dMMR/MSI-H is a key molecular subtype of gastric cancer, found in 8-22% of cases. It is typically associated with older age, female sex, distal tumor location, and intestinal histology (Lauren classification). While this subtype predicts better survival in locally advanced disease, its prognostic role in metastatic settings is less clear. Notably, dMMR/MSI-H tumors are often resistant to conventional chemotherapy. Conversely, they demonstrate exceptional sensitivity to immunotherapy. This has led to effective strategies using immune checkpoint inhibitors, either alone or combined with chemotherapy, in both neoadjuvant and advanced disease settings. However, key challenges remain. Prospective data are largely from Western populations, leaving the efficacy in Asian patients-who bear a high disease burden-less defined. Furthermore, about half of dMMR/MSI-H patients exhibit primary or acquired resistance to immunotherapy. A deeper understanding of the tumor-immune dynamics during treatment is crucial to uncover resistance mechanisms and improve patient outcomes.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Drug: Immune checkpoint inhibitors (ICIs), specifically PD-1 antibodies, PD-L1 antibodies, PD-1/CTLA-4 bispecific antibodies, or PD-1/CTLA-4 combination therapy. Regimen: 4 treatment cycles.
Drug: Oxaliplatin Regimen: 1 cycle Dosage: 130mg/m\^2
Curative-intent D2 radical gastrectomy is scheduled 4-6 weeks after completion of the fourth cycle.
Rate of pathological complete response
The proportion of subjects exhibiting no residual tumor cells in the surgical specimen and the absence of positive lymph nodes (i.e., a pathological stage of ypT0N0).
Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.
Major Pathological Response Rate
The proportion of subjects with residual viable tumor cells accounting for \<10% of the surgical specimen from the primary tumor site.
Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.
ypN stage
Lymph-node status after neoadjuvant therapy (ypN stage) will be assessed according to the American Joint Committee on Cancer (AJCC) 8th edition staging system.
Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.
R0 resection rate
The proportion of patients who undergo surgery with microscopically negative resection margins.
Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.
Event-free Survival
The time from the subject's enrollment until disease progression, disease recurrence, or death from any cause.
Time frame: The time from the initiation of treatment until disease progression, disease recurrence, death from any cause, or 3 years since enrollment.
Overall Survival
The time from the subject's enrollment until death from any cause.
Time frame: From the initiation of treatment until death from any cause or 3 years since enrollment.
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