Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Wounds and Injuries

Neoplasm Metastasis

Spinal Cord Compression

Neoplastic Processes

Spinal Cord Diseases

Central Nervous System Diseases

Spinal Cord Injuries

Susan E Bates, M.D.

One of the complications of having cancer in the spinal vertebrae is that it can spread and lead to compression of the spinal cord. Spinal cord compression is a serious event that needs to be treated quickly in order to prevent permanent damage to the spinal cord and nerves.

* Researchers currently do not have the ability to accurately predict whether cancer of the vertebrae will cause spinal cord compression. It is possible that accurate predictions could allow doctors to treat patients even before they develop symptoms of spinal cord compression, thereby preventing some of the long-term consequences.

Objectives:

* To compare patients with cancer of the spinal vertebrae with and without symptoms of spinal cord compression by looking at markers in the blood and changes on novel magnetic resonance imaging (MRI) techniques that might allow researchers to predict who will experience spinal cord compression before they actually begin to have symptoms.

Eligibility:

* One group of healthy volunteers 18 years of age and older.
* One group of patients 18 years of age and older who have cancer that has spread to the vertebrae without symptoms of spinal cord compression.
* One group of patients 18 years of age and older who have cancer that has spread to the vertebrae with symptoms of spinal cord compression.

Design:

* Healthy volunteers:
* Blood will be drawn from each volunteer for initial tests and for more specific biomarker tests.
* Comprehensive MRI of the spine, followed by a special type of MRI called diffusion tensor imaging (DTI). It is believed that DTI may be even more sensitive in revealing spinal cord abnormalities than regular MRI sequences.
* Patients with cancer of the vertebrae:
* Researchers will obtain information such as pathology reports, laboratory results, diagnosis and treatment history, physical exam (PE) information, results of scans such as x-rays, MRI, computerized tomography (CT), and positron emission tomography (PET), and planned treatment details.
* Additional blood samples will be taken for specific biomarker tests.
* Questionnaire about pain, unusual sensations or numbness, bladder or bowel problems, and mobility.
* Comprehensive MRI of the spine, followed by a DTI.
* Patients who appear to have symptoms of spinal cord compression will be offered standard radiation treatment.

Background:

* Metastatic Epidural Spinal Cord Compression (MESCC) is an acute and common complication with grave prognosis.
* Biomarkers for early detection and prediction of outcome in these patients may allow a more objective treatment decision algorithm and hopefully change the unfortunate outcome described.
* Serum S-100b, NSE and GFAP and Plasma NF-H are surrogates for neuronal damage in humans and animal models.
* Diffusion tensor imaging (DTI) has been used in brain disorders, in predicting Spinal Cord Injury outcome in animal models, and was found to be beneficial in detecting spinal cord abnormalities in human subjects with acute and slowly progressive cord compression.

Objectives:

* To compare and evaluate the feasibility and reproducibility of DTI of the spinal cord in healthy participants, to optimize the DTI Images and determine normal spine DTI values,
* To describe normal variations of serum/plasma and imaging biomarkers in healthy participants and compare these with serum/plasma and imaging biomarkers values in patients with vertebral metastases with and without spinal cord compression.
* To detect differences in the serum/plasma and imaging biomarkers in patients with vertebral metastases with and without spinal cord compressions.
* To correlate serum/plasma and imaging biomarkers differences with clinical outcomes of patients with vertebral metastases with spinal cord compression (pain, ambulation, continence and survival at 1, 3, 6 and 12 months from radiotherapy).

Eligibility:

* Healthy volunteers with no prior history or concomitant central nervous system injury or inflammatory disease, prior or planned brain or spinal cord radiation therapy or surgical procedure and with no contraindication for MR scanning.
* Patients with metastatic cancer in the spinal vertebrae, with or without spinal cord compression and with no prior history or concomitant central nervous system injury or inflammatory disease, brain metastases, prior brain or spinal cord radiation therapy or surgical procedure and with no contraindication for MR scanning.

Design:

* Preliminary DTI studies will be conducted for healthy volunteer participants to determine normal spine DTI values, choose and optimize the scanning protocol, and evaluate the presence of artifacts and reproducibility of the DTI Images. Normal values and variability of serum and plasma biomarkers will be also determined.
* Patient participants with known vertebral bone metastases with or without spinal cord compression will undergo a DTI study along with the standard MRI sequences, used to evaluate MESCC patients. Blood samples for biomarkers will be also collected.
* Patients with documented MESCC, will be treated with standard radiotherapy fields, dose and schedule. Steroid treatment will be used as clinically indicated. All study procedures will be conducted prior to any therapy. Follow- up visits are planned at 1, 3, 6, and 12 months after radiotherapy completion with history and physical, DTI and serum/plasma biomarker evaluations.

A Pilot Study to Explore Serum and Imaging Biomarkers in Patients With Spinal Cord Compression

National Cancer Institute (NCI)

Stereotactic body radiotherapy

BALAMURUGAN VELLAYAPPAN, MBBS, FRANZCR

BALAMURUGAN VELLAYAPPAN

Pre-clinical evidence suggests that radiotherapy reduces tumour-associated vasculature. The investigators will conduct a single-arm prospective study to quantify the reduction in tumour vasculature post-radiotherapy

A Study to Quantify Tumour Perfusion for Spine Metastasis Treated With Stereotactic Body Radiotherapy (SBRT)

Reduction in Tumour Perfusion for Spine Metastasis Treated With Stereotactic Body Radiotherapy (SBRT)

Reduction in vasculature measured by changes on Dynamic Contrast enhanced MRI

National University of Singapore

National University Hospital, Singapore

Dr Balamurugan Vellayappan

Spine stereotactic radiosurgery/ablative radiotherapy (SSRS) with 16 Gy in single fraction to the defined Involved Target Volume using intensity modulated radiotherapy or volumetric modulated arc therapy (VMAT or RapidArc).

SSRS with 16 Gy in single fraction to the defined Elective Target Volume using intensity modulated radiotherapy or volumetric modulated arc therapy (VMAT or RapidArc).

Image guidance spine stereotactic radiosurgery/ablative radiotherapy 1600 cGy in single fraction to Involved Target using IMRT/VMAT/RapidArc

Involved Target Stereotacic Spine Radiosurgery

Image guidance spine stereotactic radiosurgery/ablative radiotherapy 1600 cGy in single fraction to Elective Target using IMRT/VMAT/RapidArc

Elective Target Stereotacic Spine Radiosurgery

Feng-Ming Hsu, M.D., Ph.D

Feng-Ming Hsu, M.D., Ph.D.

The spine is a common metastatic site for malignancy and it can lead to serious and devastating events, including pain, neurological dysfunction, and reduction in quality of life. The radiotherapy (RT) has been the mainstay for palliating painful spinal metastases for the past decades. It is utilized to arrest the tumor growth, control pain, and stabilize or improve skeletal and/or neurological function. One of the limitations of the conventional radiotherapy is that radiation dose intensification is not achievable with conventional RT techniques due to the dose-limiting spinal cord, which is close to the vertebral body and sometimes encased by epidural lesion.

The management of patients with spine metastasis has undergone a great deal of change in the past 10 years. The concept of radiosurgery, a high dose of radiation targeted to a pathological entity and delivered in 1-5-fractions, has proven so successful at treating both benign and malignant lesions that it changed the paradigm for radiation therapy. Clinical experiences with high dose spine stereotactic radiosurgery (SSRS) for spinal metastases demonstrated both safety and efficacy. Nontheless, the patterns of clinical practice of SSRS varies considerably regarding the dose fractionation, target delineation, and dosimetry. There is lack of evidence-based recommedations for SSRS.

In our prior clinical trial comparing single fraction and multiple fractions SSRS (NCT02608866), single-fraction with 16 Gy is the preferred regimen for further evaluation since it met the predefined primary endpoint and has lower risk of treatment failure compared to the multiple-fraction arm. Regarding the target volume definition, the International Spine Radiosurgery Consortium published concensus guidelines based on expert opinions and limited case series. We proposed this randomized study to determine the preferred or acceptable definition of target volume delineation in SSRS and to evaluate their toxicity, efficacy, and patterns of failure. Our analysis will provide evidence-based recommendations as well as predictive factors regarding the clinical practice of SSRS.

Although conventionally fractionated radiation therapy has been utilized for decades, the rates of complete pain relief and local control for complex tumors are sub-optimal. The management of patients with spine metastasis has undergone a great deal of change in the past 5 years. Improvements in neuroimaging, computer- assited treatment planning, and radiation therapy techniques have led to the development of extracranial radiosurgery.

SSRS is rapidly being adopted in the clinic as preliminary applications of SSRS appears promising. However, the role of SSRS remains in its infancy and lacked high-quality evidence about the treatment schedule and lacked a solid understanding of the adverse events. The RTOG 0631 phase 2/3 study was initiated to determine whether a more intensive radiation dose delivered by image guided 16-Gy dose single fraction SRS could improve pain control and quality of life as compared with conventional EBRT in patients with localized spine metastases. Our preliminary result from previus phase 2 stereotactic spine radiosurgery trial (NCT02608866) also showed good local control with minimal side effects in the single fraction 16-Gy setting as compared with 3 fractions 24 -Gy SRS dose.

Accurate and approproate delineation of the target area is paramount to the utilization of spine SBRT. Whethr the target volume should include the entire extent of tumor and the involved anatomical compartment for intact vertebra metastasis or remained to be discussed.

Our preliminary showed that the overall treatment failure rate was only about 14% using the definition of the treating the affected spinal lesions(invovled target ) instead of treating the entire . Better dose coverage of the target vome with improved normal tissue protection can be achived with invovled field treatment without compromising the local control. Since no treamtent target consensus has been reached from current clinical practive evidence. It is pivotal to establish and collect more treatment evidence for future spinal SBRT.

There was no randomized trials to assess the SSRS treatment response and SSRS induced grade 3 or higher adverse events between these two different target delineations. Thus, we proposed the randomized study to determine the feasibility of using "Invovled Target Volume" versus "Elective Target Volume" and tried to evaluate the toxicity profile and gain robust data as well as predictive factors regarding the local control rate and risk of complications after SSRS.

Involved Versus Elective Target SSRS for Spinal Metastases

A Prospective Randomized Trial of Involved Versus Elective Target Definition in Stereotactic Spine Radiosurgery for Spinal Metastases

The rate of predefined treatment failure at 6-month after stereotactic spine radiosurgery. Treatment failure is defined as Grade 3 or higher adverse events definitely, probably, or possibly related to treatment and/or unequivocal local progression indicative of surgical intervention or re-irradiation.

National Taiwan University Hospital

Single-Fraction (SF) Stereotactic Spine Radiosurgery

Multiple-Fraction (MF) Stereotactic Spine Radiosurgery

Spine stereotactic radiosurgery/ablative radiotherapy (SSRS) with 16 Gy in single fraction to the defined target volume using intensity modulated radiotherapy or volumetric modulated arc therapy (VMAT or RapidArc).

SF-SSRS

SSRS with 24 Gy in three fractions to the defined target volume using intensity modulated radiotherapy or volumetric modulated arc therapy (VMAT or RapidArc). Treatment should be given on every other day. Treatment on the consecutive days to the same target volume is not allowed.

MF-SSRS

Feng-Ming Hsu, MD

The investigators proposed this randomized study to determine the feasibility of delivering single-fraction 16-Gy versus 3-fraction 24-Gy toward spine metastatic lesion and to evaluate their toxicity profiles. The investigators' analysis will provide robust data as well as predictive factors regarding the outcome after SSRS.

Although conventionally fractionated radiation therapy has been utilized for decades, the rates of complete pain relief and local control for complex tumors are sub-optimal. The management of patients with spine metastasis has undergone a great deal of change in the past 5 years. Improvements in neuroimaging, computer-assisted treatment planning, and radiation therapy techniques have led to the development of extracranial radiosurgery.

SSRS is rapidly being adopted in the clinic as preliminary applications of SSRS appears promising. However, the role of SSRS remains in its infancy and lacked high-quality evidence about the treatment schedule and lacked a solid understanding of the adverse events. The Radiation Therapy Oncology Group (RTOG) 0631 phase 2/3 study was initiated to determine whether a more intensive radiation dose delivered by image guided 16-Gy dose single fraction SRS could improve pain control and quality of life as compared with conventional external-beam radiotherapy in patients with localized spine metastases . While other group used treatment schedule in a total dose of 27-30 Gy in three fractions.

Serious adverse events such as vertebral compression fracture (VCF) is a fairly low-risk adverse event after conventional radiotherapy, nevertheless, the crude risk estimates for VCF after spinal stereotactic body radiation therapy is relative more frequent. Previous reports has raised the caution about the given dose and predictive factors, however; whether these two most widely used SSRS schedule (ie. single fraction versus three fractions) provide equivalent pain control and minimal side effects remained to be answered.

There was no randomized trials to assess the SSRS treatment response and SSRS induced grade 3 or higher adverse events between the two most widely adopted scheme. Thus, the investigators proposed the randomized study to determine the feasibility of delivering a single 16-Gy SRS dose versus 3 fractions 24-Gy SRS dose and tried to evaluate the toxicity profile and gain robust data as well as predictive factors regarding the risk of complications after SSRS, including VCF. The investigators will incorporate the recently developed and reported reliable Spinal Instability Neoplastic Scoring (SINS) system and well-designed patient reported outcome measures (PROMs) into the protocol to predict the adverse event and quality of life of each participant. The researchers also tried to investigate the possible associations of the potential bone biomarkers for the risk assessment of SSRS-related adverse bone events.

Since the patients were randomized for treatment arms, the effectiveness of SSRS treatment scheme and adverse profile can be investigated more properly in the present study.

Single Versus Multiple Fractionated SSRS for Spinal Metastases

A Prospective Randomized Clinical Trial of Single Versus Multiple Fractionated Stereotactic Spine Radiosurgery for Patients With Spinal Metastases

Assessed by grading based on vertebral height loss

The rate of 4-month Common Toxicity Criteria for Adverse Events version 4 grade 3 or higher adverse events definitely, probably or possibly related to treatment

European Organization for Research and Treatment of Cancer Quality of Life-Core 30 questionnaire module and Quality of Life questionnaire for palliation

•24 Gy in 3 fractions to cover at least 90% of the defined target volume

SBRT

16 Gy in 1 fraction to cover at least 90% of the defined target volume

Radiosurgery

Michael KM KAM, FRCP

Demonstrate the technical feasibility of treating spine metastases with image-guided radiosurgery/SBRT

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Pilot Study to Explore Serum and Imaging Biomarkers in Patients With Spinal Cord Compression	NCT00928382	Cancer Spine Metastasi...		18 Years - 90 Years	National Institutes of Health Clinical Center (CC)
A Study to Quantify Tumour Perfusion for Spine Metastasis Treated With Stereotactic Body Radiotherapy (SBRT)	NCT03072979	Spine Metastasi...	Stereotactic bo...	21 Years -	National University Hospital, Singapore
Involved Versus Elective Target SSRS for Spinal Metastases	NCT04033536	Secondary Malig...	Involved Target... Elective Target...	20 Years -	National Taiwan University Hospital
Single Versus Multiple Fractionated SSRS for Spinal Metastases	NCT02608866	Secondary Malig...	SF-SSRS MF-SSRS	20 Years -	National Taiwan University Hospital
Involved Versus Elective Target SSRS for Spinal Metastases	NCT04033536	Secondary Malig...	Involved Target... Elective Target...	20 Years -	National Taiwan University Hospital
Spinal met_radiosurgery/SBRT Study	NCT01231061	Spine Metastasi...	SBRT Radiosurgery	18 Years -	Chinese University of Hong Kong

Spots Global Cancer Trial Database for spine metastasis