Brain Metastases, Adult
Conditions
Brief summary
The purpose of this study is to determine the effectiveness and efficiency of Single Isocenter Multi-target Stereotactic Radiosurgery (SIMT SRS) in patients with four or more brain metastases
Detailed description
Forty patients with four or more brain metastases will be enrolled prior to radiosurgery. A planning MRI brain scan will be performed with GD-DPTA within one week prior to radiosurgery, per the standard of care. Neurocognitive (Mini-Mental Status Examination (MMSE), Trail-making test A&B, Hopkins Learning Verbal (HVLT)) and functional assessment of cancer therapy-brain (FACT- Br) will be obtained prior to radiosurgery. Dose will be prescribed to the maximum isodose line encompassing the resulting PTV using the dose guidelines as described below. The primary endpoint will be the proportion of patients who live longer than predicted based on the diagnosis-specific GPA score. The Kaplan-Meier estimator will be used to describe the survival of all patients treated with SIMT SRS. Secondary endpoints will be the rate of recurrence at the treated metastases sites, the rate of new brain metastases at a site different from the SRS-treated metastases sites, the rate of death due to neurological causes, and the prevalence of significant adverse events. Exploratory endpoints include change over time in neurocognition and quality of life, quantification of dosimetric measures, the rate of salvage therapy, the rate of radionecrosis at the SRS treatment sites, and the rate and intensity of steroid-usage post-SRS. All patients will be evaluated for neurocognitive function via MMSE, HVLT, and Trail-making tests A & B, quality of life via FACT-Br, and for local recurrence via MRI every 3 months over the course of the study. These evaluations will be done at regular follow-up evaluations or when local recurrence is suspected on the basis of symptoms. Distant recurrence is defined as the appearance of new brain metastases at a site different from that of the original metastases. Recurrence will further be defined as a new area of enhancement that measures greater than 5 millimeters in the axial plane on MRI. The length of time to recurrence of the original brain metastases will be calculated from the date of the brain metastases radiosurgery to the date that a recurrence was detected by MRI. Patients with suspected recurrent tumor and/or who are symptomatic may undergo a stereotactic biopsy to evaluate for radionecrosis versus recurrent brain metastases, as is standard of care.
Interventions
RADIATIONStereotactic radiosurgery
Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery
Sponsors
Varian Medical Systems
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. A contrast-enhanced MRI scan showing = or \> 4 brain metastases. 2. Age \>/=18 years of age. 3. KPS \>/= 70 4. Patient must have a graded prosnostic score (GPA) score 0.5 or greater 5. Life expectancy of at least 3 months 6. Postoperative patients with resected brain metastases are eligible. 7. Largest lesion \< 4cm diameter 8. Must be a candidate for MRI imaging 9. Previous cranial stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) is allowed if \> 3 months prior to SIMT 10. Must be capable of providing informed consent
Exclusion criteria
1. Primary lesion with radiosensitive histology (i.e., small cell carcinoma, germ-cell tumors, lymphoma, leukemia, and multiple myeloma). 2. Metastases within 2 mm of the optic apparatus 3. Patients unable to obtain MRI 4. Evidence of leptomeningeal disease 5. Greater than 10 brain metastases 6. Pregnant women are excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Live Longer Than Predicted According to the Graded Prognostic Assessment (GPA) Score | Up to 24 months after SRS | Calculated from the time of protocol Stereotactic RadioSurgery (SRS). The GPA incorporates four factors: age, KPS (Karnofsky Performance Score), ECM (extracranial metastases) and number of BM (brain metastases). Each factor is given a score of 0, 0.5 or 1.0 and GPA is calculated as a sum score of all four factors. The GPA has four groups: the GPA 0-1 with median survival of 2.6 months; GPA 1.5-2.5 with survival of 3.8 months; GPA 3 with median survival of 6.9 months and GPA 3.5-4.0 with the best median survival of 11 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience Local Brain Recurrence Within 1 Year of SIMT SRS Treatment | Up to 12 months after SRS | Local recurrence of brain metastases is based on serial MRIs every 3 months and estimated by Kaplan-Meier analysis. |
| Number of Participants Who Are Dead Within 1 Year of SIMT SRS Treatment Due to Neurologic Reasons | Up to 12 months after SRS | Time to neurologic death is defined as the time between initiation of SIMT SRS and death due to neurologic causes and is estimated using Kaplan-Meier analysis. |
| Number of Participants Who Experience a New Brain Metastasis at a Site Different From the Original Brain Metastasis Site 1 Year After SIMT SRS Treatment | Up to 12 months after SRS | Distant recurrence of brain metastases is based on serial MRIs every 3 months and estimated by Kaplan-Meier analysis. |
| Number of Participants Who Experience Grade 3, 4, or 5 Neurologic Adverse Events Attributable to SIMT SRS | Up to 12 months after SRS | Adverse Events only included those that were deemed by the PI to be related to the SIMT SRS treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stereotactic Radiosurgery All subjects will receive stereotactic radiosurgery(SRS) following the RTOG Stereotactic Radiotherapy Guidelines available at http://dx.doi.org/10.1016/j.prro.2011.06.014
Stereotactic radiosurgery: Linear-accelerator-based, single-isocenter, image-guided stereotactic radiosurgery | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 8 |
Baseline characteristics
| Characteristic | Stereotactic Radiosurgery |
|---|---|
| Age, Continuous | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Karnofsky performance status | 90 units on a scale (percentage) |
| Number of Metastases per participant | 6 metastases |
| Prior brain surgery for metastasis | 36 Participants |
| Prior stereotactic radiosurgery or whole brain radiation | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 39 / 40 |
| other Total, other adverse events | 16 / 40 |
| serious Total, serious adverse events | 0 / 40 |
Outcome results
Primary
Number of Participants Who Live Longer Than Predicted According to the Graded Prognostic Assessment (GPA) Score
Calculated from the time of protocol Stereotactic RadioSurgery (SRS). The GPA incorporates four factors: age, KPS (Karnofsky Performance Score), ECM (extracranial metastases) and number of BM (brain metastases). Each factor is given a score of 0, 0.5 or 1.0 and GPA is calculated as a sum score of all four factors. The GPA has four groups: the GPA 0-1 with median survival of 2.6 months; GPA 1.5-2.5 with survival of 3.8 months; GPA 3 with median survival of 6.9 months and GPA 3.5-4.0 with the best median survival of 11 months.
Time frame: Up to 24 months after SRS
Population: Participants who completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stereotactic Radiosurgery | Number of Participants Who Live Longer Than Predicted According to the Graded Prognostic Assessment (GPA) Score | 22 Participants |
Secondary
Number of Participants Who Are Dead Within 1 Year of SIMT SRS Treatment Due to Neurologic Reasons
Time to neurologic death is defined as the time between initiation of SIMT SRS and death due to neurologic causes and is estimated using Kaplan-Meier analysis.
Time frame: Up to 12 months after SRS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stereotactic Radiosurgery | Number of Participants Who Are Dead Within 1 Year of SIMT SRS Treatment Due to Neurologic Reasons | 30 Participants |
Secondary
Number of Participants Who Experience a New Brain Metastasis at a Site Different From the Original Brain Metastasis Site 1 Year After SIMT SRS Treatment
Distant recurrence of brain metastases is based on serial MRIs every 3 months and estimated by Kaplan-Meier analysis.
Time frame: Up to 12 months after SRS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stereotactic Radiosurgery | Number of Participants Who Experience a New Brain Metastasis at a Site Different From the Original Brain Metastasis Site 1 Year After SIMT SRS Treatment | 19 Participants |
Secondary
Number of Participants Who Experience Grade 3, 4, or 5 Neurologic Adverse Events Attributable to SIMT SRS
Adverse Events only included those that were deemed by the PI to be related to the SIMT SRS treatment.
Time frame: Up to 12 months after SRS
Population: Participants who completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stereotactic Radiosurgery | Number of Participants Who Experience Grade 3, 4, or 5 Neurologic Adverse Events Attributable to SIMT SRS | 0 Participants |
Secondary
Number of Participants Who Experience Local Brain Recurrence Within 1 Year of SIMT SRS Treatment
Local recurrence of brain metastases is based on serial MRIs every 3 months and estimated by Kaplan-Meier analysis.
Time frame: Up to 12 months after SRS
Population: Participants who completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stereotactic Radiosurgery | Number of Participants Who Experience Local Brain Recurrence Within 1 Year of SIMT SRS Treatment | 4 Participants |