Fractionated Radiosurgery for Painful Spinal Metastases (DOSIS)

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

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.

Study Overview

• Status: Completed
• Conditions: Pain; Neoplasm Metastasis; Neoplastic Processes; Neoplasm, Residual; Neoplasm Recurrence, Local
• Intervention / Treatment: Radiation: Radiosurgery

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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Schweinfurt, Germany
    • Leopoldina Schweinfurt
  • Wuerzburg, Germany, 97080
    • Department of Radiation Oncology, University of Wuerzburg
• Netherlands
  • Amsterdam, Netherlands
    • Netherlands Cancer Institute
• Switzerland
  • Zurich, Switzerland
    • University Hospital Zurich
• United Kingdom
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dose intensified SBRT; 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; Fractionated radiosurgery using intensity-modulated treatment planning and volumetric image-guided treatment delivery

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Collaborators: Royal Marsden NHS Foundation Trust
• Investigators: Principal Investigator: Matthias Guckenberger, MD, Department of Radiation Oncology, University of Wuerzburg

Publications and helpful links

General Publications

• Guckenberger M, Hawkins M, Flentje M, Sweeney RA. Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial. BMC Cancer. 2012 Nov 19;12:530. doi: 10.1186/1471-2407-12-530.
• Guckenberger M, Sweeney RA, Hawkins M, Belderbos J, Andratschke N, Ahmed M, Madani I, Mantel F, Steigerwald S, Flentje M. Dose-intensified hypofractionated stereotactic body radiation therapy for painful spinal metastases: Results of a phase 2 study. Cancer. 2018 May 1;124(9):2001-2009. doi: 10.1002/cncr.31294. Epub 2018 Mar 2.
• Mantel F, Sweeney RA, Klement RJ, Hawkins MA, Belderbos J, Ahmed M, Toussaint A, Polat B, Flentje M, Guckenberger M. Risk factors for vertebral compression fracture after spine stereotactic body radiation therapy: Long-term results of a prospective phase 2 study. Radiother Oncol. 2019 Dec;141:62-66. doi: 10.1016/j.radonc.2019.08.026. Epub 2019 Sep 13.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: May 7, 2012
• First Submitted That Met QC Criteria: May 7, 2012
• First Posted (Estimate): May 9, 2012

Study Record Updates

• Last Update Posted (Actual): September 4, 2019
• Last Update Submitted That Met QC Criteria: September 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Pain; Radiotherapy; Radiosurgery; Stereotactic body radiotherapy; Vertebral metastases; Spinal metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Neoplasms; Neoplasm Metastasis; Recurrence; Neoplasms, Second Primary; Neoplasm, Residual; Neoplasm Recurrence, Local; Neoplastic Processes
• Other Study ID Numbers: DOSIS