Stereotactic Radiosurgery in Metastatic Spinal Cord Compression

Study Overview
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Brief Summary
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To determine whether stereotactic radiosurgery of metastatic spinal cord compression is equivalent to decompressive surgery followed by external body radiation therapy to maintain ability to walk at 6 weeks.

Detailed Description
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Metastatic spinal cord compression (MSCC) is an acute event demanding treatment which otherwise would eventually lead to paraplegia in all patients. This is a serious condition for the individual cancer patient and burdensome for the healthcare system. A surgical intervention plus fractionated radiation therapy (FRT) is currently the standard treatment. Proposed Solution: If spinal cord dose is respected, local tumor control could be equivalent using stereotactic body radiation therapy (SBRT) with minimal risk in comparison to decompression surgery and postoperative conventional radiotherapy without the additional burden on the patient of performing an invasive surgical procedure. Clinical Impact: Patients currently requiring surgery plus radiation therapy will potentially benefit form the proposed method. Patients will potentially benefit from reduced toxicity by avoiding the surgical procedure. In addition, a shorter treatment protocol with only one fraction is beneficial. Aims: The investigators' hypothesis is that stereotactic body radiation therapy (SBRT) could be equivalent alternative in the case of patients presenting with metastatic spinal cord compression with minor neurologic deficits. Specific aims: Determine the feasibility of recruiting patients to be randomized towards SBRT vs. of surgery plus FRT Determine the ability to walk after 6 weeks measured from the starting date of treatment Determine the side-effects and quality of life metrics following both treatment arms Determine the rate of local control following therapy using MRI scan Project Plan: The investigators intend to investigate if stereotactic body radiation therapy (SBRT) could be equivalent alternative in the case of patients presenting with metastatic spinal cord compression with minor neurologic deficits

Official Title
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A Randomized Trial of Stereotactic Radiosurgery Versus Decompressive Surgery Followed by Postoperative Radiotherapy in Metastatic Spinal Cord Compression

Conditions
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Spinal Cord Compression, Neoplasm Metastasis

Intervention / Treatment
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* Procedure: Decompression surgery
* Radiation: Radiosurgery
* Radiation: Fractionated Radiotherapy
* Drug: Glucocorticoids
* Drug: Pantoprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histological or cytological confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective Patients must have localized spine metastasis from first cervical to last lumbar vertebra with evidence of radiological SCC (rSCC) on a diagnostic MRI defined as involvement or compression of either the spinal cord or the cauda equina by an epidural mass lesion or metastatic disease causing impingement, indentation or loss of definition of the thecal sac A maximum of two separate sites requiring treatment is allowed with maximum two vertebra pr. site Eligible for surgery defined by technical assessment by surgeon whether surgical decompression is possible with proper stabilization of the spine No medical co-morbidity contradicting anesthesia Patient without former treatment for metastatic spinal cord compression with either decompressive surgery and/or radiation therapy Patient with mild to moderate neurologic signs are eligible. These neurological signs include radiculopathy, dermatomal sensory change, and muscle strength of involved extremity 4/5 on MRC scale Age ≥18 years ECOG performance status ≤2 Life expectancy of greater than 3 months The effects of ionizing radiation on the developing human fetus are known to be teratogenic. For this reason women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of radiation therapy administration Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Histology of myeloma or lymphoma Patients with any spine metastasis that is not planned to be treated per protocol Spine instability due to a compression fracture or impending vertebral compression fracture Patients with rapid neurologic decline within 24 hours Bony retropulsion causing neurologic abnormality Prior radiation to the index spine Patients for whom an MRI of the spine is medically contraindicated Patients allergic to contrast dye used in MRIs Patients who are receiving any other investigational agents Patients with more than two known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events Patient with any serious neurologic condition other than MSCC that could confound the diagnosis and interpretation of radiation induced myelopathy Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Decompression surgery plus fractionated radiotherapy<br> | Procedure: Decompression surgery<br>* Patients will undergo posterior decompression/laminectomy on relevant spinal levels depending on neurological symptoms. If there is a need of spinal stabilization after decompression, patients will undergo posterior instrumentation with pedicle screws and titanium rods. Instrumentation will be done two or three levels above and below each level with metastatic affection.<br>* Other names: laminectomy;Radiation: Fractionated Radiotherapy<br>* Patients allocated to surgery will receive postoperative radiotherapy commencing between 10 to 21 days after decompressive surgery. Target should include the entire vertebral body and the vertebral arch at the operated level of the vertebral column. Patients receiving postoperative radiotherapy will receive 30 Gy in 10 fractions with 3 Gy pr. fraction. The prescribed dose should cover at least 90 % of the defined target volume.<br>Drug: Glucocorticoids<br>* All patients referred with clinical suspicion of metastatic spinal cord compression will receive high dose glucocorticoids. Dose adjusted to risc of side effects.<br>* Other names: steroids;Drug: Pantoprazole<br>* All patients receiving high dose glucocorticoids will also be prescribed with pantoprazole 40/daily to prevent gastric ulcers<br>* Other names: Proton pump inhibitor (PPI);|
| Experimental: Radiosurgery<br>Patients treated with radiosurgery/SBRT will receive a prescribed dose of 16 Gy in one fraction to cover as large a fraction as possible the defined target volume | Radiation: Radiosurgery<br>* Patients treated with radiosurgery/SBRT will receive a prescribed dose of 16 Gy in 1 fraction to cover as large a fraction as possible the defined target volume<br>* Other names: Stereotactic Body Radiotherapy;Drug: Glucocorticoids<br>* All patients referred with clinical suspicion of metastatic spinal cord compression will receive high dose glucocorticoids. Dose adjusted to risc of side effects.<br>* Other names: steroids;Drug: Pantoprazole<br>* All patients receiving high dose glucocorticoids will also be prescribed with pantoprazole 40/daily to prevent gastric ulcers<br>* Other names: Proton pump inhibitor (PPI);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ability to walk | Ability to walk determined by EQ-5D-5L | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self reported pain | self reported pain determined by EQ-5D-5L | 0, 6, 12, 26, 52 weeks | 
| Self reported bladder control | reported by questionnaire | 0, 6, 12, 26, 52 weeks | 
| Quality of life | QOL determined by EQ-5D-5L | 0, 6, 12, 26, 52 | 
| Response rate | Post interventional MRI scan with response classified according to RECIST 1.1 | 6 weeks | 
| Toxicity and interventional related complications | Determined by CTCAE 4.0 | 0, 6, 12, 26, 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiosurgery, Laminectomy, Radiotherapy, Spinal Cord Compression, Neoplasm Metastasis, Randomized Controlled Trial