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

Aziz Zaanan ^1,2, Audrey Didelot ³, Chloé Broudin ⁴

¹Université Paris Cité; Assistance Publique - Hôpitaux de Paris, Department of Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France. aziz.zaanan@aphp.fr.
²Centre de Recherche des Cordeliers, Université Paris Cité, INSERM, Sorbonne Université, Paris, France. aziz.zaanan@aphp.fr.
³Centre de Recherche des Cordeliers, Université Paris Cité, INSERM, Sorbonne Université, Paris, France.
⁴Assistance Publique - Hôpitaux de Paris, Université Paris Cité Department of Pathology, Hôpital Georges Pompidou, Paris, France.
⁵Natera, Inc, Austin, TX, USA.
⁶Assistance Publique - Hôpitaux de Paris, Université Paris Cité Department of Radiology, Hôpital Georges Pompidou, Paris, France.
⁷Université Paris Cité; Assistance Publique - Hôpitaux de Paris, Department of Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France.
⁸IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
⁹Université Paris Cité; Assistance Publique - Hôpitaux de Paris, Digestive and Oncological Surgery Department, Hôpital Européen Georges Pompidou, Paris, France.
¹⁰Institut du cancer Paris Carpem, Université Paris Cité, Assistance Publique Hôpitaux de Paris, APHP.Centre Paris, Paris, France.

⁰Université Paris Cité; Assistance Publique - Hôpitaux de Paris, Department of Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France. aziz.zaanan@aphp.fr.

Nature Communications +

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July 24, 2025

View abstract on PubMed

Summary

Monitoring circulating tumor DNA (ctDNA) in patients with locally advanced resectable (LAR) gastric/gastroesophageal junction (G/GEJ) adenocarcinoma can predict treatment response and survival outcomes. Early ctDNA clearance indicates better prognosis, while persistent positivity signals poor outcomes.

Area Of Science

Oncology
Molecular Diagnostics
Gastroenterology

Background

Locally advanced resectable (LAR) gastric/gastroesophageal junction (G/GEJ) adenocarcinomas carry a high risk of recurrence.
Current pre- and post-operative treatments offer limited risk stratification for these patients.

Purpose Of The Study

To investigate the utility of circulating tumor DNA (ctDNA) in predicting treatment response and improving risk stratification for LAR G/GEJ adenocarcinomas.
To evaluate the prognostic value of longitudinal ctDNA monitoring in relation to recurrence-free survival (RFS) and overall survival (OS).

Main Methods

Prospective PLAGAST study (NCT02674373) involving patients with LAR G/GEJ adenocarcinomas.
Plasma samples collected at four time points: before neoadjuvant therapy (NAT), during-NAT, post-NAT, and post-surgery.
Analysis of ctDNA positivity and its correlation with RFS, OS, tumor regression grade (TRG), and pathological tumor stage.

Main Results

ctDNA positivity significantly decreased across the treatment timelines (69.6% to 20%).
ctDNA-positivity at all stages (during-NAT, post-NAT, post-surgery) was associated with significantly worse RFS and OS.
Early ctDNA clearance during NAT correlated with better outcomes, whereas persistent ctDNA positivity indicated the poorest prognosis.

Conclusions

Longitudinal ctDNA monitoring is a valuable prognostic tool for patients with LAR G/GEJ adenocarcinoma.
ctDNA dynamics can potentially guide therapeutic decision-making and personalize treatment strategies for improved patient outcomes.