Epidural Anesthesia-analgesia and Long-term Survival After Lung Cancer Surgery

Study Overview
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Brief Summary
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Available studies suggest that regional anesthesia-analgesia may decrease the occurrence of recurrence/metastasis in patients after cancer surgery. However, evidences from prospective studies are still lacking. The purpose of this randomized controlled trial is to investigate the effect of epidural anesthesia-analgesia on recurrence-free survival in patients undergoing lung cancer surgery.

Detailed Description
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Lung cancer is increasing and is the leading cause of cancer death. Surgical resection is the mainstay of treatment for early stage non-small cell lung cancer. However, long-term survival after lung cancer surgery is far from optimal, and cancer recurrence or metastasis is the main reason leading to cancer death in these patients. The development of cancer recurrence/metastasis largely depends on the balance between tumor-promoting factors and immune function of the body. Studies showed that surgical manipulation releases cancer cells into circulation; and stress response induced by surgery inhibits the cell-mediated immunity. In addition, volatile anesthetics and opioids may also aggravate immunosuppression and potentially worsen long-term outcome. On the other hand, regional anesthesia can blunt surgical stress and reduce anesthetic consumption. These effects may help to preserve immune function and reduce recurrence/metastasis. However, existing evidences are insufficient to draw conclusion in this topic. The purpose of this randomized controlled trial is to test the hypothesize that regional anesthesia-analgesia may reduce recurrence/metastasis and improve long-term survival in patients after lung cancer surgery.

Official Title
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Effects of Epidural Anesthesia-analgesia on Long-term Survival in Patients After Lung Cancer Surgery: A Randomized Controlled Trial

Conditions
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Lung Cancer, Thoracic Surgery, Anesthesia, Epidural, Neoplasm Recurrence, Local, Neoplasm Metastasis

Intervention / Treatment
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* Drug: General anesthesia alone
* Drug: Combined epidural-general anesthesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (aged 18-80 years); Clinically diagnosed as primary non-small cell lung cancer of stage IA to IIIA, and scheduled for radical surgery; Agreed to receive patient-controlled analgesia after surgery. Exclusion Criteria: Distant metastasis, malignant tumor in other organs, or chemo-/radiotherapy or other anti-cancer therapy before surgery; Comorbid with autoimmune diseases, or glucocorticoid/immunosuppressant therapy within 1 year; History of schizophrenia, epilepsy or Parkinson disease, or unable to complete preoperative assessment due to severe dementia, language barrier, or end-stage disease; Severe hepatic disease (Child-Pugh classification C), renal failure (serum creatinine >442 umol/L or receiving renal replacement therapy), or American Society of Anesthesiologists classification IV or higher; History of anesthesia and/or surgery within 1 year; Contraindications to epidural anesthesia, including spinal deformity, coagulation dysfunction, local infection, and history of spinal trauma/surgery; Allergic to any medications used during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: General anesthesia alone<br>General anesthesia is performed during surgery; patient-controlled intravenous analgesia is provided after surgery. | Drug: General anesthesia alone<br>* General anesthesia is performed during surgery; patient-controlled intravenous analgesia is provided after surgery.<br>|
| Experimental: Combined epidural-general anesthesia<br>Combined epidural-general anesthesia is performed during surgery; patient-controlled epidural analgesia is provided after surgery. | Drug: Combined epidural-general anesthesia<br>* Combined epidural-general anesthesia is performed during surgery; patient-controlled epidural analgesia is provided after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival after surgery. | Time from surgery to the earliest date of recurrence/metastasis or death from any cause, whichever came first. | Up to 4 years after surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of intensive care unit admission after surgery. | Rate of intensive care unit admission after surgery. | Up to 30 days after surgery. | 
| Incidence of postoperative complications during hospital stay. | Postoperative complications are defined as new-onset conditions that are harmful to patients' recovery and required therapeutic intervention, i.e., class II or higher on the Clavien-Dindo classification. | Up to 30 days after surgery. | 
| Duration of chest tube placement. | Duration of chest tube placement. | Up to 30 days after surgery. | 
| Length of stay in hospital after surgery. | Length of stay in hospital after surgery. | Up to 30 days after surgery. | 
| Rate of all-cause mortality during hospital stay after surgery. | Rate of all-cause mortality during hospital stay after surgery. | Up to 30 days after surgery. | 
| Overall survival rate after surgery. | Time from surgery to all-cause death. | Up to 4 year after surgery. | 
| Cancer-specific survival after surgery. | Time from surgery to cancer-specific death; deaths from other causes are censored at the time of death. | Up to 4 years after surgery. | 
| Activity engagement in 1-year survivors. | Activity engagement is assessed by estimating metabolic equivalents (METs; 1 MET = 3·5 ml/min/kg resting oxygen consumption) for activity in daily life. | At the end of the first year after surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer, Surgical Resection, Epidural Anesthesia and Analgesia, Cancer recurrence/metastasis, Long-Term Outcome