Regional Anesthesia and Lung Cancer Recurrence

Study Overview
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Brief Summary
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Test the effect of combined regiona/general anesthesia on lung cancer recurrence compared to general anesthesia alone.

Detailed Description
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Surgery is the primary treatment of lung cancer, but surgery releases tumor cells into the systemic circulation. Whether this minimal residual disease results in clinical metastases is a function of host defense. At least three perioperative factors shift the balance toward initiation and progression of minimal residual disease. (1) Surgery per se depresses cell-mediated immunity, reduces concentrations of tumor-related anti-angiogenic factors (e.g., angiostatin and endostatin), and increases concentrations of pro-angiogenic factors such as VEGF. (2) Anesthesia impairs numerous immune functions, including neutrophil, macrophages, dendritic cells, T lymphocytes (T-cell), and Natural killer cell (NK-cell) functions. (3) Opioid analgesics inhibit both cellular and humoral immune function in humans, and promote tumor growth in rodents. Regional analgesia attenuates each of these adverse effects. For example, regional anesthesia largely prevents the neuroendocrine stress response to surgery by blocking afferent neural transmission. With combined regional and general anesthesia/analgesia, the amount of general anesthetic required is much reduced - as is, presumably, immune suppression. And finally, regional analgesia provides superb pain relief, essentially obliterating the need for postoperative opioids. Animal studies show that regional anesthesia improves natural kill cell function and reduces the metastatic burden in animals inoculated with carcinoma cells. Preliminary retrospective data in cancer patients showed, that paravertebral analgesia for breast cancer surgery reduced risk of recurrence or metastasis by 40% during a 2.5 to 4-year follow-up period. The investigators thus propose to evaluate the effect of combined epidural-general anesthesia compared to general anesthesia on cancer recurrence semi-annually over a period of 5 years.

Official Title
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The Effect of Adding Intraoperative Regional Anesthesia on Cancer Recurrence in Patients Undergoing Lung Cancer Resection

Conditions
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Lung Cancer

Intervention / Treatment
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* Other: General-epidural anesthesia
* Other: Balanced general anesthesia and postoperative opioids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary non-small cell lung cancer (stage 1-3) as determined according to the IASLC Lung Cancer Staging Project; Scheduled for potentially curative tumor resection; Written informed consent, including willingness to be randomized to epidural anesthesia/analgesia plus general anesthesia or to general anesthesia and postoperative opioid analgesia. Exclusion Criteria: Any contraindication to epidural anesthesia, (including coagulopathy, abnormal anatomy). Any contraindication to midazolam, propofol, sevoflurane, fentanyl, morphine, or hydromorphone. Age < 18 or > 85 years old. Other cancer not believed by the attending surgeon to be in long-term remission.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: General-epidural anesthesia<br>Epidural and general anesthesia | Other: General-epidural anesthesia<br>* General anesthesia combined with epidural anesthesia<br>|
| Active Comparator: General anesthesia<br>General anesthesia alone | Other: Balanced general anesthesia and postoperative opioids<br>* General anesthesia alone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival | The effect of regional versus general anesthesia on the primary outcome of disease-free survival (time to the earlier or recurrence or death from any cause) | up to 5 years after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NK cell function | Secondary outcomes measured at repeated perioperative time points, include NK cell function, immune-function markers (cytokines, cortisol) and pain. | up to three years post procedure | 
| Immune function markers | Secondary outcomes measured at repeated perioperative time points, include NK cell function, immune-function markers (cytokines, cortisol) and pain. | for up to 3 years post procedure | 
| Pain | Secondary outcomes measured at repeated perioperative time points, include NK cell function, immune-function markers (cytokines, cortisol) and pain. | up to 3 years post proceudure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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regional analgesia, routine general anesthesia, immune system response, lung cancer (stage 1-3)