Anesthesia Type for Brain Cancer Survival

Overseen By Emad Al Azazi, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Pediatric, Pregnant, Adrenal dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Surgery duration

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Cancer is a leading cause of death worldwide. It is estimated that approximately 55,000 Canadians are surviving with brain tumors. It is projected that around 3000 persons will be diagnosed with brain and spinal cord tumors, and approximately 75 percent patients will not survive. Out of all brain cancers, high-grade gliomas \[Glioblastoma Multiforme (GBM)\] impose highest morbidity and mortality. Therefore, it is important to explore ways in which Investigators can improve and prolong the lives of patients suffering from brain cancers, particularly high-grade glioma, which is the most common and aggressive primary brain tumor. So far the Investigators know that the surgery, chemotherapy and radiotherapy are the three corner stones management options for these patients, and majority of the research have been conducted on these three major domains. Therefore, it is imperative to explore the other variables those may impact survival characteristics. One of the integral variables of the brain cancer surgery is anesthesia. Interestingly, the role of anesthetics was explored in some other non-brain solid organ tumor surgeries. It is observed that out of the two main types of anesthesia \[one is through intravenous (propofol) and other one is gaseous (sevoflurane)\], intravenous based anesthesia maintenance regime may delay the cancer progression and prolong the recurrence free period. In addition, two very large retrospective studies with approximately 11,000 and 18,000 patients respectively, showed that as compared to gaseous (volatile anesthetics) based, intravenous (propofol) based anesthesia conferred some protection against cancer progression and was also associated with lesser overall mortality. The exact nature of these protective mechanisms is not known but in animal and other laboratory-based experiments, propofol seems to inhibit cancer formation steps, delays inflammation and provide protection from cancer cell growth. This is a feasibility study for knowing various aspects of workflow; recruitment characteristics of participants and various obstacles in implying anesthesia based protocols so that the Investigators can conduct a well-designed multicenter international randomized study.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Propofol for brain cancer survival?

Research suggests that Propofol, when used as part of total intravenous anesthesia (TIVA), may improve long-term outcomes after cancer surgeries compared to inhalation anesthesia like Sevoflurane. This has been observed in studies involving other types of cancer, such as breast and lung cancer, indicating a potential benefit in cancer survival. ^{1 2 3 4 5}

Is anesthesia for brain cancer surgery safe?

The research articles provided do not contain specific safety data on anesthesia types like Propofol or Sevoflurane for brain cancer surgery. However, these anesthetics are commonly used and generally considered safe in various medical procedures. ^{6 7 8 9 10}

How does the drug Propofol or Sevoflurane differ from other treatments for brain cancer?

The research provided does not contain relevant information about how Propofol or Sevoflurane differs from other treatments for brain cancer. ^{11 12 13 14 15}

Research Team

Tumul Chowdhury, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults over 18 years old who are scheduled for their first surgery to remove a high-grade brain tumor using general anesthesia. It's not open to children, pregnant women, those with recurrent GBM, severe adrenal problems, low-grade tumors or conditions that prevent post-op MRI.

Inclusion Criteria

I am scheduled for an elective procedure between July 1, 2022, and December 28, 2023.

I am over 18 years old.

I am scheduled for a surgery to remove a suspected severe brain tumor.

Exclusion Criteria

I am scheduled for or have had an awake brain surgery.

I am not pregnant and not a child.

I have been diagnosed with severe adrenal gland problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo elective craniotomy for suspected high-grade gliomas resection and receive either sevoflurane or propofol anesthesia

Surgery duration

1 visit (in-person)

Follow-up

Participants are monitored for progression free survival and overall survival, including post-surgery radiotherapy and chemotherapy

6 months

Regular follow-up visits

Treatment Details

Interventions

• Propofol group
• Sevoflurane group

Trial Overview The study compares two types of anesthesia in brain cancer surgery: Propofol (intravenous) and Sevoflurane (gaseous). The goal is to see if one can better prolong life by delaying cancer progression based on previous findings suggesting Propofol might be more protective.

Participant Groups

Group I: Propofol group Experimental Treatment 1 Intervention

20 patients scheduled for the elective craniotomy for suspected high-grade gliomas resection will be enrolled and further randomized to receive total intravenous anesthesia (propofol group). Standard fasting and monitoring guidelines will be instituted. All patients will be induced and intubated after administration of intravenous boluses of fentanyl, propofol and rocuronium. For the maintenance phase of anesthesia, patients in the propofol group will receive continuous infusions of propofol and remifentanil. No patients will receive nitrous oxide.

Group II: Sevoflurane group Active Control 1 Intervention

20 patients scheduled for the elective craniotomy for suspected high-grade gliomas resection will be enrolled and further randomized to receive Volatile (sevoflurane group) agent for the maintenance phase of anesthesia. Standard fasting and monitoring guidelines will be instituted. All patients will be induced and intubated after administration of intravenous boluses of fentanyl, propofol and rocuronium. For the maintenance phase of anesthesia, patients in the volatile inhalational anesthesia group will received a volatile inhalational agent (sevoflurane) and remifentanil infusion. No patients will receive nitrous oxide.

Propofol group is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Diprivan for:

• Induction and maintenance of general anesthesia or sedation

Approved in European Union as Propofol-Lipuro for:

• Induction and maintenance of general anesthesia or sedation

Approved in Canada as Propoven for:

• Induction and maintenance of general anesthesia or sedation

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

In a study of 6305 breast cancer surgery patients, those who received propofol anesthesia had a 5-year survival rate of 91.0%, compared to 81.8% for those who received sevoflurane, suggesting a potential survival advantage for propofol.

The analysis showed varying results depending on the statistical methods used, indicating that while propofol may improve long-term survival, the limitations of retrospective studies must be considered when interpreting these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia-A retrospective, multicenter, database analysis of 6305 Swedish patients. Enlund, M., Berglund, A., Ahlstrand, R., et al.[2021]

In a study involving 1764 breast cancer patients, there was no significant difference in five-year survival rates between those who received propofol and those who received sevoflurane as their anaesthetic during surgery, with survival rates of 91.9% and 92.2% respectively.

The results suggest that the choice of anaesthetic (propofol vs. sevoflurane) does not impact long-term cancer survival outcomes, as indicated by the similar survival rates and hazard ratios observed in both intention-to-treat and per-protocol analyses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane. Enlund, M., Berglund, A., Enlund, A., et al.[2023]

In a study of 1,508 patients with early-stage non-small cell lung cancer (NSCLC), those who received propofol-based total intravenous anesthesia (TIVA) had significantly better recurrence-free survival (RFS) of 7.7 years compared to 6.8 years for those who received inhalation anesthesia.

TIVA also resulted in improved overall survival (OS) with a median of 8.4 years versus 7.3 years for inhalation anesthesia, indicating that TIVA may be a more effective anesthetic approach for patients undergoing curative surgery for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of total intravenous versus inhalation anesthesia on long-term oncological outcomes in patients undergoing curative resection for early-stage non-small cell lung cancer: a retrospective cohort study. Seo, KH., Hong, JH., Moon, MH., et al.[2023]

Patients undergoing cancer surgery with propofol-based total intravenous anesthesia (TIVA) showed significantly better overall survival compared to those receiving volatile anesthesia, with a hazard ratio of 0.79, indicating a 21% reduction in the risk of death.

No significant difference in recurrence-free survival was found between the two anesthesia types, suggesting that while propofol may improve overall survival, it does not necessarily affect the likelihood of cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anesthesia and Long-term Oncological Outcomes: A Systematic Review and Meta-analysis. Chang, CY., Wu, MY., Chien, YJ., et al.[2023]

In a study of 1538 patients who underwent gastric cancer surgery, propofol-based total intravenous anesthesia (TIVA) did not show a significant difference in 1-year overall mortality compared to inhalation anesthesia, indicating similar safety profiles for both methods.

The risk of 1-year cancer-related mortality was also comparable between the TIVA and inhalation anesthesia groups, suggesting that the choice of anesthetic may not impact long-term cancer outcomes after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of 1-year mortality after gastric cancer surgery: Total intravenous anesthesia versus volatile anesthesia. Oh, TK., Kim, HH., Jeon, YT.[2020]

In a study involving 27 patients with various types of bronchogenic carcinoma, a combination treatment of DDP and VP16 resulted in a partial response in 22.3% of patients, with one patient achieving complete remission.

The treatment regimen was generally well-tolerated, with manageable side effects, including 88.8% experiencing alopecia and 77.7% experiencing nausea and/or vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin and etoposide combination in the treatment of bronchogenic carcinoma. Mazzei, T., Marino, C., Nozzoli, F., et al.[2013]

VP 16-213, a new semisynthetic epipodophyllotoxin, demonstrated clinically valuable antitumor activity in a phase II trial involving 33 patients with solid tumors and acute leukemias, particularly showing promising results in patients with oat cell carcinoma of the lung.

The drug was generally well tolerated, but it commonly caused side effects like leukothrombopenia and hair loss, indicating a need for further studies to optimize its dosage and explore its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. Jungi, WF., Senn, HJ., Beckmann, C., et al.[2013]

VP-16-213, an anticancer drug, showed significantly higher concentrations in the spinal cord compared to plasma, indicating potential for targeting central nervous system malignancies.

However, severe neurotoxicity was observed at higher doses, leading to the conclusion that VP-16-213 is not suitable for intrathecal administration due to limited diffusion and safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of intrathecal VP-16-213 in dogs. Savaraj, N., Feun, LG., Lu, K., et al.[2019]

Patupilone, a chemotherapy drug, showed a progression-free survival rate of 36% in patients with non-small cell lung cancer (NSCLC) and brain metastases, indicating its potential efficacy in this challenging population.

The treatment was associated with significant adverse events, including diarrhea (24%) and pulmonary embolisms (8%), leading to all patients discontinuing the drug, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. Nayak, L., DeAngelis, LM., Robins, HI., et al.[2018]

The study involved 13 children with diffuse intrinsic pontine glioma (DIPG) who received up to 7 cycles of direct drug infusions into the pons using convection-enhanced delivery, showing that this method is safe and well tolerated with no major surgical complications.

The treatment resulted in tumor control in 10 out of 13 patients, with a median progression-free survival of 13.0 months and overall survival of 15.3 months, indicating that this approach may improve outcomes for DIPG and warrants further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience of convection-enhanced delivery (CED) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (DIPG) in children and young adults after radiotherapy. Szychot, E., Walker, D., Collins, P., et al.[2021]

Stereotactic radiosurgery is a safe and effective treatment for acoustic tumors, achieving tumor control in 96% of patients over an average follow-up of 1.7 years, with 45% experiencing tumor shrinkage after at least 1.5 years.

Most patients returned to their normal level of function within 5 to 7 days post-treatment, although some experienced delayed complications such as facial or trigeminal neuropathy in 34% and 32% of cases, respectively, which tended to improve over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery in the treatment of patients with acoustic tumors. Lunsford, LD., Linskey, ME.[2021]

In a study of 25 patients undergoing repeat Gamma Knife (GK) surgery for vestibular schwannoma, 85% of tumors were controlled after a median follow-up of 46 months, demonstrating the long-term efficacy of this treatment.

No new facial or trigeminal nerve palsy occurred after retreatment, indicating that repeat GK surgery has low morbidity, although hearing preservation was not achieved in any of the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeat Gamma Knife surgery for vestibular schwannomas. Lonneville, S., Delbrouck, C., Renier, C., et al.[2020]

Stereotactic radiosurgery for acoustic tumors is a safe and effective treatment option, with 91% of patients discharged within 24 hours and returning to normal function within 5 to 7 days after treatment.

The treatment has a high tumor control rate of 97%, but only 23% of patients experienced a reduction in tumor size, and there is a 38% rate of useful hearing preservation after one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for acoustic tumors. Linskey, ME., Lunsford, LD., Flickinger, JC., et al.[2004]

The University of Pittsburgh is using gamma knife stereotactic radiosurgery to treat patients with acoustic tumors who cannot undergo traditional surgery, such as the elderly or those with medical contraindications.

This method delivers a precise radiation dose to the tumor while minimizing damage to surrounding tissues, and early results show promising outcomes compared to over 200 cases treated at the Karolinska Institute.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma knife: an alternative treatment for acoustic neurinomas. Kamerer, DB., Lunsford, LD., Møller, M.[2017]

In a study of 62 patients with facial paralysis after CPA tumor resection, the pattern of recovery in the first 6 months was crucial for deciding on facial reanimation surgery, as those showing no signs of recovery were unlikely to regain satisfactory function without intervention.

Early facial reanimation surgery, particularly masseteric nerve grafting, led to quicker recovery times compared to hypoglossal nerve grafting, highlighting the importance of timely surgical intervention for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Nerve Grafting for Facial Paralysis After Cerebellopontine Angle Tumor Resection With Preserved Facial Nerve Continuity. Albathi, M., Oyer, S., Ishii, LE., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia-A retrospective, multicenter, database analysis of 6305 Swedish patients. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane. [2023]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Effect of total intravenous versus inhalation anesthesia on long-term oncological outcomes in patients undergoing curative resection for early-stage non-small cell lung cancer: a retrospective cohort study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Anesthesia and Long-term Oncological Outcomes: A Systematic Review and Meta-analysis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Retrospective analysis of 1-year mortality after gastric cancer surgery: Total intravenous anesthesia versus volatile anesthesia. [2020]

6. Italy pubmed.ncbi.nlm.nih.gov

Cisplatin and etoposide combination in the treatment of bronchogenic carcinoma. [2013]

7. Switzerland pubmed.ncbi.nlm.nih.gov

[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Pharmacology of intrathecal VP-16-213 in dogs. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. [2018]

10. Japan pubmed.ncbi.nlm.nih.gov

Clinical experience of convection-enhanced delivery (CED) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (DIPG) in children and young adults after radiotherapy. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery in the treatment of patients with acoustic tumors. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Repeat Gamma Knife surgery for vestibular schwannomas. [2020]

13. United States pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for acoustic tumors. [2004]

14. United States pubmed.ncbi.nlm.nih.gov

Gamma knife: an alternative treatment for acoustic neurinomas. [2017]

15. United States pubmed.ncbi.nlm.nih.gov

Early Nerve Grafting for Facial Paralysis After Cerebellopontine Angle Tumor Resection With Preserved Facial Nerve Continuity. [2022]