker placement.

The safety of bioXmark liquid fiducials placement will be assessed by recording Adverse events (AE) potentially associated with BioXmark until rectal surgery, on average 11 weeks, or in case of omission of surgery, until 3 months after marker placement.

Potential BioXmark induced alterations in the surgical specimenon average 10-12 weeks after chemo-radiation

The surgical specimens will be evaluated for signs of marker-induced alterations.

Potential BioXmark induced alteration in the surgical specimen will be scored by 2 independent observers using a subjective scoring system.In case the markers can't be located in the surgical specimen standard clinical evaluation of the specimen will take place. If the marker got lost during tissue processing potential inflammation/perforation will be scored as follows:A) 0 = no signs of extra inflammatory changes possibly related to the fiducials, 1 = limited extra inflammatory changes possibly related to the fiducials, 2 = severe extra inflammatory changes possibly related to the fiducials; B) 0 = no perforation of the rectal possibly related to fiducials, 1 = perforation of the rectal possibly related to the fiducials

Inter-observer variation in gross tumor volume (GTV) localization with and without markersthrough the course of radiotherapy, an average of 5 weeks

The concordance index (CI) of gross tumor volume (GTV) localization between observers on kV CBCT will be determined. The CI is the ratio of the intersection and the union of the two volumes.

Visibility/visual stability of BioXmark liquid fiducial markers during the treatment coursewill be determined for the time interval between placement and the post-treatment MRI, an average of 12 weeks

Visual stability will be evaluated by scoring visibility of the markers on CT, CBCT, EPI and MRI (T1, T2 and diffusion weighted images) by 2 independent observers using a subjective scoring system: 0 = not visible, 1 = barely visible, 2 = clearly visible.

Percentage of markers lost from injection to CT acquisition for RT planningwill be determined for the time intervals through the course of radiotherapy, an average of 5 weeks

(1 - number of markers visible on the last CBCT (cone-beam computed tomography) during treatment / number of visible markers at pCT) \* 100

Effect of BioXmark liquid fiducial markers on post-treatment MRI imagesat the moment of the post-treatment MRI, on average 6-8 weeks after chemo-radiation

Potential BioXmark induced artefacts will be scored by 2 independent observers using a subjective scoring system:

Trial Locations

Locations (1)

MAASTRO Clinic

🇳🇱

Maastricht, Limburg, Netherlands

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