What question did this study set out to answer?

This research aims to assess the clinical performance of the Signatera Genome assay for predicting treatment responses in locally advanced gastric cancer.

April 5, 2026

Abstract 2331: Clinical performance of Signatera Genome assay to predict treatment response and prognosticate outcomes in patients with locally advanced (LAR) resectable gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: Results from the PLAGAST Study

Key Points

This research aims to assess the clinical performance of the Signatera Genome assay for predicting treatment responses in locally advanced gastric cancer.
Analyzed residual samples from patients with locally advanced gastric cancer in the PLAGAST study.
Designed Signatera Genome assays using tumor and normal whole-genome sequencing data.
Monitored ctDNA levels in plasma samples at multiple time points during and after neoadjuvant therapy.
Utilized Cox regression to correlate ctDNA status with disease-free and overall survival.
Median patient age was 66, with 65% being male and 57% having gastric cancer.
ctDNA positivity at post-NAT showed significantly worse recurrence-free (HR: 5.4) and overall survival (HR: 5.42).
Postoperative ctDNA positivity was linked to poorer outcomes, with HRs of 9.78 for recurrence-free survival and 12.98 for overall survival during the MRD window.
ctDNA status was identified as a significant independent risk factor for survival compared to other clinical features.

Abstract

Abstract Background: Circulating tumor DNA (ctDNA) is a clinically validated biomarker across multiple gastrointestinal cancers, used to predict recurrence risk, monitor response to neoadjuvant therapy (NAT), and detect molecular residual disease (MRD) post-definitive treatment. Signatera™ is a personalized, tumor-informed, multiplex PCR-NGS ctDNA assay that can be developed using either whole-exome sequencing (WES) or whole-genome sequencing (WGS). Initial clinical validation of Signatera Genome in select clinical contexts of a pancancer cohort showed robust performance. Here, we evaluated the performance of Signatera Genome in pts with LAR G/GEJ cancer enrolled in the PLAGAST prospective study (NCT02674373). Methods: A retrospective analysis was conducted using residual samples from pts with LAR G/GEJ cancer in the PLAGAST study (N=54). Signatera Genome assays were designed from matched tumor and normal WGS data and used to detect ctDNA in the corresponding pts’ plasma samples collected at pre-NAT (or pre-surgery for NAT-naive), during-NAT, post-NAT, and post-surgery in the MRD window (within 2−12 weeks, before adjuvant treatment). ctDNA levels were quantified as mean tumor molecules per mL of plasma (MTM/mL). Longitudinal blood samples represented time points pre-/post-definitive treatment until recurrence or the end of follow-up. The correlation between ctDNA status and disease-free survival (DFS)/overall survival (OS) was assessed using Cox regression analysis. Results: The median pt age was 66 (34-86) years. The majority of pts were males (65%), had gastric cancer (57%), and received NAT (87%). Pts with post-NAT, pre-surgery ctDNA positivity had significantly worse outcomes (RFS: HR: 5.4, 95% CI: 1.68-17.37; p=0.005; OS: HR: 5.42, 95% CI: 1.5-28.73; p=0.0085). Postoperative survival analysis demonstrated that ctDNA positivity during the MRD window was also associated with worse RFS (HR: 9.78, 95% CI: 3.41-28.07, p0.0001) and OS (HR: 12.98, 95% CI: 3.69-45.67; p0.0001). Multivariate analyses showed ctDNA status post-NAT and within the MRD window to be the most significant independent risk factor for both RFS and OS compared to other clinicopathological features (post-NAT: RFS: HR: 5.53, p=0.005; OS: HR: 6.51, p=0.029; MRD window: RFS: HR: 4.97, p=0.014; OS: HR: 4.28, p=0.031). Conclusions: Persistent ctDNA positivity at post-NAT/pre-surgery timepoint and in the MRD window were strongly prognostic of inferior outcomes. These data indicate the robust clinical performance of Signatera Genome in pts with LAR G/GEJ adenocarcinoma and support its potential clinical utility in this disease setting. Prospective clinical trials are warranted to establish the clinical utility of the assay for guiding treatment decisions. Citation Format: Aziz Zaanan, Michael Khayat, Erik Spickard, George Laliotis, Punashi Dutta, Meenakshi Malhotra, Shruti Sharma, Gabrielle Heilek, Adham Jurdi, Minetta C. Liu, Pierre Laurent-Puig. Clinical performance of Signatera Genome assay to predict treatment response and prognosticate outcomes in patients with locally advanced (LAR) resectable gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: Results from the PLAGAST Study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2331.

Ask AI

Helpful

Bookmark