Cognitive Outcome After SRS or WBRT in Patients With Multiple Brain Metastases (CAR-Study B)
- Conditions
- Neoplasm Metastasis
- Interventions
- Radiation: Gamma Knife radiosurgeryRadiation: Whole Brain Radiation Therapy
- Registration Number
- NCT02953717
- Lead Sponsor
- Elisabeth-TweeSteden Ziekenhuis
- Brief Summary
Whole Brain Radiation Therapy (WBRT) has long been the mainstay of treatment for patients with multiple brain metastases (BM). Meanwhile, Gamma Knife radiosurgery (GKRS) has been increasingly employed in the management of multiple BM to spare healthy tissue. Hence, GKRS is expected to cause fewer cognitive side effects than WBRT. Treatment of multiple BM without cognitive side effects is becoming more important, as more patients live longer due to better systemic treatment options. There are no published randomized trials yet directly comparing GKRS to WBRT in patients with multiple BM, including objective neuropsychological testing.
CAR-Study B is a prospective randomized trial comparing cognitive outcome after GKRS or WBRT in eligible patients with 11-20 BM.
- Detailed Description
CAR-Study B is a prospective randomized trial comparing cognitive outcome after GKRS or WBRT in eligible patients with 11-20 BM on a triple dose gadolinium-enhanced MRI-scan. Neuropsychological assessment will be performed at baseline and at 3, 6, 9, 12 and 15 months after treatment. Follow-up assessments will be combined with 3-monthly MRI-scans.
Patients will be randomized to either GKRS or WBRT. Groups will be balanced at baseline (prior to radiotherapy), taking into account several (stratification) factors that may influence cognitive functioning over time, such as: total tumor volume in the brain, systemic treatment, KPS, age, histology, and baseline HVLT-R total recall score.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 81
- Histologically proven malignant cancer
- 11-20 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
- No prior histologic confirmation of malignancy
- Primary brain tumor
- A second active primary tumor
- Small cell lung cancer (SCLC)
- Lymphoma
- Leukemia
- Meningeal disease
- Progressive, symptomatic systemic disease without further treatment options
- Prior brain radiation
- Prior surgical resection of BM
- Cardiovascular accident (CVA) < 2 years ago
- Additional history of a significant neurological or psychiatric disorder
- Contra indications to MRI or gadolinium contrast
- Underlying medical condition precluding adequate follow-up
- Participation in a concurrent study in which neuropsychological testing and/or health-related QOL assessments are involved
- Lack of basic proficiency in Dutch
- IQ below 85
- Severe aphasia
- Paralysis grade 0-3 according to MRC scale (Medical Research Council)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stereotactic radiosurgery (SRS) Gamma Knife radiosurgery Gamma Knife radiosurgery Whole Brain Radiation Therapy (WBRT) Whole Brain Radiation Therapy Whole Brain Radiation Therapy
- Primary Outcome Measures
Name Time Method Cognitive decline at 3 months 3 months Cognitive decline is defined as a significant decline (5 point decrease from baseline based on the Reliable Change Index (RCI) with correction for practice effects) in HVLT-R Total Recall score (verbal learning and memory test) after treatment with either GKRS or WBRT in patients with 11-20 brain metastases at time of treatment initiation.
- Secondary Outcome Measures
Name Time Method Cognitive flexibility Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT Cognitive flexibility is measured with the Controlled Oral Word Association (COWA)
Word Fluency Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT Word Fluency is measured with the Controlled Oral Word Association (COWA)
Working memory Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT Working memory is measured with the Wechsler Adult Intelligence Scale - Digit Span
Fatigue Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT Fatigue is measured with the Multidimensional Fatigue Inventory (MFI).
Distant tumor control 12 months after GKRS/WBRT Distant brain tumor control is defined as the absence of any new brain metastases, distinct from the initial 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.
Verbal memory Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT Verbal memory is measured with the Hopkins Verbal Learning Test-Revised (HVLT-R)
Motor dexterity Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT Motor dexterity is measured with the Grooved Pegboard (GP)
Health Related Quality Of Life (HRQOL) Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is used to measure HRQOL.
Depression and anxiety Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT Depression and anxiety are measured with the Hospital Anxiety and Depression Scale (HADS).
Median Overall Survival 12 months after GKRS/WBRT Overall survival is defined as the time in months from the start of treatment to the date of death or last contact if alive. Kaplan-Meier methods are used to estimate overall survival.
Processing speed Baseline and 3, 6, 9, 12 and 15 months post GKRS/WBRT Processing speed is measured with the Wechsler Adult Intelligence Scale - Digit Symbol
Local tumor control 12 months after GKRS/WBRT Local brain tumor control of the initial 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.
Trial Locations
- Locations (1)
Gamma Knife Center Tilburg, Elisabeth-TweeSteden Hospital
🇳🇱Tilburg, Noord-Brabant, Netherlands