Randomized Trial on Same-day SBRT and Surgical Stabilization for Symptomatic Spinal Metastases

Study Overview
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Brief Summary
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The BLEND RCT aims to evaluate the (cost-)effectiveness of same-day SBRT and surgical stabilization with or without decompression for the treatment of symptomatic, unstable spinal metastases on physical functioning four weeks after the start of treatment, compared with the standard of care (surgery followed by radiotherapy as soon as the wound healed sufficiently).

Detailed Description
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Rationale: Currently, patients with unstable spinal metastases receive surgical stabilization with/without decompression followed by conventional radiotherapy (cRT) or stereotactic body radiotherapy (SBRT) as soon as wound healing allows (at least 1 week). Advancements in radiotherapy techniques makes preoperative radiotherapy possible with sparing of the soft tissues overlying the surgical field. This makes it possible to shorten or even eliminate the time interval between surgery and radiotherapy. This will result in shorter and less hospital visits, earlier pain relief from irradiation, and faster return to systemic therapy without an increase in wound complications due to the short interval between surgery and radiotherapy. Objective: The BLEND RCT aims to evaluate the (cost-)effectiveness of same-day SBRT and surgery for the treatment of symptomatic, unstable spinal metastases on physical functioning four weeks after the start of the treatment, compared with the standard of care (surgery followed by radiotherapy, i.e., CRT or SBRT). Study design: A phase II randomized controlled trial within the PRospective Evaluation of interventional StudiEs on boNe metastases (PRESENT) cohort including patients with bone metastases, according to the Trials within Cohorts (TwiCs) design. Study population: Patients with symptomatic (cervical, thoracic and/or lumbar) spinal metastases and impending spinal instability requiring radiotherapy and surgical stabilization with or without decompression. Intervention: SBRT (with active dose-sparing of the surgical site) and surgical stabilization with or without decompression within 24 hours. The control group will receive the standard of care, which is surgical stabilization with or without decompression followed by cRT or SBRT as soon as the wound is healed sufficiently. Main study endpoints: The primary endpoint is physical functioning at four weeks after the start of the treatment. Secondary endpoints are pain response, duration of pain relief, length of hospital stay, time to return to systemic therapy, neurological deterioration, adverse events (e.g. wound complications), quality of life and survival. In addition, we will study the cost-effectiveness.

Official Title
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Stereotactic Body Radiotherapy and pedicLE Screw fixatioN During One Hospital Visit for Patients With Painful Unstable Spinal Metastases: A Randomized Trial (BLEND RCT)

Conditions
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Spinal Metastases

Intervention / Treatment
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* Other: Same-day SBRT and spinal surgery
* Other: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic (cervical, thoracic and/or lumbar) spinal metastases from solid tumors and (impending) spinal instability requiring radiotherapy and surgical decompression and/or stabilization Histologic proof of malignancy or radiographic/clinical characteristics indicating malignancy beyond reasonable doubt Radiographic evidence of spinal metastases Participation in PRESENT cohort, including consent for randomization into future trials Fit for (radio)surgery Age >18 years Written informed consent Exclusion Criteria: SBRT cannot be delivered, e.g. in patients who cannot lie on the treatment table because of pain Routine surgical decompression and/or stabilization and radiotherapy cannot be performed, e.g., multiple spinal metastases requiring surgical bridging of more than five vertebral levels and/or requiring radiotherapy on more than one location Prior surgery or radiotherapy to the index level(s) Multiple myeloma Neurological deficits (ASIA C, B or A), or partial neurological deficits (ASIA D) with rapid progression (hours to days) Treated with Bevacizumab and other medication with long half-life that interferes with radiotherapy Life expectancy of less than 3 months

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 |
| --- | --- |
| Experimental: Intervention<br>Patients will receive high dose, single fraction stereotactic body radiotherapy (SBRT) using differential dosing: 18 or 21 Gy on the metastasis. Within 24 hours after SBRT, patients will have surgical stabilization with or without decompression. | Other: Same-day SBRT and spinal surgery<br>* SBRT and surgical stabilization with or without decompression within 24 hours<br>|
| Active Comparator: Control<br>Patients will undergo the standard of care, which is surgical stabilization with or without decompression, followed by conventional radiotherapy (cRT) or SBRT as soon as the wound is healed sufficiently. | Other: Standard of care<br>* Surgical stabilization with or without decompression followed by cRT or SBRT as soon as the wound is healed sufficiently<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical functioning | Physical functioning is a functional scale from the EORTC QLQ-C15-PAL questionnaire. Patients rate each item on a 4-point Likert scale ranging from 1 (not at all) to 4 (very much), and scale scores were linearly transformed to a 0-100 scale. A higher score on the functional scale indicates better functioning. | at 4 weeks after the start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain response | Pain response is defined as 1) a decline in worst pain score of at least two points on an NRS of ten at the treated site without increase in analgesic use, or 2) an analgesic decrease of at least 25% without an increase in pain score. Worst pain score will be measured with the Brief Pain Inventory. | at 2, 4, 6 and 8 weeks, and 3 months after the start of treatment | 
| Duration of pain relief | Duration of pain relief as measured by the Brief Pain Inventory (BPI). | up to 3 months | 
| Duration of hospital stay | Duration of hospital stay in days | up to 3 months | 
| Days until return to systemic treatment | Days until return to systemic treatment | up to 12 months | 
| Neurological deterioration | Occurrence of neurological deterioration is defined as deterioration of more than one grade on the American Spinal Cord Injury Association (ASIA) scale as measured by physical examination by a neurologists or trained ASIA physician. | up to 12 months | 
| Change in health-related quality of life | Change in patient-reported health-related quality of life is measured by the EORTC QLQ-C15-PAL at predefined time intervals. | at 4 and 8 weeks, and 3 and 6 months after the start of treatment | 
| Change in health-related quality of life | Change in patient-reported health-related quality of life is measured by the EORTC QLQ-BM22 at predefined time intervals. | at 4 and 8 weeks, and 3 and 6 months after the start of treatment | 
| Local control | Local control according to routine imaging and electronic patient chart | up to 12 months | 
| Adverse events | Adverse events are defined as any undesirable experience occurring to a patient during the study, (likely) related to the experimental treatment procedure. All adverse events during hospital stay will be evaluated using the most recent version of the National Cancer Institute Common Toxicity Criteria of Adverse Events (CTCAE; version 5.0, version 6.0 when available at the start of the study) for acute and late toxicity. All adverse events after hospital discharge reported spontaneously by the patient or observed by the investigator or research team will be recorded up to three months after the treatments. | up to 3 months | 
| Progression free survival | Progression free survival is defined as time between treatment and first sign of progression of disease. | up to 12 months | 
| Overall survival | Overall survival is defined as time between treatment and death from any cause. | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RCT, Spinal metastases, SBRT, Surgery, Same-day treatment