WHOle Brain Irradiation or STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER)
- Conditions
- Neurocognitive DeficitQuality of LifeActivities of Daily Living
- Interventions
- Radiation: Stereotactic RadioTherapyRadiation: Whole Brain Irradiation
- Registration Number
- NCT04891471
- Lead Sponsor
- Mediterranean Institute of Oncology
- Brief Summary
This work aims to evaluate neurocognitive performance, daily activity and quality of life and local control among patients with brain metastasis (MBM) ≥ 5 due to solid tumors treated with Stereotactic RadioSurgery (SRS) or Whole Brain RadioTherapy (WBRT). This multicentric randomised controlled trial will be conducted at the Fondazione IOM (Viagrande) in collaboration with REM (Viagrande), Hospital G. Martino (Messina) and Hospital Civico ARNAS (Palermo). It will involve, within 5 years starting from 15 September 2020, the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy \> 3 months, histological confirmation of primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) of 20/30, Barthel Activities of Daily Living score 90/100, to be subjected to SRS on each brain lesion by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBRT (control arm). The primary endpoints are neurocognitive performance, quality of life and autonomy in daily-life activities variations, the first one assessed by Moca Score and Hopkins Verbal Learning Test - Revised, the second one through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL) and Brain Neoplasm (BN-20) questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatments frequency, acute and late toxicities, KPS decrease. It will be considered significant a statistical difference of at least 29% between the two arms (statistical power of 80% with a significance level of 95%). This trial has been approved by the local ethics committee on July 7th 2020 (record 70). Several studies debate what is the predominant factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiotherapy, especially if extended to the entire brain, or intracranial disease progression? Answer to this question may come from current opportunity, thanks to recent technological advancement, to treat, with significant time savings, improved patient comfort and at the same time minimizing the dose to healthy brain tissue, Multiple Brain Metastasis simultaneously, otherwise attackable only by panencephalic irradiation. The pursuit of a local control rate comparable to that obtainable with WBRT remains the fundamental prerequisite for the aforementioned related assessments.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- Age > 18
- Life expectancy > 3 months
- Brain metastases number ≥ 5
- Primary tumor histologic diagnosis
- Complete Extracranial staging
- Montreal Cognitive Assessment ≥ 20/30
- Barthel Activities of Daily Living ≥ 90/100
- KPS ≥ 70
- Signed Informed Consent
- Brain-MRI contraindications
- Contraindications to SRS
- Pregnancy
- Hemorrhagic cerebral disease
- Miliary metastases
- Massive perilesional edema
- Leptomeningeal involvement
- Previous brain irradiation
- Dementia
- Non-solid brain tumor
- Ischaemic event
- Alcohol and/or drugs abuse
- Anxiety and depression
- KPS ≤ 60
- Life expectancy < 3 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SRS/SBRT arm Stereotactic RadioTherapy Patients with five or more brain metastasis assigned by randomization to Stereotactic RadioSurgery (SRS) or Stereotactic Body RadioTherapy (SBRT) will be treated with a highly-conformal metastasis-directed single dose between 15 and 24 Gy or fractionated dose (e.g. 27 Gy in 3 fractions), respectively, depending on lesion size, while sparing clinically negative brain. The treatment will be delivered using five non-coplanar arcs and a mono-isocentric technique. WBI arm Whole Brain Irradiation Patients with five or more brain metastasis assigned by randomization to Whole Brain Irradiation (WBI) will be treated using a 3D-Conformal RadioTherapy technique for a uniform dose delivery of 30 Gy in 10 daily/fractions to the target, that is entire brain.
- Primary Outcome Measures
Name Time Method Neurocognitive changes detected through Moca Score Change from Baseline pre-Radiotherapy Neurocognitive Functional Status every three months after treatment through study completion, an average of 1 year To assess how neurocognitive performance changes after SRS/SBRT compared to WBI
Changes of Autonomy in daily activities detected through the Barthel Index Change from Baseline pre-Radiotherapy Barthel Index every three months after treatment through study completion, an average of 1 year To assess how level of autonomy in activities of daily living changes after SRS/SBRT compared to WBI
Neurocognitive changes detected through Hopkins Verbal Learning Test - Revised Change from Baseline pre-Radiotherapy Neurocognitive Functional Status every three months after treatment through study completion, an average of 1 year To assess how neurocognitive performance changes after SRS/SBRT compared to WBI
Change in quality of life detected though the EORTC QLQ-C15-PAL questionnaire Change from Baseline pre-Radiotherapy EORTC QLQ-C15-PAL questionnaire every three months after treatment through study completion, an average of 1 year To assess how quality of life changes after SRS/SBRT compared to WBI
Change in quality of life detected though the BN-20 questionnaire Change from Baseline pre-Radiotherapy BN-20 questionnaire every three months after treatment through study completion, an average of 1 year To assess how quality of life changes after SRS/SBRT compared to WBI
- Secondary Outcome Measures
Name Time Method Overall Survival after treatment completion through study completion, an average of 1 year Time from the first day of treatment to exitus
Re-treatment rate after first treatment completion through study completion, an average of 1 year Difference in needing further subsequent radiotherapy treatment between SRS/SBRT and WBI arms
Acute Central Nervous System (CNS) toxicities evaluated by means of Radiation Therapy Oncology Group (RTOG)/ European Organization for Research and Treatment of Cancer (EORTC) Radiation Toxicity Grading from treatment completion until three months later Toxicities registered within three months from treatment
Karnofsky Performance Status changing after treatment completion through study completion, an average of 1 year Evaluation of how patient's performance status modifies after treatment
Time to local failure every three months after treatment through study completion, an average of 1 year Time between treatment and cerebral disease progression detected through Magnetic Resonance imaging
Late Central Nervous System (CNS) toxicities evaluated by means of Radiation Therapy Oncology Group (RTOG)/ European Organization for Research and Treatment of Cancer (EORTC) Radiation Toxicity Grading from three months after treatment completion through study completion, an average of 1 year Toxicities registered after three months from treatment
Trial Locations
- Locations (4)
Radiation Oncology, ARNAS-Civico Hospital
🇮🇹Palermo, Italy
REM Radiotherapy (parent company of Mediterranean Institute of Oncology)
🇮🇹Viagrande, Catania, Italy
Radiation Oncology Unit - Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina
🇮🇹Messina, Italy
Fondazione Istituto Oncologico del Mediterraneo
🇮🇹Viagrande, Catania, Italy