Clinical trial NCT03748667: Accuracy for Predicting Deep Submucosal Invasion
Official title: Diagnostic Accuracy of Deep Submucosal Invasion: White Light Endoscopy vs Invasive Pattern Based on NBI/BLI ± Chromoendoscopy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Colorectal Polyp
Keywords: Endoscopy
Colonoscopy
Invasive pattern
Polypectomy
NBI
BLI
Deep submucosal invasion
JNET
Kudo pit pattern
Lead sponsor: Althaia Xarxa Assistencial Universitària de Manresa
Sponsor class: OTHER
Collaborators: name: Hospital Universitario La Fe
name: Hospital Clínico Universitario Lozano Blesa
name: University of North Carolina, Chapel Hill
name: Hospital Clinic of Barcelona
name: National Cancer Center, Japan
name: Germans Trias i Pujol Hospital
name: Hospital Universitario 12 de Octubre
name: Hospital Universitario Ramon y Cajal
name: San Francisco Veterans Affairs Medical Center
name: Hospital Universitario Virgen de la Arrixaca
name: Hospital Comarcal de Alcañiz
name: Centro Medico Teknon
First posted: 2018-11-21
Enrollment: 426
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive patients \> 18 years old who undergo a colonoscopy for any reason

Brief summary: The main aim of this study is to determine whether the assessment of the invasive pattern based on NBI with dual focus/magnification or BLI with magnification ± chromoendoscopy (NBI+CE) for predicting deep invasion is significantly more accurate than the assessment based on white light endoscopy (WLE), carried out by trained endoscopists.

Detailed description: A video with the lesion assessment, without any data on the patient, will be recorded in a device connected to the processor provided by the Principal Investigator. The name of the file will be the record ID. All the lesions will be tested by the same endoscopist in vivo and an assistant will fulfill the data collection sheet during the colonoscopy.

First, the lesions will be cleaned and observed in a stable position. Size, location, morphology, demarcated areas, and gross morphological malignant features will be evaluated. Based on these WLE characteristics, a deep invasion prediction will be performed (control test). Second, the lesion will be assessed using NBI with near focus or magnification or BLI with magnification. A second cleaning with pronase (or N-acetylcysteine if pronase is not available) if the surface cannot be clearly observed because of the presence of mucus or if crystal violet is going to be used. Crystal violet 0.05% will be used in case of polyps type 2B in the JNET classification or lesions with a demarcated area. A non-traumatic catheter (or spray catheter) will be used to spray the crystal violet over the lesion. A final prediction of deep invasion will be performed for NBI or BLI ± CE (test evaluated).

The use of a cap to observe the bottom of the lesion, fix the lesion close to the endoscope or to observe the lesion underwater immersion is strongly recommended.

The resection technique will be decided upon according to the local experience. In case of endoscopy resection (cold snare, EMR, ESD, full thickness), lesions will be removed via the anus (not through the endoscopy channel) in order to preserve their integrity. Although EMR is performed, if possible, lesions will be referred to the pathologist well oriented and pinned out on a cork based, as is standard procedure in ESD.

In order to ensure that endoscopic assessment is performed before the histology evaluation, both diagnostic assessments (control test and test evaluated) will be recorded on the REDCap database on the day of the colonoscopy. REDCap records the time and date of all changes in the variables' results. The remaining variables (demographic data, etc.) will be recorded on the data collection sheet and copied later into REDCap.

Videos of the lesion assessments will be sent to the Principal Investigator. Centralized visualization will be conducted to detect protocol violations and to exclude lesions from the study.

A blinded histology assessment will be conducted by the local pathologist and if a carcinoma with submucosal invasion is diagnosed, histology slides will be referred for an additional blinded and centralized histology evaluation at the end of the study.

Pathologists participating in the histological phase will assess all the slides with submucosal invasion and will collect the histological factors associated with lymph node metastasis.

Finally, investigators participating in the translational phase will refer paraffin blocks of 10 lesions of each JNET category (2A, 2B and 3) for genetic tests (sequencing of a panel of 45 genes and analysis of alterations in the number of copies of the genome).

Eligibility criteria: Inclusion criteria:

* Non-pedunculated type 0 lesions in Paris classification (not obvious cancers)
* Lesions larger than 10 mm

Exclusion criteria are:

* Lesions assessed as JNET 1 by the endoscopist or serrated by the pathologist
* Previous biopsy or resection attempt
* Previous CT, MR or USE
* Unavailable histology
* Inflammatory bowel disease
* Informed consent not obtained
* Protocol violation

Primary outcomes:
measure: The presence or absence of deep invasion according to the control test (WLE)
timeFrame: One day
measure: The presence or absence of deep invasion according to the test evaluated (NBI/BLI +/- CE)
timeFrame: One day
measure: The presence or absence of deep invasion according to the gold standard (histology)
timeFrame: One day
Secondary outcomes:
measure: Presence of any genetic mutations
timeFrame: one day
measure: Number of genome copies using SNP-arrays
timeFrame: one day
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco Veterans Affairs Medical Center. University of California
state: California
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Tokyo
country: Japan
facility: National Cancer Center
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
state: Aragón
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol (Can Ruti)
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Cataluña
city: Barcelona
country: Spain
facility: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
state: Cataluña
city: Manresa
country: Spain
facility: Althaia. Xarxa Assistencial Universitària de Manresa
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico de La Fe
state: Comunidad Valenciana
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
state: Murcia
city: Alcañiz
country: Spain
facility: Hospital Comarcal de Alcañiz
state: Teruel
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
Study officials:
affiliation: Althaia Xarxa Assistencial Universitària de Manresa
name: Ignasi Puig, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Backes Y, Moss A, Reitsma JB, Siersema PD, Moons LM. Narrow Band Imaging, Magnifying Chromoendoscopy, and Gross Morphological Features for the Optical Diagnosis of T1 Colorectal Cancer and Deep Submucosal Invasion: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2017 Jan;112(1):54-64. doi: 10.1038/ajg.2016.403. Epub 2016 Sep 20.
citation: Hayashi N, Tanaka S, Hewett DG, Kaltenbach TR, Sano Y, Ponchon T, Saunders BP, Rex DK, Soetikno RM. Endoscopic prediction of deep submucosal invasive carcinoma: validation of the narrow-band imaging international colorectal endoscopic (NICE) classification. Gastrointest Endosc. 2013 Oct;78(4):625-32. doi: 10.1016/j.gie.2013.04.185. Epub 2013 Jul 30.
citation: Sano Y, Tanaka S, Kudo SE, Saito S, Matsuda T, Wada Y, Fujii T, Ikematsu H, Uraoka T, Kobayashi N, Nakamura H, Hotta K, Horimatsu T, Sakamoto N, Fu KI, Tsuruta O, Kawano H, Kashida H, Takeuchi Y, Machida H, Kusaka T, Yoshida N, Hirata I, Terai T, Yamano HO, Kaneko K, Nakajima T, Sakamoto T, Yamaguchi Y, Tamai N, Nakano N, Hayashi N, Oka S, Iwatate M, Ishikawa H, Murakami Y, Yoshida S, Saito Y. Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team. Dig Endosc. 2016 Jul;28(5):526-33. doi: 10.1111/den.12644. Epub 2016 Apr 20.
citation: Puig I, Lopez-Ceron M, Arnau A, Rosinol O, Cuatrecasas M, Herreros-de-Tejada A, Ferrandez A, Serra-Burriel M, Nogales O, Vida F, de Castro L, Lopez-Vicente J, Vega P, Alvarez-Gonzalez MA, Gonzalez-Santiago J, Hernandez-Conde M, Diez-Redondo P, Rivero-Sanchez L, Gimeno-Garcia AZ, Burgos A, Garcia-Alonso FJ, Bustamante-Balen M, Martinez-Bauer E, Penas B, Pellise M; EndoCAR group, Spanish Gastroenterological Association and the Spanish Digestive Endoscopy Society. Accuracy of the Narrow-Band Imaging International Colorectal Endoscopic Classification System in Identification of Deep Invasion in Colorectal Polyps. Gastroenterology. 2019 Jan;156(1):75-87. doi: 10.1053/j.gastro.2018.10.004. Epub 2018 Oct 6.