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Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Single fraction radiosurgery will be prescribed using a Fixed Gantry Linear Accelerator

Single fraction radiosurgery will be prescribed using a robotic linear accelerator

Single fraction radiosurgery will be prescribed using a fixed gantry radiosurgery delivery system

Fixed Gantry Radiosurgery

Single fraction radiosurgery will be prescribed using a robotic radiosurgery system

Robotic Radiosurgery

Jeffrey N Greenspoon, MD FRCPC

Timothy Whelan, MD FRCPC

Anthony C Whitton, MD FRCPC

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.

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.

Robotic Compared to Fixed Gantry Radiosurgery for Brain Metastases

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

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

Local Control will be assesed using contrast enhanced MRI at 3,6 and 12 months after radiosurgery

Thermo-luminescent dosimeters will be placed on the patient during treatment delivery to measure scatter radiation dose

EQ-5D testing will be done prior to radiosurgery and at 4 weeks and at 3,6 and 12 months after radiosurgery

Once the plan is approved all dosimetric measures will be recorded.

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

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.

Ontario Clinical Oncology Group (OCOG)

Juravinski Cancer Centre Foundation

Hamilton Health Sciences Corporation

Dr. Jeffrey Noah Greenspoon Radiation Oncology Research Fellow

whole brain irradiation with 40 Gy, with fixation mask, radiation of the entire brain, skull base and meninges

irradiation of the resection margin plus 5 mm safety margin with 30 Gy in 5 fractions

Gross Tumor Volume (GTV) is defined as the visible margin of the resection on post- operative MRI and planning- CT-scan. The Clinical Treatment Volume (CTV) is the same as the GTV plus a 5 mm margin The Planning Treatment Volume (PTV) includes the CTV plus a 1mm margin.

A non-invasive immobilization is used for the planning CT and treatment delivery with an accuracy of ≤ 1mm.

Treatment planning will conform to ICRU 50/62 rules for coverage of GTV, CTV and PTV. Additionally, organs at risk are delineated according to the ICRU 62 rules.

Treatment with radiotherapy will start 2 to 3 weeks after surgery. The prescribed dose for the PTV is 30 Gy in 5 fractions.

Isodose distributions will be calculated through the target in three planes. Dose volume histograms will be reported.

sector irradiation

For whole brain radiation the entire brain, the base of the skull and the meninges are included.

Radiation is performed fractionated with 40 Gy. The caudal boundary of the radiation-target volume is between the 2. and the 3. cervical vertebra. The radiation is performed via two lateral, opposing and isocentric contra fields. The face/ventral skull is shielded with individual blocs or MLC.

The used energy for the radiation fields should be between 6 and 16 MV. The specification point of the dose or the standardization point has to be chosen in that way that the point is in the middle of the target volume. The target volume is radiated within the tolerance range of 95% - 107 %. The maximum/minimum doses in the target volume and possible doses peaks are documented.

whole brain irradiation

Johannes Kerschbaumer, MD

Christian F Freyschlag, MD

Sabine Strauss, Mag

Marcel Seiz-Rosenhagen, MD, PD

Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients.

To minimize the risk of intracranial recurrence whole brain irradiation has been established as standard adjuvant treatment in those patients. Sector irradiation resembles a brain - tissue - sparing method by focusing the irradiation in the area of the tumor bed and a surrounding 1mm security margin.

The aim of this study is to investigate whether adjuvant "sector""-irradiation following microsurgical resection is equal to adjuvant whole brain irradiation in terms of local control and superior to in terms of quality of life and neurocognitive deficits in a prospective randomized trial.

Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients. Traditionally whole-brain irradiation is the treatment of choice following surgical resection. Whole brain irradiation has been the standard approach to minimize the risk of intracranial recurrence following resection of brain metastases. Almost 2 decades ago, Patchell et al. established the superiority of resection of solitary metastases followed by whole brain irradiation compared with whole brain irradiation alone with regard to survival, local control, and length of functional independence. A following study by the same group failed to show a survival advantage for the addition of whole brain irradiation compared to surgical resection alone in patients with a solitary intracranial metastasis, although the likelihood of local and distant recurrence and death from neurological causes were significantly reduced by whole brain irradiation. Due to potential delayed neurocognitive effects associated with whole brain irradiation, investigators have evaluated the use of partial brain irradiation in the form of stereotactic radiosurgery instead of whole brain irradiation after resection of brain metastases. They showed that despite whole brain irradiation means superior control of brain recurrence in sites other than the resection bed, stereotactic radiosurgery after resection resulted in equivalent survival times and neurological preservation. In a retrospective series of 52 patients Karlovits et al. could show that stereotactic radiosurgery following surgical resection leads to equal local control compared to standard whole brain irradiation.

Study objective

The aim of this study is to investigate whether adjuvant "sector" -irradiation following microsurgical resection is equal to adjuvant whole brain irradiation in terms of local control and superior to in terms of quality of life and neurocognitive deficits in a prospective randomized trial.

Hypothesis

1. Sector irradiation is equal to whole-brain irradiation in local tumor control after 3, 6, 12 and 36 months and
2. Sector irradiation" is superior to whole-brain irradiation in terms of quality of life and neurocognitive function

Patients and Methods

Patients with a single brain metastasis amenable to surgical resection fulfilling the inclusion criteria will be consecutively enrolled in this study. After microsurgical complete resection documented by early postoperative MRI within 72 hours and histological proven brain metastasis patients will be randomized in arm A or B. Radiotherapy will start after 14th postoperative day within 3 weeks postoperatively. Study arm A means postoperative sector irradiation (30Gy), study arm B includes standard whole brain radiotherapy (40Gy). Follow up MRI will be every 3 months. Neurocognitive evaluation will be performed before radiotherapy and 6 and 12 months postoperatively. In case of local recurrence or developing further metastases a cross over to whole brain radiotherapy or focal irradiation is possible.

Sector Irradiation Versus Whole Brain Irradiation for Brain Metastasis

Sector Irradiation Versus Whole Brain Irradiation After Resection of Singular or Solitary Brain Metastasis - a Prospective Randomized Monocentric Trial

standardized assessment via "EORTC QLQ-C30/BN20" and the "FACT-Br" - questionary at 3, 6, 12 and 36 months after date of randomization

Neurocognitive testing by independent neuropsychologist at 3, 6, 12 and 36 months after date of randomization

Need of adjuvant steroid, assessed at 3, 6, 12 and 36 months after date of randomization

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Robotic Compared to Fixed Gantry Radiosurgery for Brain Metastases	NCT01353573	Metastatic Mali...	Fixed Gantry Ra... Robotic Radiosu...	18 Years -	Hamilton Health Sciences Corporation
Sector Irradiation Versus Whole Brain Irradiation for Brain Metastasis	NCT01667640	Metastatic Mali...	sector irradiat... whole brain irr...	18 Years - 80 Years	Medical University Innsbruck
Sector Irradiation Versus Whole Brain Irradiation for Brain Metastasis	NCT01667640	Metastatic Mali...	sector irradiat... whole brain irr...	18 Years - 80 Years	Medical University Innsbruck

Spots Global Cancer Trial Database for metastatic malignant neoplasm to the adult brain