Anesthesia, Epidural, Lung Cancer, Neoplasm Metastasis, Neoplasm Recurrence, Local, Thoracic Surgery
Conditions
Keywords
Lung Cancer, Surgical Resection, Epidural Anesthesia and Analgesia, Cancer recurrence/metastasis, Long-Term Outcome
Brief summary
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
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.
Interventions
General anesthesia is performed during surgery; patient-controlled intravenous analgesia is provided after surgery.
Combined epidural-general anesthesia is performed during surgery; patient-controlled epidural analgesia is provided after surgery.
Sponsors
Peking University First Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Adult patients (aged 18-80 years); 2. Clinically diagnosed as primary non-small cell lung cancer of stage IA to IIIA, and scheduled for radical surgery; 3. Agreed to receive patient-controlled analgesia after surgery.
Exclusion criteria
1. Distant metastasis, malignant tumor in other organs, or chemo-/radiotherapy or other anti-cancer therapy before surgery; 2. Comorbid with autoimmune diseases, or glucocorticoid/immunosuppressant therapy within 1 year; 3. History of schizophrenia, epilepsy or Parkinson disease, or unable to complete preoperative assessment due to severe dementia, language barrier, or end-stage disease; 4. 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; 5. History of anesthesia and/or surgery within 1 year; 6. Contraindications to epidural anesthesia, including spinal deformity, coagulation dysfunction, local infection, and history of spinal trauma/surgery; 7. Allergic to any medications used during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-free survival after surgery. | Up to 4 years after surgery. | Time from surgery to the earliest date of recurrence/metastasis or death from any cause, whichever came first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of postoperative complications during hospital stay. | Up to 30 days after surgery. | 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. |
| Rate of intensive care unit admission after surgery. | Up to 30 days after surgery. | Rate of intensive care unit admission after surgery. |
| Duration of chest tube placement. | Up to 30 days after surgery. | Duration of chest tube placement. |
| Length of stay in hospital after surgery. | Up to 30 days after surgery. | Length of stay in hospital after surgery. |
| Rate of all-cause mortality during hospital stay after surgery. | Up to 30 days after surgery. | Rate of all-cause mortality during hospital stay after surgery. |
| Overall survival rate after surgery. | Up to 4 year after surgery. | Time from surgery to all-cause death. |
| Cancer-specific survival after surgery. | Up to 4 years after surgery. | Time from surgery to cancer-specific death; deaths from other causes are censored at the time of death. |
| Activity engagement in 1-year survivors. | At the end of the first year after surgery. | Activity engagement is assessed by estimating metabolic equivalents (METs; 1 MET = 3·5 ml/min/kg resting oxygen consumption) for activity in daily life. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall survival in cancer patients. | Up to 4 years after surgery. | Time from surgery to all-cause death. |
| Cancer-specific survival in cancer patients. | Up to 4 years after surgery. | Time from surgery to cancer-specific death; deaths from other causes are censored at the time of death. |
| Number of CD8+ and FOXP3+ T cells per mm2 tumor area (sub-study). | After resection of lung adenocarcinoma specimens | Immunohistochemical staining of CD8 and FOXP3 molecules in excised lung adenocarcinoma specimens. Performed in part of enrolled patients. |
| Percentage of NK-cells and T-cell subgroups in peripheral blood (sub-study). | Peripheral blood samples collected before induction, at the end of surgery and at 24 hours after surgery. | Measured by flow cytometry. Performed in part of enrolled patients. |
| Rate of chronic pain at 3 month and 6 month after surgery (sub-study). | At 3 months and 6 months after surgery. | Chronic pain is measured with the Brief Pain Inventory (BPI), neuropathic pain screening questionnaire (ID pain), and McGill Pain Questionnair (MPQ). Performed in part of enrolled patients. |
| Recurrence-free survival in cancer patients. | Up to 4 years after surgery. | Time from surgery to the earliest date of recurrence/metastasis or death from any cause, whichever came first. |
| Pain intensity after surgery. | During the first 3 days after surgery. | Assessed with the numeric rating score, an 11-point scale where 0 = no pain and 10 = the most severe pain. |
Countries
China
Outcome results
None listed