Evaluation of the Reliability of the Determination of MisMatch Repair Deficiency Status by Endoscopic Biopsies in Oesophagus and Gastric Adenocarcinoma. (BIOPSYGAST MMR)

Gastro-esophageal adenocarcinoma is one of the most common cancer in the world and the fourth most common cancer in France with more than 6,000 cases per year. For non-metastatic patients, a preoperative chemotherapy is recommended.

As colorectal adenocarcinomas, gastroesophageal cancers (OGC) could be caused by a failure of DNA repair related to the loss of expression of one of the DNA repair proteins (MLH1, MSH2, PMS2, MSH6) (deficient MMR (dMMR)). The prevalence of tumors with dMMR is evaluated at 14% (Choi et al, 2014; Kim et al, 2015). This proportion reaches 25% among patients over 70 years old. Evidence suggests that patients with dMMR tumors do not benefit from neoadjuvant chemotherapy (Smyth et al, 2017), which may even have a negative impact, especially in elderly patients, and which should be discussed in this particular situation. The decision of neo-adjuvant chemotherapy must be taken very quickly after the endoscopic diagnosis.

The investigators will evaluate the diagnostic performance of the determination of dMMR status by endoscopic biopsies of OGC.

Moreover, there is no clear recommendation for the determination of dMMR status in OGC especially regarding the size of the forceps to use to ensure the quality of samples and the best molecular techniques for dMMR status determination.

Methods In this prospective study, the investigators will include patients who will benefit from an upper endoscopy within 5 French hospital centers (Saint-Louis, Lariboisière, Beaujon, Bichat and Avicenne) linked to the NORDICAP network. If a suspect lesion of OGC is discovered during the gastroscopy, the endoscopist will perform at least 8 endoscopic biopsies, according to the recommendations, and by the mean of 2 kinds of forceps: standard biopsy forceps and a large capacity biopsy forceps. The clinical and follow-up data will be prospectively collected and will include demographics data, cancer stage, lymph node invasion, treatment history, recurrence and survival data. The investigators will assess MSI status by genotyping and MMR proteins expression by immunochemistry (IHC), performed, for each patient, on both biopsies and surgical tumor samples.

Expected results This study will allow us to compare diagnostic performance of endoscopic biopsies to surgical samples for the assessment of dMMR status. Likewise, the investigators will compare the diagnostic performance of the two kinds of endoscopic forceps and of IHC and genotyping for the determination of dMMR phenotype. It will enable us to establish recommendations for the benefit of gastro-enterologists and pathologists.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastro-oesophageal Adenocarcinoma
• Intervention / Treatment: Device: Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps; Device: Order of forceps : First large capacity biopsy forceps and second standard biopsy forceps

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas APARICIO; Phone Number: +33142499597; Email: thomas.aparicio@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Eligible criteria :

• Patient having endoscopic oesogastroduodenal endoscopy for suspicion of oesogastro-duodenal adenocarcinoma.
• Benefiting from the social security system

Inclusion Criteria:

• Patient having endoscopy biopsies in front of a suspicious lesion suggestive of gastroesophageal adenocarcinoma

Exclusion Criteria:

• Minor patient (<18 years old)
• known pregnancy
• Major patient under tutorship or curatorship
• Contraindication to gastric biopsies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps	Device: Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps; Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps
Other: Order of forceps : First large capacity biopsy forceps and second standard biopsy forceps	Device: Order of forceps : First large capacity biopsy forceps and second standard biopsy forceps; Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity (Se) of the determination of the dMMR status by the endoscopic biopsies performed at the time of the initial high endoscopy	The sensitivity will be evaluated by comparing the endocospic result with that obtained by the analysis of the specimen considered as the reference examination.	at inclusion
Specificity (Spe) of the determination of the dMMR status by the endoscopic biopsies performed at the time of the initial high endoscopy	The specificity will be evaluated by comparing the endocospic result with that obtained by the analysis of the specimen considered as the reference examination.	at inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	up to 36 months
Positive likelihood ratios	at inclusion
Negative likelihood ratios	at inclusion
Sensitivity of dMMR status diagnosis according to the forceps (standard and large capacity biopsy forceps )	at inclusion
Specificity of dMMR status diagnosis according to the forceps (standard and large capacity biopsy forceps )	at inclusion
Sensitivity of dMMR status diagnosis according to the techniques (immunohistochemistry and PCR)	at inclusion
Specificity of dMMR status diagnosis according to the techniques (immunohistochemistry and PCR)	at inclusion
Sensitivity of the diagnosis of MR status according to the location on the biopsies (esophagus, gastroesophageal junction, fundus, antrum)	at inclusion
Specificityof the diagnosis of MR status according to the location on the biopsies (esophagus, gastroesophageal junction, fundus, antrum)	at inclusion
Sensitivity of dMMR status diagnosis according to the number of techniques used (two techniques or one technique)	at inclusion
Specificity of dMMR status diagnosis according to the number of techniques used (two techniques or one technique)	at inclusion
Survival without recurrence	up to 36 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: February 24, 2021
• First Submitted That Met QC Criteria: February 24, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 3, 2021
• Last Update Submitted That Met QC Criteria: March 1, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: APHP180152

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No