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

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.

References

  1. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393:1948–57.

    Article  PubMed  Google Scholar 

  2. Feingold PL, Kwong ML, Davis JL, Rudloff U. Adjuvant intraperitoneal chemotherapy for the treatment of gastric cancer at risk for peritoneal carcinomatosis: a systematic review. J Surg Oncol. 2017;115:192–201.

    Article  PubMed  Google Scholar 

  3. Borgstein ABJ, van Berge Henegouwen MI, Lameris W, Eshuis WJ, Gisbertz SS, Dutch Upper GICA. Staging laparoscopy in gastric cancer surgery. A population-based cohort study in patients undergoing gastrectomy with curative intent. Eur J Surg Oncol. 2021;47:1441–8.

    Article  PubMed  Google Scholar 

  4. Jamel S, Markar SR, Malietzis G, Acharya A, Athanasiou T, Hanna GB. Prognostic significance of peritoneal lavage cytology in staging gastric cancer: systematic review and meta-analysis. Gastric Cancer. 2018;21:10–8.

    Article  CAS  PubMed  Google Scholar 

  5. Japanese Gastric Cancer A. Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition). Gastric Cancer. 2023;26:1–25.

    Article  Google Scholar 

  6. American Joint Committee on Cancer. AJCC Cancer Staging Manual 8th Edition 2017.

  7. Lordick F, Carneiro F, Cascinu S, Fleitas T, Haustermans K, Piessen G, et al. Gastric cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33:1005–20.

    Article  CAS  PubMed  Google Scholar 

  8. Glehen O, Passot G, Villeneuve L, Vaudoyer D, Bin-Dorel S, Boschetti G, et al. GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study. BMC Cancer. 2014;14:183.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Koemans WJ, van der Kaaij RT, Boot H, Buffart T, Veenhof A, Hartemink KJ, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II). BMC Cancer. 2019;19:420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Valletti M, Eshmuminov D, Gnecco N, Gutschow CA, Schneider PM, Lehmann K. Gastric cancer with positive peritoneal cytology: survival benefit after induction chemotherapy and conversion to negative peritoneal cytology. World J Surg Oncol. 2021;19:245.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yoshida K, Yasufuku I, Terashima M, Young Rha S, Moon Bae J, Li G, et al. International retrospective cohort study of conversion therapy for stage IV gastric cancer 1 (CONVO-GC-1). Ann Gastroenterol Surg. 2022;6:227–40.

    Article  PubMed  Google Scholar 

  12. Mezhir JJ, Posner MC, Roggin KK. Prospective clinical trial of diagnostic peritoneal lavage to detect positive peritoneal cytology in patients with gastric cancer. J Surg Oncol. 2013;107:794–8.

    Article  PubMed  Google Scholar 

  13. Corcoran RB, Chabner BA. Application of cell-free DNA analysis to cancer treatment. N Engl J Med. 2018;379:1754–65.

    Article  CAS  PubMed  Google Scholar 

  14. Maron SB, Chase LM, Lomnicki S, Kochanny S, Moore KL, Joshi SS, et al. Circulating tumor DNA sequencing analysis of gastroesophageal adenocarcinoma. Clin Cancer Res. 2019;25:7098–112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Van’t Erve I, Rovers KP, Constantinides A, Bolhuis K, Wassenaar EC, Lurvink RJ, et al. Detection of tumor-derived cell-free DNA from colorectal cancer peritoneal metastases in plasma and peritoneal fluid. J Pathol Clin Res. 2021;7:203–8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–9.

    Article  Google Scholar 

  17. Zhao D, Yue P, Wang T, Wang P, Song Q, Wang J, et al. Personalized analysis of minimal residual cancer cells in peritoneal lavage fluid predicts peritoneal dissemination of gastric cancer. J Hematol Oncol. 2021;14:164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cristiano S, Leal A, Phallen J, Fiksel J, Adleff V, Bruhm DC, et al. Genome-wide cell-free DNA fragmentation in patients with cancer. Nature. 2019;570:385–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jacquet P, Sugarbaker PH. Peritoneal-plasma barrier. Cancer Treat Res. 1996;82:53–63.

    Article  CAS  PubMed  Google Scholar 

  20. Pu X, Li Z, Wang X, Jiang H. Ascites and serial plasma circulating tumor DNA for predicting the effectiveness of hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis. Front Oncol. 2022;12:791418.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

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