Image-Guided Surgery for Brain Tumor

Overseen By Elaine Hamel

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Utah

Disqualifiers: Prior glioma, Other malignancy, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests advanced MRI techniques to improve brain tumor surgery. It evaluates how MR perfusion (a scan showing blood flow) and 2-HG spectroscopy (a scan showing tumor metabolism) can aid in treating gliomas, a type of brain tumor. Participants in Cohort 1 will receive these advanced scans before and during surgery, while Cohort 2 will have standard imaging only. The trial seeks participants diagnosed with certain types of gliomas who are undergoing surgery, radiation, and chemotherapy. As an unphased trial, this study offers patients the chance to contribute to groundbreaking research that could enhance surgical outcomes for glioma patients.

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 prior data suggests that these MRI techniques are safe for brain tumor surgery?

Research shows that both 2HG spectroscopy and MR perfusion scans are generally safe for humans. Studies on 2HG spectroscopy indicate it effectively detects certain mutations in brain tumors. This method primarily measures a substance called 2-hydroxyglutarate in gliomas, a type of brain tumor, and no significant safety concerns have been reported.

For MR perfusion scans, research has found them valuable for assessing brain conditions like tumors by measuring blood flow in the brain. Studies have not reported any major safety issues with MR perfusion, and it is often part of regular brain assessments.

Both imaging techniques are non-invasive, meaning they don't require surgery, which generally reduces risks for patients. While no procedure is completely without risk, available data suggests these imaging methods are well-tolerated and safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores advanced imaging techniques to improve brain tumor surgeries. Unlike standard imaging, 2HG spectroscopy and MR perfusion scans provide detailed metabolic and blood flow information about the tumor. This can help surgeons distinguish between healthy and malignant tissues more precisely during operations, potentially leading to better outcomes. By fine-tuning surgical precision, these methods aim to increase the effectiveness of tumor removal while minimizing damage to healthy brain areas.

What evidence suggests that these imaging techniques are effective for brain tumor surgery?

Research has shown that a special imaging technique called 2HG spectroscopy can effectively detect a substance called 2-hydroxyglutarate (2HG) in brain tumors. This is particularly useful for tumors with certain genetic changes, such as IDH1 or IDH2 mutations, which are linked to better patient outcomes. In this trial, participants in Cohort 1, Group B will undergo 2HG spectroscopy scans.

Another valuable imaging method is MR perfusion scans. These scans allow doctors to assess blood flow through the tumor, aiding in understanding the tumor's behavior and adjusting treatment plans. This technique has accurately identified whether a tumor is growing or if changes result from treatment effects. Participants in Cohort 1, Group A will undergo MR perfusion scans. Together, these advanced imaging methods can enhance the surgical treatment of gliomas by providing detailed insights into the tumor's nature and behavior. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with suspected high-grade gliomas who are fit enough for surgery, chemo, and radiation. They must have a life expectancy over 12 weeks and be able to follow the study's procedures. It's not open to those with prior glioma diagnosis, other cancers needing treatment within 3 years, or conditions preventing standard brain radiation.

Inclusion Criteria

Life expectancy > 12 weeks

I can care for myself but may need occasional help.

I am eligible for surgery, radiation, and chemotherapy as standard treatments.

Exclusion Criteria

I have been diagnosed with a brain tumor before.

I do not expect to need treatment for another cancer within 3 years.

I cannot receive 6000 grays of radiation to my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Imaging

Cohort 1 participants undergo MR perfusion scan or 2-HG spectroscopy prior to surgery. Cohort 2 undergoes standard of care imaging.

1 day

Intraoperative Imaging

Cohort 1 participants undergo intraoperative MR perfusion or 2-HG spectroscopy. Cohort 2 undergoes standard of care intraoperative MRI.

1 day

Follow-up

Participants are monitored for surgical complications at post-op, hospital discharge, 1-month, 3-months, 6-months, and 1 year following surgery.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• 2HG Spectroscopy Scan
• MR Perfusion Scan

Trial Overview

The trial tests if using advanced MRI techniques before and during surgery can help in treating gliomas better than just standard imaging. Cohort 1 gets MR perfusion scans or 2HG spectroscopy plus intraoperative MRI; Cohort 2 only has standard care imaging.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 1 Intervention

During the analysis for cohort 1, we found significant differences in the pre MRI samples and the post intraoperative MRI samples. Cohort 2, which will include 10 additional patients, has be created to confirm these differences. Unlike cohort 1, advanced imaging (2-HG spectroscopy and MR perfusion) is not needed to make this comparison. The standard of care intraoperative MRI sequences used routinely will be sufficient for these 10 new samples. The specific aim of Cohort 2 is: 1\. Compare areas from initial surgery with that of extended resection after intraoperative SOC MRI in 10 additional subjects (Cohort 2).

Group II: Cohort 1, Group B (non-enhancing tumor) Experimental Treatment 1 Intervention

Group B patients will undergo standard tumor preoperative imaging and 2HG spectroscopy scan prior to surgical resection. Group A patients will undergo standard intraoperative imaging along with 2HG spectroscopy scan during surgical resection.

Group III: Cohort 1, Group A (contrast enhancing tumor) Experimental Treatment 1 Intervention

Group A patients will undergo standard tumor preoperative imaging and MR perfusion scan prior to surgical resection. Group A patients will undergo standard intraoperative imaging along with MR perfusion scan during surgical resection.

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

Using 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS), researchers successfully detected 2-hydroxyglutarate (2HG) in IDH-mutant glioblastomas, with a sensitivity of 100% and specificity of 92.59%.

While IDH-mutant glioblastomas showed significantly higher levels of 2HG compared to non-mutant types, the presence of high 2HG did not correlate with longer overall survival, indicating that while 2HG is a reliable biomarker, it may not predict patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy. Natsumeda, M., Motohashi, K., Igarashi, H., et al.[2018]

Edited magnetic resonance spectroscopy (MRS) can effectively identify IDH-mutant gliomas preoperatively, showing a sensitivity of 80% and specificity of 81% when using a 2-hydroxyglutarate (2-HG) cutoff greater than 0.

In patients with grades II and III gliomas, the specificity of the method increased to 100%, indicating that edited MRS is a promising tool for accurately diagnosing IDH mutation status in gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Determination of Isocitrate Dehydrogenase Mutation in Gliomas Using Spectral Editing MRS: A Prospective Study. Nguyen, TB., Melkus, G., Taccone, M., et al.[2021]

The study successfully optimized a 7T magnetic resonance spectroscopy (MRS) technique to selectively detect 2-hydroxyglutarate (2HG) in brain tumors, achieving improved discrimination from other metabolites like GABA, glutamate, and glutamine.

In vivo detection of 2HG was achieved in all 12 glioma patients, with concentrations ranging from 1.0 to 6.2 mM, indicating that this method can reliably identify low levels of 2HG in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo detection of 2-hydroxyglutarate in brain tumors by optimized point-resolved spectroscopy (PRESS) at 7T. Ganji, SK., An, Z., Tiwari, V., et al.[2019]

The study demonstrates that using a long echo time (TE = 97 ms) in magnetic resonance spectroscopy significantly improves the detection of 2-hydroxyglutarate (2HG) in patients with IDH-mutated gliomas compared to a short echo time (TE = 35 ms).

This research involved 22 subjects with IDH-mutated gliomas and seven healthy volunteers, highlighting the method's potential for better diagnosing and monitoring gliomas by enhancing the visibility of 2HG, a key metabolite associated with these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of short- and long-TE ¹H MRS at 3 T for in vivo detection of 2-hydroxyglutarate in brain tumors. Choi, C., Ganji, S., Hulsey, K., et al.[2021]

The optimized semi-LASER magnetic resonance spectroscopy technique significantly improves the detection of 2-hydroxyglutarate (2-HG) in IDH-mutated glioma tumors, allowing for better diagnosis and patient stratification.

This method not only enhances the visibility of the 2-HG peak but also reduces signal overlap with other metabolites like glutamate and glutamine, making it a promising tool for investigating tumor metabolism at 3 Tesla.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved localisation for 2-hydroxyglutarate detection at 3T using long-TE semi-LASER. Berrington, A., Voets, NL., Plaha, P., et al.[2023]

The study evaluated the use of MR spectroscopy (MRS) to detect the oncometabolite D-2-hydroxyglutarate (2HG) in 39 patients suspected of having glioma, finding that the 2HG/Cr ratio significantly improved diagnostic sensitivity and accuracy compared to measuring 2HG concentration alone.

While the overall diagnostic accuracy of 2HG detection was 73.33%, the 2HG/Cr ratio achieved a sensitivity of 85.71% and specificity of 87.5%, indicating that this method could be a valuable tool in the pre-operative assessment of glioma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic performance of edited 2HG MR spectroscopy of central glioma in the clinical environment. Juskanič, D., Mištinová, JP., Hollý, S., et al.[2022]

2-hydroxyglutarate (2HG) is a promising biomarker for diagnosing IDH-mutated gliomas, but its quantification using proton magnetic resonance spectroscopy (1H-MRS) is complicated due to overlapping signals from other substances.

This review highlights the biochemical role of 2HG in gliomas and summarizes various 1H-MRS techniques, providing insights into the current challenges and advancements in accurately diagnosing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-Vivo Proton Magnetic Resonance Spectroscopy of 2-Hydroxyglutarate in Isocitrate Dehydrogenase-Mutated Gliomas: A Technical Review for Neuroradiologists. Kim, H., Kim, S., Lee, HH., et al.[2018]

In a study of 45 patients with grade 2 and 3 gliomas, 2HG levels were successfully detected in 93% of IDH-mutant patients, indicating that in vivo MR spectroscopy is a reliable method for assessing this oncometabolite.

Higher levels of 2HG were associated with poorer progression-free survival (PFS), suggesting that 2HG could serve as a predictive biomarker for disease outcomes in glioma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spectroscopic imaging of D-2-hydroxyglutarate and other metabolites in pre-surgical patients with IDH-mutant lower-grade gliomas. Autry, AW., Lafontaine, M., Jalbert, L., et al.[2022]

A new proton magnetic resonance spectroscopy (1H-MRS) method using ultrahigh magnetic fields (≥ 7T) can noninvasively detect and quantify the oncometabolite 2-hydroxyglutarate (2-HG) in brain tumors, providing a way to differentiate between IDH1 and IDH2 mutations.

This technique not only distinguishes IDH-mutant tumors from healthy tissue but also reveals that IDH2 mutations produce more 2-HG than IDH1 mutations, which could help in monitoring tumor progression and patient responses to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Quantification of 2-Hydroxyglutarate in Human Gliomas with IDH1 and IDH2 Mutations. Emir, UE., Larkin, SJ., de Pennington, N., et al.[2022]

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