Malignant Glioma
Conditions
Keywords
Recurrent
Brief summary
The purpose of this study is to assess the central nervous system (CNS) toxicity in patients with recurrent malignant gliomas treated with concurrent Avastin and stereotactic radiosurgery (SRS).
Detailed description
In this pilot study, 15 human subjects with recurrent, unifocal malignant gliomas up to 5-cm in maximum dimension no longer responding to conventional chemotherapy but able to tolerate further chemotherapy will be enrolled. The primary endpoint of this study will be the proportion of patients who experience CNS toxicity, with secondary endpoints progression-free survival, overall survival, steroid dosage, development of radionecrosis, quality of life, objective radiographic response and performance status.
Interventions
RADIATIONStereotactic Radiosurgery (SRS)
Tumor Volume \< 2.0cm receives 24 Gy in 1 fraction Tumor Volume 2.0-2.9cm receives 18 Gy in 1 faction Tumor Volume 3.0-4.9cm receives 25 Gy in 5Gy/fraction
DRUGBevacizumab
Bevacizumab (Avastin) 10 mg/kg given the day before SRS and 2 weeks after SRS
Sponsors
Genentech, Inc.
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* History of malignant glioma (WHO Grade III or IV) of the brain treated with some combination of surgery, biochemotherapy and conventionally fractionated external beam radiotherapy * Radiotherapy completed at least 6 months prior to recurrence * Age 18 years and older * New or enlarging contrast-enhancing and/or 18FDG-avid nodule, at least 1 cm diameter * Estimated life expectancy of 3 months or longer
Exclusion criteria
* Avastin therapy within 21 days of start of participation * Contraindication to Avastin therapy or brain MRI * Presence of bleeding diathesis or coagulopathy * History of prior arterial thrombotic event, myocardial infarction, angina, CVA, TIA, CABG angioplasty or stenting within 6 months. * Inadequately controlled hypertension (defined as systolic blood pressure * New York Heart Association (NYHA) Grade II or greater congestive heart failure * Clinically significant vascular disease * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to onset of treatment * Prior history of hypertensive crisis or hypertensive encephalopathy * History of abdominal fistula or GI perforation within 6 months prior to onset of treatment * Serious non-healing wound, active ulcer or untreated bone fracture * Proteinuria demonstrated by Urine Protein Creatinine ratio \> 1.0 * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Central Nervous System (CNS) Toxicity | 2 months after Stereotactic Radiosurgery | Number of participants who experience Grade 3 or higher adverse events in the Nervous System Disorder domain of Common Toxicity Criteria for Adverse Events (CTCAE) v4.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Response at Month 2 | 2 months after SRS | Radiographic response at 2 months after stereotactic radiosurgery (SRS) assessed by MRI and based on modified Response Assessment in Neuro-Oncology (RANO) criteria.Per RANO, complete response (CR) is the disappearance of all target lesions;Partial Response(PR)is a \>=30% decrease in the sum of the longest diameter of target lesions. |
| Overall Survival(OS) | 2 years | Time in months from the start of stereotactic radiosurgery (SRS) to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve. |
| Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS) | 2 months after SRS | Quality of life as measured by the change in Functional Assessment of Cancer Therapy-Brain (FACT-Br) scores from baseline to 2 months after SRS. The FACT-Br (version 4) is comprised of the Functional Assessment of Cancer Therapy-General (FACT-G), a 27-item core questionnaire evaluating the domains of physical, family/social, emotional and functional well-being, with the addition of 23 brain cancer specific questions. The FACT-G total score is the sum of the four FACT-G domain scores. The Brain Cancer Subscale (BrCS) is the sum of 19 brain cancer specific questions. The FACT-Br Trial Outcome Index (TOI) is the sum of the BrCS score and the physical and family/social domain scores. The FACT-Br total score is the sum of the FACT-G total score and the BrCS score. Higher scores for all scales indicate improved quality of life (QOL).Change score = score at 2 months after SRS - score at baseline. Positive change scores indicate improved quality of life. |
| Cognition at 2 Months After Stereotactic Radiosurgery (SRS)as Measured by the Mini-Mental State Exam ( MMSE) | 2 months after SRS | Cognition as measured by the change in the Mini-Mental State Exam (MMSE) scores from baseline to 2 months after SRS. The MMSE is an 11-item measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall and language. The maximum score is 30. Change score = score at 2 months after SRS - score at baseline. Higher scores for this scale indicate improved quality of life(QOL). Positive change scores indicate improved cognition. |
| Cognition at 2 Months After Stereotactic Radiosurgery (SRS) as Measured by the Trail Making Test (TMT) | 2 months after SRS | Cognition as measured by the change in scores on the Trail Making Test (TMT). The TMT consists of two parts. Part A (TMT-A) requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for Part B (TMT-B) except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task. Shorter time scores indicates improved cognition. Change score = score at 2 months after SRS - score at baseline. Negative change scores indicate improved cognition. |
| Performance Status at 2 Months After Stereotactic Radiosurgery (SRS) | 2 months after SRS | Number of patients with a 10% decline in Karnofsky Performance Status (KPS) from baseline to 2 months after SRS. KPS is rated on a 0 to 100 scale representing a patient's ability to perform normal activity, ability to do active work, and the need for assistance. A score of 100 is perfect health and 0 represents death. |
| Steroid Usage After Stereotactic Radiosurgery (SRS) | 2 months after SRS 2 months after SRS 2 months after SRS | Number of patients using steroids at baseline and at 2 months after SRS. |
| Progression-free Survival (PFS) | 1 year | Time in months from the start of stereotactic radiosurgery (SRS) to the date of first progression according to Revised Assessment in Neuro-Oncology (RANO)criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Per RANO, progression is defined as a 20% increase in the sum of the longest diameter of target lesions,or a measurable increase in a non-target lesion or the appearance of new lesions. |
| Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): K-trans | 2 months after SRS | DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. K-trans is the widely accepted MR method for quantitating brain tumor microvascular permeability( a measure of blood transport.) K-trans will indicate a combination of both flow and permeability properties of tissue. K-trans will indicate the tissue perfusion per unit volume with a reduction in K-trans suggesting an increased anti-tumor effect and potentially improved outcome. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS. |
| Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): AUC | 1 week after SRS | DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Area under the curve (AUC) is utilized to measure the signal enhancement ratio washout volume and could be predictive of cancer treatment response. It is possible AUC could be used as a prognostic indicator of the eventual response. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS. |
| Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): AUC | 2 months after SRS | DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Area under the curve (AUC) is utilized to measure the signal enhancement ratio washout volume and could be predictive of cancer treatment response. It is possible AUC could be used as a prognostic indicator of the eventual response. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS. |
| Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): EVF | 1 week after SRS | DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. By measuring extracellular extravascular volume fraction (EVF) it is possible to gain information on brain tissue perfusion. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS. |
| Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): EVF | 2 months after SRS | DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS. |
| Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): ADC | 1 week after SRS | DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Diffusion-weighted imaging, dependent on motion of water molecules, provides information regarding tissue integrity. Apparent diffusion coefficient (ADC) values in the normal brain parenchyma, and those in brain tumors were measured. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS. |
| Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): ADC | 2 months after SRS | DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Diffusion-weighted imaging, dependent on motion of water molecules, provides information regarding tissue integrity. Apparent diffusion coefficient (ADC) values in the normal brain parenchyma, and those in brain tumors were measured. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS. |
| Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): K-trans | 1 week after SRS | DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. K-trans is the widely accepted MR method for quantitating brain tumor microvascular permeability( a measure of blood transport.) K-trans will indicate a combination of both flow and permeability properties of tissue. K-trans will indicate the tissue perfusion per unit volume, with a reduction in K-trans suggesting an increased anti-tumor effect and potentially improved outcome. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS. |
Countries
United States
Participant flow
Recruitment details
Recruitment period Jan 2, 2010-Jan 12, 2011 Location: Radiation Oncology Clinic
Participants by arm
| Arm | Count |
|---|---|
| Stereotactic Radiosurgery Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Stereotactic Radiosurgery |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 50.27 years STANDARD_DEVIATION 11.3 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 1 / 15 |
Outcome results
Primary
Central Nervous System (CNS) Toxicity
Number of participants who experience Grade 3 or higher adverse events in the Nervous System Disorder domain of Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.
Time frame: 2 months after Stereotactic Radiosurgery
Population: The number of participants with CNS toxicity is reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic Radiosurgery | Central Nervous System (CNS) Toxicity | 1 participants |
Secondary
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
Quality of life as measured by the change in Functional Assessment of Cancer Therapy-Brain (FACT-Br) scores from baseline to 2 months after SRS. The FACT-Br (version 4) is comprised of the Functional Assessment of Cancer Therapy-General (FACT-G), a 27-item core questionnaire evaluating the domains of physical, family/social, emotional and functional well-being, with the addition of 23 brain cancer specific questions. The FACT-G total score is the sum of the four FACT-G domain scores. The Brain Cancer Subscale (BrCS) is the sum of 19 brain cancer specific questions. The FACT-Br Trial Outcome Index (TOI) is the sum of the BrCS score and the physical and family/social domain scores. The FACT-Br total score is the sum of the FACT-G total score and the BrCS score. Higher scores for all scales indicate improved quality of life (QOL).Change score = score at 2 months after SRS - score at baseline. Positive change scores indicate improved quality of life.
Time frame: 2 months after SRS
Population: Intent to Treat; only 10 patients out of 15 completed the month 2 questionnaire.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stereotactic Radiosurgery | Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS) | FACT-G: physical well-being ( range: 0-28) | -2.9 units on a scale | Standard Error 1 |
| Stereotactic Radiosurgery | Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS) | FACT-G: Family/Social Well-being ( range: 0-28) | -0.1 units on a scale | Standard Error 0.9 |
| Stereotactic Radiosurgery | Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS) | FACT-G: Emotional Well-being ( range: 0-24) | -0.4 units on a scale | Standard Error 1.4 |
| Stereotactic Radiosurgery | Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS) | FACT-G: Functional Well-being ( range: 0-28) | -1.2 units on a scale | Standard Error 1.3 |
| Stereotactic Radiosurgery | Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS) | FACT-G: Total Score ( range: 0-108) | -4.6 units on a scale | Standard Error 3.8 |
| Stereotactic Radiosurgery | Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS) | FACT-Br: BrCS ( range: 0-76) | 0.8 units on a scale | Standard Error 2.7 |
| Stereotactic Radiosurgery | Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS) | FACT-Br: TOI ( range: 0-132) | -3.2 units on a scale | Standard Error 3.6 |
| Stereotactic Radiosurgery | Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS) | FACT-Br: Total Score ( range: 0-184) | -3.7 units on a scale | Standard Error 4.9 |
Secondary
Cognition at 2 Months After Stereotactic Radiosurgery (SRS)as Measured by the Mini-Mental State Exam ( MMSE)
Cognition as measured by the change in the Mini-Mental State Exam (MMSE) scores from baseline to 2 months after SRS. The MMSE is an 11-item measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall and language. The maximum score is 30. Change score = score at 2 months after SRS - score at baseline. Higher scores for this scale indicate improved quality of life(QOL). Positive change scores indicate improved cognition.
Time frame: 2 months after SRS
Population: Intent to Treat: only 14 patients out of 15 completed the month 2 questionnaire
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stereotactic Radiosurgery | Cognition at 2 Months After Stereotactic Radiosurgery (SRS)as Measured by the Mini-Mental State Exam ( MMSE) | 0.3 units on a scale | Standard Error 0.2 |
Secondary
Cognition at 2 Months After Stereotactic Radiosurgery (SRS) as Measured by the Trail Making Test (TMT)
Cognition as measured by the change in scores on the Trail Making Test (TMT). The TMT consists of two parts. Part A (TMT-A) requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for Part B (TMT-B) except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task. Shorter time scores indicates improved cognition. Change score = score at 2 months after SRS - score at baseline. Negative change scores indicate improved cognition.
Time frame: 2 months after SRS
Population: Intent to treat: only 14 of 15 patients completed the month 2 questionnaire
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stereotactic Radiosurgery | Cognition at 2 Months After Stereotactic Radiosurgery (SRS) as Measured by the Trail Making Test (TMT) | TMT-A | 0.6 seconds | Standard Error 3.3 |
| Stereotactic Radiosurgery | Cognition at 2 Months After Stereotactic Radiosurgery (SRS) as Measured by the Trail Making Test (TMT) | TMT-B | -15.5 seconds | Standard Error 9.4 |
Secondary
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): ADC
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Diffusion-weighted imaging, dependent on motion of water molecules, provides information regarding tissue integrity. Apparent diffusion coefficient (ADC) values in the normal brain parenchyma, and those in brain tumors were measured. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Time frame: 1 week after SRS
Population: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): ADC | Baseline | 980 10(-6) mm^2/s |
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): ADC | One week post SRS | 980 10(-6) mm^2/s |
Comparison: This was a test on the change from baseline to the post-SRS time point for all patients.p-value: 0.76Wilcoxon signed rank
Secondary
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): AUC
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Area under the curve (AUC) is utilized to measure the signal enhancement ratio washout volume and could be predictive of cancer treatment response. It is possible AUC could be used as a prognostic indicator of the eventual response. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Time frame: 1 week after SRS
Population: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): AUC | Baseline | 2.1 mmol/kg∙s |
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): AUC | One week post SRS | 1.4 mmol/kg∙s |
Comparison: This was a test on the change from baseline to the post-SRS time point for all patients.p-value: 0.02Wilcoxon signed rank
Secondary
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): EVF
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. By measuring extracellular extravascular volume fraction (EVF) it is possible to gain information on brain tissue perfusion. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Time frame: 1 week after SRS
Population: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): EVF | Baseline | 0.58 10(-1) |
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): EVF | One week post SRS | 0.48 10(-1) |
Comparison: This was a test on the change from baseline to the post-SRS time point for all patients.p-value: 0.53Wilcoxon signed rank
Secondary
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): K-trans
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. K-trans is the widely accepted MR method for quantitating brain tumor microvascular permeability( a measure of blood transport.) K-trans will indicate a combination of both flow and permeability properties of tissue. K-trans will indicate the tissue perfusion per unit volume, with a reduction in K-trans suggesting an increased anti-tumor effect and potentially improved outcome. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Time frame: 1 week after SRS
Population: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): K-trans | Baseline | 6.7 10(-2) min(-1) |
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): K-trans | One week post SRS | 4.1 10(-2) min(-1) |
Comparison: This was a test on the change from baseline to the post-SRS time point for all patients.p-value: 0.04Wilcoxon signed rank
Secondary
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): ADC
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Diffusion-weighted imaging, dependent on motion of water molecules, provides information regarding tissue integrity. Apparent diffusion coefficient (ADC) values in the normal brain parenchyma, and those in brain tumors were measured. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Time frame: 2 months after SRS
Population: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): ADC | Baseline | 980 10(-6) mm^2/s |
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): ADC | 2 months after SRS | 990 10(-6) mm^2/s |
Comparison: This was a test on the change from baseline to the post-SRS time point for all patients.p-value: 0.34Wilcoxon signed rank
Secondary
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): AUC
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Area under the curve (AUC) is utilized to measure the signal enhancement ratio washout volume and could be predictive of cancer treatment response. It is possible AUC could be used as a prognostic indicator of the eventual response. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Time frame: 2 months after SRS
Population: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): AUC | Baseline | 2.1 mmol/kg∙s |
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): AUC | 2 months after SRS | 0.1 mmol/kg∙s |
Comparison: This was a test on the change from baseline to the post-SRS time point for all patients.p-value: 0.0005Wilcoxon signed rank
Secondary
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): EVF
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Time frame: 2 months after SRS
Population: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): EVF | 2 months after SRS | 0 10(-1) |
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): EVF | Baseline | 0.58 10(-1) |
Comparison: This was a test on the change from baseline to the post-SRS time point for all patients.p-value: 0.002Wilcoxon signed rank
Secondary
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): K-trans
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. K-trans is the widely accepted MR method for quantitating brain tumor microvascular permeability( a measure of blood transport.) K-trans will indicate a combination of both flow and permeability properties of tissue. K-trans will indicate the tissue perfusion per unit volume with a reduction in K-trans suggesting an increased anti-tumor effect and potentially improved outcome. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Time frame: 2 months after SRS
Population: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): K-trans | Baseline | 6.7 10(-2) min(-1) |
| Stereotactic Radiosurgery | Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): K-trans | 2 months after SRS | 0 10(-2) min(-1) |
Comparison: This was a test on the change from baseline to the post-SRS time point for all patients.p-value: 0.002Wilcoxon signed rank
Secondary
Overall Survival(OS)
Time in months from the start of stereotactic radiosurgery (SRS) to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Time frame: 2 years
Population: Intent to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stereotactic Radiosurgery | Overall Survival(OS) | 14.4 months |
Secondary
Performance Status at 2 Months After Stereotactic Radiosurgery (SRS)
Number of patients with a 10% decline in Karnofsky Performance Status (KPS) from baseline to 2 months after SRS. KPS is rated on a 0 to 100 scale representing a patient's ability to perform normal activity, ability to do active work, and the need for assistance. A score of 100 is perfect health and 0 represents death.
Time frame: 2 months after SRS
Population: Intent to Treat: only 13 out of 15 patients completed month 2 KPS scores
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic Radiosurgery | Performance Status at 2 Months After Stereotactic Radiosurgery (SRS) | 11 participants |
Secondary
Progression-free Survival (PFS)
Time in months from the start of stereotactic radiosurgery (SRS) to the date of first progression according to Revised Assessment in Neuro-Oncology (RANO)criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Per RANO, progression is defined as a 20% increase in the sum of the longest diameter of target lesions,or a measurable increase in a non-target lesion or the appearance of new lesions.
Time frame: 1 year
Population: Intent to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stereotactic Radiosurgery | Progression-free Survival (PFS) | 3.9 months |
Secondary
Radiographic Response at Month 2
Radiographic response at 2 months after stereotactic radiosurgery (SRS) assessed by MRI and based on modified Response Assessment in Neuro-Oncology (RANO) criteria.Per RANO, complete response (CR) is the disappearance of all target lesions;Partial Response(PR)is a \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: 2 months after SRS
Population: Intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stereotactic Radiosurgery | Radiographic Response at Month 2 | Complete response | 0 Participants |
| Stereotactic Radiosurgery | Radiographic Response at Month 2 | Partial Response | 0 Participants |
| Stereotactic Radiosurgery | Radiographic Response at Month 2 | Stable Disease | 10 Participants |
| Stereotactic Radiosurgery | Radiographic Response at Month 2 | Progressive Disease | 4 Participants |
| Stereotactic Radiosurgery | Radiographic Response at Month 2 | Not Evaluable | 1 Participants |
Secondary
Steroid Usage After Stereotactic Radiosurgery (SRS)
Number of patients using steroids at baseline and at 2 months after SRS.
Time frame: 2 months after SRS 2 months after SRS 2 months after SRS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stereotactic Radiosurgery | Steroid Usage After Stereotactic Radiosurgery (SRS) | 2 months after SRS | 4 participants |
| Stereotactic Radiosurgery | Steroid Usage After Stereotactic Radiosurgery (SRS) | Baseline | 2 participants |