Stereotactic Body Radiotherapy Boost After Palliative Radiotherapy for Spinal Cord Compression

Study Overview
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Brief Summary
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Spinal cord compression (SCC) is a devastating complication of advanced malignancy, and can cause significant deterioration in function and quality of life (QoL). The goal of treatment is to improve functional status and symptoms, but the optimal treatment regimen for these patients has not been thoroughly established. Many patients with SCC present with uncontrolled systemic disease and poor performance status, and are not eligible for standard surgical resection. They are generally treated with 3D conformal palliative RT (3DCRT) alone, however recent trials suggest that less than 70% of patients are ambulatory, that the re-establishment of ambulation in non-ambulatory patients is poor, and the duration of improvement is guarded with radiotherapy alone. Recently, stereotactic body radiotherapy (SBRT) used alone or after previous radiotherapy to treat spinal metastasis has demonstrated superior results in pain control, tumour response and durability. SBRT requires time for careful planning, and many patients with neurologic symptoms must be treated immediately to prevent progression. Therefore the role of SBRT is still unclear in this patient population, although it seems to be a potential alternative to surgical decompression in patient not suitable for surgery. The investigators propose a feasibility study to investigate the potential benefits of dose escalation with a sequential SBRT boost to urgent 3D CRT in the setting of SCC. This regimen will allow inoperable patients to receive urgent 3DCRT while simultaneously creating the opportunity for superior outcomes with SBRT. The investigators also aim to characterize the effect on motor function and ambulation, pain and QoL. This study could stimulate further multi-center randomized trials in this area, improve motor function and patient-reported QoL, and contribute to improving oncology care in Canada in a meaningful way.

Official Title
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Stereotactic Body Radiotherapy (SBRT) Boost Following Urgent 3D Conformal Radiotherapy in the Treatment of Metastatic Epidural Spinal Cord Compression (SCC): A Phase I Feasibility Trial

Conditions
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Spinal Cord Compression, Cauda Equina Syndrome, Stereotactic Body Radiotherapy

Intervention / Treatment
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* Radiation: 3D CRT plus SBRT boost


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of metastatic malignancy (radiologic or pathologic) Evidence of disease in vertebral body with epidural component such that Bilsky radiologic score is 1c-2 on MRI (abuts spinal cord without cord compression (1c), or spinal cord compression but with visible CSF (2) Motor function (MF) of 3 or greater Exclusion Criteria: Surgical candidate Instability of vertebral bodies with or without bony retropulsion requiring surgical intervention or hardware placement Previous radiotherapy course to same region of spine with overlapping fields (prior to phase I course) at discretion of treating radiation oncologist No CT or MRI within previous 3 months Life expectancy estimated <3 months Performance status KPS<40 On active chemotherapy or targeted therapy or immunotherapy (must be stopped for at least one week prior to and following) Pregnant or lactating Contraindications to radiotherapy (eg. active autoimmune disease requiring medication) Inability to lie flat comfortably for at least 20 minutes Age < 18

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
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm pilot study of standard of care 3D conformal radiotherapy plus Stereotactic body radiotherapy (SBRT) boost
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBRT boost<br>Standard radiotherapy (3D conformal, urgent palliative radiotherapy) plus stereotactic body radiotherapy (SBRT) boost | Radiation: 3D CRT plus SBRT boost<br>* Patients will receive urgent standard 3D conformal radiotherapy (3D CRT) of plus stereotactic boost to tumor causing spinal cord compression (SCC). Initial dose for 3D CRT will be either 8Gy in 1 fraction or 20Gy in 5 fractions, with SBRT boost dose15Gy in 2 fractions of 12Gy in 2 fractions (depending on 8Gy/1 or 20Gy/5 initial RT dose respectively), delivered within three weeks of first treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of accrual | Success determined by accrual of 30 patients with SBRT boost is planned and delivered to 80% of these | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor Function Description: | Motor strength evaluated by 8 point scale (0= Complete paraplegia, 1= Palpable or visible muscle contractions, 2= Active movement of the leg without gravity, 3= Active movement of the leg against gravity, 4= Active movement againt mild resistance, 5= Active movement against intermediate resistance, 6= Active movement against strong resistance, 7= Normal strength) | 4 weeks (primary), 12 weeks, 6 months | 
| Overall Quality of Life (QoL) | Change in total QoL score over time per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-c30) | 4 weeks, 12 weeks, 6 months | 
| Pain Response | Change in level of pain over time on 10 point scale with 0 meaning no pain and 10 meaning severe pain (patient-reported) | 4 weeks, 12 weeks, 6 months | 
| Local Control | Assessment of tumor volume (maximum size in 3 dimension) by Magnetic Resonance Imaging (MRI) | 12 weeks, 6 months | 
| Toxicity | Treatment-related toxicity graded by Common Terminology for Adverse Events (CTCAE 4.03) | 4 weeks, 12 weeks, 6 months | 
| Overall Survival | Survival time from first radiotherapy treatment (3D CRT) in days | 4 weeks, 12 weeks, 6 months | 
| Bone metastasis- specific Quality of Life | Change in total QoL score over time per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Bone Metastasis-22 (EORTC QLQ BM-22) | 4 weeks, 12 weeks, 6 months |