Fractionated Radiosurgery for Painful Spinal Metastases (DOSIS)

• Local tumor control [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  Local tumor control at the treated vertebral levels and regional tumor control at the neighbouring vertebrae assessed in MRI and CT imaging
• Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Cancer specific mortality [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Quality of life [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  Quality of life using the EQ-5D and EORTC QLQ-BM22
• Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  Acute and late toxicity according to NCI CTCAE v 4.0

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.

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.

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

• Experimental: A: Long life expectancy
  Patients with long life expectancy based on the modified Mizumoto Score (0-4 points) 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
  Intervention: Radiation: Radiosurgery
• Experimental: B: intermediate life expectancy
  Patients with intermediate life expectancy based on the modified Mizumoto Score (5-9 points) will be treated with 5 fractions of 7Gy in involved parts of the vertebra and 4Gy in not-involved parts using a simultaneous integrated boost
  Intervention: Radiation: Radiosurgery

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