Carbon Fiber Transpedicular Screws in Treatment of Spinal Metastatic Disease

Carbon Fiber Transpedicular Screws in Treatment of Spinal Metastatic Disease and Stereotactic Radiotherapy

Background: Spinal metastatic disease constitute a serious clinical problem in oncology. Bones are the third most common organ where metastases are located, and the spine is the place where they are most often located. Due to the complexity of the clinical problem, metastatic spine disease remains of interest to many medical specialties: neurosurgery, orthopedics, clinical oncology, radiotherapy and rehabilitation. With the development of modern diagnostic methods and wider access to them, the demand for neurosurgical treatment in this group of patients is growing. Surgical treatment is undertaken in cases of spinal cord compression, instability, spinal deformation or pain that is resistant to radiotherapy. The standard treatment in most cases is posterior instrumentation of the spine using titanium pedicle screws. Unfortunately, these systems cause numerous artifacts in diagnostic imaging, both in CT and MRI. These distortions make it difficult to plan radiotherapy and determine the optimal dose that would avoid healthy tissues. Moreover, artifacts could make difficult postoperative follow-ups aimed at assessing local recurrence. The solution to these problems is the use of radiolucent implants. There are systems based on carbon fibers embedded in PEEK which do not cause typical artifacts for titanium implants.

Study plan: The open, three-arm, prospective randomized study is planned to involve 226 patients with metastatic disease of the spine, with a known or undiagnosed primary site. Patients will be qualified for 2 types of interventions. The first one includes treatment with stereotactic radiotherapy (SBRT) in the first stage of treatment and early instrumentation of the spine with titanium implants. The second type of intervention includes patients qualified for surgical treatment using spine stabilization and postoperative SBRT. Patients within this arm will be randomized into two groups differing in the type of material the instrumentation is made of: carbon-PEEK or titanium. The study group will be patients stabilized with carbon implants, and the control group will be those who will have titanium implants.

Study population: The study includes adult patients with metastatic spine disease, with a known or unknown primary tumor, qualified for SBRT and surgical treatment.

Assumed effects: It is assumed that the treatment proposed in the project would extend progression free survival by several months or achieve local control in an additional 5% of patients. Moreover, by improving the quality of imaging, earlier diagnosis of local recurrences and implementation of appropriate locoregional treatment would be possible.

Study Overview

• Status: Recruiting
• Conditions: Metastasis Spine; Metastatic Spinal Cord Compression
• Intervention / Treatment: Procedure: Transpedicular spinal stabilization - carbon fibers-based implants; Radiation: Stereotactic body radiotherapy; Procedure: Transpedicular spinal stabilization - titanium implants

• Study Type: Interventional
• Enrollment (Estimated): 226
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kamil Krystkiewicz, PhD; Phone Number: +48426895341; Email: kamil.krystkiewicz@gmail.com
• Study Contact Backup: Name: Marcin Tosik, PhD; Phone Number: +48426895341; Email: sekretariat.neurochirurgia@kopernik.lodz.pl

Study Locations

• Poland
  • Łódzkie
    • Łódź, Łódzkie, Poland, 93-513
      • Recruiting
      • Copernicus Memorial Hospital in Lodz
      • Contact: Krystkiewicz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Metastatic spinal disease,
• ECOG quality of life of 0-2,
• Eligibility for SBRT treatment,
• Expected survival time >3 months,
• Signed informed consent to participate in the study,
• Sufficient organ capacity allowing to survive the perioperative period.

Exclusion Criteria:

• Primary tumor of the spine,
• Age <18 years old,
• Expected survival time <3 months,
• Eligibility for palliative radiotherapy,
• No informed consent to participate in the study,
• Pregnancy or breastfeeding,
• The advancement of the disease preventing the technical use of implants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transpedicular spinal stabilization using carbon system + SBRT; Transpedicular spinal stabilization using a radiolucent composite system made of carbon fibers and PEEK followed by stereotactic radiotherapy of the spine at a dose of 5x5 Gy (25 Gy in the total dose)	Procedure: Transpedicular spinal stabilization - carbon fibers-based implants; Transpedicular stabilization with carbon fiber and PEEK-based implants in one of the two possible variants - first involves a large skin incision and separation of the back extensor muscles; second is associated with minimally invasive, which is percutaneous procedure that allows the stabilization with implants without the need to detach the muscles, using only a small skin incision.; Radiation: Stereotactic body radiotherapy; Spinal tumors will be treated with stereotactic body radiotherapy at a dose of 5x5 Gy (25 Gy in a total dose); either prior to or post-surgical treatment, accordingly the allocation to one of the study arms.; Other Names: SBRT
Active Comparator: Transpedicular spinal stabilization using titanium system + SBRT; Transpedicular spinal stabilization using a titanium system followed by stereotactic radiotherapy of the spine at a dose of 5x5 Gy (25 Gy in the total dose)	Radiation: Stereotactic body radiotherapy; Spinal tumors will be treated with stereotactic body radiotherapy at a dose of 5x5 Gy (25 Gy in a total dose); either prior to or post-surgical treatment, accordingly the allocation to one of the study arms.; Other Names: SBRT; Procedure: Transpedicular spinal stabilization - titanium implants; Transpedicular stabilization with titanium implants in one of the two possible variants - first involves a large skin incision and separation of the back extensor muscles; second is associated with minimally invasive, which is percutaneous procedure that allows the stabilization with implants without the need to detach the muscles, using only a small skin incision.
Sham Comparator: SBRT + Transpedicular spinal stabilization using titanium system; Transpedicular spinal stabilization using a titanium system preceded with stereotactic spine radiotherapy at a dose of 5x5 Gy (25 Gy in the total dose) as the first stage of treatment	Radiation: Stereotactic body radiotherapy; Spinal tumors will be treated with stereotactic body radiotherapy at a dose of 5x5 Gy (25 Gy in a total dose); either prior to or post-surgical treatment, accordingly the allocation to one of the study arms.; Other Names: SBRT; Procedure: Transpedicular spinal stabilization - titanium implants; Transpedicular stabilization with titanium implants in one of the two possible variants - first involves a large skin incision and separation of the back extensor muscles; second is associated with minimally invasive, which is percutaneous procedure that allows the stabilization with implants without the need to detach the muscles, using only a small skin incision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The assessment of time to local recurrence after treatment with SBRT.	5 years
The assessment of frequency of local recurrence after treatment with SBRT.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DICE convergence factor evaluation between groups of patients.	The use of convergence factor assessment will allow for comparison of similarity in planned SBRT between all groups. This will allow an indirect assessment of difficulties in planning treatment by a radiotherapist using objective tools.	1 day
The subjective difficulty of planning radiotherapy treatment.	Using a numerical scale from 0-10, the radiotherapist will assess the difficulty of planning, tumor coverage, and delineation of the spinal cord depending on the group assessed in the study.	1 day
The frequency of radiation complications assessed according to the National Cancer Institute Common Toxicity Criteria (NCI CTC).	Titanium instrumentation generates significant artifacts in radiological imaging used for radiotherapy planning. The use of opaque, radiolucent material allows for radiotherapy planning to cover a smaller area. This may reduce the incidence of radiation-related complications in nearby organs (OAR - organ at risk). These complications will be assessed by the radiation therapist according to the standardized NCI CTC scale. Potentially smaller quantity of organ complications could be an advantage supporting the use of carbon implants.	5 years
Failure rate of stabilizing systems.	Titanium and carbon fiber show similar biocompatibility. The biomechanical properties of these materials are also similar. In vitro studies have shown a similar effect failure rate of carbon pedicle screws compared to standard titanium ones. However, carbon rods have greater flexibility and structure connected using these may show more frequent loosening in vivo, especially in cases with impaired sagittal balance. This was not an issue analyzed in the literature. The frequency of instrument failure is of great importance for clinical practice because most such cases require operative revision.	5 years
Pain assessment on the VAS scale between groups.	One of the goals of surgical treatment is to treat mechanical pain caused by segmental instability. SBRT is a good method of treating biological pain. There are no comparisons of analgesic effects between transpedicular systems. Greater pain reduction allows for more effective and longer ability to walk, lower consumption of painkillers, and lower incidence of complications related to immobilization (thrombosis, bedsores, respiratory infections), which also has pharmacoeconomic implications.	5 years
Frequency of postoperative infections.	Postoperative wound infections are an inherent complication of surgical procedures. The longer the procedure, the more often inflammatory complications are observed, especially in oncological population, which has a higher average age of treated patients, a greater number of burdens, frequent immunosuppression due to systemic treatment, and malnutrition in the form of decreased biochemical parameters (total protein and albumin). Titanium has good properties in this aspect. Bacterial biofilms, is rarely formed on it, which means that patients can be treated more often without the need to remove the implants. It is unclear how carbon fiber system will perform in these cases. There are not made of metal, but of carbon fiber embedded in polymer. Assessment of the frequency of inflammatory complications and their course will provide the answer to whether This instrumentation allows for a similar management strategy in clinical settings.	5 years
Differences in dosimetric parameter Dmin PTV/CTV.		1 day
Differences in dosimetric parameter D95.		1 day
Differences in dosimetric parameter D98.		1 day
Differences in dosimetric parameter D100.		1 day
Differences in dosimetric parameter conformity index (CI) / homogeneity index (HI)).		1 day

Collaborators and Investigators

• Sponsor: Copernicus Memorial Hospital
• Collaborators: Medical Research Agency, Poland

Publications and helpful links

General Publications

• Boriani S, Tedesco G, Ming L, Ghermandi R, Amichetti M, Fossati P, Krengli M, Mavilla L, Gasbarrini A. Carbon-fiber-reinforced PEEK fixation system in the treatment of spine tumors: a preliminary report. Eur Spine J. 2018 Apr;27(4):874-881. doi: 10.1007/s00586-017-5258-5. Epub 2017 Aug 16.
• Cofano F, Di Perna G, Monticelli M, Marengo N, Ajello M, Mammi M, Vercelli G, Petrone S, Tartara F, Zenga F, Lanotte M, Garbossa D. Carbon fiber reinforced vs titanium implants for fixation in spinal metastases: A comparative clinical study about safety and effectiveness of the new "carbon-strategy". J Clin Neurosci. 2020 May;75:106-111. doi: 10.1016/j.jocn.2020.03.013. Epub 2020 Mar 12.
• Nevelsky A, Borzov E, Daniel S, Bar-Deroma R. Perturbation effects of the carbon fiber-PEEK screws on radiotherapy dose distribution. J Appl Clin Med Phys. 2017 Mar;18(2):62-68. doi: 10.1002/acm2.12046. Epub 2017 Feb 7.
• Ringel F, Ryang YM, Kirschke JS, Muller BS, Wilkens JJ, Brodard J, Combs SE, Meyer B. Radiolucent Carbon Fiber-Reinforced Pedicle Screws for Treatment of Spinal Tumors: Advantages for Radiation Planning and Follow-Up Imaging. World Neurosurg. 2017 Sep;105:294-301. doi: 10.1016/j.wneu.2017.04.091. Epub 2017 May 3.
• Neal MT, Richards AE, Curley KL, Patel NP, Ashman JB, Vora SA, Kalani MA. Carbon fiber-reinforced PEEK instrumentation in the spinal oncology population: a retrospective series demonstrating technique, feasibility, and clinical outcomes. Neurosurg Focus. 2021 May;50(5):E13. doi: 10.3171/2021.2.FOCUS20995.
• Lindtner RA, Schmid R, Nydegger T, Konschake M, Schmoelz W. Pedicle screw anchorage of carbon fiber-reinforced PEEK screws under cyclic loading. Eur Spine J. 2018 Aug;27(8):1775-1784. doi: 10.1007/s00586-018-5538-8. Epub 2018 Mar 1.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2033

Study Registration Dates

• First Submitted: February 17, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: stereotactic body radiotherapy; spinal cord compression; metastatic spinal disease; carbon fiber reinforced implants
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Wounds and Injuries; Neoplastic Processes; Spinal Cord Diseases; Spinal Cord Injuries; Neoplasm Metastasis; Spinal Cord Compression; Anti-Infective Agents, Local; Anti-Infective Agents; Carbon Fiber
• Other Study ID Numbers: 2023/ABM/01/00013

Drug and device information, study documents

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