Multi -paramEtric Imaging to Assess Treatment REsponse After Stereotactic Radiosurgery of Brain Metastases (METRE)

November 10, 2020 updated by: Royal Marsden NHS Foundation Trust

Multi-paramEtric Imaging to Assess Treatment REsponse After Stereotactic Radiosurgery of Brain Metastases

After stereotactic radiosurgery (SRS) of brain metastases, patients undergo a standard brain magnetic resonance imaging (MRI) to assess treatment response 12 weeks after completion of treatment. The interpretation of this standard MRI can sometimes be challenging as it can be difficult to differentiate tumour getting bigger/returning (progression/recurrence) from expected radiotherapy treatment-related changes known as radionecrosis. This study is a pilot brain imaging study that is investigating if readily available forms of imaging such as contrast-clearance analysis MRI (also known as TRAMs) and/or 18 Fluoromethyl-choline positron emission tomography/computerised tomography (18F-choline PET/CT) are equivalent to multi-parametric MRI in their ability to differentiate tumour from radionecrosis. Multi-parametric MRI has the most evidence for its ability to discriminate tumour from radionecrosis but is resource intensive and not routinely available in most centres.

Study Overview

Status

Unknown

Conditions

Detailed Description

Differentiating tumour progression/recurrence from radionecrosis post- stereotactic radiosurgery (SRS) of brain metastases can be at times challenging on standard brain MRI. This is because radionecrosis mimics the appearances of tumour progression by appearing as contrast enhancing lesions on standard MRI.The definitive way of differentiating this is surgical excision of the area in question and histopathological evaluation. But this is not always feasible in clinical practice as not all areas of the brain are surgically accessible and an en bloc (complete) resection is needed for the result to be meaningful.

The next best option we have is the multi-parametric MRI which typically consists of three components-MR perfusion, MR diffusion and MR spectroscopy. This investigation is resource intensive, requiring considerable input form MR physics, neuroradiology reporting time , is not routinely available in all centres and hence not viable for routine clinical practice.

Therefore there is an urgent need for a reliable and viable form of imaging modality that helps differentiate tumour from radionecrosis when assessing treatment response post-SRS. It is important to be able to do this accurately as the management of both conditions are entirely different.

Currently the Royal Marsden Hospital is using contrast-clearance analysis MRI (TRAMs) to help differentiate tumour from radionecrosis if the changes seen on standard brain MRI post-SRS are deemed to be unclear. Contrast-clearance analysis MRI (TRAMs) is FDA approved and conforms to European standards (CE marked), yet has sparse evidence on its efficacy. There is some evidence for the use of 18F-choline PET/CT in primary brain tumours (gliomas) but more evidence is needed for its use in brain metastases.

Given that surgical excision is not always feasible for reasons explained above, in this study the investigators consider the muti-parametric MRI as the gold standard investigation for discriminating tumour from radionecrosis.

This pilot brain imaging study is seeking to determine if contrast-clearance analysis MRI (TRAMs) and/or 18F-choline PET/CT are equivalent to multi-parametric MRI in their ability to reliably differentiate between tumour progression/recurrence and radionecrosis. If contrast clearance analysis MRI (TRAMs) and/or 18F-choline PET/CT are found to be equivalent to multi- parametric MRI then it gives the investigators increased confidence in the findings of these readily available imaging modalities, helping treating clinicians to make rapid and reliable management plans- ultimately improving patient outcomes.

Study Type

Observational

Enrollment (Anticipated)

12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Non-small cell lung cancer patients with brain metastases who have undergone primary stereotactic radiosurgery for their brain metastases. These patients have had a follow up standard brain MRI to assess treatment response and this has been discussed in the stereotactic radiosurgery multidisciplinary team meeting (MDT) and the MDT has deemed that the changes seen are unclear as to whether they represent tumour progression or radionecrosis.

Description

Inclusion Criteria:

  • Patients with brain metastases whose primary cancer originates from the lung and whose histology is that of non-small cell lung cancer (NSCLC)
  • Patient should have had SRS as their primary treatment for their brain metastases
  • Follow-up standard brain MRI post-SRS has been discussed in the SRS multi-disciplinary team meeting (MDT)
  • The changes seen on the post-SRS follow-up standard MRI are deemed unclear by the SRS MDT as to whether they represent tumour progression or radionecrosis.
  • It is >=12 weeks since completion of SRS

Exclusion Criteria:

  • Prior SRS or external beam radiotherapy to the same area
  • Children (age < 18)
  • Pregnant women
  • Adults that lack capacity to consent
  • Contraindications to intravenous gadolinium contrast and/or 18F-choline radiotracer
  • Contraindications to MRI scanning (for example pacemaker )

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Imaging to asess treatment response post-SRS

There will be only one group. All recruited patients will have 3 scans, the multi-parametric MRI, contrast-clearance analysis MRI (TRAMs) and 18F-choline-PET/CT.

This is a non interventional study. Only the results of the contrast-clearance analysis MRI (TRAMs) will be used to make clinical decisions (as this is the current standard of care at the recruiting site). The multi-parametric MRI and 18F-choline PET/CT will be treated as research scans.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Equivalence of the contrast-clearance analysis MRI (TRAMs) and/or 18F-Choline PET/CT to multi-parametric MRI in differentiating tumour progression/recurrence from radionecrosis post stereotactic radiosurgery of brain metastases.
Time Frame: Primary outcome will be measured after the last visit of last patient-about 8 months from first recruited patient.

Patients will be classified into two groups according to the result of each scan with either tumour progression/recurrence or radionecrosis (i.e. tumour or no tumour).

Patients will have all three scans within two weeks of each other, and then each imaging technique will be reviewed and reported by neuroradiologists as either disease or no disease. All three scans will be assessed once.

The sensitivity, specificity, positive and negative predictive values in detecting tumour and prevalence will be calculated for the two scan methods where multi-parametric MRI will be used as the definitive diagnosis as we consider this as the gold standard in this study. The two scan methods are contrast-clearance analysis MRI (TRAMs) and 18F-choline PET/CT classification (tumour or no tumour) which will be compared against multi-parametric MRI. These separate measurements will be aggregated to obtain the primary outcome measurement (equivalence).
Primary outcome will be measured after the last visit of last patient-about 8 months from first recruited patient.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary endpoints are exploratory and will focus on correlating quantitative imaging derived parameters from contrast-clearance analysis MRI (TRAMs) and 18F-choline PET/CT with quantitative parameters in multi-parametric MRI.
Time Frame: This can be measured after the last visit of last patient-about 8 months from first recruited patient.
Each imaging technique, multi-parametric MRI (this scan has 3 components), contrast-clearance analysis MRI (TRAMs) and 18F-choline PET, measures different quantitative parameters to assess for the presence of tumour. Examples of quantitative parameters include for multi-parametric MRI: relative cerebral blood volume, apparent diffusion coefficient, choline to n-acetylcysteine ratio; contrast-clearance analysis MRI (TRAMs): volume of red versus blue areas on the treatment assessment maps; 18F-Choline PET: uptake value of the 18F-choline. These separate measurements will be aggregated to measure a single outcome, outcome 2 which is - is there a correlation between quantitative parameters from TRAMs and 18F-choline PET/CT and multi-parametric MRI.
This can be measured after the last visit of last patient-about 8 months from first recruited patient.
Correlation of the three scan results with the actual clinical outcomes for the patients-ie tumour or radionecrosis.
Time Frame: Analysed only after a follow-up period of at least 6 months for all patients post completion of study investigations-about 14 months from first recruited patient and 6 months from last recruited patient.

Results from the three imaging modalities contrast-clearance analysis MRI (TRAMs), 18F-choline PET/CT, multi-parametric MRI, will be compared with the actual clinical outcomes for the patients (i.e. tumour progression/recurrence or radionecrosis) which will be known with more certainty after a period of follow-up of 6 months has elapsed following the study imaging investigations. This follow-up involves collecting routine standard brain MRI scan results (reports and/or images) and clinical review letters from the primary team.

The sensitivity, specificity, positive and negative predictive values in detecting tumour and prevalence for the three scan methods will be compared against actual clinical outcomes. These separate measurements will be aggregated to measure outcome 3, which is - is there a correlation between the three scans and actual clinical outcomes for the patient.
Analysed only after a follow-up period of at least 6 months for all patients post completion of study investigations-about 14 months from first recruited patient and 6 months from last recruited patient.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Royal Marsden NHS Foundation Trust

Collaborators

National Institute for Health Research, United Kingdom

Investigators

  • Principal Investigator: Liam Welsh, MBBS,FRCR, Royal Marsden Hospital NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2020

Primary Completion (Anticipated)

August 1, 2021

Study Completion (Anticipated)

August 1, 2021

Study Registration Dates

First Submitted

November 3, 2020

First Submitted That Met QC Criteria

November 10, 2020

First Posted (Actual)

November 12, 2020

Study Record Updates

Last Update Posted (Actual)

November 12, 2020

Last Update Submitted That Met QC Criteria

November 10, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCR5331

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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