MRI Study of Changes in Blood-Brain/Tumor-Barrier Permeability in Patients With Brain Metastases During and After Radiotherapy

This study aims to assess changes in vascular permeability in the brain tumor, and in the surrounding brain, due to radiation therapy, using Magnetic Resonance Imaging (MRI).

Study Overview

• Status: Completed
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: Single Fraction Stereotactic Radiosurgery (SRS); Device: Magnetic Resonance Imaging (MRI) Assessments; Radiation: Fractionated Whole Brain Radiation Therapy (WBRT); Radiation: Fractionated Stereotactic Radiation Therapy (FSRT)

• Study Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with brain metastasis receiving radiotherapy.

Description

Inclusion Criteria:

• Patients with a histological confirmed malignancy and presence of intraparenchymal brain metastases
• Patients are treated by WBRT, SRS, or FSRT
• Age greater than or equal to 18 years
• A life expectancy of greater than or equal to 8 weeks
• Karnofsky performance status (an assessment of general well being and ability to do activities of daily living; scale ranges from 0 to 100 where 100 is perfect health) greater than or equal to 60
• Informed consent with signed study-specific informed consent form

Exclusion Criteria:

• Major medical or psychiatric illness, which, in the investigator's opinion, will prevent completion of the protocol
• Patients with lepto-meningeal metastases documented by Magnetic Resonance Imagine (MRI), Computed Tomography (CT), or Cerebrospinal Fluid (CSF) evaluation
• For patients that will undergo Whole Brain Radiation Therapy (WBRT), previous WBRT is not allowed. Patients who have had brain metastases managed by Stereotactic Radiosurgery (SRS), Fractionated Stereotactic Radiation Therapy (FSRT), or surgery are eligible
• For patients that will undergo Stereotactic Radiosurgery (SRS), previous Whole Brain Radiation Therapy (WBRT) within 5 months prior to study entry is not allowed. Prior Stereotactic Radiosurgery (SRS), Fractionated Stereotactic Radiation Therapy (FSRT), or surgery is allowed if current treatment will be for a lesion(s) not previously treated.
• For patients that will undergo Fractionated Stereotactic Radiation Therapy (FSRT), previous Whole Brain Radiation Therapy (WBRT) within 5 months prior to study entry is not allowed. Prior Stereotactic Radiosurgery (SRS), Fractionated Stereotactic Radiation Therapy (FSRT), or surgery is allowed if current treatment will be for a lesion(s) not previously treated.
• Patients unable to undergo or tolerate MRI scans (presence of cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, etc).
• Patients should have no contraindications to having a contrast enhanced Magnetic Resonance Imaging (MRI) scan. These contraindications will be assessed at the time of enrollment using the guidelines set up and in clinical use by the University of Michigan.
• Women who are pregnant are excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Stereotactic Radiosurgery (SRS); Patients with brain metastases receiving single fraction Stereotactic Radiosurgery (SRS). This intervention is not assigned by the investigator. Treatment has been decided prior to study enrollment. MRI scans will be performed approximately 1-2 weeks prior to SRS, and 1-2 weeks and 1 month after SRS. The MRI scan will include a routine clinical MRI series.	Radiation: Single Fraction Stereotactic Radiosurgery (SRS); Intervention will not be assigned by the investigator. Treatment determination will be made prior to study enrollment.; Device: Magnetic Resonance Imaging (MRI) Assessments; MRI scans will include a routine clinical MRI series.
Whole Brain Radiation Therapy; Patients with brain metastases receiving fractionated (spread out over time) Whole Brain Radiation Therapy (WBRT). This intervention is not assigned by the investigator. Treatment has been decided prior to study enrollment. MRI scans will be performed approximately 1-2 weeks prior to RT, at the end of RT and 1 month after RT. The MRI scan will include a routine clinical MRI series.	Device: Magnetic Resonance Imaging (MRI) Assessments; MRI scans will include a routine clinical MRI series.; Radiation: Fractionated Whole Brain Radiation Therapy (WBRT); Intervention will not be assigned by the investigator. Treatment determination will be made prior to study enrollment.
Stereotactic Radiation Therapy; Patients with brain metastases receiving fractionated (spread out over time) Stereotactic Radiation Therapy (FSRT). This intervention is not assigned by the investigator. Treatment has been decided prior to study enrollment. MRI scans will be performed approximately 1-2 weeks prior to FSRT, during the last week of RT but before the last fraction and 1 month after RT. The MRI scan will include a routine clinical MRI series.	Device: Magnetic Resonance Imaging (MRI) Assessments; MRI scans will include a routine clinical MRI series.; Radiation: Fractionated Stereotactic Radiation Therapy (FSRT); Intervention will not be assigned by the investigator. Treatment determination will be made prior to study enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1	Fifty metastatic lesions from 21 patients received WBRT and 14 lesions from 9 patients treated by SRS were analyzed. Permeability of BTB (Blood-Tumor-Barrier) was quantified by the transfer constant, Ktrans, derived from dynamic contrast enhanced (DCE)-MRI that were acquired pre, 1-2 weeks after starting, and 1-month post-radiotherapy. A percentage volume of the BM with Ktrans >0.005 min-1 (%Vall) was used to evaluate the extent of BTB opening pre-RT and subsequent changes after receiving radiotherapy. The 50 lesions, from the 21 patients treated with Whole Brain Radiation Therapy, were divided into two subgroups: low-leaky (%Vall <50%) and high-leaky, based upon pre-RT measurements. Of the 50 lesions, 7 were classified as low leaky and 43 were classified as high leaky. All 14 SRS lesions were classified as high leaky.	Pre-Treatment, 1-2 Weeks Post Treatment (SRS), 1 Month Post Treatment
Change in Magnitude and Regional Variability of Blood Tumor Barrier (BTB)/Blood Brain Barrier (BBB) Permeability (Per Minute) in Tumor, Tumor Margin, Normal Brain and Brain Metastases	An in-house program, based on a general kinetic model, along with an MRI contrast agent, Gadopentetic Acid (Gd-DTPA), will be used to estimate vascular permeability (per minute).	Week -2 to -1, End of Treatment (WBRT), 1-2 Weeks Post Treatment (SRS), 1 Month Post Treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean K^Trans During and After Radiation Therapy	Effect of radiation dose on vascular permeability (per minute) of the Blood Tumor Barrier (BTB)/Blood Brain Barrier (BBB). Permeability of BTB was quantified by Ktrans.	Pre-treatment and 1 Month Post Treatment

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Yue Cao, Ph.D., University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: November 13, 2013
• First Submitted That Met QC Criteria: January 7, 2014
• First Posted (Estimate): January 9, 2014

Study Record Updates

• Last Update Posted (Actual): July 26, 2019
• Last Update Submitted That Met QC Criteria: May 23, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: UMCC 2005.003; HUM00043426 (Other Identifier: University of Michigan)