Activities of Daily Living, Neurocognitive Deficit, Quality of Life
Conditions
Keywords
multiple brain metastasis, neurocognitive decay, whole brain radiotherapy, stereotactic radiosurgery, stereotactic body radiotherapy, quality of life, solid tumor, Activities of Daily Living, best supportive care, palliative radiotherapy
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.
Interventions
RADIATIONStereotactic RadioTherapy
To treat only brain metastasis identified through Magnetic Resonance imaging by means of stereotactic radiotherapy (experimental intervention) to determine if sparing of clinically uninvolved brain implies a better neurocognitive performance, quality of life and level of autonomy in activities of daily living respect to Whole Brain Irradiation (active comparator).
RADIATIONWhole Brain Irradiation
To irradiate the entire brain, site of at least 5 parenchymal metastasis.
Sponsors
University of Messina
University of Palermo
Mediterranean Institute of Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Italy
Contacts
Primary ContactGianluca Ferini
Outcome results
None listed