DETECT: DEfining the Target volume for Endoluminal radiation boosting in patients with reCTal cancer

To date, the backbone for treating non-metastatic rectal cancer is surgical
resection of the rectum and the perirectal fat that surrounds it. Depending on
gross tumor characteristics, patients may receive neoadjuvant radiotherapy or
neoadjuvant concurrent chemoradiotherapy to reduce the locoregional recurrence
rate. With the currently used neoadjuvant concurrent chemoradiation schedule a
complete tumor response is achieved in 10-20% of all patients. In patients with
a clinical complete response, omission of surgery with thorough follow-up
(*watch and wait*) and salvage surgery at the time of local recurrence can be
considered instead of surgery. Surgery related morbidity and side effects, like
for example a colostomy, can then be avoided.
A very promising approach to increase the rate of complete responders while
still preserving rectal function is to add an endoluminal radiation boost to
the residual tumor in patients with limited residual disease after concurrent
chemoradiotherapy. These endoluminal techniques allow for a more localized
boost compared to external beam radiotherapy (EBRT), which enables radiation
dose escalation to the tumor and limits the radiation induced toxicity. Various
series have shown that endoluminal boosting results in high complete response
rates (60-86%) and limited toxicity in selected patients.
Unfortunately, widespread introduction of endoluminal techniques is hampered by
a lack of fundamental knowledge on the definition of the treatment volume. In
order to achieve tumor control not only the macroscopic tumor, also known as
the gross tumor volume (GTV), but also the microscopic tumor spread (MTS) needs
to be treated. Crucial information regarding the treatment margins needed to
cover this microscopic spread is currently lacking.
This project will for the first time provide hard data regarding MTS in all
directions from the macroscopic tumor in pathology specimens, as seen by eye
(endoscopically & rectoscopically) and on imaging (endo-ultrasound, MRI) of a
prospective cohort of patients who undergo a surgical resection after
neoadjuvant treatment for rectal cancer. These data will be used to develop
evidence based guidelines for target volume definition in rectal endoluminal
radiation boosting.
Such guidelines are essential to improve the quality of rectal endoluminal
radiation boosting and to facilitate the widespread availability of the
techniques. High quality endoluminal radiation boosting will increase the
clinical complete response rates and allow omission of surgery in rectal cancer
patients. Surgery related morbidity, such as a permanent colostomy can then be
avoided.

Primary objective
To determine the maximum distance of microscopic tumor spread per patient in
all directions from the macroscopic tumor remnant in the pathology specimen.

Main secondary objectives
- To determine the maximum distance of microscopic tumor spread per patient in
all directions from the macroscopic tumor remnant as seen by eye
(endoscopically/rectoscopically) and/or on imaging (endo-ultrasound, MRI).
- To determine the treatment margin (in the various directions) relative to the
macroscopic tumor to cover 90% and 95% of all microscopic tumor spread.

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.

Patients will receive the same standard care that they would receive when not
participating in a study: among others flexible endoscopy, MRI, surgery,
pathological processing/analysis. In addition to this, they will undergo a
rectoscopy and 3D endo-ultrasound before TME surgery. For Maastro and MUMC+
patients, the 3D endo-ultrasound and rectoscopy will be performed on the same
day as the surgery, reducing the study burden for the patient, and under
general anaesthesia, further reducing the burden for the patient. Application
of general anaesthesia is part of standard care (part of TME surgery). For CZE
patients, the endoscopy and endorectal ultrasound are part of standard care and
both procedures will be performed a few days before TME surgery. Based on the
results of the endoscopy, the physician will decide if an ultrasound will be
performed or not for CZE patients. The rectoscopy and 3D-ultrasound bear a very
limited safety risk. No follow-up visits related to the trial will be
necessary.