Stereotactic Radiosurgery in Treating Patients With Spinal Metastases

Study Overview
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Brief Summary
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RATIONALE: Stereotactic radiosurgery can send x-rays directly to the tumor and cause less damage to normal tissue. It may also help patients with spinal metastases live more comfortably. PURPOSE: This phase I trial is studying the side effects and best dose of stereotactic radiosurgery in treating patients with spinal metastases.

Detailed Description
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OBJECTIVES: To implement CyberKnife® technology for improving palliation in patients with spinal metastases. To determine the maximum tolerated dose of CyberKnife® hypofractionated stereotactic radiosurgery in these patients. To evaluate functional and diffusion MRI parameters in the spinal cord and tumor after treatment with Cyberknife® radiosurgery. OUTLINE: Patients undergo placement of gold fiducial markers at the time of open surgical resection or percutaneous needle biopsy. Patients then undergo CyberKnife® hypofractionated stereotactic radiosurgery over 30-90 minutes daily for 2-3 days. Patients undergo functional MRI and diffusion tensor imaging at baseline and then at 6 weeks and 6 months after completion of treatment. Patients also complete a pain questionnaire at baseline and then at 3, 6, 9, 12, 18, and 24 months after completion of treatment. After completion of study treatment, patients are followed periodically for up to 2 years.

Official Title
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Cyberknife Radiosurgery for Improving Palliation of Metastatic Tumors of the Spine

Conditions
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Metastatic Cancer

Intervention / Treatment
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* Other: questionnaire administration
* Procedure: diffusion tensor imaging
* Procedure: functional magnetic resonance imaging
* Radiation: hypo-fractionated SRS
* Radiation: single-fraction SRS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DISEASE CHARACTERISTICS: Histologically confirmed metastatic spinal tumor Localized spinal metastasis, defined as one of the following: Solitary spinal metastasis Two contiguous spinal levels No more than 2 adjacent spinal levels involved by a single tumor Involvement of ≤ 3 separate sites (e.g., C5, T5, and T12) Tumor size ≤ 5 cm PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Life expectancy ≥ 6 months Negative pregnancy test Fertile patients must use effective contraception Must be ambulatory Exclusion Criteria: Not pregnant or nursing No spinal instability No rapid neurological decline No bony retropulsions causing neurological abnormalities No total paraplegia for > 48 hours No psychological issues that would preclude completion of study treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior treatment for spinal tumor that would result in potential overlap of radiotherapy fields No treatment that is expected to exceed spinal cord tolerance or other regional normal tissue tolerance No tumors that are exquisitely radiosensitive and controlled with conventional radiotherapy (e.g., lymphoma, leukemia, multiple myeloma, or germ cell tumors)

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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase I study with 2 parallel groups of dose escalation using a 3 +3 design to determine the maximum tolerated dose of the radiation with the FDA approved device. There are three dose cohorts in each group, thus 6 arms.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-fraction radiosurgery; 16 Gray<br>Subjects able to achieve the spinal cord dose constraints for single-fraction SRS stereotactic radiosurgery Radiation: stereotactic radiotherapy at 16 Gray Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging | Other: questionnaire administration<br>* prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment<br>Procedure: diffusion tensor imaging<br>* prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy<br>Procedure: functional magnetic resonance imaging<br>* prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter<br>Radiation: single-fraction SRS<br>* two to three consecutive daily sessions within one week for 3 cohorts- for 3 cohorts- Cohort 1 = 16 Gy; Cohort 2 = 18 Gy; Cohort 3 = 20 Gy<br>|
| Experimental: Hypo-fractionated radiosurgery; 21 Gray<br>Subjects unable to achieve the spinal cord dose constraints for single-fraction radiosurgery (SRS), based on tumor location and expected tolerance dose to the adjacent normal tissue, will be offered hypo-fractionated SRS (3 fractions) Radiation: stereotactic radiotherapy Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging hypo-fractionated radiation therapy at 21 Gray | Other: questionnaire administration<br>* prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment<br>Procedure: diffusion tensor imaging<br>* prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy<br>Procedure: functional magnetic resonance imaging<br>* prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter<br>Radiation: hypo-fractionated SRS<br>* two to three consecutive daily sessions within one week for 3 cohorts- Cohort 1 = 21 Gy; Cohort 2 = 24 Gy; Cohort 3 = 27 Gy<br>|
| Experimental: Single-fraction radiosurgery; 18 Gray<br>Subjects able to achieve the spinal cord dose constraints for single-fraction SRS stereotactic radiosurgery Radiation: stereotactic radiotherapy at 18 Gray Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging | Other: questionnaire administration<br>* prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment<br>Procedure: diffusion tensor imaging<br>* prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy<br>Procedure: functional magnetic resonance imaging<br>* prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter<br>Radiation: single-fraction SRS<br>* two to three consecutive daily sessions within one week for 3 cohorts- for 3 cohorts- Cohort 1 = 16 Gy; Cohort 2 = 18 Gy; Cohort 3 = 20 Gy<br>|
| Experimental: Single-fraction radiosurgery; 20 Gray<br>Subjects able to achieve the spinal cord dose constraints for single-fraction SRS stereotactic radiosurgery Radiation: stereotactic radiotherapy at 20 Gray Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging | Other: questionnaire administration<br>* prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment<br>Procedure: diffusion tensor imaging<br>* prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy<br>Procedure: functional magnetic resonance imaging<br>* prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter<br>Radiation: single-fraction SRS<br>* two to three consecutive daily sessions within one week for 3 cohorts- for 3 cohorts- Cohort 1 = 16 Gy; Cohort 2 = 18 Gy; Cohort 3 = 20 Gy<br>|
| Experimental: Hypo-fractionated radiosurgery; 24 Gray<br>Subjects unable to achieve the spinal cord dose constraints for single-fraction radiosurgery (SRS), based on tumor location and expected tolerance dose to the adjacent normal tissue, will be offered hypo-fractionated SRS (3 fractions) Radiation: stereotactic radiotherapy Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging hypo-fractionated radiation therapy at 24 Gray | Other: questionnaire administration<br>* prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment<br>Procedure: diffusion tensor imaging<br>* prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy<br>Procedure: functional magnetic resonance imaging<br>* prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter<br>Radiation: hypo-fractionated SRS<br>* two to three consecutive daily sessions within one week for 3 cohorts- Cohort 1 = 21 Gy; Cohort 2 = 24 Gy; Cohort 3 = 27 Gy<br>|
| Experimental: Hypo-fractionated radiosurgery; 27 Gray<br>Subjects unable to achieve the spinal cord dose constraints for single-fraction radiosurgery (SRS), based on tumor location and expected tolerance dose to the adjacent normal tissue, will be offered hypo-fractionated SRS (3 fractions) Radiation: stereotactic radiotherapy Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging hypo-fractionated radiation therapy at 27 Gray | Other: questionnaire administration<br>* prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment<br>Procedure: diffusion tensor imaging<br>* prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy<br>Procedure: functional magnetic resonance imaging<br>* prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter<br>Radiation: hypo-fractionated SRS<br>* two to three consecutive daily sessions within one week for 3 cohorts- Cohort 1 = 21 Gy; Cohort 2 = 24 Gy; Cohort 3 = 27 Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose - single fraction | Maximum tolerated dose of CyberKnife® hypofractionated stereotactic radiosurgery | 6 weeks | 
| Maximum tolerated dose - hypofraction | Maximum tolerated dose of CyberKnife® hypofractionated stereotactic radiosurgery | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of pain | Pain as measured by the Brief Pain Inventory and Roland scale | baseline and then at 3, 6, 9, 12, 18, and 24 months after completion of treatment | 
| Spinal cord response | Spinal cord response as measured by functional MRI | baseline and then at 6 weeks and 6 months after completion of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal cord metastases