Aneuploidy may be used as a more sensitive diagnostic tool to detect peritoneal metastasis compared to conventional cytology and imaging techniques. Our aim is to establish whether aneuploidy as detected in cfDNA (as a measure for ctDNA) in PLF of patients with GC may hold value as an additional staging and tumor evaluation method in GC patients.

To ensure the appropriate treatment strategy for gastric cancer, various methods are employed to determine clinical disease stage. Peritoneal metastases are common in gastric cancer, but accurately detecting these peritoneal metastasis using conventional imaging techniques remains challenging. To increase the sensitivity of staging when gastric cancer appears resectable on CT imaging, a diagnostic peritoneal staging laparoscopy (DLS) is performed. During DLS, the abdominal cavity is inspected for the presence of macroscopic peritoneal metastasis. Furthermore, a peritoneal lavage with saline is performed, and the collected fluid is examined by a pathologist for the presence of cancer cells. However, the sensitivity of this cytological evaluation is limited, and as a result of false negative results, patients currently unjustly undergo treatment with curative intent, exposing them to the risks and side-effects of surgery and intensive perioperative chemotherapy. A more sensitive technique to detect peritoneal metastases during staging would lead to better personalized treatment; less toxic palliative treatment, or more intensive peritoneum-directed therapy in a trial setting in selected patients.

A more sensitive diagnostic tool to detect peritoneal metastasis compared to conventional cytology and imaging techniques may be the detection of ctDNA. One way to detect ctDNA is by assessing aneuploidy, as its presence reflects the fraction of circulating tumor DNA within cell-free DNA.

Objective:To assess the value of ctDNA detection using aneuploidy analyses of peritoneal lavage fluid using mFAST-SeqS method in a prospective cohort of patients with gastric cancer who undergo a staging laparoscopy, in addition to the current staging methods (cytology, radiology, laparoscopy) and blood ctDNA analysis.

Gastric cancer patients:

Inclusion Criteria:

• Age ≥18 years old;
• Written informed consent according to the ICH-GCP and national/local regula-tions.

Exclusion Criteria:

- Language difficulty, dementia or altered mental status prohibiting the under-standing and giving of informed consent.

non-cancer controls:

Inclusion criteria:

• Operable patients who will undergo a planned diagnostic laparoscopy for a benign indication bariatric or gallbladder disease);
• Age ≥18 years old;
• Written informed consent according to the ICH-GCP and national/local regulations.

Exclusion criteria:

• Active inflammation or infection;
• Subjects with previous malignancies are excluded unless a complete remission was achieved at least 5 years prior to study entry (exceptions include but are not limited to, non-melanoma skin cancers; in situ bladder cancer, or in situ co-lon cancers; in situ cervical cancers/dysplasia; or breast carcinoma in situ).

Gastric cancer patients:

Patients who will undergo DLS for GC or GEJ carcinoma

Non-cancer controls:

Operable patients who will undergo a planned diagnostic laparoscopy for a benign indication (bariatric or gallbladder disease);