Cognitive Outcome After Gamma Knife Radiosurgery in Patients With Brain Metastases (CAR-Study A)

Study Overview
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Brief Summary
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Stereotactic radiosurgery (SRS) is increasingly applied in patients with brain metastases (BM) and is expected to have less adverse effects on cognitive functioning than Whole Brain Radiation Therapy (WBRT). Because cognitive functions are essential for daily functioning, and may affect therapy compliance and quality of life in general, a full understanding of cognitive functioning in patients with BM after SRS is essential. CAR-Study A is a prospective study to evaluate cognitive functioning in patients with 1-10 BM accepted for treatment with Gamma Knife radiosurgery (GKRS).

Detailed Description
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CAR-Study A is a prospective study to evaluate cognitive functioning after GKRS in patients with 1-10 newly diagnosed brain metastases on a triple dose gadolinium-enhanced MRI-scan. Neuropsychological assessment will be performed at baseline and at 3, 6, 9, 12, 15, and 21 months after treatment. Follow-up assessments will be combined with 3-monthly MRI-scans.

Official Title
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Cognitive Outcome After Gamma Knife Radiosurgery in Patients With 1-10 Brain Metastases

Conditions
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Neoplasm Metastases

Intervention / Treatment
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* Radiation: Gamma Knife radiosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven malignant cancer 1-10 newly diagnosed brain metastases on a triple dose gadolinium-enhanced MRI-scan Maximum total tumor volume 30 cm3 Lesion ≥ 3 mm from the optic apparatus Age ≥ 18 years Karnofsky Performance Status (KPS) ≥ 70 Anticipated survival > 3 months Exclusion Criteria: No prior histologic confirmation of malignancy Primary brain tumor A second active primary tumor Small cell lung cancer Lymphoma Leukemia Meningeal disease Progressive, symptomatic systemic disease without further treatment options Prior brain radiation Prior surgical resection of brain metastases Additional history of a significant neurological or psychiatric disorder Participation in a concurrent study in which neuropsychological testing and/or health-related QOL assessments are involved Contra indications to MRI or gadolinium contrast Underlying medical condition precluding adequate follow-up Lack of basic proficiency in Dutch IQ below 85 Severe aphasia Paralysis grade 0-3 according to MRC scale (Medical Research Council)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Stereotactic radiosurgery (SRS)<br>Gamma Knife radiosurgery (GKRS) | Radiation: Gamma Knife radiosurgery<br>* Gamma Knife radiosurgery will be performed with a Leksell Gamma Knife® Icon, Elekta Instruments, AB. Depending upon the tumor volume, a dose of 18-25 Gy will be prescribed with 99-100% coverage of the target<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in verbal memory | Verbal memory is measured with the Hopkins Verbal Learning Test-Revised (HVLT-R) | Baseline and 3, 6, 9, 12, 15, and 21 months post GKRS | 
| Change in cognitive flexibility | Cognitive flexibility is measured with the Trail Making Test B (TMT B) | Baseline and 3, 6, 9, 12, 15, and 21 months post GKRS | 
| Change in word fluency | Word Fluency is measured with the Controlled Oral Word Association (COWA) | Baseline and 3, 6, 9, 12, 15, and 21 months post GKRS | 
| Change in working memory | Working memory is measured with the Wechsler Adult Intelligence Scale - Digit Span | Baseline and 3, 6, 9, 12, 15, and 21 months post GKRS | 
| Change in processing speed | Processing speed is measured with the Wechsler Adult Intelligence Scale - Digit Symbol | Baseline and 3, 6, 9, 12, 15, and 21 months post GKRS | 
| Change in motor dexterity | Motor dexterity is measured with the Grooved Pegboard (GP) | Baseline and 3, 6, 9, 12, 15, and 21 months post GKRS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Related Quality Of Life (HRQOL) | The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is used to measure HRQOL. | Baseline and 3, 6, 9, 12, 15, and 21 months post GKRS | 
| Fatigue | Fatigue is measured with the Multidimensional Fatigue Inventory (MFI). | Baseline and 3, 6, 9, 12, 15, and 21 months post GKRS | 
| Depression and anxiety | Depression and anxiety are measured with the Hospital Anxiety and Depression Scale (HADS). | Baseline and 3, 6, 9, 12, 15, and 21 months post GKRS. | 
| Median Overall Survival | Overall survival is defined as the time in months from the start of GKRS to the date of death or last contact if alive. Kaplan-Meier methods are used to estimate overall survival. | 12 months after GKRS | 
| Local tumor control | Local brain tumor control of the initial GKRS-treated lesions is defined as a complete, partial, or stable response, or less than a 25% increase in diameter on contrast-enhanced MRI follow-up and not requiring resection. Any initial treated lesions increased by more than 25% in diameter on contrast-enhanced MRI or required resection will be considered a local failure. | 12 months after GKRS | 
| Distant tumor control | Distant brain tumor control is defined as the absence of any new brain metastases, distinct from the initial GKRS-treated lesion(s), on follow-up MRI. The appearance of one or more new lesions in the brain by contrast-enhanced follow-up MRI is considered distant failure. | 12 months after GKRS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain metastases, Cognition, Radiosurgery, Stereotactic radiosurgery, Gamma Knife Radiosurgery, Quality of Life, Fatigue, Anxiety, Depression