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Improving diagnostic accuracy of identifying gastric cancer patients with peritoneal metastases: tumor-guided cell-free DNA analysis of peritoneal fluid


Detection of peritoneal dissemination (PD) in gastric cancer (GC) patients remains challenging. The feasibility of tumor-guided cell-free DNA (cfDNA) detection in prospectively collected peritoneal fluid (ascites and peritoneal lavage) was investigated and compared to conventional cytology in 28 patients. Besides conventional cytology, next generation sequencing was performed on primary tumor DNA and cell-free DNA from peritoneal fluid. Patients were retrospectively grouped into: a positive group (with PD) and a negative group (without PD). Detectable mutations were found in the primary tumor of 68% (n = 19). Sensitivity of PD detection by tumor-guided cfDNA analysis was 91%, compared to 64% by conventional cytology. Within the positive group (n = 11), tumor-guided cfDNA was detected in all patients with ascites samples (4/4, 100%) and in 86% (6/7) of the lavage samples, opposed to 4/4 (100%) patients with ascites and 43% (3/7) with lavage by conventional cytology. Within the negative group (n = 8), conventional cytology was negative for all samples. In two patients, tumor-guided cfDNA was detected in peritoneal lavage fluid. Interestingly, these 2 patients developed PD within 6 months, suggesting a prognostic value of tumor-guided cfDNA detection. This study showed that tumor-guided cfDNA detection in peritoneal fluids of GC patients is feasible and superior to conventional cytology in detecting PD.

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Fig. 1: Flowchart of patient selection and grouping of patients and samples.
Fig. 2: Mutational landscape found in 29 peritoneal fluid samples of 19 patients with gastric cancer.
Fig. 3: Overview of study patients and samples.
Fig. 4: Diagnostic accuracy of conventional cytology versus detection of cell-free tumor DNA analysis calculated per patient in a study group of 17 patients with PD (n = 11) and without PD (n = 6) at the time of sampling.

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Data availability

The data generated in this study are available upon request from the corresponding author.


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Dr. F.J.C. ten Kate (Isala) and Dr. M. Kocken (Spaarne) for their contribution regarding sample collection.


KvdS received a research grant from the Dutch Cancer Society (KWF).

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Conceptualization: KvdS, JWvS, MCB, LLK; Methodology: KvdS, JWvS, MCB, LLK; Formal Analysis: KvdS, EV, MCB, LLK; Resources: LLK; Data Curation: KvdS, JWvS, NH, KJH, AAFAV, EV, MCB, LLK; Writing-original draft: KvdS, JWvS, MV, MCB, LK; Writing-Review, editing: KvdS, JWvS, MAV, JMvD, NH, KJH, AAFAV, EV, JvdB, PS, MN, TvW, MCB, LLK; Visualization; KvdS; Supervision: JWvS, MAV, MCB, LLK; Funding: KvdS, JWvS, LLK.

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Correspondence to Liudmila L. Kodach.

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van der Sluis, K., van Sandick, J.W., Vollebergh, M.A. et al. Improving diagnostic accuracy of identifying gastric cancer patients with peritoneal metastases: tumor-guided cell-free DNA analysis of peritoneal fluid. Oncogene 43, 1877–1882 (2024).

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