A Prospective Study of the Safety and Efficacy of 3D-printed Non-rigid Biomimetic Implant in Cervical and Thoracolumbar Spine

Study Overview
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Brief Summary
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Vertebral body resection is a wide accepted procedure in tumor resection, deformity correction, and anterior decompression in spondylosis, ossification of posterior longitudinal ligaments, and spondylodiscitis surgery. However, reconstruction of segmental defect is still challenging to spine surgeon, especially in 3-column resection, such as total en bloc spondylectomy in tumor patients. Various graft or prosthesis for reconstruction has been reported, such as structural allograft, Harms mesh cages, expandable cages, and carbon fiber stackable cages. There are no high evidence level study examining the superiority of those different methods. Recently, 3D printed vertebral body replacement has been reported in different disease entities as well, such as tumor, Kümmell's disease in osteoporosis, and spondylosis. 3D printed implant comes with superiority in production of complex geometries and regularity of the fine surface detailed that promote bone ingrowth. Although, 3D-printed titanium vertebra could achieved bone integration in human, a systemic review showed that the subsidence noted in 31.4% of spine surgery with 3D printed implants. In spine surgery, the fixation construct is sufficiently stiff, interbody motion can be reduced, and loading sharing promotes bone fusion. On the other hand, if the reconstruction is too stiff, stress shielding at fusion site occurs. The concept of dynamic fusion, as opposed to rigid fusion, has been demonstrated by an anterior cervical interbody fusion study in porcine model, demonstrating good bone formation, less postfusion stiffness, and a trend to less subsidence. Thus, we developed a 3D printed, custom-made, biomimetic prosthesis, with non-rigid structure, which has been tested in biomechanical study and porcine model, showing good bone formation and less stiffness as well. Therefore, we proposed a prospective clinical study to investigate safety, subsidence, and fusion of this prosthesis.

Detailed Description
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This is a single-arm prospective observational phase I clinical study to investigate the safety of the non-rigid 3D printed custom-made biomimetic implant. The implants are made of Titanium alloy. Patient receiving 1- to 3-level corpectomy at cervical and thoracolumbar spine. At first stage, we plan to enroll 3 cervical patients, and 3 thoracolumbar patients with non-rigid 3D printed custom-made biomimetic reconstructions. After 3 months observation after the last patients enrolled, we will conduct an interim investigation to investigate those 6 patients. if there is no re-operations due to acute post-operative reconstruction failure. We will continue the study. Total 9 cervical patients, and 9 thoracolumbar patients will be enrolled. Patients are evaluated preoperatively, right after surgery, and 1, 3, 6, 12 months postoperatively. Measure outcomes included overall success, VAS neck and back pain, patient satisfaction, anxiety score, SF-12 MCS/PCS, complications, subsequent surgery rate, and subsidence and fusion rate on radiological examination. Radiological evaluation, including X-ray and computed tomography, will be done pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. In addition, neck disability index (NDI) will be evaluated in cervical patents, and SORGSQ 2.0 self-reported questionnaire will be applied for all oncology patients. The primary endpoint was a FDA composite definition of success comprising clinical improvement and absence of major complications and secondary surgery events.

Official Title
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A Prospective Study of the Safety and Efficacy of 3D-printed Custom-made Non-rigid Biomimetic Implant for Anterior Column Reconstruction in Cervical and Thoracolumbar Spine

Conditions
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Spinal Tumor

Intervention / Treatment
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* Device: 3D-printed custom-made non-rigid biomimetic implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20 - 79 years; Patient meet the indication for 1- to 3- level corpectomy, for primary bone tumor at spine, or metastatic tumor at spine. Deficit confirmed by CT, MRI, and X-ray; Pathology level located from C3 to L5. Physically and mentally able and willing to comply with the protocol; Signed informed consent; NTU Spine Multidisciplinary Board confirmed tumor excision surgery is indicated. Life expectancy longer than 6 months (Tokuhashi Scoring System) Exclusion Criteria: Patient does not meet the indication of corpectomy, which is under the surveillance. More than three vertebrae required corpectomy; Corpectomy levels above C3 and below L5 T-score less than -2.5 Known allergy to device materials - such as titanium Any diseases or conditions that would preclude accurate clinical evaluation; Daily, high-dose oral and/or inhaled steroid or a history of chronic use of high dose steroids; BMI > 35 Life expectancy less than 6 months - (Tokuhashi Scoring System) The subject has received radiation therapy or chemotherapy at the trial site within one year; Anterior spine surgery has been received at or near the spine surgery site; The subject has systemic infection,or focal vertebral infection or trauma; The subject has endocrine disorders or metabolic disorders known to affect bone formation, such as: Paget's disease, renal osteodystrophy, hypothyroidism; The subject has neuromuscular diseases, those at risk of instability, implant fixation failure or postoperative care complications, including: spina bifida, cerebral palsy, and multiple sclerosis; Osteopenia, osteomyelitis; Pregnant women.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3D-printed<br>We developed a 3D printed, custom-made, biomimetic prosthesis, with non-rigid structure, which has been tested in biomechanical study and porcine model, showing good bone formation and less stiffness as well. Therefore, we proposed a prospective clinical study to investigate safety, subsidence, and fusion of this prosthesis. | Device: 3D-printed custom-made non-rigid biomimetic implant<br>* We developed a 3D printed, custom-made, biomimetic prosthesis, with non-rigid structure, which has been tested in biomechanical study and porcine model, showing good bone formation and less stiffness as well. Therefore, we proposed a prospective clinical study to investigate safety, subsidence, and fusion of this prosthesis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | We will follow up the condition of participants with treatment-related adverse events as assessed by CTCAE v4.0. | Patient were evaluated at 12 months postoperatively. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of change in the subsidence | In a medical sense, subsidence refers to the collapse or settling of bone located immediately next to an implantable device in direction of the loading force. It is uasually recorded in millimeters. It was assessed on radiological examination. Radiological evaluation, including X-ray and computed tomography. | Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. | 
| The percentage of patients with successful fusion | The fusion rate is the percentage of patients with successful fusion over a specific range of follow up. The outcomes about fusion rate of bone was assessed on radiological examination. Radiological evaluation, including X-ray and computed tomography. | Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. | 
| Pain score | Pain score was assessed by Visual Analogue Scale. (0 means no pain, while 10 is the most painful situation). | Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. | 
| Short form-12 mental component score | The minimum value of mental component scale (MCS-12) is 18.7, and the maximum value of MCS-12 is 65.2. Higher scores mean a better outcome. | Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. | 
| Anxiety score | Anxiety score was assessed by Beck Anxiety Inventory (The minimum value is 0 and the maximum value is 63. A higher score means a worse outcome). | Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. | 
| Neck Disability Index (NDI) | Physical function was assessed by Neck Disability Index (NDI), it will be evaluated only in cervical patents. An improvement in Neck Disability Index (NDI) score of at least 30 points for a patient with a preoperative NDI score of 60 or greater; or an improvement of at least 50% of preoperative NDI score for patients with a preoperative score of less than 60. | Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. | 
| Patient Satisfaction Questionnaire | Patients will be surveyed by Patient Satisfaction Questionnaire. There are two questions on the questionnaire to evaluate if they are satisfied with their treatment and if they will recommend their respective surgery to a friend. | Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. | 
| Short form-12 physical component score | The minimum value of physical component scale (PCS-12) is 18.4 and the maximum value of PCS-12 is 57.8. | Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Tumor, Reconstruction