Brain Metastases
Conditions
Brief summary
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).
Interventions
Intervention will not be assigned by the investigator. Treatment determination will be made prior to study enrollment.
RADIATIONSingle Fraction Stereotactic Radiosurgery (SRS)
Intervention will not be assigned by the investigator. Treatment determination will be made prior to study enrollment.
RADIATIONFractionated Whole Brain Radiation Therapy (WBRT)
Intervention will not be assigned by the investigator. Treatment determination will be made prior to study enrollment.
MRI scans will include a routine clinical MRI series.
Sponsors
University of Michigan Rogel Cancer Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1 | Pre-Treatment, 1-2 Weeks Post Treatment (SRS), 1 Month Post Treatment | 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. |
| 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 | Week -2 to -1, End of Treatment (WBRT), 1-2 Weeks Post Treatment (SRS), 1 Month Post Treatment | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean K^Trans During and After Radiation Therapy | Pre-treatment and 1 Month Post Treatment | 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. |
Countries
United States
Participant flow
Recruitment details
Only participants enrolled onto SRS and Whole Brain Radiation Therapy arms were evaluated for the study outcomes.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Single Fraction Stereotactic Radiosurgery (SRS): Intervention will not be assigned by the investigator. Treatment determination will be made prior to study enrollment.
Magnetic Resonance Imaging (MRI) Assessments: MRI scans will include a routine clinical MRI series. | 9 |
| 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.
Fractionated Whole Brain Radiation Therapy (WBRT): Intervention will not be assigned by the investigator. Treatment determination will be made prior to study enrollment.
Magnetic Resonance Imaging (MRI) Assessments: MRI scans will include a routine clinical MRI series. | 21 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Alternate Treatment Given | 0 | 0 | 3 |
| Overall Study | Death | 1 | 5 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 6 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | Stereotactic Radiosurgery (SRS) | Whole Brain Radiation Therapy | Total |
|---|---|---|---|
| Age, Continuous | 51 years | 58 years | 55.5 years |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 18 Participants |
| Sex: Female, Male Male | 2 Participants | 10 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 21 |
| serious Total, serious adverse events | 0 / 9 | 0 / 21 |
Outcome results
Primary
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).
Time frame: Week -2 to -1, End of Treatment (WBRT), 1-2 Weeks Post Treatment (SRS), 1 Month Post Treatment
Primary
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.
Time frame: Pre-Treatment, 1-2 Weeks Post Treatment (SRS), 1 Month Post Treatment
Population: Fifty metastatic lesions from 21 patients received WBRT and 14 lesions from 9 patients treated by SRS were analyzed. All lesions were classified as high or low leaky dependent upon pre-RT permeability values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stereotactic Radiosurgery (SRS) | Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1 | 1-2 Weeks Post RT | 74.4 percentage of gross tumor volume | Standard Error 8.4 |
| Stereotactic Radiosurgery (SRS) | Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1 | Pre-RT | 78.6 percentage of gross tumor volume | Standard Error 7.4 |
| Stereotactic Radiosurgery (SRS) | Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1 | 1 Month Post RT | 75.3 percentage of gross tumor volume | Standard Error 5.8 |
| Whole Brain Radiation Therapy (High Leaky Lesions) | Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1 | 1-2 Weeks Post RT | 81.3 percentage of gross tumor volume | Standard Error 2.5 |
| Whole Brain Radiation Therapy (High Leaky Lesions) | Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1 | Pre-RT | 85.6 percentage of gross tumor volume | Standard Error 2.1 |
| Whole Brain Radiation Therapy (High Leaky Lesions) | Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1 | 1 Month Post RT | 76.7 percentage of gross tumor volume | Standard Error 4.1 |
| Whole Brain Radiation Therapy (Low Leaky Lesions) | Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1 | Pre-RT | 6.4 percentage of gross tumor volume | Standard Error 3.1 |
| Whole Brain Radiation Therapy (Low Leaky Lesions) | Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1 | 1 Month Post RT | 52.6 percentage of gross tumor volume | Standard Error 13.5 |
| Whole Brain Radiation Therapy (Low Leaky Lesions) | Percentage of the Gross Tumor Volume With a BTB Opening of Ktrans > 0.005 Min-1 | 1-2 Weeks Post RT | 30.2 percentage of gross tumor volume | Standard Error 13.1 |
Secondary
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.
Time frame: Pre-treatment and 1 Month Post Treatment