Introduction. 1. Background information Juxta-medullary tumors are mostly benign tumors in the spinal
canal that may cause neurological deficits due to spinal cord or nerve root
compression. The knowledge about the natural course of the disease, optimal
treatment regarding timing of surgery and surgical approach are based on case series
from different institutions around the world. Moreover, little is known about the
long-term clinical and functional outcome after tumor resection, indicators of
quality of treatment and quality of life after surgery.
Main treatment option of juxta-medullary tumors is a neurosurgical resection. The main
goal of the surgery is to decompress the neuro structures in order to reveal neurological
deficits. However, achieving gross total resection (GTR) is important in order to achieve
long progression free survival (PFS).
Therefore, the surgeon should choose the appropriate surgical approach to achieve these
goals. Several publications show that GTR, whenever possible, is essential, as subtotal
resection is the main reason of tumor regrowth or recurrence. Moreover, revision surgery
due to tumor recurrence is one of the main risk factors of unfavorable outcome, probably
to intradural adhesions, related to the first procedure. Due to the mostly benign nature
of juxtamedullary tumors, it would be very difficult to evaluate overall survival (OS)
and progression free survival (PFS) within this progressive registry in the short run.
For this reason, data should be kept for late cohort analysis after longer intervals.
Probably up to 20 years, as previous publications reported recurrence of spinal
meningioma after GTR 10 years or more after surgery.
On the other hand, too large exposure may lead to impaired recovery after surgery,
eventual higher blood loss during surgery and thus longer stay in hospital (LOS) and
impaired quality of life. Moreover, extensive bone resection may lead to spinal
instability requiring instrumentation, during index surgery or during further follow up
in case of postoperative deformity).
In addition to the oncological outcome, the neurological outcome is also very important.
Depending on the localization of the tumor, its form and compression of intra-spinal
structures such as the spinal cord or nerve roots many patients develop neurological
deficits. Besides GTR the other goal of resection is the neurological recovery of these
patients. Previous reports show that the time point of surgery is important in order to
achieve full recovery. However, most of the data is derived from retrospective case
series. One of the aims of this registry is to prove this hypothesis. These neurological
deficits are, as mentioned above, related to the localization of the tumor within the
spine, Tumors in the cervical spine would cause mainly gait ataxia, spasticity, and
weakness in the upper extremities while tumors in the lumbar spine would lead to deficits
in the lower extremities in combination to disturbances of bladder, bowl, and sexual
functions. These functions should be evaluated and monitored, before and after treatment.
Other concerns are safety requirements in order to prevent peri-operative complications.
For example, the role of intra-operative neurophysiological monitoring. Some authors
recommend the utilization intra operative monitoring, however, the evidence level is very
low. Other open questions are for example the utility of microscope, methods for dura
closure and thrombosis prevention.
On the other hand, some tumors can be treated with irradiation, some studies showed
efficacy of this method mainly in the case of Schwannomas and meningiomas. In case of
residual tumor or tumor progression irradiation can be also performed to prevent further
growth.
Lastly, in comparison to the methods mentioned above, a wait-and-see approach can be used
for asymptomatic patients or those with mild symptoms. In this case, clinical and imaging
examinations are performed at regular intervals to check the neurological status and the
tumor. This can also be done for longer periods of time because of the benign nature of
these tumors with the slow growth. in case of new neurological deficits of or progression
surgical treatment should be advocated. Overall, it is not certain at what point therapy
is indicated, especially in asymptomatic patients. Because many of these tumors are
discovered by coincidence during imaging, which was performed due to other symptoms.
2 Rationale of the study The rationale of the trial is to define benchmarks on quality of
life, functionality and neurological outcome after resection of juxtamedullary tumors.
Furthermore, to assess and define benchmarks of quality indicators of the treatment.
These measurements would be essential for future studies.
Further rationales are to find out the optimal timing, method, and approach to treat
juxta-medullary tumors. Because of the low incidence of juxta-medullary tumors, a
multi-center trial seems to be essential. This would allow us to analyze a large number
of patients, much more than any other published paper. Moreover, the different protocols
and standards approaches in each center would allow conducting Comparative Effectiveness
Research (CER).
3 Aims The goal of this study is to establish a multicenter cohort of patients operated
on juxtamedullary tumors. With especial emphasis on functional outcome, quality
indicators (QI) and quality of life after surgery three months after surgery. Causes of
unfavorable outcome should be determined.
The main hypothesis is that early and less-invasive surgery with maximal extents of
resection would lead to a more favorable outcome. In the future the registry would help
assessing further hypothesis can be answered on the base of comparative effectiveness
research (CER), examples of these hypothesis are:
1. Functional and neurological outcome in comparison to preoperative status. Comparison
between Panties with good preoperative McCormick score (1-2) and those with a high
preoperative score (3-5).
2. Risk-factors for non-favorable outcome. 3. Non-Inferiority to achieve gross total resection via unilateral approaches. 4. Question whether laminectomy as approach may cause mor pain and impact quality of
life. 5. Risk factors for the development of CFS Leaks. 6. Does bed rest prevent CSF leaks. 7. Does laminectomy elevate the risk of CSF leaks. 8. Does the utility of intraoperative neurophysiological monitoring (IOM) influence
surgical outcome: rate of GTR and neurological outcome. 9. Rate of postoperative kyphosis and deformity in laminectomy in comparison to
non-laminectomy. 10. Is facetectomy required for GTR of dumbbell tumors?
11. Risk factors for non-complete resection.Primary outcomes are determined by:
Quality of life based on the questionnaire (EQ-D5) Extent of tumor resection (see CRF):
according to surgeon: 1. Meningioma: Simpson grade 1 and 2 2. Schwannoma: complete
resection, including nerve root 3. Cauda ependymoma: complete resection, including filum
terminale according to postoperative MRI, 3 months after surgery 4. Other: surgeon's
decision Neurological status (McCormick Score) (see CRF), 3 months after surgery
Secondary Outcome Imaging: preoperative and postoperative MRI Volumetry Spinal canal
occupancy ratio in %
Further patient reported outcomes:
Functionality: Neck disability index (NDI) for tumors in the cervical spine, Oswestry
disability index (ODI) for tumors in the thoracic and lumbar spine (see CRF) Local and
radicular pain (VAS 1-10) (see CFR) Neurological status: motor function of each limb,
ataxia and gait (mJOA score) (see CRF) HADS score- based score for anxiety Questionnaire
on bladder, bowl, sexual functionality.Quality indicators (QI):
Length of hospital stay 30- and 90-days readmission Nosocomial infections Blood loss
Duration of surgery Progression of the disease or recurrence Other adverse events
Mortality Assessment of adverse events according to Common Terminology Criteria for
Adveres Events (CTCAE) 5.0 and severity according to the Ibañez scale (see CRF) CSF
leakage is defined as one, when CSF leakage is identified on imaging of clinicaly and
treatment is required: operative or conservative (Lumbar drain for example) Postoperative
kyphosis of deformity is defined, when symptomatic (for example pain) or evident on
imaging (for example kyphotic fracture on MRI) Methodology All patients treated in one of
the study centers are recorded in a databank (Redcap, see below), which includes
information about admission, symptoms, other diseases, treatment, quality indicators and
questionnaires regarding quality of life and functionality. Data should be recorded in an
anonymized in each center (see below).
For the analysis the CRF includes information about admission, surgery, discharge, and 3
months (90 days) after surgery. In addition, patients should fill out questionnaires on
quality of life (EQ-D5) and functionality (ODI or NDI). Later, yearly visits can be
completed to have long term results in the future regarding progression free survival
(PFS) and overall survival (OS). The CRF is attached to this document.
Univariate and multivariate statistics would be applied to prove which variables might
lead to a favorable or unfavorable outcome.
A minimum number of one hundred (N=100) inclusions seems to be adequate in order to
perform reasonable analysis. In the event of nonsufficient recruitment, results and
further recruitment would be discussed two years after initiation of the study, and
annually thereafter.
