Clinical trial NCT01594892: Fractionated Radiosurgery for Painful Spinal Metastases
Official title: Dose-intensified Image-Guided Fractionated Radiosurgery for Spinal Metastases (DOSIS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neoplasm Metastasis
Neoplastic Processes
Neoplasm Recurrence, Local
Neoplasm, Residual
Pain
Keywords: Spinal metastases
Vertebral metastases
Radiosurgery
Radiotherapy
Stereotactic body radiotherapy
Pain
Lead sponsor: Wuerzburg University Hospital
Sponsor class: OTHER
Collaborators: name: Royal Marsden NHS Foundation Trust
First posted: 2012-05-09
Enrollment: 60
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Evaluation of the single intervention - dose-intensified SBRT
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients, in whom pain is decreased in response to treatment
timeFrame: Change in pain from baseline to 3 months post-treatment
Secondary outcomes:
measure: Local tumor control
timeFrame: 2 years
measure: Local tumor control
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: Patient-assessed 5 dimensions of patient's quality-of-life
timeFrame: Changes in quality of life from baseline to 3 months post-treatment
measure: Patient-assessed overall health status
timeFrame: Changes in quality of life from baseline to 3 months post-treatment
measure: Number of patients developing acute toxicity
timeFrame: Changes from baseline up to 6 weeks post-treatment
measure: Number of patients developing late toxicity
timeFrame: Changes from >6weeks up to 2 years post-treatment
Other outcomes:
Locations:
city: Schweinfurt
country: Germany
facility: Leopoldina Schweinfurt
city: Wuerzburg
country: Germany
facility: Department of Radiation Oncology, University of Wuerzburg
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Zurich
country: Switzerland
facility: University Hospital Zurich
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital NHS Foundation Trust
Study officials:
affiliation: Department of Radiation Oncology, University of Wuerzburg
name: Matthias Guckenberger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.