Supramarginal Resection for Brain Cancer

(G-SUMIT Trial)

Recruiting at 5 trial locations

Overseen by Farhad Pirouzmand, MD, MSc, FRCSC

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Sunnybrook Health Sciences Centre

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing if removing an extra 1 cm of brain tissue around a newly diagnosed high-grade glioma can help patients live longer and prevent cancer from returning. It focuses on patients with tumors in locations suitable for this type of surgery.

Do I have to stop taking my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What data supports the idea that Supramarginal Resection for Brain Cancer is an effective treatment?

The available research shows that achieving a complete removal of the tumor, known as gross total resection (GTR), is linked to increased survival in patients with glioblastoma, a type of brain cancer. There is interest in supramarginal resection, which involves removing even more tissue around the tumor, as it might offer additional benefits. However, the effectiveness of supramarginal resection compared to GTR is still debated, and more studies are needed to confirm its potential advantages. Some studies suggest it could help prevent the tumor from becoming more aggressive, but it also comes with a higher risk of temporary side effects. Overall, while supramarginal resection shows promise, its benefits over standard GTR are not yet fully proven. ^{1 2 3 4 5}

What safety data exists for supramarginal resection in brain cancer treatment?

The safety data for supramarginal resection (SMR) in brain cancer treatment, particularly glioblastoma, indicates that SMR can prolong progression-free survival without increasing postoperative surgical complications compared to gross total resection (GTR). A meta-analysis found no significant difference in the rate of complications such as meningitis, intracranial hemorrhage, and CSF leaks between SMR and GTR. Additionally, strategies like image-guided surgery and neuromonitoring are used to enhance the safety of SMR by minimizing the risk of resecting functionally eloquent brain tissue. ^{1 5 6 7 8}

Is supramarginal resection a promising treatment for brain cancer?

Yes, supramarginal resection is a promising treatment for brain cancer. It has been shown to significantly extend the time patients live without the cancer getting worse compared to the standard gross total resection. Importantly, it does this without increasing the risk of surgical complications. ^{1 3 5 6 9}

Research Team

Alireza Mansouri, MD MSc FRCSC

Principal Investigator

Penn State Cancer Institute

Damon Scales, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Farhad Pirouzmand, MD, MSc, FRCSC

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

This trial is for adults aged 18-80 with a first-time high-grade glioma brain tumor in a location that's safe to operate on. They must have a Karnofsky Performance Score of at least 60, be able to consent, and have an MRI showing the tumor. It's not for those who've had previous craniotomy (except biopsy), other cancers, blood clotting issues, or certain types of widespread brain tumors.

Inclusion Criteria

My tumor is in a place where it can be safely accessed.

I or someone who makes decisions for me can understand and agree to join the study.

My brain tumor shows up on MRI scans with a specific contrast.

Exclusion Criteria

Intraoperative histopathological diagnosis not consistent with HGG

My brain tumor affects multiple areas or has spread across the middle of my brain.

My cancer has spread to other parts of my body.

Treatment Details

Interventions

• Conventional (i.e. GTR) resection (Surgery)
• Supramarginal resection (Surgery)

Trial Overview The G-SUMIT trial is testing if cutting out an extra centimeter around the visible tumor on MRI improves overall survival without worsening neurological function or quality of life after surgery. Patients are randomly assigned to either this new 'supramarginal' resection method or the standard one.

Participant Groups

Group I: Supramarginal resection (intervention arm) Experimental Treatment 1 Intervention

Planned resection beyond the Gadolinium (GAD)-enhancing region extending to either at least 1 cm into non-enhancing tissue, or the nearest non-enhancing sulcal boundary/ventricle wall if these structures are closer than 1 cm.

Group II: Conventional (i.e. GTR) resection Experimental Treatment 1 Intervention

Planned resection of ≥95% of the GAD-enhancing regions of tumor without expanding the resection beyond this margin.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Sunnybrook Research Institute

Collaborator

Trials

33

Recruited

216,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

A consensus definition for supratotal resection (SpTR) of glioblastoma was established, with 85.7% of surveyed neurosurgeons agreeing that it includes gross total resection plus some removal of noncontrast-enhancing tumor.

The study identified specific tumor locations, such as anterior temporal and right frontal glioblastomas, as the most suitable candidates for SpTR, which may help in designing future clinical trials to evaluate its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Crowdsourced Consensus on Supratotal Resection Versus Gross Total Resection for Anatomically Distinct Primary Glioblastoma. Khalafallah, AM., Rakovec, M., Bettegowda, C., et al.[2022]

In a study involving 27 surgeons and 113 patients, gross total resection (GTR) was achieved in 82% of cases during surgery, but only 45% of patients showed GTR on postoperative MRI, indicating a significant discrepancy between surgical assessment and imaging results.

Despite 16.3% of patients having operable residual enhancing disease, no patients underwent early repeat surgery due to a perceived lack of clinical benefit, suggesting a need for further research to explore the potential survival advantages of addressing residual disease promptly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Residual enhancing disease after surgery for glioblastoma: evaluation of practice in the United Kingdom. Ma, R., Chari, A., Brennan, PM., et al.[2023]

Cytoreductive surgery techniques for malignant glioma, particularly supramarginal resection, are still under debate, with current evidence lacking high-grade support for their oncological benefits.

While extending resection may improve outcomes for some tumors, recent studies indicate that over 50% of patients experience temporary deficits, highlighting the need for more prospective studies to evaluate the safety and long-term effects of these surgical approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is it all a matter of size? Impact of maximization of surgical resection in cerebral tumors. Kamp, MA., Dibué-Adjei, M., Cornelius, JF., et al.[2020]

A systematic review of 11 studies involving 2056 glioblastoma patients found that supratotal resections (SpTR) may lead to improved overall survival (OS) compared to gross total resections (GTR), with a median OS improvement of 10.5 months.

Patients undergoing anatomical SpTR had a 35% lower risk of mortality compared to those who had GTR, suggesting that extending the resection beyond the visible tumor may be beneficial, although the studies reviewed showed significant variability in design and quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of supratotal versus gross total resection for glioblastoma. Jackson, C., Choi, J., Khalafallah, AM., et al.[2021]

Marginal or supramarginal resection of gliomas, whether high-grade or low-grade, is increasingly recognized as important for improving patient outcomes.

This approach may enhance the effectiveness of treatment by ensuring more complete removal of tumor tissue, potentially leading to better survival rates and reduced recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorescent Guided Surgery in the Surgical Management of Glioma: The Dawn of a New Era. Fountas, KN.[2020]

A meta-analysis of 11 studies involving 3158 records found that supramarginal resection (SMR) significantly prolongs progression-free survival (PFS) in glioblastoma patients compared to gross total resection (GTR), with a median PFS increase of 8.44 months.

Importantly, the rate of postoperative complications, such as meningitis and intracranial hemorrhage, did not differ between the SMR and GTR groups, suggesting that SMR can enhance treatment outcomes without increasing surgical risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of Supramarginal Resection versus Gross Total Resection in Glioblastoma: Can We Enhance Progression-Free Survival Time and Preserve Postoperative Safety? Wach, J., Vychopen, M., Kühnapfel, A., et al.[2023]

A review of 10 studies involving 3221 patients indicates that more extensive surgical resection of glioblastomas, particularly targeting peri-tumoral infiltrated areas, is associated with improved overall survival rates.

The use of image-guided surgery and neuromonitoring can enhance the safety and efficacy of these aggressive surgical strategies, helping to minimize the risk of damaging critical brain functions during resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supramarginal resection of glioblastoma: 5-ALA fluorescence, combined intraoperative strategies and correlation with survival. Certo, F., Stummer, W., Farah, JO., et al.[2020]

Supramaximal resection (SMR) of left-sided eloquent glioblastoma, performed using awake craniotomy and functional mapping, significantly improves overall survival (21.55 months) and progression-free survival (4.51 months) compared to gross-total resection (GTR) (15.49 months and 3.59 months, respectively).

The study, which included 102 patients, found that SMR did not increase postoperative complications or affect neurological function, indicating it is a safe alternative to GTR, especially when greater extent of peritumoral resection is achieved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical supramaximal resection for newly diagnosed left-sided eloquent glioblastoma: safety and improved survival over gross-total resection. Di, L., Shah, AH., Mahavadi, A., et al.[2023]

References

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

A Crowdsourced Consensus on Supratotal Resection Versus Gross Total Resection for Anatomically Distinct Primary Glioblastoma. [2022]

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

Residual enhancing disease after surgery for glioblastoma: evaluation of practice in the United Kingdom. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Is it all a matter of size? Impact of maximization of surgical resection in cerebral tumors. [2020]

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

A systematic review and meta-analysis of supratotal versus gross total resection for glioblastoma. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Fluorescent Guided Surgery in the Surgical Management of Glioma: The Dawn of a New Era. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of Supramarginal Resection versus Gross Total Resection in Glioblastoma: Can We Enhance Progression-Free Survival Time and Preserve Postoperative Safety? [2023]

7. Italy pubmed.ncbi.nlm.nih.gov

Supramarginal resection of glioblastoma: 5-ALA fluorescence, combined intraoperative strategies and correlation with survival. [2020]

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

Radical supramaximal resection for newly diagnosed left-sided eloquent glioblastoma: safety and improved survival over gross-total resection. [2023]

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

Supratotal Resection: An Emerging Concept of Glioblastoma Multiforme Surgery-Systematic Review And Meta-Analysis. [2023]