NOMAD-GI: Molecular-guided Non-operative Management and Organ Preservation Strategy After Precision Therapy in Gastrointestinal Cancers

Korábbi kezelés

• 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.

Más betegség

• Uncontrolled progressive metastatic disease or clinical deterioration that precludes evaluation for the study treatment strategy.
• Severe comorbidities or medical conditions that make continued follow-up or additional treatment evaluation clinically inappropriate.
• Patients with conditions that require immediate radical surgery or other urgent treatment according to multidisciplinary clinical assessment and who cannot safely undergo the predefined study evaluation.

Egyéb

• Patients who are unable to undergo appropriate clinical, radiological, endoscopic, or pathological assessment required for response evaluation or follow-up.
• Inability or unwillingness to comply with the predefined follow-up schedule.
• Withdrawal of informed consent for prospective participants.
• Insufficient clinical information to determine eligibility, treatment response, treatment strategy, or follow-up outcomes.

• 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.
• Presence of at least one molecular biomarker that may support selection of precision therapy, including but not limited to:
  • Mismatch repair deficiency or microsatellite instability-high (dMMR/MSI-H);
  • Pathogenic or likely pathogenic POLE or POLD1 mutation;
  • High programmed death ligand 1 combined positive score (PD-L1 CPS), when applicable to the tumor type and treatment strategy;
  • Tumor mutational burden-high (TMB-H);
  • Epstein-Barr virus-positive status (EBV-positive), when applicable;
  • Human epidermal growth factor receptor 2 (HER2) positivity;
  • Claudin 18.2 (CLDN18.2) positivity;
  • Fibroblast growth factor receptor 2 (FGFR2) alteration;
  • Mesenchymal-epithelial transition factor (MET) amplification or other actionable MET alteration;
  • Neurotrophic tyrosine receptor kinase (NTRK) gene fusion;
  • Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation;
  • Other clinically actionable molecular alterations recognized according to contemporary clinical practice.
• Receipt of molecular biomarker-guided precision therapy before assessment for non-operative management or organ-preservation strategy. Precision therapy may include immune checkpoint inhibitor therapy, targeted therapy, or a combination of systemic therapies according to the participant's tumor type, molecular profile, clinical stage, and standard clinical practice.
• After completion or adequate exposure to precision therapy, achievement of a favorable clinical response that may support consideration of non-operative management or organ-preservation strategy, including clinical complete response (cCR), near-complete response (near-cCR), major tumor regression, or other predefined favorable response categories.
• Multidisciplinary team (MDT) evaluation has been performed to determine whether non-operative management, local treatment, organ-preservation strategy, or radical surgery is appropriate.
• Adequate clinical information is available for assessment of treatment response, including appropriate imaging, endoscopic evaluation, pathological evaluation, or other clinically indicated examinations.
• Ability and willingness to comply with the predefined surveillance and follow-up schedule.
• For the prospective cohort, written informed consent is obtained before enrollment and study-specific data collection.
• For the retrospective cohort, eligible clinical data are available in the institutional medical records and may be used according to institutional ethics approval and applicable regulations.