Trial Outcomes & Findings for MRI Study of Changes in Blood-Brain/Tumor-Barrier Permeability in Patients With Brain Metastases During and After Radiotherapy (NCT NCT02031237)

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

52 participants

Primary outcome timeframe

Pre-Treatment, 1-2 Weeks Post Treatment (SRS), 1 Month Post Treatment

Results posted on

2019-07-26

Participant Flow

Only participants enrolled onto SRS and Whole Brain Radiation Therapy arms were evaluated for the study outcomes.

Participant milestones

Participant milestones
Measure	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.	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.	Stereotactic Radiation Therapy Patients with brain metastases receiving fractionated (spread out over time) Stereotactic Radiation Therapy (FSRT). This intervention has not been assigned by the investigator. Treatment is decided prior to enrollment.
Overall Study STARTED	14	35	3
Overall Study COMPLETED	9	21	0
Overall Study NOT COMPLETED	5	14	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	Stereotactic Radiation Therapy Patients with brain metastases receiving fractionated (spread out over time) Stereotactic Radiation Therapy (FSRT). This intervention has not been assigned by the investigator. Treatment is decided prior to enrollment.
Overall Study Death	1	5	0
Overall Study Physician Decision	0	1	0
Overall Study Withdrawal by Subject	2	2	0
Overall Study Protocol Violation	2	6	0
Overall Study Alternate Treatment Given	0	0	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stereotactic Radiosurgery (SRS) n=9 Participants 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.	Whole Brain Radiation Therapy n=21 Participants 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.	Total n=30 Participants Total of all reporting groups
Age, Continuous	51 years n=5 Participants	58 years n=7 Participants	55.5 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Stereotactic Radiosurgery (SRS) n=14 lesions 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 prior to SRS, at 1-2 weeks post SRS, 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.	Whole Brain Radiation Therapy (High Leaky Lesions) n=43 lesions 43 Lesions from 21 Patients were highly leaky. Participants 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 prior to RT, at 1-2 weeks post RT and 1 month after RT. The MRI scan will include a routine clinical MRI series. An in-house program developed to estimate vascular permeability voxel-by voxel was used to classify this WBRT group as " High Leaky" (more permeable) based upon their baseline MRI scan.	Whole Brain Radiation Therapy (Low Leaky Lesions) n=7 lesions 7 Lesions from 21 Patients were classified as low leaky. Participants 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 prior to RT, at 1-2 weeks post RT and 1 month after RT. The MRI scan will include a routine clinical MRI series. An in-house program developed to estimate vascular permeability voxel-by voxel was used to classify this WBRT group as " High Leaky" (more permeable) based upon their baseline MRI scan.
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	85.6 percentage of gross tumor volume Standard Error 2.1	6.4 percentage of gross tumor volume Standard Error 3.1
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	81.3 percentage of gross tumor volume Standard Error 2.5	30.2 percentage of gross tumor volume Standard Error 13.1
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	76.7 percentage of gross tumor volume Standard Error 4.1	52.6 percentage of gross tumor volume Standard Error 13.5

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Stereotactic Radiosurgery (SRS)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Whole Brain Radiation Therapy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Yue Cao

University of Michigan Comprehensive Cancer Center

Phone: (734) 936-8695

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place