Stereotactic Body Radiotherapy Followed by Surgical Stabilization in Spinal Metastases (BLEND-II)

Stereotactic Body Radiotherapy Followed by Surgical Stabilization for Patients With Unstable Spinal Metastases: Cohort Study According to the IDEAL Recommendations

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.

Study Overview

• Status: Withdrawn
• Conditions: Neoplasm Metastasis; Surgery; Spinal Neoplasms; Radiosurgery
• Intervention / Treatment: Other: SBRT followed by surgical stabilization within 24-48 hours

Detailed Description

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands
    • UMC Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

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: SBRT followed by surgical stabilization within 48 hours; SBRT and surgical stabilization will be performed within a 24 to 48-hour time window instead of today's standard of care of two weeks between surgical stabilization and conventional radiotherapy.

Other: SBRT followed by surgical stabilization within 24-48 hours; In a first step, patients will undergo SBRT with active sparing of the surgical site. Patients will receive high dose, single to few fractions radiotherapy consisting of a boost to the metastases exclusively. The bony compartment containing the metastatic lesion will receive an elective dose in order to treat subclinical disease. Treatment planning is performed on the pre-treatment CT and MRI data in radiotherapy position that are mutually registered to yield information on all relevant structures for planning. Dose constraints are set for the organ at risks based on institution specific guidelines. All patients will be treated with on online position verification protocol based on institution specific guidelines. Hereafter, surgical intervention will be performed to the standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain response	Pain response is defined as a decrease in initial worst pain score by at least 2 points on a Numeric Rating Scale (NRS) of 10 at the treated site, without increase in analgesic use, or an analgesic decrease of at least 25% without an increase in pain score	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of pain relief	Duration of pain relief, as measured by the Brief Pain Inventory (BPI)	Through hospital stay, an average of 3 days
Length of hospital stay	Length of hospital stay in days	Through hospital stay, an average of 3 days
30-day mortality	Mortality after 30 days	30 days
Neurological status	American Spinal Injury Association (ASIA) scale as measured by physical examination of neurologists or trained ASIA physician	Through hospital stay, an average of 3 days
Neurological deterioration	Defined as a deterioration on the American Spinal Injury Association (ASIA) scale of more than one level	Through hospital stay, an average of 3 days
Adverse events	Adverse events will be scored using a SAVES form	Through hospital stay, an average of 3 days

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Investigators: Principal Investigator: Jorrit-Jan Verlaan, MD, PhD, UMC Utrecht

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: September 18, 2021
• First Posted (Actual): September 29, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Musculoskeletal Diseases; Neoplastic Processes; Spinal Diseases; Bone Diseases; Bone Neoplasms; Neoplasms; Neoplasm Metastasis; Spinal Neoplasms
• Other Study ID Numbers: NL76750.041.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD may be shared when requested through the principal investigator

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No