Clinical trial NCT04774367: Evaluation of the Reliability of the Determination of MisMatch Repair Deficiency Status by Endoscopic Biopsies in Oesophagus and Gastric Adenocarcinoma.
Official title: Evaluation of the Reliability of the Determination of MisMatch Repair Deficiency Status by Endoscopic Biopsies in Oesophagus and Gastric Adenocarcinoma.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Gastro-oesophageal Adenocarcinoma
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-03-01
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Sensitivity (Se) of the determination of the dMMR status by the endoscopic biopsies performed at the time of the initial high endoscopy
timeFrame: at inclusion
measure: Specificity (Spe) of the determination of the dMMR status by the endoscopic biopsies performed at the time of the initial high endoscopy
timeFrame: at inclusion
Secondary outcomes:
measure: Positive likelihood ratios
timeFrame: at inclusion
measure: Negative likelihood ratios
timeFrame: at inclusion
measure: Sensitivity of dMMR status diagnosis according to the forceps (standard and large capacity biopsy forceps )
timeFrame: at inclusion
measure: Specificity of dMMR status diagnosis according to the forceps (standard and large capacity biopsy forceps )
timeFrame: at inclusion
measure: Sensitivity of dMMR status diagnosis according to the techniques (immunohistochemistry and PCR)
timeFrame: at inclusion
measure: Specificity of dMMR status diagnosis according to the techniques (immunohistochemistry and PCR)
timeFrame: at inclusion
measure: Sensitivity of the diagnosis of MR status according to the location on the biopsies (esophagus, gastroesophageal junction, fundus, antrum)
timeFrame: at inclusion
measure: Specificityof the diagnosis of MR status according to the location on the biopsies (esophagus, gastroesophageal junction, fundus, antrum)
timeFrame: at inclusion
measure: Sensitivity of dMMR status diagnosis according to the number of techniques used (two techniques or one technique)
timeFrame: at inclusion
measure: Specificity of dMMR status diagnosis according to the number of techniques used (two techniques or one technique)
timeFrame: at inclusion
measure: Overall survival
timeFrame: up to 36 months
measure: Survival without recurrence
timeFrame: up to 36 months
Other outcomes:
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