Robotic Compared to Fixed Gantry Radiosurgery for Brain Metastases

Study Overview
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Brief Summary
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Radiosurgery is precisely delivered high dose radiation. It can be performed using multiple cobalt sources, a modified traditional gantry-based linear accelerator or a robotic linear accelerator. The treatment of brain metastases represents the most common indication for radiosurgery while new indications for this technology are continually being discovered. With the increasing importance of radiosurgery and the resource implications for radiotherapy programs the investigators have proposed the first direct technological comparison of robotic to linear accelerator radiosurgery for brain metastases.

Detailed Description
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Radiosurgery can be performed using multiple Co-60 sources, a modified traditional gantry-based linear accelerator, or a robotic linear accelerator. Each technique has its own advantages and disadvantages. Co-60 radiosurgery has very precise target localization by using a rigid immobilization device. The requirement for rigid immobilization limits its treatments to the head and neck. Robotic radiosurgery permits precise radiation to be delivered without the requirement for rigid immobilization. Robotic radiosurgery uses real-time imagining, allowing it to track the cancer or internal structures as they move during treatment. Another advantage is that it can deliver many small beams of radiation (as many as 200) in a limited time period and can treat lesions anywhere in the body. A traditional gantry-based linear accelerator normally requires some form of immobilization and requires more time for multiple isocentre set up but can provide both radiosurgery and conventional treatments. Brain metastases occur in up to 50% of patients with cancer. It has been reported up to 65% of patients with brain metastases will present with one to three lesions. This represents 18,000 patients in Ontario each year who would be eligible for radiosurgery as part of their management. Randomized trials have demonstrated improved palliation and overall survival when radiosurgery is added to conventional whole brain radiation therapy (WBRT). As a result the treatment of brain metastases currently represents the largest resource use for radiosurgery. During the commissioning and initial use of the first robotic radiosurgery device in Ontario (CyberKnife) the investigators became aware of its potential advantages for the treatment of brain metastases. Treatment planning time and on treatment time with robotic radiosurgery appeared to be better than with a traditional linear accelerator and patients appeared to be more comfortable with the minimal/ non-invasive immobilization required. Surprisingly, there were very little direct comparisons of robotic radiosurgery with other techniques in the literature and only one prospective randomized trial comparing two different approaches to delivering Co-60 radiosurgery was identified. Given the increasing importance of radiosurgery and the resource implications for radiation treatment programs in Ontario, this study is proposed to conduct a direct comparison of robotic to traditional linear accelerator radiosurgery for brain metastases. The primary outcome will be treatment planning and delivery time and an important secondary outcome is patient comfort. Treatment planning time will include immobilization preparation, CT simulation, image fusion, radiation planning and treatment plan quality assurance. Treatment delivery time will include patient set up, target localization and treatment delivery. The Juravinski Cancer Centre (JCC) and McMaster University are uniquely posed to perform this comparison with access to both robotic and linear accelerator radiosurgery techniques as well as research methodology expertise in clinical trials technology assessment, and health services research.

Official Title
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A Randomized Trial of Robotic Compared to Fixed Gantry Radiosurgery for Brain Metastases

Conditions
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Metastatic Malignant Neoplasm to the Adult Brain

Intervention / Treatment
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* Radiation: Fixed Gantry Radiosurgery
* Radiation: Robotic Radiosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1-3 brain metastases from a confirmed primary extra-cranial site Exclusion Criteria: Any brain metastasis >3cm in maximal diameter Easter Cooperative Oncology Group (ECOG) performance status >2 Prior surgical resection or radiosurgery of a brain metastasis Lesion causing significant mass effect (>1cm midline shift) Lesion located <5mm from optic chiasm or within the brainstem Requires more than one fraction of radiosurgery Primary disease histology unknown, lymphoma or germ cell tumor

Ages Eligible for Study
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Minimum Age: 18 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fixed Gantry Radiosurgery<br>Single fraction radiosurgery will be prescribed using a Fixed Gantry Linear Accelerator | Radiation: Fixed Gantry Radiosurgery<br>* Single fraction radiosurgery will be prescribed using a fixed gantry radiosurgery delivery system<br>* Other names: Linear Accelerator Radiosurgery;|
| Experimental: Robotic Radiosurgery<br>Single fraction radiosurgery will be prescribed using a robotic linear accelerator | Radiation: Robotic Radiosurgery<br>* Single fraction radiosurgery will be prescribed using a robotic radiosurgery system<br>* Other names: CyberKnife Radiosurgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiosurgery planning and delivery time | Radiosurgery Planning Time: 1) Immobilization Device Fitting 2) CT Simulation and Data Aquisition 3) Treatment Planning 4) Quality Assurance Treatment Delivery Time: 1) Patient Setup 2) Target Localization 3) Plan Delivery | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Control | Local Control will be assesed using contrast enhanced MRI at 3,6 and 12 months after radiosurgery | One Year | 
| Scattered Radiation Dose | Thermo-luminescent dosimeters will be placed on the patient during treatment delivery to measure scatter radiation dose | 14 Days | 
| Quality of Life | EQ-5D testing will be done prior to radiosurgery and at 4 weeks and at 3,6 and 12 months after radiosurgery | One Year | 
| Dosimetry | Once the plan is approved all dosimetric measures will be recorded. | 7 Days | 
| Acute Toxicity | NCI Common Terminology Criteria for Adverse Events Version 4 will be used to assess acute toxicity up to and including the 3 month post radiosurgery visit | 3 months | 
| Late Toxicity | NCI Common Terminology Criteria for Adverse Events version 4 will be used to assess late toxicity from the 3 month visit to the 12 month visit. | One Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain Neoplasms, Neoplasm Metastasis, Neoplasms