Relationship Between Perioperative Treatment Efficacy and The Tumor Microenvironment for Locally Advanced Resectable Gastric Cancer.

Official title

An Observational Study of Relationship Between Perioperative Treatment Efficacy and The Tumor Microenvironment for Locally Advanced Resectable Gastric and Gastro-oesophageal Junction Adenocarcinoma

Overview

Perioperative drug treatment has gradually become the standard regimen for locally advanced gastric cancer, whereas only a subset of patients could benefit from it. Therefore, one major challenge for perioperative drug treatment is to construct promising biomarkers and to screen out potential beneficial patients. Recent evidence has revealed that tumor microenvironment (TME) is highly associated with the prognosis of gastric cancer. Meanwhile, tumor microenvironment score (TMEscore) established with transcriptomic data is a robust biomarker for predicting prognosis and guiding individualized immunotherapy strategies. However, its predictive value for perioperative drug treatment outcomes warrants further exploration and validation. The study is a multi-center, observational study to evaluate the relationship between the efficacy of perioperative treatment and tumor microenvironment in patients with locally advanced resectable gastric and gastro-oesophageal junction adenocarcinoma, aiming at further determining the predictive value of TMEscore and establishing a comprehensive treatment-efficacy evaluation system for gastric cancer.

Detailed description

Perioperative drug treatment has gradually become the standard regimen for locally advanced gastric cancer, whereas only a subset of patients could benefit from it. Therefore, one major challenge for perioperative drug treatment is to construct promising biomarkers and to screen out potential beneficial patients. Recent evidence has revealed that tumor microenvironment (TME) is highly associated with the prognosis of gastric cancer. Meanwhile, tumor microenvironment score (TMEscore) established with transcriptomic data is a robust biomarker for predicting prognosis and guiding individualized immunotherapy strategies. However, its predictive value for perioperative drug treatment outcomes warrants further exploration and validation. The study is a multi-center, observational study to evaluate the relationship between the efficacy of perioperative treatment and tumor microenvironment in patients with locally advanced resectable gastric and gastro-oesophageal junction adenocarcinoma, aiming at further determining the predictive value of TMEscore and establishing a comprehensive treatment-efficacy evaluation system for gastric cancer. Eligible subjects were selected according to the inclusion criteria and exclusion criteria. After the successful screening, the patients were treated in accordance with the clinical guidelines and the actual conditions. The residual tissue samples of the primary tumor were collected to conduct the tumor microenvironment detection. After routine neoadjuvant therapy, followed by a restaging of the tumor status and surgery. The residual surgical specimens were collected to conduct the tumor microenvironment detection analysis.

Interventions

• Other non-intervention
  non-intervention

Primary outcome measures

• Major pathologic response (MPR) rate [Time frame: From the initiation date of first cycle to the date of surgery, an average of 10 weeks]

Secondary outcome measures (3)

• Pathological complete response (pCR) rate [Time frame: From the initiation date of first cycle to the date of surgery, an average of 10 weeks]
• R0 resection rate [Time frame: From the initiation date of first cycle to the date of surgery, an average of 10 weeks]
• Disease-free Survival (DFS) [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Histologically or cytologically confirmed locally advanced resectable gastric and gastro-oesophageal junction adenocarcinoma at the stage of cT2-T4aNxM0 (AJCC 8th) without distant metastases and without infiltration of adjacent structures and organs.
• 18-75 years old.
• Willing to provide residual tumor tissues after routine clinical diagnosis for tumor microenvironment detection analysis.
• Patients agree to participate in the study and sign the informed consent.
• Patients need to receive perioperative drug therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.

Exclusion criteria

• Human epidermal growth factor receptor 2 (HER2) is positive, that is, tissue immunohistochemical staining (IHC) (3+) or IHC (2+), and tissue fluorescence in situ hybridization (FISH) is positive.
• Patients with major cardiovascular and cerebrovascular diseases (such as congestive heart failure, unstable heart colic, atrial fibrillation, stroke, transient ischemic attack, etc.).
• Allergies or contraindications to common chemotherapy drugs, immunotherapy drugs or the ingredients.
• Women who are pregnant, breast-feeding.
• Other conditions the investigator believes that it is not suitable to participate in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Nanfang Hospital, Southern Medical University — Guangzhou

Publications

• Shi M, Zeng D, Luo H, Xiao J, Li Y, Yuan X, Huang N, Wu J, Zheng S, Wu J, Li S, Rong X, Wang C, Jiang L, Mao Q, Qiu W, Guo J, Deng Q, Sun H, Lu X, Yu Y, Lai Y, Fang Y, Zhou R, Wang L, Huang X, Kong Y, Li J, Liang L, Bin J, Liao Y, Liao W. Tumor microenvironment RNA test to predict immunotherapy outcomes in advanced gastric cancer: The TIMES001 trial. Med. 2024 Nov 8;5(11):1378-1392.e3. doi: 10.101 PMID 39089261

Identifiers

NCT: NCT04850729 · NFEC-2021-082

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗