Alternative study was set up

The aim of this study is to assess pain response after combining stereotactic body radiotherapy (SBRT) and pedicle screw fixation in a 48-hour window for the treatment of painful unstable metastases of the thoracic and/or lumbar spine.

Rationale Sixty-five percent of cancer patients with terminal illness have bone metastases, with debilitating pain often as the severe consequence. The spine is the most common location for bone metastases. Standard treatment of unstable vertebral metastases consists of stabilizing surgery, followed by external beam radiotherapy after two weeks. Although this approach is effective in 60-70% of patients, it is has several downsides. Firstly, because of the two weeks interval between surgery and external beam radiotherapy, necessary for sufficient wound healing, it takes time before radiotherapy-induced pain relief is achieved. Moreover, the surgical implants used cause scatter artifacts on planning computed tomography images which prohibits high-resolution imaging and accurate targeting of the lesion. Multiple hospital visits (ranging from 1 to 10) are needed for administration of external beam irradiation, and in about 30-40% of patients no adequate pain response is achieved. An alternative treatment strategy, which would lead to faster pain relief in a higher proportion of patients with less hospital visits, would be highly desirable from the patient's perspective. Secondly, this strategy delays the start of systemic therapy.

Objective The main outcome of this study is pain response 4 weeks after start of the treatment.

Study design Prospective cohort study nested within the PRESENT cohort being a phase 2b study according to the IDEAL recommendations

Study population All patients, male and female, with impending spinal instability requiring surgical intervention and radiotherapy at the University Medical Center Utrecht

Intervention The combined treatment of stereotactic body radiotherapy and pedicle screw fixation in a 24 to 48-hour window for the treatment of painful unstable metastases of the cervical, thoracic and/or lumbar spine.

Main study parameters/endpoints The main outcome of this study is pain response after 4 weeks

Nature and extent of the burden and risks associated with participation, benefit and group relatedness In the preceding BLEND First-in-man study, the investigators have observed no Serious Adverse Events after a median follow-up of 13 months demonstrating the safety and feasibility of this approach.

Inclusion Criteria:

• Participation in PRESENT cohort
• Painful radiosensitive metastases from solid tumors in the cervical, thoracic or lumbar spine needing surgical stabilization
• Histologic proof of malignancy or radiographic/clinical characteristics indicating malignancy beyond reasonable doubt
• Radiographic evidence of spinal metastases
• Fit for (radio)surgery
• Age > 18 years at the time of given informed consent in the PRESENT cohort.
• Written informed consent

Exclusion Criteria:

• SBRT cannot be delivered, e.g. in patients who cannot lie on the treatment table because of pain
• Surgery cannot be performed, e.g. in patients with multiple spinal metastases that cannot be bridged
• Previous surgery or radiotherapy to index lesion
• Neurological deficits (ASIA C, B or A)
• Partial neurological deficits (ASIA D) with rapid progression (hours to days)
• Non-ambulatory patients
• Patient in hospice or with < 3 months life expectancy
• Medically inoperable or patient refused surgery
• Radiosensitizing systemic treatment that cannot reasonably be stopped (for example immunotherapy and EGFR inhibitors)

IPD may be shared when requested through the principal investigator