18F-FET-PET/MRI vs Standard MRI Alone for Stereotactic RadioTherapy Planning for High Grade Brain Gliomas (FETSMaRT)

18F-FET-PET/MRI Versus Standard MRI Alone for Stereotactic RadioTherapy Planning for High Grade Brain Gliomas: A Pilot Study

Amino acid PET imaging for brain gliomas is gaining acceptance for the diagnosis and monitoring of disease. This is commonly performed in Europe. There is an opportunity to develop this tracer for use in Ontario, specifically for accurate delineation of disease for therapy planning and for prediction of disease recurrence, which is difficult with conventional imaging and clinical assessment techniques. The goals of this project are to develop this tracer in our local setting for use in our patients, provide evidence in the Ontario setting of its utility in addressing these unmet needs, and provide pilot evidence for future clinical trials.

Gliomas are primary malignancies of the brain. The most aggressive and common form is glioblastoma multiforme (GBM), which accounts for more than 60% of all primary brain malignancies . The standard of care for patients with glioblastoma is maximally safe resection of the enhancing tumor regions and the necrotic core followed by radiotherapy with concurrent temozolomide. MRI is widely accepted as the method of choice for treatment planning and for following these patients to predict and to detect recurrent disease.

High grade gliomas represent the most common primary brain malignancy and prognosis remains poor. The most common subtype is glioblastoma which has a 5-year survival rate of approximately 5% . Despite advances in MRI techniques, prediction and diagnosis of treatment failure remains a challenge. The result is frequent imaging mixed with uncertainty regarding the presence of viable tumor versus post-treatment effects. Furthermore, follow-up of these patients represents a high cost to the health system while symptom or disease control remains limited. A more accurate means identifying viable tumor is needed to guide management, reduce costs, and ultimately to improve patient survival and quality of life.

0-(2-18F-Fluoroethyl)-L-Tyrosine positron emission tomography (FET) is an amino acid agent derived from tyrosine that is able to cross the blood brain barrier. It has been studied primarily in diagnosis and detection of tumor recurrence in glioblastomas with emerging evidence for its use in brain metastases. Compared to conventional MRI, FET-PET has been shown to delineate geographically distinct tumor volume in newly diagnosed GBM suggesting the complementarity of the two modalities.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioma, Malignant
• Intervention / Treatment: Diagnostic test: 0-(2-18F-Fluoroethyl)-L-Tyrosine

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N2M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• >= 18 years of age
• High grade brain glioma (Grade 3 and 4)
• No prior radiation or systemic treatment for high grade glioma

• Planned to undergo radiation therapy with the following regimens:

  • Grade 3: 54-60 Gy over 30 fractions with temozolomide
  • Grade 3: 40Gy over 15 fractions with temozolomide
  • Grade 4: 60 Gy over 30 fractions, with or without temozolomide o Grade 4: 40 Gy over 15 fractions, with or without temozolomide
• Able to tolerate PET/MRI scan with intravenous contrast
• Willing to provide informed consent.

Exclusion Criteria:

• MRI contraindication
• Creatinine clearance < 30mL/min
• Inability to lie still for 40 minutes
• Gadolinium allergy
• Prior PET imaging
• Positive pregnancy test
• Breastfeeding
• Patient unable to follow the protocol for any reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: High Grade Glioma; 0-(2-18F-Fluoroethyl)-L-Tyrosine (FET) PET/MRI for planning of radiation therapy of post-operative grade III/IV glioma patients

Diagnostic test: 0-(2-18F-Fluoroethyl)-L-Tyrosine; 0-(2-18F-Fluoroethyl)-L-Tyrosine positron emission tomography (FET) is an amino acid agent derived from tyrosine that is able to cross the blood brain barrier. It has been studied primarily in diagnosis and detection of tumor recurrence in glioblastomas with emerging evidence for its use in brain metastases. Compared to conventional MRI, FET-PET has been shown to delineate geographically distinct tumor volume in newly diagnosed GBM suggesting the complementarity of the two modalities.; Other Names: FET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observe recurrence/evaluate diagnostic performance of PET-FET/MRI vs MRI alone	To estimate the rate of change in management due to 18F-FET-PET/MRI when used in addition to standard of care MRI.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate tumor volume changes	Evaluate differences in total tumor volume as defined by 18F-FET-PET versus MRI pre-operatively	12 Months
Evaluate recurrence	Evaluate diagnostic performance of FET-PET/MRI versus MRI alone for predicting recurrence at 12 months.	12 Months
Analysis of PET Data	Develop and test new MRI and PET analyses to improve recurrence prediction using machine learning and conventional statistical models	12 Months

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Investigators: Principal Investigator: Amit Singnurkar, MD, MBA, Sunnybrook Healthcare Centre

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2021
• Primary Completion (Actual): January 31, 2025
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: July 10, 2024
• First Posted (Actual): July 15, 2024

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Glioma; Glioblastoma; FET; FET-PET; PET, 0-(2-18F-Fluoroethyl)-L-Tyrosine
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: 3728

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No