Fractionated Radiosurgery for Painful Spinal Metastases

Not Applicable

Completed

• Conditions: Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplastic Processes; Pain; Neoplasm, Residual
• Interventions: Radiation: Radiosurgery

• Registration Number: NCT01594892
• Lead Sponsor: Wuerzburg University Hospital

Brief Summary

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

The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study.

1. 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.

2. 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.

3. 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.

Study Timeline

• Study Start: 2012-04
• Study First Submitted: 2012-05-07
• Study First Submitted QC: 2012-05-07
• Study First Posted: 2012-05-09
• Primary Completion: 2015-07
• Study Completion: 2017-07
• Status Verified: 2019-08
• Last Update Submitted: 2019-09-02
• Last Update Posted: 2019-09-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Established histological diagnosis of a malignant tumour (primary or metastatic)

2. Vertebral metastasis confirmed via biopsy or radiology

3. Pain in the involved spinal region or free of pain under pain medication

4. Fully consenting patients, >18 years old

5. Karnofsky Performance Index ≥60%

6. Good or intermediate life expectancy according to the modified prognostic Mizumoto Score (score ≤ 9)

7. Patient must be able to tolerate fixation systems and 30 minutes treatment time

8. Discussed in interdisciplinary tumour board

9. 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

1. Short life expectancy according to the modified Mizumoto Sore
2. "Radiosensitive" histologies (i.e. lymphoma, SCLC, multiple myeloma)
3. Non-ambulatory status
4. Progressive neurological symptoms/deficit
5. > 3 involved vertebral levels
6. > 2 treatment sites
7. Spine instability
8. Previous radiotherapy at the involved levels

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose intensified SBRT	Radiosurgery	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.

Primary Outcome Measures

Name	Time	Method
Number of patients, in whom pain is decreased in response to treatment	Change in pain from baseline to 3 months post-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

Secondary Outcome Measures

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

Trial Locations

Locations (5)

The Royal Marsden Hospital NHS Foundation Trust; 🇬🇧 Sutton, United Kingdom

Netherlands Cancer Institute; 🇳🇱 Amsterdam, Netherlands

University Hospital Zurich; 🇨🇭 Zurich, Switzerland

Leopoldina Schweinfurt; 🇩🇪 Schweinfurt, Germany

Department of Radiation Oncology, University of Wuerzburg; 🇩🇪 Wuerzburg, Germany