The NOMAD-GI study is a single-center, bidirectional cohort study designed to evaluate the safety and efficacy of molecular biomarker-guided non-operative management (NOM) and organ preservation strategies after precision therapy in patients with gastrointestinal cancers.
Patients with actionable molecular biomarkers, including dMMR/MSI-H, POLE mutation, PD-L1 high expression, tumor mutational burden-high (TMB-H), Epstein-Barr virus positivity (EBV+), HER2 positivity, CLDN18.2 positivity, and other actionable genomic alterations, will be enrolled.
After immune checkpoint inhibitor or targeted therapy, patients achieving favorable clinical responses will undergo multidisciplinary team (MDT) evaluation and receive either non-operative management, local treatment, or radical surgery according to individualized treatment decisions.
The study aims to establish a molecular-driven organ preservation paradigm for gastrointestinal cancers and evaluate whether NOM can provide comparable oncological outcomes while improving functional outcomes and quality of life.
Adults aged 18 years or older at the time of study enrollment.
Histologically confirmed gastrointestinal malignancy, including gastric cancer, gastroesophageal junction cancer, esophageal cancer, or colorectal cancer.
Mismatch repair deficiency or microsatellite instability-high (dMMR/MSI-H);
Pathogenic or likely pathogenic POLE or POLD1 mutation;
Uncontrolled progressive metastatic disease or clinical deterioration that precludes evaluation for the study treatment strategy.
Patients who are unable to undergo appropriate clinical, radiological, endoscopic, or pathological assessment required for response evaluation or follow-up.
Previous treatment history or concurrent medical conditions that, in the judgment of the multidisciplinary team, preclude reliable assessment of tumor response or implementation of the predefined surveillance strategy.
Severe comorbidities or medical conditions that make continued follow-up or additional treatment evaluation clinically inappropriate.