Supramarginal Resection for Brain Cancer

(G-SUMIT Trial)

Not currently recruiting at 5 trial locations

Overseen By Ainy Zahid, HBSc.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Multi-focal tumor, Metastatic cancer, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new surgical method for treating high-grade glioma, a type of brain cancer. Researchers aim to determine if removing an extra 1 cm of tissue beyond the visible tumor on an MRI can extend patients' lives without worsening their quality of life. Participants are divided into two groups: one undergoes traditional surgery (conventional resection, or GTR), while the other receives the new, extended surgery (supramarginal resection). The trial seeks individuals with a specific type of brain tumor that has not been previously removed and is in a location safe for surgery. Participants must be able to understand and consent to join the study. As an unphased trial, it offers patients the chance to contribute to innovative research that could enhance future surgical outcomes.

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 prior data suggests that this surgical technique is safe for brain cancer patients?

Research suggests that supramarginal resection, a type of brain surgery, might extend the lives of patients with certain brain tumors. Studies have shown that patients undergoing this surgery lived longer than those who had the standard procedure. Specifically, one study found that 72.46% of patients were alive two years after supramarginal resection, compared to 21.26% after the standard surgery.

Regarding safety, current evidence indicates that supramarginal resection does not increase the risk of post-surgery complications. However, the studies conducted so far lack the highest quality, necessitating further research. This surgical technique continues to be studied to confirm these findings and ensure its safety for all patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about supramarginal resection for brain cancer because it offers a different approach to removing tumors. Unlike conventional surgeries that aim to remove just the visible tumor, supramarginal resection goes further by extending at least 1 cm beyond the Gadolinium-enhancing tumor regions. This technique may better target cancer cells that have infiltrated surrounding tissues, potentially improving patient outcomes. By thoroughly addressing tumor margins, this method hopes to reduce recurrence rates and offer patients a better chance at long-term survival.

What evidence suggests that this trial's treatments could be effective for brain cancer?

In this trial, participants will undergo either supramarginal resection or conventional resection. Previous studies have shown potential benefits in removing brain tumors beyond the visible edge, a technique called supramarginal resection. Research suggests this approach may improve survival rates for patients with high-grade gliomas, a type of brain cancer. Specifically, removing at least 1 cm beyond the visible tumor was linked to better outcomes. A review of studies indicated that this method could delay cancer progression without increasing surgical risks. While more research is needed, early findings are promising for improving patient survival without added risks. ^{1 4 5 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo either supramarginal or conventional tumor resection

1 day

1 visit (in-person)

Post-surgery Monitoring

Participants are monitored for neurological function and global disability

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for overall survival, progression-free survival, and quality of life

12 months

Regular 3-month interval clinical and MRI follow-up

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Supratotal resection (SpTR) for glioblastoma (GBM) significantly improves overall survival and progression-free survival compared to other surgical methods, based on a meta-analysis of 13 retrospective studies.

The analysis showed a hazard ratio of 0.77 for overall survival and 0.20 for progression-free survival, indicating that SpTR is a more effective surgical approach for patients with GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supratotal Resection: An Emerging Concept of Glioblastoma Multiforme Surgery-Systematic Review And Meta-Analysis. Aziz, PA., Memon, SF., Hussain, M., et al.[2023]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9254510/

Glioma supra marginal incision trial) study protocol - PMC In this phase II pilot randomized control trial (RCT), we aim to assess the feasibility of “supra-marginal” resection extending 1 cm beyond the enhancing tumor ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9248270/

Influence of Supramarginal Resection on Survival Outcomes ... Previous studies have reported a survival benefit when a minimum EOR of approximately 70% is achieved on T1-weighted imaging with contrast enhancement. Driven ...

3. mdpi.com mdpi.com/2072-6694/15/6/1772

A Systematic Review and Meta-Analysis of Supramarginal ... The results of this study suggest that while the current evidence is of low quality, SMR may improve PFS without affecting postoperative surgical complications.

4. advances-oncology.com advances-oncology.com/article/S2666-853X(25)00004-9/abstract

Maximal Extent of Resection, Including Supramaximal ... Supratotal (ie, supramarginal, supracomplete, supramaximal) resections may improve outcomes for newly diagnosed glioblastoma and IDH-mutant astrocytomas.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586819317436

Supramaximal resection: A systematic review of its safety, ... The included articles yielded a total of 2019 surgically treated glioblastoma patients, 13.5% of whom underwent SMR. Preliminary results suggest SMR of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12388742/

Supramarginal Resection of Metastatic Brain Tumors: A Meta ... The incidence of 2-year survival among the GTR group was 21.26%, whereas the supramarginal resection group showed an incidence of 72.46%.

7. thejns.org thejns.org/view/journals/j-neurosurg/136/1/article-p1.xml

Influence of supramarginal resection on survival outcomes ... SMR is associated with improved OS in patients with IDH-wt GBM who undergo GTR of CE tumor. At least 20% SMR of the CE tumor was associated with beneficial OS.