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Longitudinal circulating tumor DNA analysis during treatment of locally advanced resectable gastric or gastroesophageal junction adenocarcinoma: the PLAGAST prospective biomarker study

Author

Listed:
  • Aziz Zaanan

    (Hôpital Européen Georges Pompidou
    Sorbonne Université)

  • Audrey Didelot

    (Sorbonne Université)

  • Chloé Broudin

    (Hôpital Georges Pompidou)

  • George Laliotis

    (Inc)

  • Erik Spickard

    (Inc)

  • Punashi Dutta

    (Inc)

  • Aurélien Saltel-Fulero

    (Hôpital Georges Pompidou)

  • Francesco Giulio Sullo

    (Hôpital Européen Georges Pompidou
    IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”)

  • Margot Pizzamiglio

    (Hôpital Européen Georges Pompidou)

  • Antoine Mariani

    (Hôpital Européen Georges Pompidou)

  • Widad Lahlou

    (Hôpital Européen Georges Pompidou)

  • Meenakshi Malhotra

    (Inc)

  • Shruti Sharma

    (Inc)

  • Himanshu Sethi

    (Inc)

  • Adham Jurdi

    (Inc)

  • Minetta C. Liu

    (Inc)

  • Pierre Laurent-Puig

    (Sorbonne Université
    APHP.Centre Paris)

Abstract

Patients with locally advanced resectable (LAR) gastric/gastroesophageal junction (G/GEJ) adenocarcinomas have a high recurrence risk despite pre- and post-operative treatment. In the PLAGAST prospective study (NCT02674373), we investigated the ability of circulating tumor DNA (ctDNA) to predict treatment response and improve risk stratification. Plasma samples were prospectively collected before neoadjuvant therapy (NAT), during-NAT, post-NAT, and post-surgery. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints were overall survival (OS), tumor regression grade (TRG), and pathological tumor stage. ctDNA positivity decreased over these four therapeutic timelines (69.6%, 51.2%, 26.8%, and 20%, respectively). ctDNA-positivity was associated with significantly worse outcomes during-NAT (RFS: HR = 6.17, P = 0.002; OS: HR = 4.71, P = 0.022), post-NAT (RFS: HR = 5.26, P = 0.001; OS: HR = 7.35, P = 0.001) and after surgery (RFS: HR = 12.94, P

Suggested Citation

  • Aziz Zaanan & Audrey Didelot & Chloé Broudin & George Laliotis & Erik Spickard & Punashi Dutta & Aurélien Saltel-Fulero & Francesco Giulio Sullo & Margot Pizzamiglio & Antoine Mariani & Widad Lahlou &, 2025. "Longitudinal circulating tumor DNA analysis during treatment of locally advanced resectable gastric or gastroesophageal junction adenocarcinoma: the PLAGAST prospective biomarker study," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62056-7
    DOI: 10.1038/s41467-025-62056-7
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