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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study evaluates the use of specialized magnetic resonance imaging (MRI) techniques including magnetic resonance (MR) perfusion and 2-hydroxyglutarate (2HG) spectroscopy in the surgical treatment of gliomas. Cohort 1 participants will undergo an MR perfusion scan or 2-HG spectroscopy prior to surgery and intra-operatively. Cohort 2 participants will only undergo standard of care imaging and tumor acquisition. Participant participation will end at the completion of surgery and will be transitioned to standard of care follow-up.

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 treatment 2HG Spectroscopy Scan for brain tumors?

Research shows that detecting 2-hydroxyglutarate (2HG) using MR spectroscopy can help identify certain types of brain tumors, like IDH-mutant gliomas, which are linked to better outcomes. This method helps doctors understand the tumor's characteristics and may guide treatment decisions. ^{1 2 3 4 5}

Is image-guided surgery for brain tumors using 2HG MRS safe for humans?

The research articles focus on the detection of 2-hydroxyglutarate (2HG) in brain tumors using magnetic resonance spectroscopy (MRS) techniques, but they do not provide specific safety data for humans. However, MRS is a non-invasive imaging technique generally considered safe for human use. ^{1 3 4 6 7}

How does image-guided surgery for brain tumors differ from other treatments?

Image-guided surgery for brain tumors is unique because it uses advanced imaging techniques to precisely locate and remove tumors, potentially improving surgical accuracy and outcomes. This approach is different from traditional surgery, which may rely more on the surgeon's visual and tactile feedback, and it can be particularly beneficial for tumors with specific genetic mutations, like those involving isocitrate dehydrogenase (IDH) mutations, by allowing for better detection and monitoring of tumor-related metabolites such as 2-hydroxyglutarate (2HG). ^{1 2 3 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

References

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

In vivo detection of 2-hydroxyglutarate in brain tumors by optimized point-resolved spectroscopy (PRESS) at 7T. [2019]

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

In-Vivo Proton Magnetic Resonance Spectroscopy of 2-Hydroxyglutarate in Isocitrate Dehydrogenase-Mutated Gliomas: A Technical Review for Neuroradiologists. [2018]

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

Preoperative Determination of Isocitrate Dehydrogenase Mutation in Gliomas Using Spectral Editing MRS: A Prospective Study. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Diagnostic performance of edited 2HG MR spectroscopy of central glioma in the clinical environment. [2022]

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

Spectroscopic imaging of D-2-hydroxyglutarate and other metabolites in pre-surgical patients with IDH-mutant lower-grade gliomas. [2022]

6. England 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. [2021]

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

Improved localisation for 2-hydroxyglutarate detection at 3T using long-TE semi-LASER. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy. [2018]

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

Noninvasive Quantification of 2-Hydroxyglutarate in Human Gliomas with IDH1 and IDH2 Mutations. [2022]