Intraoperative Radiotherapy in Treating Spinal Metastases

Study Overview
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Brief Summary
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In order to provide theoretical evidence for the comprehensive and standardized treatment of spinal metastases with pathological fractures and/or spinal cord compression, the investigators conduct this trial to investigate the efficacy and safety of IORT and postoperative SBRT in adjuvant treatment of metastatic spinal tumors after posterior decompression surgery by recruiting patients with spinal metastases who met the inclusion criteria, and randomly divided them into the following treatment cohorts: 1) decompression surgery + IORT (15-20 Gy, 20-50min）; 2) decompression surgery and postoperative SBRT(30Gy, 5 fractions, 3 weeks).

Detailed Description
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Spine is the most common metastatic site for advanced malignancies, accounting for about 70% of all patients with bone metastasis. Approximately 40% -70% of patients with advanced cancer eventually develop spinal metastases. Spinal metastases require multidisciplinary treatments, and surgical decompression surgery is the preferred treatment in managing spinal metastases with bone related events, especially those with spinal cord compression. The purpose of decompression surgery is to directly relieve nerve compression, alleviate pain, rebuild spinal stability, and reduce tumor burden, which improves the quality of life, and extend the life span indirectly. At the same time, radiotherapy is also an indispensable treatment for spinal metastases after surgical decompression. The purpose of radiotherapy is to remove residual tumor lesions, alleviate pain, and prevent further pathological fractures. Recent years have witnessed the rapid development of stereotactic bone radiotherapy (SBRT). As reported, SBRT can not only increase the radiation dose at the tumor site, but also reduce radiation damage to the spinal cord and surrounding normal tissues, which is the preferred adjuvant treatment for patients with metastatic spinal tumors. However, SBRT has the several risks, including radiation myelitis, delayed vertebral pathological fractures, local skin allergies, radiotherapy side effects in the esophagus and lungs, and duodenal perforation. Moreover, stereotactic radiotherapy technology has higher costs compared to traditional external beam radiotherapy. Recently, the application of intraoperative radiotherapy (IORT) can effectively reduce the direct radiation for surrounding normal tissues and maximally eliminate the residual tumor cells. The advantages of IORT include: ① immediate reduction of the possibility of tumor cell expansion after surgery; ② Safe direct radiation and effective protection of normal tissues beyond the radiation depth; ③ To effectively protect adjacent normal tissues, light-limiting tubes with different diameters can be selected based on the size and range of tumor; ④ Shortening treatment course with lower costs and better compliance; ⑤ Slight systemic side effects and bone marrow suppression. To the knowledge, no research focuses on the efficacy of IORT and SBRT in the adjuvant treatment of spinal metastases. Therefore, in order to provide theoretical evidence for the comprehensive and standardized treatment of spinal metastases with pathological fractures and/or spinal cord compression, the investigators conduct this trial to investigate the efficacy and safety of IORT and postoperative SBRT in adjuvant treatment of metastatic spinal tumors after posterior decompression surgery by recruiting patients with spinal metastases who met the inclusion criteria, and randomly divided them into the following treatment cohorts: 1) decompression surgery + IORT (15-20 Gy, 20-50min）; 2) decompression surgery and postoperative SBRT(30Gy, 5 fractions, 3 weeks).

Official Title
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The Efficacy and Safety of Intraoperative Radiotherapy Vesus Stereotactic Body Radiotherapy in Managing Spinal Metastases: A Prospective, Single-center, Open-label, Non-inferior, Randomized Controlled Trial

Conditions
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Spinal Metastases

Intervention / Treatment
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* Radiation: Intraoperative radiotherapy (IORT)
* Radiation: Stereotactic body radiotherapy (SBRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of spinal metastases; Estimated survival time more than 3 months; The spinal instability neoplastic score (SINS) >12; The general condition allows to recieve surgery; Single or multiple metastatic lesions with only one site presenting epidural spinal cord compression; signed informed consent. Exclusion Criteria: Clinical diagnosis of primary spinal tumors; Presence of metastases in central nerve system; Isolated lesion undergoing en bloc resection; Mental disorder and/or intellectual dificiency; Refusing to accept follow-up; without signing informed consent.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 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
Interventional Model Description: Decompression surgery + IORT (15-20 Gy, 20-50min） Decomression surgery + postoperative SBRT ( 30Gy, 5 fractions, 3 weeks)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Decompression surgery + IORT<br>Decompression surgery + IORT (15-20 Gy, 20-50min） | Radiation: Intraoperative radiotherapy (IORT)<br>* Intraoperative radiotherapy (IORT, 15-20 Gy, 20-50min)<br>|
| Active Comparator: Decompression surgery + postoperative SBRT<br>Decompression surgery + postoperative SBRT (30Gy, 5 fractions, 3 weeks) | Radiation: Stereotactic body radiotherapy (SBRT)<br>* postoperative stereotactic body radiotherapy (SBRT, 30Gy, 5 fractions, 3 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control rate | The local control of tumor in the surgical field | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health-related quality of life | The Functional Assessment of Cancer Therapy -General (FACT-G) Scale (Minimum: 0; Maximum: 108 ) is utilized to evaluate the health-related quality of life after treatments, and higher scores mean a worse outcome. | 2 years | 
| Progression-free survival | The survival time between the day after treatments and the date of any evidence proving tumor progression or final follow-up | 2 years | 
| Overall survival | The survival time between the day after treatments and the date of all-cause death or final follow-up | 2 years | 
| Radiation-related complications | The complications assciated with the radiation process | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal metastases, intraoperative radiotherapy, stereotactic body radiotherapy, decompression surgery