This clinical study is a parallel, prospective observational single-centre trial in patients presenting with 5 to 30 brain metastases. Patients to receive either stereotactic radiosurgery (SRS) alone or SRS plus whole brain radiation (WBRT) will be enrolled.
The current standard of care for patients with limited brain metastases (1 to 4) is stereotactic radiosurgery (SRS) alone. This has evolved from the traditional standard of care in treating patients with whole brain radiation (WBRT). Studies in patients with limited (less than 5) brain metastases have shown that WBRT is harmful with respect to neurocognition and does not improve patient survival compared to SRS alone. As a result, SRS alone now is considered the standard of care treatment for patients with limited metastases. However, there is a lack of high quality prospective randomized evidence on the role of SRS in patients with 5 or more brain metastases to guide treatment. Therefore, this study seeks to prospectively compare SRS alone versus SRS plus WBRT in patients with 5 to 30 brain metastases.
Study Type
OBSERVATIONAL
Enrollment
126
SRS or hypofractionated stereotactic radiation delivered via the Leksell Gammknife Perfexion/Icon radiosurgery system. Hypofractionated stereotactic radiotherapy 25-32.5 Gy in 5 fractions or 24-27 Gy in 3 fractions at the discretion of the radiation oncologist Maximum diameter of metastasis (doses in single fraction): ≤ 2 cm: 15-20 Gy \> 2 cm and ≤ 3 cm: 15-18 Gy \> 3 cm and ≤ 4 cm: 15 Gy Tumour location (doses in single fraction): Brainstem: 15 Gy Hypofractionated stereotactic radiotherapy 25-32.5 Gy in 5 fractions may be used for lesions \> 2 cm at the discretion of the radiation oncologist Note: SRS dosing reduced by 20% (for all prescriptions \> 15 Gy) when patient is randomized to SRS + WBRT arm
WBRT 20 Gy in 5 fractions or 30 Gy in 10 fractions at the discretion of the radiation oncologist
Sunnybrook Odette Cancer Centre
Toronto, Ontario, Canada
Neurocognitive function
Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall using the Reliable Change Index (RCI)
Time frame: 2 months post treatment
Neurocognitive function - HVLT-R
Hopkins Verbal Learning Test-Revised (HVLT-R) (Total Recall, Delayed Recall, Delayed Recognition)
Time frame: 2 months, 4 months, 6 months, and 9 months
Neurocognitive function - Trail Making Test
Trail Making Test (TMT, Part A and Part B)
Time frame: 2 months, 4 months, 6 months, and 9 months
Neurocognitive function - Controlled Oral Word Association
Controlled Oral Word Association (COWA)
Time frame: 2 months, 4 months, 6 months, and 9 months
Neurocognitive function - Clinical Trial Battery Composite
Clinical Trial Battery Composite (CTB COMP) score
Time frame: 2 months, 4 months, 6 months, and 9 months
Local control of sites initially treated by SRS
Defined by the response criteria stipulated in the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria guideline
Time frame: 2 months, 4 months, 6 months, and 9 months
Distant tumour control within the brain
Distant brain failure is defined as the appearance of one or more new lesions on a diagnostic-quality, contrast-enhanced MRI within the brain at sites other than those initially treated by SRS
Time frame: 2 months, 4 months, 6 months, and 9 months
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Overall central nervous system (CNS) response
Response will be recorded for each individual target lesion and for overall central nervous system (CNS) response as a composite of radiographical CNS target and non-target lesion responses, corticosteroid use, and clinical status defined as per RANO-BM criteria
Time frame: 2 months, 4 months, 6 months, and 9 months
Overall survival
Response recorded for survival
Time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months
Measure of Quality of Life
Health-Related QoL as measured by Functional Assessment of Cancer Therapy - Brain (FACT-Br) instrument
Time frame: 2 months, 4 months, 6 months, and 9 months
Incidence of Brain Salvage therapy During Follow-up
Number/proportion of patients requiring salvage therapy and type of salvage therapy, for progressive intracranial disease during follow-up
Time frame: 2 months, 4 months, 6 months, and 9 months