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

Oncogene (2024)Cite this article

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Abstract

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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Acknowledgements

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

Funding

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

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Author notes

  1. These authors contributed equally: Mirjam C. Boelens, Liudmila L. Kodach.

Authors and Affiliations

  1. The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Surgical Oncology, Amsterdam, The Netherlands

    Karen van der Sluis, Johanna W. van Sandick, Niek Hugen, Koen J. Hartemink & Alexander A. F. A. Veenhof

  2. The Netherlands Cancer Institute- Antoni van Leeuwenhoek, Department of Gastrointestinal Oncology, Amsterdam, The Netherlands

    Marieke A. Vollebergh & Jolanda M. van Dieren

  3. The Netherlands Cancer Institute- Antoni van Leeuwenhoek, Department of Pathology, Amsterdam, The Netherlands

    Els Verhoeven, José G. van den Berg, Petur Snaebjornsson, Michael Noe, Tom van Wezel, Mirjam C. Boelens & Liudmila L. Kodach

  4. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    Petur Snaebjornsson

Authors
  1. Karen van der Sluis
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  14. Liudmila L. Kodach
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Contributions

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.

Corresponding author

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 (2024). https://doi.org/10.1038/s41388-024-03034-z

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