Accuracy for Predicting Deep Submucosal Invasion

Colorectal Cancer Clinical Trial

— NBIBLI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03748667
• Other study ID #: CEIC 18/53
• Status: Completed
• Start date: December 1, 2018
• Est. completion date: October 30, 2022

Study information

• Verified date: September 2023
• Source: Althaia Xarxa Assistencial Universitària de Manresa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 426
• Est. completion date: October 30, 2022
• Est. primary completion date: September 28, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Colorectal Polyp

Intervention

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.
• 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.

Locations

Country	Name	City	State
Japan	National Cancer Center	Tokyo
Spain	Hospital Comarcal de Alcañiz	Alcañiz	Teruel
Spain	Hospital Universitari Germans Trias i Pujol (Can Ruti)	Badalona	Cataluña
Spain	Centro Médico Teknon	Barcelona
Spain	Hospital Clínic de Barcelona	Barcelona	Cataluña
Spain	Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)	Barcelona	Cataluña
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Althaia. Xarxa Assistencial Universitària de Manresa	Manresa	Cataluña
Spain	Hospital Universitario y Politécnico de La Fe	Valencia	Comunidad Valenciana
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza	Aragón
United States	University of North Carolina	Chapel Hill	North Carolina
United States	San Francisco Veterans Affairs Medical Center. University of California	San Francisco	California

Sponsors (13)

Lead Sponsor

Collaborator

Althaia Xarxa Assistencial Universitària de Manresa

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

Countries where clinical trial is conducted

United States,  Japan,  Spain, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The presence or absence of deep invasion according to the control test (WLE)	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.	One day
Primary	The presence or absence of deep invasion according to the test evaluated (NBI/BLI +/- CE)	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.	One day
Primary	The presence or absence of deep invasion according to the gold standard (histology)	Deep invasion will be diagnosed if sm invasion =1000 µm is measured according to the Japanese guidelines by the central pathologists.	One day
Secondary	Presence of any genetic mutations	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.	one day
Secondary	Number of genome copies using SNP-arrays	Number of copies using SNP-arrays.	one day