Establishment of an image-guided brachytherapy procedure that is feasible for a multicenter randomized trial
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To establish an image-guided brachytherapy procedure for rectal cancer that is
feasible for use in a multicenter randomized trial.
The protocol will be declared feasible and robust for multicenter use if in
both institutes 4/5 patients have been treated without defined violations. The
following events are considered violations:
* Patients not completing the brachytherapy (i.e. 4 fractions) due to
non-compliance
* Geographic miss of the tumor bed (as determined by review by PI)
* Inability to reproduce the planning position of the applicator during the
treatment (as determined by review by PI)
* Inappropriate assignment of the planned first dwell position on the planning
CT data set (more than 4 times the slice thickness; i.e. more than 8 mm in
cranial caudal direction)
* Incorrect calculation of the indexer length on treatment days
* Improper channel assignment during a daily treatment
* Inappropriate assignment of the channel rotational position (more than ± 5o,
or more than 1.5 mm misalignment between x-ray markers in channels 1 and 5 as
seen on a daily radiograph)
* Planning criteria not met:
o 90% of the clinical target volume will receive at least 90% of the
prescribed dose (D90> 23,4 Gy).
o Organs at risk: cumulative D2cc (EQD2, using */*=3): bladder < 90 Gy;
sigmoid < 75 Gy, bowel < 75 Gy.
Secondary outcome
* Evaluation of willingness of patients to undergo an image-guided
brachytherapy procedure.
* Refinement of repeated quantitative MR imaging for response monitoring for
later use in the randomized trial.
* Definition of an optimal PA procedure for histological analysis of whole
mount slides, for later use in the randomized trial
* Development of methods for registration of MRI data to pathology slides
Background summary
Preoperative external beam radiotherapy (EBRT) for rectal cancer has shown to
be effective in reducing local recurrence, but comes at a price of acute and
late toxicity. In order to reduce toxicity without compromising oncological
outcome, high dose rate (HDR) endorectal brachytherapy (BT) has been introduced
in a single center phase II study, with excellent results. Based on the smaller
irradiated volume, less toxicity (both acute and late effects) can be expected
with BT compared to EBRT.
At present in the Netherlands, brachytherapy for rectal cancer is given at the
LUMC and NKI-AVL as definitive treatment after external-beam radiotherapy.
Further optimization to allow image guided brachytherapy is necessary before
the technique can be implemented nationwide in a multi-center setting. For this
optimization we will perform a pilot study as described below. The
brachytherapy technique will be optimized, and we will develop methods to
correlate MRI changes, pathology changes and dose distribution in normal
tissue. The pilot study will be used to develop feasible methods and generate
hypotheses that will be tested in a multicenter randomized phase III study.
Study objective
Establishment of an image-guided brachytherapy procedure that is feasible for a
multicenter randomized trial
Study design
The study will be carried out in the departments of radiotherapy of the LUMC
and the Netherlands Cancer Institute (NKI). A total of 20 patients will be
included and receive HDR endorectal BT in 4 fractions of 6.5 Gy. The first 5
patients will receive BT at the LUMC. In this group, the BT procedure will be
optimized and the subsequent 5 patients will then be treated at the LUMC to
validate this updated procedure. After that, 5 patients in LUMC and 5 in
NKI-AVL will be treated according to the definitive protocol to evaluate
feasibility in multi-center setting. In the LUMC, 2 other radiation oncologists
will be involved for the last five patients to test the procedure. The protocol
will be declared feasible and robust for multicenter use if in both institutes
4/5 patients have been treated without defined violations.
Intervention
HDR endorectal brachytherapy: 4 fractions of 6.5 Gy within 7 days. TME surgery
will be performed 8 weeks after the first fraction of radiotherapy.
Study burden and risks
Endoscopy and marker placement
The endoscopy and fiducial marker placement will last about 30 minutes. The
expected complication risks of the endoscopy and the marker placement are very
limited. A very low rate of pain, bleeding or infectious complications has been
reported in previous transrectal marker placement or rectal marker placement
studies. Similar results have been found in the recently performed REMARK study
with gold fiducial markers.
Imaging
Patients will undergo the multi-parametric MRI exam 3 additional times in this
study. In this exam 15 ml of the contrast agent Dotarem (Gadoteric acid,
concentration 0.5M) is administered intravenously. No adverse effects are known
of the administration of a second dose one week after the regular exam. The
repeat of the MRI exam causes a negligible risk for the patient.
Endorectal brachytherapy
Expected complications of endorectal brachytherapy are limited. As reported by
Vuong et al., proctitis grade 3 occurs in all patients, but resides before
surgery. Based on the results of Vuong, no increased risk of local recurrence
is expected. Reduced long-term toxicity will be the major benefit for
participating patients.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
* Adenocarcinoma of the rectum
* Clinically T1-2N1 or T3N0 with > 5 mm extramural invasion or T3N1 tumor
* No threatened or involved mesorectal fascia on MRI
* Eligible for 5x5 Gy according to the Dutch guidelines
* Cranial edge of the tumor below sigmoid curvature on MRI
* Caudal margin of the tumor above dentate line (endoscopic observation)
* Tumors with an adequate (>2 cm) lumen to allow the positioning of the applicator (e.g. non obstructive tumor)
* WHO performance status 0-2 (Appendix B)
* Age > 18 years
Exclusion criteria
* Extramesorectal (e.g. iliac, lateral) pelvic lymph node involvement
* Previous pelvic irradiation
* Extension of tumor into the anal canal
* Contra-indication for endoscopic placement of gold-markers such as coagulopathy (prothrombin time < 50% of control; partial thromboplastin time > 50 seconds) or anticoagulantia (marcoumar, sintrom or new oral anticoagulants) that cannot be stopped.
* Contra-indications for a MRI exam with Gadolinium according to the institutional policy
* Pregnancy
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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In other registers
| Register | ID |
|---|---|
| CCMO | NL60244.058.16 |