Clinical trial NCT04891471: WHOle Brain Irradiation or STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER)
Official title: WHOle Brain Irradiation and STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER): a Prospective Comparative Study of Neurocognitive Outcomes, Level of Autonomy in Daily Activities and Quality of Life
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neurocognitive Deficit
Quality of Life
Activities of Daily Living
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
Lead sponsor: Mediterranean Institute of Oncology
Sponsor class: OTHER
Collaborators: name: University of Messina
name: University of Palermo
First posted: 2021-05-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Neurocognitive changes detected through Moca Score
timeFrame: Change from Baseline pre-Radiotherapy Neurocognitive Functional Status every three months after treatment through study completion, an average of 1 year
measure: Changes of Autonomy in daily activities detected through the Barthel Index
timeFrame: Change from Baseline pre-Radiotherapy Barthel Index every three months after treatment through study completion, an average of 1 year
measure: Change in quality of life detected though the EORTC QLQ-C15-PAL questionnaire
timeFrame: Change from Baseline pre-Radiotherapy EORTC QLQ-C15-PAL questionnaire every three months after treatment through study completion, an average of 1 year
measure: Neurocognitive changes detected through Hopkins Verbal Learning Test - Revised
timeFrame: Change from Baseline pre-Radiotherapy Neurocognitive Functional Status every three months after treatment through study completion, an average of 1 year
measure: Change in quality of life detected though the BN-20 questionnaire
timeFrame: Change from Baseline pre-Radiotherapy BN-20 questionnaire every three months after treatment through study completion, an average of 1 year
Secondary outcomes:
measure: Time to local failure
timeFrame: every three months after treatment through study completion, an average of 1 year
measure: Overall Survival
timeFrame: after treatment completion through study completion, an average of 1 year
measure: Re-treatment rate
timeFrame: after first treatment completion through study completion, an average of 1 year
measure: 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
timeFrame: from treatment completion until three months later
measure: 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
timeFrame: from three months after treatment completion through study completion, an average of 1 year
measure: Karnofsky Performance Status changing
timeFrame: after treatment completion through study completion, an average of 1 year
Other outcomes:
Locations:
city: Viagrande
country: Italy
facility: Fondazione Istituto Oncologico del Mediterraneo
state: Catania
city: Viagrande
country: Italy
facility: REM Radiotherapy (parent company of Mediterranean Institute of Oncology)
state: Catania
city: Messina
country: Italy
facility: Radiation Oncology Unit - Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina
city: Palermo
country: Italy
facility: Radiation Oncology, ARNAS-Civico Hospital
Study officials:
affiliation: REM Radiotherapy (parent company of Mediterranean Institute of Oncology)
name: Gianluca Ferini
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ferini G, Viola A, Valenti V, Tripoli A, Molino L, Marchese VA, Illari SI, Rita Borzi G, Prestifilippo A, Umana GE, Martorana E, Mortellaro G, Ferrera G, Cacciola A, Lillo S, Pontoriero A, Pergolizzi S, Parisi S. Whole Brain Irradiation or Stereotactic RadioSurgery for five or more brain metastases (WHOBI-STER): A prospective comparative study of neurocognitive outcomes, level of autonomy in daily activities and quality of life. Clin Transl Radiat Oncol. 2021 Dec 2;32:52-58. doi: 10.1016/j.ctro.2021.11.008. eCollection 2022 Jan.