WHOle Brain Irradiation or STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER)

Mediterranean Institute of Oncology

Status: Enrolling

Conditions: Quality of Life; Neurocognitive Deficit; Activities of Daily Living

Treatments: Radiation: Whole Brain Irradiation; Radiation: Stereotactic RadioTherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT04891471

70/2020/CECT2

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

100 participants in 2 patient groups

SRS/SBRT arm

Experimental group

Description:

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.

Treatment:

Radiation: Stereotactic RadioTherapy

WBI arm

Active Comparator group

Description:

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.

Treatment:

Radiation: Whole Brain Irradiation