Fractionated Radiosurgery for Painful Spinal Metastases

Study Overview
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Brief Summary
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It is the study hypothesis that hypo-fractionated image-guided radiosurgery significantly improves pain relief compared to historic data of conventionally fractionated radiotherapy. Primary endpoint is pain response 3 months after radiosurgery, which is defined as pain reduction of ≥2 points at the treated vertebral site on the 0 to 10 Visual Analogue Scale. 60 patients will be included into this II trial.

Detailed Description
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The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study. A prognostic score for overall survival will be used for selection of patients with longer life expectancy to allow for analysis of long-term efficacy and safety. Fractionated radiosurgery will be performed with the number of treatment fractions adjusted to either good (10 fractions) or intermediate (5 fractions) life expectancy. Fractionation will allow inclusion of tumors immediately abutting the spinal cord due to higher biological effective doses at the tumor - spinal cord interface compared to single fraction treatment. Dose intensification will be performed in the involved parts of the vertebrae only, while uninvolved parts are treated with conventional doses using the simultaneous integrated boost concept.

Official Title
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Dose-intensified Image-Guided Fractionated Radiosurgery for Spinal Metastases (DOSIS)

Conditions
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Neoplasm Metastasis, Neoplastic Processes, Neoplasm Recurrence, Local, Neoplasm, Residual, Pain

Intervention / Treatment
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* Radiation: Radiosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established histological diagnosis of a malignant tumour (primary or metastatic) Vertebral metastasis confirmed via biopsy or radiology Pain in the involved spinal region or free of pain under pain medication Fully consenting patients, >18 years old Karnofsky Performance Index ≥60% Good or intermediate life expectancy according to the modified prognostic Mizumoto Score (score ≤ 9) Patient must be able to tolerate fixation systems and 30 minutes treatment time Discussed in interdisciplinary tumour board The following types of spinal tumours are eligible: Recurrent / residual tumours after surgery Tumours in medically inoperable patients or patients deemed inoperable due to limited life expectancy / tumour load Lesions associated with significant surgical risk Exclusion Criteria: Short life expectancy according to the modified Mizumoto Sore Radiosensitive histologies (i.e. lymphoma, SCLC, multiple myeloma) Non-ambulatory status Progressive neurological symptoms/deficit > 3 involved vertebral levels > 2 treatment sites Spine instability Previous radiotherapy at the involved levels

Ages Eligible for Study
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Minimum Age: 19 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: Evaluation of the single intervention - dose-intensified SBRT
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose intensified SBRT<br>Depending on the modified Mizumoto Score (0-4 points or 5-9 points) patients will be treated with 10 fractions of 4.85Gy in involved parts of the vertebra and 3Gy in not-involved parts using a simultaneous integrated boost or with 5 fractions of 7Gy in involved parts of the vertebra and 4Gy in not-involved parts using a simultaneous integrated boost, respectively. | Radiation: Radiosurgery<br>* Fractionated radiosurgery using intensity-modulated treatment planning and volumetric image-guided treatment delivery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients, in whom pain is decreased in response to treatment | Decrease in pain by ≥2 points at the treated vertebral site on the 0 (no pain) to 10 (the severest pain) Visual Analogue Scale without analgesic increase | Change in pain from baseline to 3 months post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local tumor control | At the treated vertebral levels assessed with MRI | 2 years | 
| Local tumor control | At the treated vertebral levels assessed with CT imaging | 2 years | 
| Overall survival | Death from any cause | 2 years | 
| Patient-assessed 5 dimensions of patient's quality-of-life | Measured with the 5-level (no problems, slight problems, moderate problems, severe problems, and extreme problems) EuroQol 5-Dimension Questionnaire (EQ-5D) questionnaire | Changes in quality of life from baseline to 3 months post-treatment | 
| Patient-assessed overall health status | Measured with the EuroQol Visual Analog Scale from 0 (the worst health you can imagine) to 100 (the best health you can imagine) | Changes in quality of life from baseline to 3 months post-treatment | 
| Number of patients developing acute toxicity | Measured with NCI CTCAE v 4.0 | Changes from baseline up to 6 weeks post-treatment | 
| Number of patients developing late toxicity | Measured with NCI CTCAE v 4.0 | Changes from >6weeks up to 2 years post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiosurgery, Radiotherapy, Stereotactic body radiotherapy, Spinal metastases, Vertebral metastases, Pain