Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
tumors metastatic to brain, unspecified adult solid tumor, protocol specific
Brief summary
RATIONALE: Stereotactic radiosurgery may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Giving stereotactic radiosurgery before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well stereotactic radiosurgery works in treating patients with brain metastases.
Detailed description
OBJECTIVES: Primary * To estimate the rate of recurrence at the surgical site in patients with brain metastases treated with neoadjuvant stereotactic radiosurgery (SRS) compared with historical data documenting recurrence at the surgical site after surgical resection and whole-brain radiotherapy (WBRT). Secondary * To estimate the rate of salvage WBRT, SRS, or surgery in patients treated with neoadjuvant SRS alone. * To determine the volume of adjacent normal brain parenchyma irradiated in these patients. * To estimate the rate of new brain metastases outside of the neoadjuvant SRS site in these patients. * To estimate the quality of life of these patients after neoadjuvant SRS alone. * To assess the effect of SRS and surgical intervention on the preservation of neurocognitive functioning in these patients. * To determine the clinical significance (mass effect, cognitive functioning, and other symptoms) of locally recurrent brain metastases at the time of their occurrence in these patients. * To estimate the rate of death due to neurologic causes, defined as death attributable to the progression of neurological disease, in these patients. * To estimate the overall survival of these patients. OUTLINE: Patients undergo stereotactic radiosurgery over 30 to 90 minutes. Approximately 2-4 weeks later, patients undergo surgical resection of brain metastasis. Quality of life and neurocognitive function are assessed periodically using the FACT-Br subscales and Mini-Mental State Exam. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 1 year.
Interventions
PROCEDUREtherapeutic conventional surgery
Surgery of a single brain metastasis.
RADIATIONstereotactic radiosurgery
Pre-operative single fraction SRS
Sponsors
National Cancer Institute (NCI)
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
DISEASE CHARACTERISTICS: * Diagnosis of brain metastases from an extracranial primary site * Tumor ≤ 4 cm in maximal extent in any plane on contrast MRI * Scheduled to undergo gross total resection of a single brain metastasis confirmed by histology * Up to 4 metastases allowed provided the largest mass is amenable to surgical resection and all non-resected masses are amenable to stereotactic radiosurgery (SRS) * RTOG Recursive Partitioning Analysis (RPA) class 1 or 2, as defined by the following: * RPA class 1: Karnofsky performance status (KPS) 70-100%; age \< 65 years; controlled primary disease; and no extracranial metastatic disease * RPA class 2: KPS 70-100%; uncontrolled primary disease; and/or extracranial metastatic disease * No lesion located in anatomic regions that are not amenable to SRS, including the brain stem, optic apparatus, or eloquent cortex * No primary lesion with radiosensitive histology (e.g., small cell carcinoma, germ cell tumors, lymphoma, leukemia, or multiple myeloma) * No radiographic or cytologic evidence of leptomeningeal disease PATIENT CHARACTERISTICS: * See Disease Characteristics * Not pregnant or nursing * Negative pregnancy test * No concurrent uncontrolled illness including, but not limited to, any of the following: * Symptomatic congestive heart failure * Unstable angina pectoris * Psychiatric illness * No contraindication to SRS, whole-brain radiotherapy, or MRI PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior brain surgery other than resection of metastasis * No prior brain radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Local Recurrence at the Surgical Site Within 12 Months After Stereotactic Radiosurgery (SRS) | Within 12 months after SRS | Number of patients with local recurrence at the surgical site within 12 months after stereotactic radiosurgery (SRS) as measured by magnetic resonance imaging (MRI). To determine local recurrence, we evaluated follow-up MRI's for reappearance of a lesion in exactly the same site in the brain as the first lesion(s). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of Adjacent Normal Brain Parenchyma Irradiated | At time of SRS | Volume of adjacent normal brain parenchyma irradiated during stereotactic radiosurgery (SRS). |
| Number of Patients With New Brain Metastases Outside of the Pre-operative Stereotactic Radiosurgery (SRS) Site | Within 24 months post-SRS | Number of patients with new brain metastases outside of the pre-operative stereotactic radiosurgery (SRS) site. |
| Quality of Life After Stereotactic Radiosurgery (SRS) as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) | Administered at baseline and every 3 months post-SRS | Quality of life as measured by the change in FACT-Br scores from baseline. 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. Change score = score post-SRS minus the score at baseline. Positive change scores indicate improved quality of life. |
| Number of Patients Receiving Salvage Whole-brain Radiotherapy, Stereotactic Radiosurgery (SRS), or Surgery | Within 24 months post-SRS | Number of patients receiving salvage whole-brain radiotherapy, stereotactic radiosurgery (SRS), or surgery |
| Clinical Significance of Locally Recurrent Brain Metastases | 24 months post-SRS | Number of patients with clinical significance (mass effect, cognitive functioning, and other symptoms) of locally recurrent brain metastases at the time of their occurrence. |
| Number of Patients Who Died Due to Neurological Causes | Within 24 months post-SRS | Number of patients who died due to neurological causes defined as death attributable to the progression of neurological disease. |
| Overall Survival (OS) | 24 months after SRS | Time in months from the date of stereotactic radiosurgery (SRS) to the 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. |
| Preservation of Neurocognitive Functioning as Measure by the Mini-Mental State Exam (MMSE) | Administered at baseline and every 3 months post-SRS | Cognition as measured by the change in the Mini-Mental State Exam (MMSE) scores from baseline. 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 post-SRS minus the score at baseline. Positive change scores indicate improved cognition. |
Countries
United States
Participant flow
Recruitment details
The subjects were consented and interviewed in a private room in the Duke clinics. The patients came to Duke Radiology Center, found to be eligible and then provided options by the neuro-radiologist. They were consented by the research nurse at one of these visits.
Pre-assignment details
The only reason that enrolled participants were excluded from the trial prior to treatment assignment was if there were development of any exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Pre-OP SRS SRS pre-operatively with the planned target volume defined as the tumor plus a 3-mm margin.
therapeutic conventional surgery : Surgery of a single brain metastasis.
stereotactic radiosurgery : Pre-operative single fraction SRS | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Pre-OP SRS |
|---|---|
| Age Continuous | 55.7 Years STANDARD_DEVIATION 15.1 |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Number of Patients With Local Recurrence at the Surgical Site Within 12 Months After Stereotactic Radiosurgery (SRS)
Number of patients with local recurrence at the surgical site within 12 months after stereotactic radiosurgery (SRS) as measured by magnetic resonance imaging (MRI). To determine local recurrence, we evaluated follow-up MRI's for reappearance of a lesion in exactly the same site in the brain as the first lesion(s).
Time frame: Within 12 months after SRS
Population: Intent-to-treat; 1 patient was not included in this analysis as they were unable to undergo surgery after SRS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-Operative SRS | Number of Patients With Local Recurrence at the Surgical Site Within 12 Months After Stereotactic Radiosurgery (SRS) | 0 Participants |
Secondary
Clinical Significance of Locally Recurrent Brain Metastases
Number of patients with clinical significance (mass effect, cognitive functioning, and other symptoms) of locally recurrent brain metastases at the time of their occurrence.
Time frame: 24 months post-SRS
Population: There are no patients for this analysis because none had a local recurrence.
Secondary
Number of Patients Receiving Salvage Whole-brain Radiotherapy, Stereotactic Radiosurgery (SRS), or Surgery
Number of patients receiving salvage whole-brain radiotherapy, stereotactic radiosurgery (SRS), or surgery
Time frame: Within 24 months post-SRS
Population: Intent-to-treat; 1 patient was not included in this analysis as they were unable to undergo surgery after SRS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-Operative SRS | Number of Patients Receiving Salvage Whole-brain Radiotherapy, Stereotactic Radiosurgery (SRS), or Surgery | 2 participants |
Secondary
Number of Patients Who Died Due to Neurological Causes
Number of patients who died due to neurological causes defined as death attributable to the progression of neurological disease.
Time frame: Within 24 months post-SRS
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-Operative SRS | Number of Patients Who Died Due to Neurological Causes | 0 participants |
Secondary
Number of Patients With New Brain Metastases Outside of the Pre-operative Stereotactic Radiosurgery (SRS) Site
Number of patients with new brain metastases outside of the pre-operative stereotactic radiosurgery (SRS) site.
Time frame: Within 24 months post-SRS
Population: Intent-to-treat; 1 patient was not included in this analysis as they were unable to undergo surgery after SRS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-Operative SRS | Number of Patients With New Brain Metastases Outside of the Pre-operative Stereotactic Radiosurgery (SRS) Site | 2 participants |
Secondary
Overall Survival (OS)
Time in months from the date of stereotactic radiosurgery (SRS) to the 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: 24 months after SRS
Population: Intent-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pre-Operative SRS | Overall Survival (OS) | 6.6 Months |
Secondary
Preservation of Neurocognitive Functioning as Measure by the Mini-Mental State Exam (MMSE)
Cognition as measured by the change in the Mini-Mental State Exam (MMSE) scores from baseline. 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 post-SRS minus the score at baseline. Positive change scores indicate improved cognition.
Time frame: Administered at baseline and every 3 months post-SRS
Population: Data for this outcome was erroneously not gathered.
Secondary
Quality of Life After Stereotactic Radiosurgery (SRS) as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
Quality of life as measured by the change in FACT-Br scores from baseline. 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. Change score = score post-SRS minus the score at baseline. Positive change scores indicate improved quality of life.
Time frame: Administered at baseline and every 3 months post-SRS
Population: Data for this outcome was erroneously not gathered.
Secondary
Volume of Adjacent Normal Brain Parenchyma Irradiated
Volume of adjacent normal brain parenchyma irradiated during stereotactic radiosurgery (SRS).
Time frame: At time of SRS
Population: Data for this outcome was not collected.