The Impact of Inhalation vs Total Intravenous Anesthesia on the Immune Status and Mortality in Patients Undergoing Breast Cancer Surgery: a Prospective Double-Blind Randomized Clinical Trial.

Study Overview
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Brief Summary
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Even decade ago it was believed that the choice method of anesthesia did not affect the course of the oncological process, but recent evidence has begun to emerge that inhalation anesthesia vs TIVA is associated with a higher number of adverse outcomes. Apparently, it makes sense to conduct mRCT in order to assess the effect of IA on immune system in patients operated on for breast cancer comprehensively. The results of that kind of RCT may finally give us an answer whether the choice of anesthesia affects the immune status of patients undergoing surgery for breast cancer. The evaluation of complications and long-term survival will allow to recommend to use or not to use IA for this type of surgery. Objective: The Impact of Inhalation vs Total Intravenous Anesthesia on the Immune Status and Mortality in Patients Undergoing Breast Cancer Surgery

Detailed Description
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The power calculation for this study was based on an assessment of Neutrophil-lymphocyte ratio (NLR) in patients undergoing breast cancer resection with total intravenous and inhalation anesthesia in two studies: Cho J.S. et al., 2017 - 48 patients (PMID: 28924368, TIVA group: NLR = 3.37 ± 1.27; inhalation group: NLR = 3.85 ± 1.46) Ní Eochagáin A. et al., 2018 - 116 patients (PMID: 29457215, TIVA group: NLR = 3.20 ± 1.37; inhalation group: NLR = 4.10 ± 1.90). The pooled mean NLR in the TIVA group is 3.25±1.34, in the inhalation anesthesia group: 4.03±1.78. Difference in means (effect size): 0.78, for level α=0.05, power 1-β=80% and expected standard deviation of 1.5, 65 patients in each group should be recruited, taking into account a 10% margin (total number of patients: 130).

Official Title
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The Impact of Inhalation vs Total Intravenous Anesthesia on the Immune Status and Mortality in Patients Undergoing Breast Cancer Surgery: a Prospective Double-Blind Randomized Clinical Trial (TeMP - Trial).

Conditions
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Anesthesia, Breast Cancer

Intervention / Treatment
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* Drug: Sevoflurane
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The age of the patients is from 45 to 74 years; Primary operable breast cancer (BC) without prior chemotherapy; Cytologically confirmed breast malignant tumor of IA-IIA stages (T1-2, N0, M0); Signed informed consent. Exclusion Criteria: Acute cerebrovascular accident (CVA) occurred in the previous 6 months; Myocardial infarction (MI) occurred in the previous 6 months; Acute arterial thrombosis occurred in the previous 6 months; Acute venous thromboembolism occurred in the previous 6 months; Subarachnoid hemorrhage occurred during the previous 3 months; Chronic kidney disease (CKD) stage 3B-5; Сhronic heart failure (NYHA) class 3-4; Pregnancy; History of another location cancer; History of drug addiction; Autoimmune diseases in history; Post-randomization: withdrawal of informed consent (refusal to continue participating in the study); Post-randomization: surgical intervention, performed not in full (verified non-resected lesions in the early p/o period, 2 weeks p/o).

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhalation anesthesia<br> | Drug: Sevoflurane<br>* induction of anesthesia with propofol, maintenance of anesthesia with sevoflurane during breast cancer surgery<br>|
| Active Comparator: Total intravenous anesthesia<br> | Drug: Propofol<br>* propofol-based total intravenous anesthesia during breast cancer surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutrophil-lymphocyte ratio | Absolute number of neutrophils divided by the absolute number of lymphocytes | 1 hour after surgery | 
| Neutrophil-lymphocyte ratio | Absolute number of neutrophils divided by the absolute number of lymphocytes | 24 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Matrix metallopeptidase 9 | ng/mL | 1 hour after surgery | 
| Matrix metallopeptidase 9 | ng/mL | 24 hour after surgery | 
| C-reactive protein | mg/L | 1 hour after surgery | 
| C-reactive protein | mg/L | 24 hour after surgery | 
| Natural killer cells of blood (CD3-CD16 +) | Absolute number (х 10^9 /L) | 1 hour after surgery | 
| Natural killer cells of blood (CD3-CD16 +) | Absolute number (х 10^9 /L) | 24 hour after surgery | 
| Immunoregulatory index of T helpers (CD3 + CD4 +) / cytotoxic T cells (CD3 + CD8 +) | the ratio of T helper cells to cytotoxic T cells | 1 hour after surgery | 
| Immunoregulatory index of T helpers (CD3 + CD4 +) / cytotoxic T cells (CD3 + CD8 +) | the ratio of T helper cells to cytotoxic T cells | 24 hour after surgery | 
| IL-6 | pg/ml | 1 hour after surgery | 
| IL-6 | pg/ml | 24 hour after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthesia, Breast Cancer, Phagocyte Cell Dysfunction, Immune Suppression, Inhalation anesthesia, volatile anesthesia, total intravenous anesthesia, interleukins, phagocytosis, neutrophil-lymphocyte ratio, natural killers, oncology