Biomarker Investigation for Early Gastric Cancer Detection

GASTROTRACK is a prospective, single-center clinico-biological cohort study conducted at Centre Léon Bérard (Lyon, France).

Participants undergoing upper gastrointestinal endoscopy will provide saliva and gastric juice samples. Tissue biopsies obtained during routine clinical care will undergo standard histopathological examination to establish the final diagnosis and classify participants as cancer or non-cancer. Patients diagnosed with advanced or metastatic non-operable GEC will continue longitudinal follow-up within the study.

For these patients, blood samples will be collected at predefined time points during standard clinical care. Tumor tissue collected during diagnostic procedures will also be analyzed. Saliva and gastric juice samples will be studied for miRNA expression and microbiome composition while plasma and tumor samples will be analyzed for ctDNA, circulating biomarkers, transcriptomic features and tumor microenvironment characteristics.

Through this multidisciplinary and translational approach, GASTROTRACK aims to support the development of risk-adapted diagnostic and surveillance strategies for gastric and gastroesophageal junction cancers.

• Saliva sampling (Procedure): Saliva will be collected during gastroscopy visit, before the intervention takes place.
• Gastric juice sampling (Procedure): Gastric juice will be collected during gastroscopy, at the beginning of the intervention.
• Blood sampling (Procedure): Blood samples will be collected at 3 timepoints during visits scheduled as part of standard of care: at C1D1 pre-dose (1st line treamtent after diagnosis), at C5D1 pre-dose (1st line treatment) and in case of disease progression during or after 1st line treatment.
• Tumor sampling (Procedure): Tumor samples collected if medically indicated during gastroscopy and at disease progression as part of standard of care will be used.

Primary outcomes

• Diagnostic performance of salivary and gastric juice biomarker signatures for identifying gastric and gastroesophageal junction cancer (GEC). [At gastroscopy]: Presence or absence of gastric or gastroesophageal junction cancer confirmed by histopathological examination following gastroscopy. Biomarker signatures derived from salivary and gastric juice miRNA expression profiles and microbiome composition will be evaluated through positive predictive value to discriminate patients with GEC from patients without GEC.

Secondary outcomes

• Presence of circulating tumor DNA (ctDNA) at baseline. [Baseline (C1D1 pre-dose)]: Detection of ctDNA in plasma collected at treatment initiation in patients with non operable GEC. Percentage of participants with detectable ctDNA.
• Longitudinal variation of ctDNA. [From baseline through disease progression (up to 24 months after last patient enrolled)]: Changes in ctDNA levels measured in serial plasma samples collected during follow-up.
• Association between ctDNA status and progression-free survival. [Up to 24 months after last patient enrolled]: Progression-free survival according to detectable versus non-detectable ctDNA.
• Association between ctDNA status and overall survival. [Up to 24 months after last patient enrolled]: Overall survival according to detectable versus non-detectable ctDNA.
• Plasma cytokine concentrations at baseline. [Baseline (C1D1 pre-dose)]: Plasma concentrations of cytokines measured using multiplex cytokine assays in patients with non operable GEC.
• Association between cytokine concentrations and progression occurrence. [Up to 24 months after last patient enrolled]
• Progression-free survival according to cytokine concentrations. [Up to 24 months after last patient enrolled]
• Overall survival according to cytokine concentrations. [Up to 24 months after last patient enrolled]
• Tumor transcriptomic profiles measured by RNA sequencing. [At gastroscopy and at disease progression (if available)]: Transcriptomic signatures identified using RNA sequencing on tumor samples collected at diagnosis and, if available, at disease progression.
• Tumor microenvironment characteristics measured by multiplex immunofluorescence (multi IF). [At gastroscopy and at disease progression (if available)]: Characterization of immune and stromal cell populations in tumor samples using multi IF.
• Association between microenvironment features and disease progression occurrence. [Up to 24 months after last patient enrolled]
• Overall survival associated with tumor microenvironment features. [Up to 24 months after last patient enrolled]
• Performance of an integrated multi-parametric biomarker model for prediction of survival outcomes. [Up to 24 months after last patient enrolled]: Integration of microbiome and miRNA signatures on saliva and gastric juice, ctDNA, plasma cytokine, tumor micro-environment features for the prediction of survival outcomes in patients with GEC .

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* I1. Patients ≥ 18 years at the day of signing informed consent.
* I2. Patients referred for upper gastrointestinal endoscopy due to upper GI symptoms such as dysphagia, unexplained anemia, persistent dyspepsia or melena or following initial GEC diagnosis in another institution.
* I3. Patients who have understood, dated, and signed the written voluntary informed consent form.
* I4. Patients affiliated with or benefiting from medical insurance.

Exclusion Criteria:

* E1. Patients with known active malignancy. Exceptions include adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer.
* E2. Patients with known genetic predisposition such as Lynch syndrome or hereditary diffuse gastric cancer.
* E3. Any condition contraindicating any procedure required by the protocol.
* E4. Patients presenting a psychological, familial, geographical, or social situation that, in the investigator's judgment, could potentially prevent the signing of informed consent and/or compliance with study procedures.
* E5. Pregnant or breast-feeding women.