Pre- Versus Post-operative SRS for Resectable Brain Metastases

Study Overview
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Brief Summary
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The purpose of this study is to determine if performing radiotherapy (SRS) prior to surgery results in better treatment outcomes than performing surgery before radiotherapy for patients with brain metastases. Brain metastases occur when cancer cells from a primary cancer (e.g. lung, breast, colon) travel through the bloodstream and spread (metastasize) to the brain. As these new tumors grow they apply pressure and change how healthy brain tissue works. This can lead to a loss of brain function and worsening quality of life. Treatments for patients whose cancer has spread to the brain is often surgery, radiation therapy (radiotherapy) or a combination of both. Surgery is one the main treatments for brain tumors. To remove the tumor, a neurosurgeon makes an opening in the skull and attempts to the remove the entire tumor. If the tumor is too close to important brain tissue, the surgeon may attempt to remove part of the tumor. Removal of the tumor from the brain tissue is called resection. The complete or partial removal of tumor helps to relieve symptoms by reducing pressure on healthy tissues and reduces the amount of tumor that needs to be treated by radiotherapy. One type of radiotherapy used to treat brain metastases is stereotactic radiosurgery (SRS). SRS uses many focused radiation beams to treat tumors within the brain. Unlike surgery, there is no incision or cut being made. Instead, SRS uses an accurate map of your brain to deliver a precise beam of radiation to the tumors. The radiation damages the tumor cells forcing them to shrink and die off. The focused radiation beams also limit damage to healthy brain tissue minimizing side effects. Surgery followed by radiotherapy is a standard treatment for brain metastases. However, there are still risks associated with the combination of treatments. This study plans to investigate whether performing surgery prior to SRS results in improved quality of life and decreased side effects.

Official Title
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A Randomized Controlled Trial of Pre-operative Versus Post-operative Stereotactic Radiosurgery for Patients With Surgically Resectable Brain Metastases

Conditions
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Brain Metastases

Intervention / Treatment
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* Procedure: Brain Surgery
* Radiation: Stereotactic Radiosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Pathologically-proven primary malignancy ECOG 0-2 Ability to complete neurocognitive testing without assistance from family or friends. Previous SRS to lesions other than the one being resected is allowed Patients of childbearing / reproductive potential must have a negative urine or serum pregnancy test ≤7 days before enrollment Participants capable of giving informed consent, or if appropriate participants having an acceptable individual capable of giving consent Exclusion Criteria: Patients who have received prior WBRT, or SRS to the lesion being resected at time of study accrual Patients unable to undergo MRI scan (e.g. pacemaker) Leptomeningeal disease Germ cell tumor, small cell lung cancer or hematological primary malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Surgical Resection followed by SRS (Non-Experimental)<br>Surgical Resection followed by SRS within 3 weeks of surgery date. | Procedure: Brain Surgery<br>* Surgery to remove brain metastases<br>Radiation: Stereotactic Radiosurgery<br>* SRS uses many focused radiation beams to treat tumors within the brain<br>* Other names: SRS;|
| Experimental: SRS followed by Surgical Resection (Experimental)<br>SRS followed by surgery within 1 week of radiotherapy end date. | Procedure: Brain Surgery<br>* Surgery to remove brain metastases<br>Radiation: Stereotactic Radiosurgery<br>* SRS uses many focused radiation beams to treat tumors within the brain<br>* Other names: SRS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Control | To compare local control (in months) of pre-operative versus post-operative SRS | This will be assessed at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Control | To compare local control (in months) of pre-operative versus post-operative SRS | This will be assessed at 6 and 24 months. | 
| Distant Brain Recurrence Rate | To compare Distant Brain Recurrence Rate (%) of pre-operative versus post-operative SRS | This will be assessed at 6,12 and 24 months. | 
| Leptomeningeal Recurrence Rate | To compare the Leptomeningeal Recurrence Rate (%) of pre-operative versus post-operative SRS | This will be assessed at 6,12 and 24 months. | 
| Overall Survival | Overall survival will be compared between both treatment arms | This will be assessed at 6,12 and 24 months. | 
| Hopkins Verbal Learning Test | Participants are scored using a points based system on Total Recall, Delayed Recall, Retention (% retained), and a Recognition Discrimination Index. | This will be assessed at 3,6,9,12,16 and 24 months. | 
| Controlled Oral Word Association | Participants are scored on their ability to generate words starting with a specific letter in a one minute timeframe. | This will be assessed at 3,6,9,12,16 and 24 months. | 
| Trial Making Tests | Participants are scored on their ability to complete the test within a certain timeframe. | This will be assessed at 3,6,9,12,16 and 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurosurgery, Stereotactic Radiosurgery