DETECT: Target Volume for Rectal Endoluminal Radiation Boosting

Официальное название

DETECT: Defining the Target Volume for Endoluminal Radiation Boosting in Patients With Rectal Cancer

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест Ultrasound
  3D endorectal ultrasound.
• Диагностический тест Rectoscopy
  Rigid rectoscopy.
• Другое Scan, e.g. CT (resection specimen)
  For some patients, images of the resection specimen (note: NOT of the patients) during the pathological process will be acquired.

Первичные конечные точки

• Maximum distance of microscopic tumor spread per patient in all directions from the macroscopic tumor remnant in the pathology specimen [Срок оценки: During post-resection pathological analysis (i.e. approximately 14 days post-resection)]

Вторичные конечные точки (8)

• 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 [Срок оценки: During post-resection pathological analysis (i.e. approximately 14 days post-resection)]
• Maximum distance of microscopic tumor spread per patient in all directions from the macroscopic tumor remnant in the pathology specimen excluding ypT0 patients [Срок оценки: During post-resection pathological analysis (i.e. approximately 14 days post-resection)]
• 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 [Срок оценки: During post-resection pathological analysis (i.e. approximately 14 days post-resection)]
• 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 [Срок оценки: During post-resection pathological analysis (i.e. approximately 14 days post-resection)]
• 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 [Срок оценки: 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).]
• Maximum distance of microscopic tumor spread per patient in all directions from the macroscopic tumor remnant as seen by eye and/or on imaging [Срок оценки: 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.]
• Treatment margin (in the various directions) relative to the macroscopic tumor to cover 90% and 95% of all microscopic tumor spread [Срок оценки: 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.]
• Evaluation of risk factors for the presence and/or the extent of microscopic tumor spread identified by the meta-analysis we performed [Срок оценки: 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.]

Критерии участия

Критерии включения

• ≥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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Нидерланды · 3 центра

• Maastro — Maastricht
• Maastricht University Medical Center — Maastricht
• Catharina Hospital — Eindhoven

Публикации

• van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011 Jun;12(6):575-82. doi: 10.1016/S1470-2045(11)70097-3. Ep PMID 21596621
• Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. doi: 10.1016/S0140-6736(09)60484 PMID 19269519
• Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, Rutten H, Pahlman L, Glimelius B, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007 Nov;246(5):693-701. doi: 10.1097/01.sla.0000257358.56863.ce. PMID 17968156
• Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, van Dam RM, Jansen RL, Sosef M, Leijtens JW, Hulsewe KW, Buijsen J, Beets GL. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011 Dec 10;29(35):4633-40. doi: 10.1200/JCO.2011.37.7176. Epub 2011 Nov 7. PMID 22067400
• Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010 Sep;11(9 PMID 20692872
• Rijkmans EC, Cats A, Nout RA, van den Bongard DHJG, Ketelaars M, Buijsen J, Rozema T, Franssen JH, Velema LA, van Triest B, Marijnen CAM. Endorectal Brachytherapy Boost After External Beam Radiation Therapy in Elderly or Medically Inoperable Patients With Rectal Cancer: Primary Outcomes of the Phase 1 HERBERT Study. Int J Radiat Oncol Biol Phys. 2017 Jul 15;98(4):908-917. doi: 10.1016/j.ijrobp.201 PMID 28366579
• Sun Myint A, Smith FM, Gollins S, Wong H, Rao C, Whitmarsh K, Sripadam R, Rooney P, Hershman M, Pritchard DM. Dose Escalation Using Contact X-ray Brachytherapy After External Beam Radiotherapy as Nonsurgical Treatment Option for Rectal Cancer: Outcomes From a Single-Center Experience. Int J Radiat Oncol Biol Phys. 2018 Mar 1;100(3):565-573. doi: 10.1016/j.ijrobp.2017.10.022. Epub 2017 Oct 20. PMID 29229327
• Appelt AL, Ploen J, Harling H, Jensen FS, Jensen LH, Jorgensen JC, Lindebjerg J, Rafaelsen SR, Jakobsen A. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015 Aug;16(8):919-27. doi: 10.1016/S1470-2045(15)00120-5. Epub 2015 Jul 5. PMID 26156652

Идентификаторы

NCT: NCT04927897 · NL77886.068.21

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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