Detection of Aneuploidy in Cell Free DNA to Improve the Sensitivity of Diagnostic Peritoneal Lavage in Gastric Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Other: collection additional peritoneal lavage fluid

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 63

Contacts and Locations

• Study Contact: Name: Jessie Huizer, Drs.; Phone Number: +31107034523; Email: t.j.huizer@erasmusmc.nl
• Study Contact Backup: Name: Niels Guchelaar; Email: n.guchelaar@erasmusmc.nl

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3015GD
    • Erasmus MC
    • Contact: Niels Guchelaar; Email: n.guchelaar@erasmusmc.nl
    • Contact: Jessie Huizer, Drs; Phone Number: +31107034523; Email: t.j.huizer@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

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);

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Gastric cancer patients; Operable patients who will undergo DLS for GC. Patients will be identified from the MDT (multidisciplinary tumor board).	Other: collection additional peritoneal lavage fluid; collection additional peritoneal lavage fluid
non-cancer controls; Patients who will undergo a planned laparoscopy for bariatric or gallbladder disease	Other: collection additional peritoneal lavage fluid; collection additional peritoneal lavage fluid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity mFast-SeqS	The primary endpoint is the sensitivity of the mFast-SeqS technique in patients with GC, and refers to the ability of the mFast-SeqS technique to correctly identify patients with the pres-ence of tumor cells in the peritoneal cavity.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS	No locoregional or distant recurrence of disease,	2 years
Concordance detection rates peritoneal dissemination	• Concordance of detection rates of peritoneal dissemination will be analyzed using cohen's kappa/mcNemar's test	4 years

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Investigators: Principal Investigator: Bianca Mostert, MD, Erasmus Medical Center; Principal Investigator: Sjoerd Lagarde, MD, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: March 7, 2024
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: cfDNA; peritoneal metastasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Chromosome Aberrations; Stomach Neoplasms; Aneuploidy
• Other Study ID Numbers: MEC-2024tba

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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