Clinical trial NCT04927897: DETECT: Target Volume for Rectal Endoluminal Radiation Boosting
Official title: DETECT: Defining the Target Volume for Endoluminal Radiation Boosting in Patients With Rectal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Rectal Cancer
Keywords: Rectal Cancer
Microscopic Tumor Spread
Target Volume Definition
Endoluminal Radiation Boosting
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
Collaborators: name: Maastricht University Medical Center
name: Catharina Ziekenhuis Eindhoven
First posted: 2021-06-16
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a limited (ycT1-3N0) residual tumor after neoadjuvant radiotherapy or long-course chemoradiotherapy for rectal adenocarcinoma.

Brief summary: The aim of the study is to provide prospective data regarding microscopic tumor spread in all directions from the macroscopic tumor in pathology specimens, as seen by eye, and on imaging to define the target volume for endoluminal radiation boosting in rectal cancer patients.

Detailed description: This study is a prospective multicentre cohort trial in ≥50 patients with a residual ycT1-3N0 tumor after neoadjuvant chemoradiotherapy or radiotherapy for rectal adenocarcinoma at least 6 weeks after the neoadjuvant treatment.

In addition to standard workup and treatment (e.g. a flexible endoscopy and an MRI scan at 6-8 weeks post-neoadjuvant therapy), patients will undergo pre-operatively, after induction of general anaesthesia, an endorectal ultrasound and rigid rectoscopy as study procedures if these procedures are not already part of standard workup. Furthermore, the pathological specimens of some patients will be scanned using MR imaging during certain parts of the pathological process.

Objectives include determining the maximum distance of microscopic tumor spread per patient in all directions, creating a tissue deformation model to account for changes due to e.g. fixation and pathological processing, using this tissue deformation model to translate the microscopic tumor spread back to the in vivo situation (e.g. back to in vivo MRI scans, 3D endo-ultrasounds), and evaluating/determining risk factors for the presence and/or extent of microscopic tumor spread.

This data will be used for target volume definition in rectal endoluminal radiation boosting.

Eligibility criteria: Inclusion Criteria:

* ≥18 years of age and capable of giving informed consent.
* ycT1-3N0(\*) residual(\*\*) histology confirmed rectal adenocarcinoma after neoadjuvant radiotherapy or long-course chemoradiotherapy for which patients will undergo TME surgery.
* Minimal interval between end of neoadjuvant chemoradiotherapy or radiotherapy: 6 weeks.

(\*)= as determined by clinical assessment (digital rectal examination, endoscopy with or without biopsy) and/or MRI. Biopsy/histology around the time of diagnosis is adequate; no biopsy/histology is needed after neoadjuvant therapy.

(\*\*)= including tumor regrowths/local recurrence after an initial clinical complete response and a "watch and wait" approach. These patients will also be included after the local recurrence has been determined using endoscopy and/or MRI.

Exclusion Criteria:

* Patient has received brachytherapy as part of neoadjuvant treatment.
* \<18 years of age or incapable of giving informed consent.
* Patient has not been treated with neoadjuvant radiotherapy or long-course chemoradiotherapy.
* Patient will not undergo TME surgery for a ycT1-3N0 residual histology confirmed rectal adenocarcinoma.
* Interval between end of neoadjuvant therapy and surgery is \<6 weeks.

Primary outcomes:
measure: Maximum distance of microscopic tumor spread per patient in all directions from the macroscopic tumor remnant in the pathology specimen
timeFrame: During post-resection pathological analysis (i.e. approximately 14 days post-resection)
Secondary outcomes:
measure: Maximum distance of microscopic tumor spread per patient from the macroscopic tumor remnant in the pathology specimen, reported separately for MTS perpendicular to the bowel wall and for MTS parallel to the bowel wall
timeFrame: During post-resection pathological analysis (i.e. approximately 14 days post-resection)
measure: Maximum distance of microscopic tumor spread per patient in all directions from the macroscopic tumor remnant in the pathology specimen excluding ypT0 patients
timeFrame: During post-resection pathological analysis (i.e. approximately 14 days post-resection)
measure: Maximum distance of microscopic tumor spread per patient in all directions from the macroscopic tumor remnant in the pathology specimen only including patients with microscopic tumor spread
timeFrame: During post-resection pathological analysis (i.e. approximately 14 days post-resection)
measure: Maximum distance of microscopic tumor spread per patient in all directions from the macroscopic tumor remnant in the pathology specimen only for patients with regrowths
timeFrame: During post-resection pathological analysis (i.e. approximately 14 days post-resection)
measure: Tissue deformation factor/model to compensate for tissue deformation due to removal of the specimen from the body, formalin fixation and tissue processing at the pathology department
timeFrame: The tissue deformation model will be created once all required data (e.g. MRI scans, rectoscopy images, endorectal ultrasound images) is available (approximately 14 days post-surgery for the final included patient).
measure: Maximum distance of microscopic tumor spread per patient in all directions from the macroscopic tumor remnant as seen by eye and/or on imaging
timeFrame: When the tissue deformation model is finished (approximately 3 months after all data for every patient is available). For the imaging time frames: please refer to the description.
measure: Treatment margin (in the various directions) relative to the macroscopic tumor to cover 90% and 95% of all microscopic tumor spread
timeFrame: Once the microscopic tumor spread is determined for all patients (approximately 14 days post-surgery for the final included patient), the treatment margins will be calculated.
measure: Evaluation of risk factors for the presence and/or the extent of microscopic tumor spread identified by the meta-analysis we performed
timeFrame: ypT stage is determined during post-resection pathological analysis (i.e. approximately 14 days post-resection). The time interval is determined at the day of surgery.
Other outcomes:
measure: Identification of potential risk factors for the presence and the extent of microscopic tumor spread not yet identified by our meta-analysis
timeFrame: Most are determined during post-resection path. analysis (approx. 14 days post-resection). ycT stage is determined approx. 6-10 weeks post-neoadjuvant treatment (multidisciplinary team), in vivo imaging is done approx 6-8 weeks post-neoadjuvant treatment
measure: Analysis of (re)biopsy material
timeFrame: Biopsy material is obtained at time of diagnosis.
Locations:
city: Maastricht
country: Netherlands
facility: Maastro
state: Limburg
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
state: Noord-Brabant
Study officials:
affiliation: Maastro
name: Maaike Berbée, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastro
name: Evert Van Limbergen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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