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Radiotherapy to the whole brain is standard treatment for cancer that has spread to the brain (brain metastases) as it treats both the metastases that can be seen on scans and the brain metastases that are too small to be seen on scans.
This study will use a novel radiotherapy technique, called volumetric modulated arc therapy (VMAT), to treat patients with brain metastases. This technique allows delivery of both a standard radiation dose to the whole brain as well as a higher radiation dose to the brain metastases at the same time.
The study will assess the effectiveness of using VMAT in treating brain metastases, and examine its potential side-effects.
This is a Phase II prospective clinical trial. Following registration, patients will be required to undertake a baseline questionnaire assessment of daily living activities using the Modified Barthel's index, as well as cognitive assessment using MMSE.
Patients will undergo MRI scan of the brain for radiotherapy planning purposes. During radiotherapy planning and for each of the five radiotherapy fractions, patients will be immobilised in a custom fitted stereotactic mask system, to minimise head movement. During treatment, patients will have daily online setup corrections to ensure treatment accuracy.
Patients will be treated with WBRT/SIB using VMAT, delivering a total of 20 Gy in 5 fractions to the whole brain and 50Gy in 5 fractions to the brain metastases, delivered once daily on working days. Anti-nausea and anti-inflammatory medication will be prescribed to minimise acute toxicity.
Following therapy completion, patients will be seen every 3 months for the 1st year, then every 6 months thereafter. At each clinic visit, clinicians or study investigators will monitor for toxicity from therapy, document neurologic symptoms and signs and performance status as well as Modified Barthel's index and cognitive assessment.
Patients will have contrast-enhanced MRI brain at 3 months and 1 year, and contrast-enhanced CT brain at 6 months and 9 months in the first year and every 6 months after the first year. Serum creatinine levels will be done prior to each scan to ensure safety of intravenous contrast administration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Whole brain radiotherapy | Experimental | whole brain radiotherapy (WBRT) and a simultaneous integrated boost (SIB) using volumetric modulated arc therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| whole brain radiotherapy (WBRT) and a simultaneous integrated boost (SIB) using volumetric modulated arc therapy | Radiation | Patients will be treated with WBRT/SIB using VMAT, delivering a total of 20 Gy in 5 fractions to the whole brain and 50Gy in 5 fractions to the brain metastases, delivered once daily on working days. |
| Measure | Description | Time Frame |
|---|---|---|
| 3 month treatment response of metastases evaluated using contrast-enhanced MRI scan of brain | 3 months post treatment |
| Measure | Description | Time Frame |
|---|---|---|
| 1-year local control of treated metastases evaluated with contrast-enhanced MRI scan of brain | 1 year post-treatment | |
| 1-year brain control of metastases evaluated with contrast-enhanced MRI scan of brain | 1 year post-treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alan M Nichol, MD | British Columbia Cancer Agency | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| BC Cancer Agency - Vancouver Centre | Vancouver | British Columbia | V5Z 4E6 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33239056 | Derived | Chan M, Ferguson D, Ni Mhurchu E, Yuan R, Gondara L, McKenzie M, Olson R, Thiessen B, Lalani N, Ma R, Nichol A. Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy. Radiat Oncol. 2020 Nov 25;15(1):271. doi: 10.1186/s13014-020-01717-x. | |
| 26678660 | Derived |
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| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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|
| Median survival | No time frame |
| Both acute neurological toxicity (within 3 months of treatment) and late neurological toxicity (beyond 3 months of treatment | 3 months and beyond |
| Time to decline in activities of daily living evaluated using the Modified Barthel index | No time frame |
| Time to decline in cognition evaluated with the Mini-mental state examination | No time frame |
| Nichol A, Ma R, Hsu F, Gondara L, Carolan H, Olson R, Schellenberg D, Germain F, Cheung A, Peacock M, Bergman A, Vollans E, Vellani R, McKenzie M. Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study. Int J Radiat Oncol Biol Phys. 2016 Feb 1;94(2):312-21. doi: 10.1016/j.ijrobp.2015.10.017. Epub 2015 Oct 22. |
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |