The purpose of this study is to investigate the safety and efficacy of conversion therapy using HFRT combined with ICT in locally advanced or metastatic unresectable GEJA.
Histologically and/or cytologically confirmed diagnosis of locally advanced gastroesophageal junction adenocarcinoma (GEJA), Siewert type I-III, with staging of cT3-4, any N, M0 or cT2 N+, M0, according to the AJCC 8th edition.
Resectable locally advanced disease as determined by multidisciplinary team (MDT) assessment.
Age ≥18 years, regardless of sex.
ECOG performance status of 0 or 1.
Diagnosed as mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) by immunohistochemistry or gene testing.
Evidence of peritoneal or multi-organ metastatic disease, as confirmed by chest and abdominal CT, bone scan, or MRI (in cases with suspected osseous lesions).
History of or concurrent other malignancies within the past 5 years, excluding cured basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
Known allergy to any component of the investigational drugs, history of severe hypersensitivity, or any contraindication to study drugs.