Local Radiotherapy Following Complete Resection of a Brain Metastasis

Amsterdam UMC, location VUmc70 enrolled

Overview

Objective: To improve local control following complete resection of a single brain metastasis using fractionated local stereotactic radiotherapy, whilst maintaining neurological functioning, neurocognition and quality of life. Study design: Multicenter randomized phase III, with at least three high-volume Dutch centers participating in the trial. Stratification on primary tumor type and age. Study population: Patients undergoing complete resection of a single brain metastasis, confirmed by an early (i.e. within 72 hours) postoperative contrast-enhanced MR scan. Study intervention: Patients will be randomized between observation alone (standard arm) and local stereotactic radiotherapy in three fractions of 8 Gy to the surgical cavity (study arm). Main study parameters: Primary objective: local control rate at 6 months. Secondary objectives: local control rate at 12 months, neurological functioning, freedom from clinical neurological progression, performance status, quality of life, toxicity, steroid use, neurocognition and overall survival.

The objective of this study is to improve local control following complete resection of a single brain metastasis of solid tumors using fractionated local stereotactic radiotherapy, whilst maintaining neurological functioning, neurocognition and quality of life. The study is performed in the form of a multicenter randomized phase III, with at least three high-volume Dutch centers participating in the trial. Stratification will be performed on primary tumor type and age. A total of 70 patients will be included. Inclusion is restricted to patients who underwent a complete resection of a single brain metastasis, confirmed by an early (i.e. within 72 hours) postoperative contrast-enhanced magnetic resonance (MR) scan. Patients will be randomized between observation alone (standard arm) and local stereotactic radiotherapy in three fractions of 8 Gy to the surgical cavity (study arm).The main study parameters are: local control rate at 6 months (primary outcome measure) and local control rate at 12 months, neurological functioning, freedom from clinical neurological progression, performance status, quality of life, toxicity, steroid use, neurocognition and overall survival (secondary outcome measures). Follow up will be performed at three-monthly interval during the first two years, including MRI scans. Quality of life questionaires and neurocognitive functioning tests will be performed at fixed intervals during follow-up.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age of 18 years or older. * Radiologically confirmed complete resection of a single brain metastasis on a contrast-enhanced MRI within 72 h after resection. * Primary solid tumor, excluding hematologic malignancy, germ cell tumor, small cell lung cancer. * Stable extracranial tumor (primary tumor and/or systemic metastases) during the last three months with or without treatment or progressive extracranial tumor and/or systemic metastases for which effective treatment is available. * World Health Organization (WHO) performance score 0-2. * Ability to provide written informed consent. Exclusion Criteria: * Prior treatment for brain metastases (i.e. surgery, stereotactic radiotherapy or WBRT). * Distant brain metastases or radiological findings on MRI suspected for leptomeningeal tumor spread on the postoperative MRI. * Concurrent use of systemic therapy during local stereotactic radiotherapy

Outcomes

Primary Outcomes

local control rate

as assessed on follow-up MRI scans

Time frame: at 6 months

Secondary Outcomes

Decrease in neurocognitive test results using the Hopkins Verbal Learning Test Revised (HVLT-R), in full cohorts

Neurocognitive testing will be performed at baseline, at three, six and twelve months follow-up using the Hopkins Verbal Learning Test Revised (HVLT-R). The HVLT-R is one of the components used to form the core set of cognitive tests recommended to use in oncology trials. This test measures immediate memory span, provides a learning curve, measures both short-term and longer-term retention, and allows for a comparison between retrieval efficiency and learning. This version includes 3 learning trials of a 12-word list, an interval of 20 minutes a delayed recall, and a recognition trial consisting of the target words interspersed with distractor words. The score on the recognition trial is the total number of correct response. This measure has adequate psychometric properties and 6 multiple forms.