1. Spine Oncology: Required Reading for the Neuroradiologist
Wende N Gibbs, MD, Paul E Kim, MD, and Meng Law, MBBS, FRACR
Department of Neuroradiology
University of Southern California, Keck School of Medicine
# 1968

2. Disclosures of Commercial Interest
None of the authors or their immediate family members have a financial relationship with a commercial organization that may have a direct or indirect interest in the content of this presentation

3. Objectives
Provide a comprehensive overview of the current multidisciplinary treatment options for osseous spinal metastatic disease
Describe the NOMS paradigm: an important new decision-making tool that is used by spine surgeons and oncologists to provide optimized, individualized treatment
Detail specific classification systems utilized in NOMS, with emphasis on information that neuroradiologists should provide the multidisciplinary treatment team
Discuss the emerging role that radiologists play in treatment of select patients with spine metastases

4. Introduction 1.6 million new cancer cases per year in the US1
Osseous spinal metastases occur in up to 40% of cancer patients2
Advances in spine oncology – new technologies and therapeutic options - have increased patient survival
Radiologists play a vital role in patient management, providing data used in decision-making and in some cases, minimally invasive treatments

5. Spinal Metastases: Treatment
Spinal metastases have a significant impact on quality of life, as a result of disabling pain, fracture, or paralysis secondary to cord compression
Treatment goals include:
Effective pain palliation
Maintenance or recovery of neurological function and ambulation
Local durable pain control
Spinal stability
Improved quality of life
52-year-old man with metastatic lung cancer producing spinal cord compression

6. Spinal Metastases: Treatment
Treatment decisions are based upon the individual patient’s symptoms, tumor type, and comorbidities
Treatment options include:
Surgery*
Radiation*
Chemotherapy
Immunotherapy
Radionuclides
Hormonal therapy
55-year-old man with metastatic renal cell
carcinoma.
L4 pathologic fracture was treated with surgical resection and stabilization followed by radiation therapy.
Surgery improved approaches
Chemo:
Hormonal: breast prostate, thyroid
Bioimmunotherapy – RCC, melanoma, sarcoma
Tartgeted : receptor blockers, kinase inhibitors, checkpoint inhibitors
Generally reserved for sensitive tumors causing little or no symptoms
Radiation:
*Surgery and radiation are presently the most effective treatments for spinal metastases

7. The NOMS Framework
The NOMS Framework3 is a recent, widely accepted decision-making paradigm that provides spine oncology specialists with a common language to optimize multidisciplinary management
The framework considers four aspects of disease status:
Neurologic
Oncologic
Mechanical stability
Systemic status
Integration of these four factors determines the choice of radiation, surgery, and/or systemic therapy

8. The NOMS Framework Treatment Decision Neurologic Oncologic Mechanical
(Cord compression/myelopathy)
Oncologic
(Is the tumor radiosensitive?)
Mechanical
(Is the spine stable?)
Systemic
(Can the patient tolerate surgery?)
Treatment Decision
Low-grade cord compression (ESCC grade 0 or 1) without myelopathy
Yes
External beam radiation (EBR) No
Stabilization then EBR
Stereotactic radiosurgery (SRS)
Stabilization then SRS
High-grade cord compression (ESCC grade 2 or 3) with or without myelopathy
EBR
Decompression +/- stabilization then SRS
Stabilization* then EBR
*Stabilization options include open surgical intervention and minimally invasive options, such as percutaneous cement augmentation for patients who cannot tolerate open surgery.
Modified from Laufer, I et al. The Oncologist 2013

9. The NOMS Framework
Neurologic status focuses primarily on the degree of spinal cord compression from epidural tumor extension or pathologic fracture
Myelopathy and functional radiculopathy are secondary clinical considerations
The radiology assessment is paramount at this decision point
The radiologist utilizes the Epidural spinal cord compression grading scale (ESCC)4
Six point system designed by the Spine Oncology Study Group
Graded on axial T2-weighted images or post contrast images at the level of greatest compression
Treatment based upon ESCC grade:
Low grade (0-1): in a mechanically stable spine, radiation is the initial treatment
High-grade (2-3): treated with surgery before radiation in all cases except: a highly radiosensitive tumor in a mechanically stable spine, or a patient who cannot tolerate surgery

10. The NOMS Framework
The Patchell trial5 published in 2005 initiated a major change in the treatment of spinal metastases
First large randomized controlled trial comparing surgical decompression with conventional radiotherapy in the setting of metastatic spinal cord compression
Patients undergoing both surgery and radiation compared with radiation alone had better outcomes in terms of ambulation, continence, narcotic requirement, and survival
Class 1 evidence to support initial treatment of high grade spinal cord compression with open surgery
For this reason, in the NOMS framework treatment based upon ESCC grade is as follows:
Low grade (0-1): in a mechanically stable spine, radiation is the initial treatment
High-grade (2-3): treated with surgery before radiation in all cases except: a highly radiosensitive tumor in a mechanically stable spine, or a patient who cannot tolerate surgery

11. Grade 0 Grade 1a Grade 1b Grade 1c Grade 2 Grade 3
Epidural Spinal Cord Compression (ESCC) grading scale
Grade 0: osseous disease only.
Grade 1a: epidural involvement without thecal sac deformation.
Grade 1b: thecal sac deformation without cord contact.
Grade 1c: thecal sac deformation with cord contact.
Grade 2: cord compression with preservation of some CSF.
Grade 3: cord compression with complete effacement of CSF.
Modified from Bilsky, M et al. Neurosurgery: Spine 2010.

12. ESCC Grade 0 Grade 1c Grade 1a Grade 2 Grade 1b Grade 3
Epidural Spinal Cord Compression (ESCC) grading scale
Grade 0: osseous disease only.
Grade 1a: epidural involvement without thecal sac deformation.
Grade 1b: thecal sac deformation without cord contact.
Grade 1c: thecal sac deformation with cord contact.
Grade 2: cord compression with preservation of some CSF.
Grade 3: cord compression with complete effacement of CSF.
The ESCC is typically based upon axial T2-weighted images at the level of greatest compression. T1-weighted post contrast images may be used for clarity.

13. The NOMS Framework
Very sensitive
Sensitive
Not sensitive
Lymphoma
Breast
Colon
Myeloma
Prostate
Renal cell
Small cell lung
Thyroid
Melanoma
Sarcoma
Squamous adenoca lung
Oncologic assessment focuses primarily on tumor radiosensitivity
Radiosensitivity was defined by tumor response to conventional external beam radiation therapy (EBRT)
Typically delivered as a total of 24–50 Gy in fractionated (multiple) doses of 1.8–3 Gy
Radiation delivered to all structures in the field
Dose limited by most radiosensitive structure (spinal cord)
Stereotactic radiosurgery (SRS) is an advance that allows image-guided conformal radiation doses in close proximity to the spinal cord
High dose in single fraction or 3-5 fractions
Submillimeter precession
Spares radiosensitive structures
SRS v cEBRT:
Increased dose per fraction
Fewer fractions
Higher biologically effective dose
Conventional EBRT
SRS

14. Stereotactic Radiosurgery (SRS)
Radiosurgery requires accurate identification of target tissues and surrounding normal structures for submillimeter radiation delivery accuracy
Both CT and MRI are utilized for planning when possible
CT is the standard method for localization and is the most commonly used modality for treatment simulation, providing clear visualization of sclerotic and lytic tumor components
MRI is most useful for target tumor delineation and epidural and paravertebral extension
CT myelography with the patient in treatment position yields clear images and superior delineation of the spinal cord, especially in patients with surgical hardware
Treatment simulation: Lumbar injection of myelographic contrast followed by CT myelogram with patient in treatment position.
The myelogram provides superior images in the patient with surgical hardware at the treatment site.

15. Stereotactic Radiosurgery Treatment Plan
Treatment planning CT slice thickness </= 2mm
Axial T1-w and T2-w MRI slice thickness </= 3mm fused to treatment planning CT
CT with myelogram and PET for spinal cord and tumor delineation in select circumstances
The treatment plan delineates radiation dose to tumor and surrounding structures: the tumor received a high dose, while the spinal cord is spared.

16. What about this case? Can SRS be used to target the tumor without dosing the spinal cord?
SRS plan for a different patient without epidural tumor or cord compression
Metastatic renal cell carcinoma with high grade cord compression (ESCC grade 2)

17. Separation Surgery
Radioresistant tumors with high grade cord compression (ESCC grades 2 or 3) require surgical decompression and stabilization before radiation
Separation surgery involves minimal tumor resection to separate the tumor margin from spinal cord so that the bulk of the mass can be treated with radiation
The assumed safe maximum radiation dose to the spinal cord is approximately 14Gy
In the absence of surgical separation of tumor from cord, the requisite tumorcidal radiation dose cannot be delivered without risking cord toxicity

18. The NOMS Framework
Mechanical instability caused by metastatic disease is defined as: movement related pain, symptomatic or progressive deformity, and/or neural compromise under physiologic loads
Mechanical instability is an indication for stabilization regardless of neurologic or oncologic status
A commonly used scoring system, the Spinal Instability and Neoplastic Score (SINS)6, classifies patients into those with stable lesions versus unstable lesions requiring initial surgical consultation
5 radiologic components and 1 clinical component (pain)
Stabilization options
Pedicle screw instrumentation
Open instrumentation
Percutaneous cement augmentation: the preferred treatment for painful metastases without cord compression

19. 0-6 = Stable 7-12 = Indeterminate 13-18 = Unstable Total score
Location
Osseous characteristics
Radiographic alignment
Vertebral body collapse
Involvement of posterior elements
Pain
Junctional spine
(occiput-C2, C7-T2, T11-L1, L5-S1)
Score = 3
Subluxation
Score = 4
>50% collapse
Bilateral
Yes
Mobile spine
(C3-6, L2-4)
Score = 2
Lytic
Deformity
(kyphosis, scoliosis)
< 50% collapse
Semi-rigid spine
(T3-10)
Score = 1
Mixed (lytic and blastic)
No collapse
>50% body involved
Unilateral
Occasional, not mechanical
Rigid spine
(S2-5)
Score = 0
Blastic
Normal
None No
0-6 = Stable
7-12 = Indeterminate
13-18 = Unstable
Total score
Spinal Instability Neoplastic Scale. The scores for the five radiographic components and one clinical component are added together to yield a total SINS score ranging from 0 to 18.
Modified from Fisher CG, Spine 2010.

20. Location (L4) = Mobile [2] Osseous character = Lytic [2]
Alignment = Normal [0]
Collapse = >50% [3]
Posterior elements = bilateral [3]
Pain = Yes, mechanical [3]
Total SINS score = 13 UNSTABLE
This patient with metastatic renal cell carcinoma had pre-surgical tumor embolization, surgical stabilization with corpectomy and graft placement followed by SRS.
7-12 = Indeterminate
13-18 = Unstable

21. 65-year-old woman with metastatic breast cancer.
Sagittal and axial post-contrast fat-saturated images demonstrate metastatic infiltration of the L5 vertebral body with epidural and paravertebral tumor extension.
7-12 = Indeterminate
13-18 = Unstable
The radiologist provided the treatment team with the SINS score as well as the ESCC grade (Grade 2).
Location (L5) = Junctional [3]
Osseous character = lytic [2]
Alignment = Normal [0]
Collapse = None [0]
Posterior elements = Bilateral [3]
Pain = Severe [3]
Total SINS score = 11 INDETERMINATE

22. High grade cord compression (ECSS Grade 2) = surgery before radiation
T9 Lesion:
Location (T9) = Semi-rigid [1]
Osseous character = lytic [2]
Alignment = Normal [0]
Collapse = None [0]
Posterior elements = Unilateral [1]
Pain = Occasional [1]
Total SINS score = 5 Stable
Multiple metastases:
grade each separately
T12 Lesion:
Location (T12) = Junctional [3]
Osseous character = lytic [2]
Alignment = Normal [0]
Collapse = None [0]
Posterior elements = Bilateral [3]
Pain = Severe [3]
Total SINS score = 11 Indeterminate
T2W
Prostate mets T9, 10, 12
7-12 = Indeterminate
13-18 = Unstable
High grade cord compression (ECSS Grade 2) = surgery before radiation

23. The NOMS Framework
Systemic status is an important consideration in decision making: the ability to tolerate a proposed intervention is a function of tumor burden and comorbidities
Certain tumor histologies may predispose to shortened survival, and preclude benefit from certain interventions
High surgical complication rates are undesirable for patients with a limited life expectancy
Minimally invasive procedures for pain palliation are popular options for such patients
Radiologists have an increasing role in treatment of patients with painful spinal metastases: cement augmentation and tumor ablation
Tumor Type
Median survival
Lung
4 months
Breast
24-36 months
Lymphoma/Myeloma
> 48 months

24. Cement Augmentation and Ablation
Vertebroplasty and kyphoplasty are now among the most commonly used treatments for pain resulting from mechanical instability
Percutaneous ablative therapy can treat pain and in some cases provide local tumor control
Ablation is used as an adjunct or alternative therapy in patients without cord compression
Radiofrequency ablation (RFA) uses thermal energy to produce coagulation necrosis of pain fibers and tumor
Microwave ablation is a subtype of RFA that produces larger and hotter ablation zones
Cryoablation uses freezing temperatures to destroy tumor
72-year-old man with metastatic hepatocellular carcinoma with T10 metastasis.
CT guided radiofrequency ablation and kyphoplasty was performed. Pain before the procedure was 10/10. After the procedure, the pain was 3/10.

25. a b c d
35-year-old with metastatic lung adenocarcinoma with severe back pain at the T9 level
The sagittal post-contrast fat-saturated image (a) demonstrates a metastasis within the anterior and mid T9 vertebral body.
There was no pathologic compression, epidural tumor, or cord compression. This metastasis was deemed amenable to treatment with percutaneous radiofrequency ablation and cement augmentation.
The T9 vertebral body was biopsied and radiofrequency ablation was performed (b), followed by cavity creation and cement augmentation (c).
A post-contrast image (d) from MRI obtained two weeks later shows the non-enhancing ablation cavity and cement. Enhancement in the inferior and posterior aspects of the vertebral body likely relates to the procedure, as it was not present on the pre-procedure images.
The day after ablation and augmentation, the patient reported near complete relief of his back pain.

26. Post-treatment Imaging
Indications for post treatment imaging include:
Establishing a postoperative baseline
Assessing for immediate and long term complications
Routine surveillance
MRI is preferred, but CT and PET have useful adjunct roles
Local control: absence of progression within the treated area on serial imaging (2-3 consecutive MRI 6-8 weeks apart)
Local progression:
Increase in tumor volume or linear dimension
New or progressive epidural tumor
Neurological deterioration attributable to preexisting epidural disease with equivocal increase in size of epidural tumor
Local progression. Despite surgery and radiation, this patient’s residual renal cell carcinoma continued to increase in size

27. Post-treatment Imaging
Complications in the immediate post treatment time period:
Hematoma
Infection
CSF leak
Hardware failure
Late complications:
Tumor recurrence
Treatment effects
Post radiation vertebral compression fracture
Radiation myelopathy A C D B
RCC post separation surgery and stabilization followed by SRS. T1-W postcontrast image (A) of metastatic renal cell carcinoma to L2 with high grade cord compression. Separation surgery and stabilization was performed (B). The patient developed a painful pathologic compression of L2 (C). Kyphoplasty was performed. After further collapse, the stabilizing rod broke (D). The hardware was replaced.
A 35-year-old man with renal cell carcinoma presented with an L2 vertebral body metastasis and leg pain. Initially, the patient underwent posterolateral T12–L4 instrumentation with L2 circumferential decompression. (B, C) Two years later, he presented (B) and was found to have a progressive pathological fracture (C), and kyphoplasty was performed. (D) The patient presented again, 6 months after the kyphoplasty, with progressive back pain, and imaging showed a progressive lumbar kyphotic deformity and rod fracture. (E) The patient underwent operative rod replacement and did well after the procedure.
separation surgery for MESCC. Large surgical series of patients with metastatic spinal tumors report hardware failure in 2.2% to 16% of patients [ Common instrumentation complications include fracture or dislodgment of screws, rods, plates, hooks, and cages. Because of the heterogeneous nature of these series, it is difficult to compare directly the various instrumentation techniques.
Separation surgery: rate of hardware failure 2-16%7

28. Complications: Myelopathy
Dose dependent risk
< 45 to 50 Gy in standard fractionation (18–20 Gy / fraction) has less than a 5% probability of myelopathy within 5 years and is considered within tolerance8
Several studies show that 10Gy for single-fraction SRS poses low risk for myelopathy
Biologic response of cord after radiation
Vascular endothelial cell death
Disruption of blood-spinal cord barrier
Demyelination and necrosis
Predictive factors for myelopathy include:
Age
Sex
Primary site
Dose per fraction
Total dose
Maximum spinal cord dose
Tumor volume
60-year-old woman with history of metastatic lung cancer. Sagittal T1-W image (A) shows fatty infiltration of the vertebral marrow in the treated spinal segment. The T2-W fat-saturated image (B) shows ill-defined T2 hyperintensity in the spinal cord at those levels, reflecting radiation myelopathy. A B
Sharan2014
Molecular pathology of radiation myelopathy. Demyelination and focal to confluent necrosis represent the hallmark of radiation myelopathy, as demonstrated by the absence of Luxol blue staining in rat spinal cord white matter at 20 weeks after 22 Gy (a, blue). White matter lesions are associated with disruption of the blood–spinal cord barrier shown by albumin leakage (b, albumin immunohistochemistry), tissue hypoxia (c, nitroimidazole EF5 immunohistochemistry) and upregulation of HIFα and VEGF, as demonstrated by an increase in reactive glia immunopositive for HIFα (d) and VEGF (e).
The biologic response of the spinal cord after radiation is a continuously evolving process. Death of vascular endothelial cells and disruption of the blood–spinal cord barrier leads to a complex injury response, resulting in demyelination and tissue necrosis. At present, there is no evidence that the pathobiology of cord injury after SBRT is different from that after standard fractionation. Although permanent myelopathy has become a rare complication following conventional fractionated radiation treatment, cases of radiation myelopathy have re-emerged with the increasing role of spine stereotactic body radiation therapy and reirradiation.

29. Complications: Compression Fracture
There is an 10-40% risk of compression fracture after single fraction radiosurgery8.9
Factors that put the patient at highest risk include:
Lytic metastases
Location in thoracolumbar or lumbar segments
Age greater than 55 years
Pre-existing fracture or deformity
Pain
For this reason, some institutions perform prophylactic cement augmentation before radiation or chemotherapy
sharan2014
This 70-year-old patient with a lytic, painful lumbar breast cancer metastasis with pre-existing fracture is at high risk for post treatment compression fracture

30. Conclusion
Advances in spine oncology have improved treatment and survival for patients with osseous spinal metastatic disease
To add value to the multidisciplinary treatment team, we should be familiar with and report data relevant to the NOMS framework, Epidural spinal cord compression grading scale (ESCC), and Spinal instability neoplastic score (SINS), as these are widely utilized by spinal surgeons and oncologists for patient management and decision-making
Radiologists have new opportunities to provide direct, minimally-invasive treatment for these patients, requiring maintenance of interventional skills and knowledge of the most current tools and techniques

31. References
1. American Cancer Society, Cancer Facts and Figures 2016, Available at: Accessed January 1, 2016.
2. Thibault I, Chang EL, Sheehan J, et al. Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group. Lancet Oncol. 2015;16(16):e
3. Laufer I, Rubin DG, Lis E, et al. The NOMS framework: approach to the treatment of spinal metastatic tumors. Oncologist. 2013;18(6):
4. Bilsky MH, Laufer I, Fourney DR, et al. Reliability analysis of the epidural spinal cord compression scale. J Neurosurg Spine. 2010;13(3):324-8.
5. Patchell RA, Tibbs PA, Regine WF, et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005;366(9486):643-8.
6. Fisher CG, Versteeg AL, Schouten R, et al. Reliability of the spinal instability neoplastic scale among radiologists: an assessment of instability secondary to spinal metastases. AJR Am J Roentgenol. 2014;203(4):
7. Amankulor NM, Xu R, Iorgulescu JB, et al. The incidence and patterns of hardware failure after separation surgery in patients with spinal metastatic tumors. Spine J. 2014;14(9):
8. Sharan AD, Szulc A, Krystal J, Yassari R, Laufer I, Bilsky MH. The integration of radiosurgery for the treatment of patients with metastatic spine diseases. J Am Acad Orthop Surg. 2014;22(7):
9. Jawad MS, Fahim DK, Gerszten PC, et al. Vertebral compression fractures after stereotactic body radiation therapy: a large, multi-institutional, multinational evaluation. J Neurosurg Spine. 2016;:1-9.