NBIBLI: Accuracy for Predicting Deep Submucosal Invasion

Sponsor

Althaia Xarxa Assistencial Universitària de Manresa (Other)

Overall Status

Recruiting

CT.gov ID

NCT03748667

Collaborator

Hospital Universitario La Fe (Other), Hospital Clínico Universitario Lozano Blesa (Other), University of North Carolina, Chapel Hill (Other), Hospital Clinic of Barcelona (Other), National Cancer Center, Japan (Other), Germans Trias i Pujol Hospital (Other), Hospital Universitario 12 de Octubre (Other), Hospital Universitario Ramon y Cajal (Other), San Francisco Veterans Affairs Medical Center (U.S. Fed), Hospital Universitario Virgen de la Arrixaca (Other), Hospital Comarcal de Alcañiz (Other), Centro Medico Teknon (Other)

1,158

Enrollment

Locations

Anticipated Duration (Months)

82.7

Patients Per Site

2.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Colorectal Polyp	Diagnostic Test: White light endoscopy (WLE) Diagnostic Test: NBI/BLI +/- chromoendoscopy (NBIBLI +/- CE)

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).

Study Design

Study Type:

Observational

Anticipated Enrollment :

1158 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

Diagnostic Accuracy of Deep Submucosal Invasion: White Light Endoscopy vs Invasive Pattern Based on NBI/BLI ± Chromoendoscopy

Actual Study Start Date :

Dec 1, 2018

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Patients with colorectal polyps Patients with non-pedunculated type 0 lesions in Paris classification (not obvious cancers) larger than 10 mm	Diagnostic Test: White light endoscopy (WLE) Subjective endoscopic assessment of deep submucosal invasion based on the presence of gross morphological malignant features, morphology and size. Diagnostic Test: NBI/BLI +/- chromoendoscopy (NBIBLI +/- CE) Endoscopic assessment of deep submucosal invasion with NBI and dual focus/magnification or BLI and magnification. In the case of demarcated areas or JNET 2B, Kudo pit pattern assessment with crystal violet will be performed.

Arm

Intervention/Treatment

Patients with colorectal polyps

Patients with non-pedunculated type 0 lesions in Paris classification (not obvious cancers) larger than 10 mm

Diagnostic Test: White light endoscopy (WLE)

Subjective endoscopic assessment of deep submucosal invasion based on the presence of gross morphological malignant features, morphology and size.

Diagnostic Test: NBI/BLI +/- chromoendoscopy (NBIBLI +/- CE)

Endoscopic assessment of deep submucosal invasion with NBI and dual focus/magnification or BLI and magnification. In the case of demarcated areas or JNET 2B, Kudo pit pattern assessment with crystal violet will be performed.

Outcome Measures

Primary Outcome Measures

The presence or absence of deep invasion according to the control test (WLE) [One day]
Deep invasion will subjectively be diagnosed based on the presence of gross morphological malignant features, morphology and size. No single malignant feature, specific morphology or size is required. The importance given to each criterion and the final diagnosis of deep invasion is based on the personal experience of the endoscopist.
The presence or absence of deep invasion according to the test evaluated (NBI/BLI +/- CE) [One day]
Deep invasion will be diagnosed in case of: JNET type 3 or JNET 2B + Kudo Vn pit pattern or JNET 2B and Kudo Vi pit pattern fulfilling all the following criteria: severe Kudo Vi pit pattern + presence of a demarcated area + size (demarcated area) >6 mm for PG or 3 mm for NPG.
The presence or absence of deep invasion according to the gold standard (histology) [One day]
Deep invasion will be diagnosed if sm invasion ≥1000 μm is measured according to the Japanese guidelines by the central pathologists.

Secondary Outcome Measures

Presence of any genetic mutations [one day]
Sequencing of a panel of colorectal cancer genes: the 45 genes will be sequenced frequently mutated in colorectal cancer, through the protocols established in the center Executor: APC, TP53, FBXW7, SOX9, ATM, SMAD4, KRAS, PIK3CA, AMER1, FAT4, ARID1A, BRAF, NRAS, CTNNB1, TCF7L2, ERBB2, MET, EGFR, HRAS, SETD2, DLC1, CDKN2A, PTEN, ARID2, FAT1, POLE, POLD1, NOTCH1, BRCA2, LRP1B, KMT2C, KMT2D, DAPK1, CSMD1, MUC16, ADAMTS15, SYNE1, PCLO, ZFHX4, RYR3, RYR2, RELN, IRS2, GNAS, DMBT1.
Number of genome copies using SNP-arrays [one day]
Number of copies using SNP-arrays.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Francisco Veterans Affairs Medical Center. University of California	San Francisco	California	United States	94121
2	University of North Carolina	Chapel Hill	North Carolina	United States	27599
3	National Cancer Center	Tokyo		Japan	104-0045
4	Hospital Clínico Universitario Lozano Blesa	Zaragoza	Aragón	Spain	50009
5	Hospital Universitari Germans Trias i Pujol (Can Ruti)	Badalona	Cataluña	Spain	08916
6	Hospital Clínic de Barcelona	Barcelona	Cataluña	Spain	08036
7	Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)	Barcelona	Cataluña	Spain	08036
8	Althaia. Xarxa Assistencial Universitària de Manresa	Manresa	Cataluña	Spain	08243
9	Hospital Universitario y Politécnico de La Fe	Valencia	Comunidad Valenciana	Spain	46009
10	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar	Murcia	Spain	30120
11	Hospital Comarcal de Alcañiz	Alcañiz	Teruel	Spain	44600
12	Centro Médico Teknon	Barcelona		Spain	08022
13	Hospital Ramón y Cajal	Madrid		Spain	28034
14	Hospital 12 de Octubre	Madrid		Spain	28041