Mapping Molecular Markers of Brain Tumour Activity Using MRI

In Vivo Molecular Mapping of Adult Primary Brain Tumour Activity Using Novel Magnetic Resonance Imaging (MRI): a Pilot Study

Regions of tumour whose cells (the building blocks of the tumour) are actively multiplying generate a particular type of molecular footprint (consisting of various types of proteins) compared to tumours whose cells are relatively stable. In addition, tumour cells begin to develop a network of blood vessels that not only supply them with nutrients and oxygen, but also provide a pathway for tumour spread. There is a critical period between when these proteins and blood vessel network develops, and when tumour growth is visible using current MRI scanning. Therefore, making the process of tumour activity visible on clinical MRI scans is an important step in demonstrating and anticipating tumour growth. The study aims to do this by utilising various novel and non-invasive MRI techniques.

This project is a collaboration between research groups at King's College London (UK) and the Erasmus University Rotterdam (The Netherlands). The novel MRI techniques will be incorporated into the pre-surgical imaging protocol of patients with primary brain tumours. The images will be compared with molecular measurements made from biopsies taken during surgery to show that they accurately map where activity is high and low within the tumour.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioma
• Intervention / Treatment: Diagnostic test: Advanced MRI sequences

Detailed Description

Patients recruited into this study will be those for whom a surgical resection or biopsy of a primary brain tumour has already been planned by the King's College Hospital Neuro-oncology team. All patients in the UK arm of this international study will be recruited at the King's College Hospital site. Research imaging performed on patients enrolled in this study will take place at the Guy's and St Thomas' Hospital site.

For patients who have consented to be included in our research study, novel MRI techniques will be included in addition to the standard primary brain tumour imaging protocol, to provide additional information about the nature of the primary tumour: for example, the structural components and metabolism.

The MRI scan will last approximately 60 minutes, which is approximately 30 minutes longer than the standard brain tumour biopsy protocol. Further MRI scans will be performed after surgery and, if necessary, at recurrence (up to a maximum of three scans per patient) to look at advanced imaging changes at each time-point alongside structural changes. These additional scans should also last a maximum of 60 minutes.

All patients will undergo surgery for biopsy/resection of the tumour as part of the standard of care. All routine surgical procedures, pre-surgical and post-surgical care will take place predominantly at King's College Hospital site. Before craniotomy takes place for tumour resection, the neurosurgeon will take 3 tissue samples of the tumour. This will occur via stereotactic (computer-guided) biopsies. A needle will be guided through to a location of interest determined by the novel MRI techniques. This should result in an extension of the surgery time of approximately 30 minutes (10 minutes per biopsy), in addition to the approximately 4 hours needed for the surgery.

After removal, each biopsy specimen is put into a suitable container for preservation. The container will be de-identified and shipped to the Department of Pathology, Erasmus University Rotterdam, The Netherlands where the specimen will be securely stored.

The samples will be cut and slide-mounted for staining. When looking at the specimen under a microscope, particular features which suggest how aggressive the tumour is will be looked for. Information gathered from the tissue biopsies will then be compared and matched to information on the original MRI scan to see whether the novel images obtained can accurately predict the aggressiveness of different parts of the tumour.

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

Contacts and Locations

• Study Contact: Name: Thomas C Booth, PhD; Phone Number: 07977509937; Email: thomasbooth@nhs.net

Study Locations

• United Kingdom
  • London, United Kingdom
    • King's R&I department
    • Contact: Professor Reza Razavi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Individuals of 18 years or older
• Referred for surgery (resection or biopsy) of primary brain tumour
• Written informed consent

Exclusion Criteria:

• Contra-indication for MRI contrast
• Inability to give consent
• Have received/are receiving chemotherapy at time of MRI
• Patient is pregnant or planning to become pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Brain tumour patients; Patients will be those undergoing routine care of primary brain tumours. Study group patients will undergo additional MRI sequences and biopsies in addition to the standard of care.	Diagnostic test: Advanced MRI sequences; Advanced MRI sequences which look to a) determine structure of a primary brain tumour and b) metabolism within a primary brain tumour

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of the MRI signal intensity (advanced MRI sequence 1; arbitrary units) and glioma protein concentration (g/L) in a 1 x 1 x 1 cm region of interest (R value)	MRI signal will be recorded from different regions of interest within a glioma where stereotactic surgical biopsies taken and protein concentration determined.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of the MRI signal intensity (advanced MRI sequence 2; arbitrary units) and glioma metabolite concentration (g/L) in a 1 x 1 x 1 cm (R value)	MRI signal will be recorded from different regions of interest within a glioma where stereotactic surgical biopsies taken and metabolite concentration determined.	5 years

Collaborators and Investigators

• Sponsor: King's College Hospital NHS Trust
• Collaborators: King's College London; Erasmus Medical Center
• Investigators: Principal Investigator: Thomas C Booth, PhD, King's College London

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2022
• Primary Completion (Anticipated): May 1, 2027
• Study Completion (Anticipated): May 1, 2027

Study Registration Dates

• First Submitted: November 10, 2021
• First Submitted That Met QC Criteria: November 21, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: 288219

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