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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| dMMR/MSI-H GC | Experimental | Immunotherapy with induction chemotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immunotherapy | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | From the initiation of treatment to the date of surgery, an average of 14 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From the initiation of treatment to the date of surgery, an average of 14 weeks. |
| ypN stage |
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Inclusion Criteria:
cT≥2, any N, M0, assessed by the investigator as potentially resectable and planned for preoperative treatment followed by surgery.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhaoqing Tang | Contact | 021-64041990 | tang.zhaoqing@zs-hospital.sh.cn |
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Informed consent forms did not include provisions for public data sharing
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| Induction chemotherapy | Drug | Drug: Oxaliplatin Regimen: 1 cycle Dosage: 130mg/m^2 |
|
| D2 radical gastrectomy | Procedure | Curative-intent D2 radical gastrectomy is scheduled 4-6 weeks after completion of the fourth cycle. |
|
Lymph-node status after neoadjuvant therapy (ypN stage) will be assessed according to the American Joint Committee on Cancer (AJCC) 8th edition staging system. |
| 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. | 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. | 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. | From the initiation of treatment until death from any cause or 3 years since enrollment. |
| ID | Term |
|---|---|
| C536928 | Turcot syndrome |
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| ID | Term |
|---|---|
| D007167 | Immunotherapy |
| D060828 | Induction Chemotherapy |
| ID | Term |
|---|---|
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D004358 | Drug Therapy |
| D012074 | Remission Induction |
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