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

Aziz Zaanan (), Audrey Didelot, Chloé Broudin, George Laliotis, Erik Spickard, Punashi Dutta, Aurélien Saltel-Fulero, Francesco Giulio Sullo, Margot Pizzamiglio, Antoine Mariani, Widad Lahlou, Meenakshi Malhotra, Shruti Sharma, Himanshu Sethi, Adham Jurdi, Minetta C. Liu and Pierre Laurent-Puig
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Aziz Zaanan: Hôpital Européen Georges Pompidou
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
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

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: 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

Date: 2025
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DOI: 10.1038/s41467-025-62056-7

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