In this study, perioperative propranolol β-blockade was administered to patients with surgically resectable primary gastrointestinal tumors to explore the safety, efficacy, and alleviation of perioperative psychological stress. At the same time, a multi-omics study was conducted using clinical samples to explore the activation of anti-tumor immune response and its mechanism.
This is a single-center, randomized controlled pilot exploratory clinical study to enroll 20 patients with surgically resectable primary gastric cancer and 20 patients with surgically resectable primary colorectal cancer. Each enrolled patient will be assigned a case number. This case number and the patient's initials will be entered on each page of the case report form. Trial group (10 patients with gastric cancer and 10 patients with intestinal cancer): Enrolled patients will be hospitalized for 10-14 days of preoperative propranolol β-blockade monotherapy prior to surgery (including the day of surgery) for evaluation of efficacy and safety. Control group (10 cases of gastric cancer and 10 cases of intestinal cancer): no propranolol drug treatment. Patients will be observed during the treatment period and at 6 months, 12 months and 24 months after treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Enrolled patients began receiving propranolol alone orally twice daily (10 mg bid) 10-14 days prior to surgery, and after 3 days of treatment, the dose of propranolol was increased to 20 mg bid daily until the day of surgery if the following three predefined criteria were met: systolic blood pressure greater than 90 mmHg, heart rate greater than 60 bpm, and no significant symptoms (e.g., syncope, insomnia, fatigue). The patient continues to be treated from 1 week after surgery.From 1 week after surgery, patients continue propranolol for 3 weeks. Patients will be monitored daily for symptoms, blood pressure, and heart rate and will be followed for observation at 6, 12, and 24 months after surgery until disease progression or clinical death, unless intolerable toxicity occurs and the patient refuses to continue treatment. The efficacy and safety of the preoperative propranolol β-blockade regimen in patients with gastrointestinal tract tumors was evaluated using the study objectives in S
Huashan Hospital, Fudan University
Shanghai, Shanghai Municipality, China
RECRUITINGAnxiety Depression Scale Scores
Hamilton Anxiety Scale. The higher the score, the worse the symptoms.
Time frame: Within two years of enrollment
heart rate
Sympathetic nervous system activation index
Time frame: From enrollment to 24 days postoperatively
Heart rate variability
Sympathetic nervous system activation index
Time frame: From enrollment to 24 days postoperatively
blood preasure
Sympathetic nervous system activation index
Time frame: From enrollment to 24 days postoperatively
Norepinephrine levels
Sympathetic nervous system activation index
Time frame: From enrollment to 24 days postoperatively
blood glucose
Sympathetic nervous system activation index
Time frame: From enrollment to 24 days postoperatively
SaO2
Sympathetic nervous system activation index
Time frame: From enrollment to 24 days postoperatively
RNA-seq of tumor tissue
Tumor tissues were examined by RNA-seq to assess the alteration of tumor microenvironment before and after treatment, and to explore the possible alteration of activation pathways (DAMP, RIG-I, NF-kB, JAK-STAT, etc.).
Time frame: Baseline and during surgery
RNA-seq of peripheral blood PBMCs
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Peripheral blood PBMCs were examined by RNA-seq to assess the alteration of tumor microenvironment before and after treatment, and to explore the possible alteration of activation pathways (DAMP, RIG-I, NF-kB, JAK-STAT, etc.).
Time frame: Baseline and during surgery
Flow cytometry of peripheral blood PBMC
Flow cytometry was applied to the peripheral blood PBMC to assess the changes in the systemic immune system and tumor immune microenvironment before and after treatment, and to explore new subpopulations of immune cells with characteristic alterations.
Time frame: Baseline and during surgery
Flow cytometry of tumor tissues
Flow cytometry was applied to the tumor tissues to assess the changes in the systemic immune system and tumor immune microenvironment before and after treatment, and to explore new subpopulations of immune cells with characteristic alterations.
Time frame: Baseline and during surgery
ELISA detection of tumor tissue
Tumor tissues were examined using ELISA to explore functional changes in specific immune cell subsets before and after preoperative propranolol treatment.
Time frame: Baseline and during surgery
ELISA detection of peripheral blood PBMCs
Functional changes in specific immune cell subsets before and after preoperative propranolol treatment were explored using ELISA for peripheral blood PBMC.
Time frame: Baseline and during surgery
2-year OS rate
Time frame: Two years after surgery
2-year RFS rate
Time frame: Two years after surgery