VOLUME 35 • NUMBER 21 • JULY 20, 2017

JOURNAL OF CLINICAL ONCOLOGY R E V I E W A R T I C L E

Integrating Evidence-Based Medicine for Treatment of Spinal

Metastases Into a Decision Framework: Neurologic,
Oncologic, Mechanicals Stability, and Systemic Disease
Ori Barzilai, Ilya Laufer, Yoshiya Yamada, Daniel S. Higginson, Adam M. Schmitt, Eric Lis, and Mark H. Bilsky

Author affiliations and support information

(if applicable) appear at the end of this
article.
Published at jco.org on June 22, 2017.
Corresponding author: Mark H. Bilsky,
MD, Department of Neurosurgery,
Memorial Sloan Kettering Cancer Center,
1275 York Ave, New York, NY 10065;
e-mail: bilskym@mskcc.org.
© 2017 by American Society of Clinical
Oncology
0732-183X/17/3521w-2419w/$20.00
A B S T R A C T
Patients with cancer are frequently affected by spinal metastases. Treatment is palliative, with the
principle goals of pain relief, preservation of neurologic function, and improvement in quality of life. In
the past decade, we have witnessed a dramatic change in the treatment paradigms due to the
development of improved surgical strategies and systemic and radiation therapy. The most im-
portant change to these paradigms has been the integration of spinal stereotactic radiosurgery
(SSRS), allowing delivery of tumoricidal radiation doses with sparing of nearby organs at risk. High-
dose SSRS provides durable tumor control when used either as definitive therapy or as a post-
operative adjuvant therapy. Integration of SSRS has fundamentally changed the indications for and
type of surgery performed for metastatic spine tumors. Although the role for surgical intervention is
well established, a clear trend toward less-aggressive, often minimally invasive techniques has been
observed. Targeted therapies are also rapidly changing the way cancer is being treated and have
demonstrated improved survival for a number of malignancies. As these treatment decisions
become more complex, a multidisciplinary approach including medical oncologists, radiation on-
cologists, surgeons, interventionalists, and pain specialists is required. In this article, the current
evidence affecting the treatment of spinal metastases is integrated into a decision framework that
considers four principal assessments of a patient’s spine disease: NOMS (neurologic, oncologic,
mechanical instability, and systemic disease).

J Clin Oncol 35:2419-2427. © 2017 by American Society of Clinical Oncology

ambulation, maintenance of spinal stability, du-

INTRODUCTION
Approximately 40% of all people with cancer
develop spinal metastases.1,2 Almost 20% of pa-
tients diagnosed with spinal metastases progress
to symptomatic spinal cord compression. 3-5
These metastases most commonly affect the
thoracic spine (70%), followed by the lumbar
(20%) and cervical spine (10%).6 The com-
bination of an aging population at risk for
developing cancer and the widespread availability
of improved diagnostic imaging, such as magnetic
resonance and 18F-labeled fluorodeoxyglucose pos-
itron emission tomography, have increased the scope
of this problem. Furthermore, targeted therapies are
extending survival for many patients with can-
cer, requiring the treatment goals for metastatic
spine tumors to shift from short-term palliation
to long-term durable control.
Specific treatment goals for patients with
DOI: https://doi.org/10.1200/JCO.2017. spine metastases are palliative, including preser-
72.7362 vation or restoration of neurologic function and
rable local tumor control, and improved quality of
life. Treatment options have evolved from simple
decisions regarding the need for either conven-
tional external beam radiation therapy (cEBRT)
or surgery to complex multimodality assessments
commensurate with the development of numerous
effective treatments, most importantly, spine ste-
reotactic radiosurgery (SSRS) and minimally in-
vasive spine procedures. A decision framework,
NOMS (neurologic, oncologic, mechanical instabil-
ity, and systemic disease), has been developed to
facilitate decision making in the evolving and
increasingly important treatment of metastatic
spine tumors.
THE NOMS FRAMEWORK
The NOMS decision framework7 provides a com-
prehensive assessment of four sentinel decision
points: neurologic, oncologic, mechanicals sta-
bility, and systemic disease. This framework

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 Barzilai et al
standardizes the assessment of metastatic spine tumors and allows
for the incorporation of evidence-based medicine and the rational
use of new radiation, surgical, interventional radiology, and systemic
therapies (Fig 1). The neurologic assessment evaluates both clinical
and radiologic parameters, including the presence of myelopathy,
functional radiculopathy, and the degree of epidural spinal cord
compression (ESCC). A validated magnetic resonance–based ESCC
scoring system is used to define the extent of epidural spinal cord
compression, and patients are dichotomized into high-grade and
low-grade ESCC groups (Fig 2). The oncologic consideration is
based on the expected tumoral response, principally to radiation but
also to systemic therapy. The neurologic and oncologic assessments
are combined to determine the optimal radiation strategy to achieve
tumor control and/or the need for a surgical intervention. Me-
chanical instability is a separate consideration, because symptomatic
pathologic fractures do not respond to radiation alone. Patients
diagnosed with mechanical instability typically require stabilization
with bone cement or spinal instrumentation. The fourth consid-
eration is the extent of systemic disease and medical comorbidities
that affect the risk-benefit ratio of a proposed intervention, taking
into account the overall expected survival and the ability of a patient
to tolerate spine-specific treatment.
NEUROLOGIC AND ONCOLOGIC ASSESSMENTS
The Role of cEBRT
Historically, spinal metastases were treated using cEBRT,
commonly delivered to a total dose of 30 Gy in 10 fractions. A
review of the published literature demonstrates radiosensitivity
stratifications on the basis of tumor histology.9-11 Hematologic
malignancies and selective solid tumors, such as seminoma, breast,
prostate, and ovarian carcinomas, are considered to be favorable
Low-grade ESCC
Neurologic
no myelopathy
High-grade ESCC
± myelopathy
Oncologic
Radiosensitive
Radioresistant/
previously radiated
Separation surgery
Mechanical
Stable
Unstable
Able to tolerate
Systemic
surgery
Unable to tolerate
surgery
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responders (ie, radiosensitive).12,13 The remainder of the solid
tumors are considered to be unfavorable responders (ie, radio-
resistant), including sarcoma, melanoma, renal cell, thyroid, he-
patocellular, colorectal, and non–small-cell lung carcinoma.9-13
Several studies confirm that patients with favorable histologies
are more likely to have good postradiation ambulation and remain
ambulatory longer than patients with unfavorable histologies.13,14
Katagiri et al15 found that 72% of patients with favorable histol-
ogies exhibited improvement in their motor strength, functional
ability, and pain scores, with only a 33% success rate in unfavorable
tumors. Maranzano et al11 showed recovery of ambulation in 67%
of patients with breast cancer compared with only 20% in hepa-
tocellular carcinoma. The duration of response was 10 to 16 months
for radiosensitive tumors compared with 3 months for radioresistant
tumors. It is currently accepted that regardless of the degree of ESCC,
patients with radiosensitive tumors and no evidence of myelopathy
can be treated effectively with cEBRT, obviating the need for surgical
intervention.9,11
The Role of SSRS
The biggest advancement in the treatment of spinal metastases
has been the evolution and integration of SSRS. The introduction
of high–dose per fraction conformal radiation for use in the treatment
of patients with spinal metastases has facilitated the delivery of cy-
totoxic tumoral doses and completely changed treatment paradigms.16
High-dose single (16 to 24 Gy) or hypofractionated (24 to 30 Gy in
two or three fractions) SSRS offers a significantly higher biologic
effective dose and more precise dose delivery to the tumor with
shorter treatment schedules compared with the cEBRT. The improved
tumor control with SSRS is proposed to be a result of an increased
percentage of lethal double-stranded DNA breaks, endothelial dys-
function mediated through the acid sphingomyelinase pathway, and
immunogenic CD8+ T cell–mediated responses.17,18 The safe and
Radiation
cEBRT
SRS
Fig 1. The neurologic, oncologic, mechani-
cals stability and systemic disease framework.
cEBRT, conventional external beam radiation
therapy; ESCC, epidural spinal cord compres-
sion; SRS, stereotactic radiosurgery. Adapted
with permission from Laufer et al.7
Stabilization
JOURNAL OF CLINICAL ONCOLOGY
 Current Decision Making for Spinal Metastases: NOMS
1c
1b
1a
0
Schematic representation of the 6-point ESCC grading scale.
Grade 0 Bone-only disease
Grade 1a Epidural impingement, without deformation of thecal sac
Grade 1b Deformation of thecal sac, without spinal cord abutment
Grade 1c Deformation of thecal sac, with spinal cord abutment, without cord compression
Grade 2 Spinal cord compression, with CSF visible around the cord
Grade 3 Spinal cord compression, no CSF visible around the cord
effective implementation of SSRS is the result of technological
advancements in patient immobilization, image guidance, inverse
treatment planning, and sophisticated delivery systems.19,20
Redefining Radiosensitivity
Multiple authors have reported excellent outcomes with spine
radiosurgery for traditionally radioresistant histologies in patients
with minimal or no spinal cord compression (ESCC 0 to 1c). In
a prospective trial by Garg et al,21 61 patients who had 63 tumors of
the noncervical spine were enrolled and received SSRS as a first-line
treatment in doses that ranged from 16 to 24 Gy single fraction.
The actuarial 18-month imaging local control rate for all patients
was 88%, and no significant differences in outcomes were noted
with respect to tumor histology.21 Guckenberger et al22 reported
the results of a multi-institutional analysis of 387 patients treated
with SBRT with 2-year local control of 84%. The cohort was
composed of patients with various solid tumor histologies, and the
median treatment dose was 24 Gy in three fractions.22 In a recent,
large, single-institution experience, Yamada et al23 described a total
of 811 lesions treated in 657 patients with single-fraction SSRS. The
prescription dose ranged from 18 to 26 Gy, and, for analysis, dosing
was considered as a continuous variable. The median dose that
covered 95% of the planning target volume was 16.44 Gy in the
low-dose group and 22.40 Gy in the high-dose group. Local failure
rates for the low- and high-dose groups were 5% versus 0.41% at
12 months, 15% versus 1.6% at 24 months, and 20% versus 2.1% at
48 months, respectively. Of note, 82% of the tumors were radi-
oresistant histologies, and responses were determined to be both
histology and volume independent.23 SSRS yields a clinical benefit
regardless of histology, providing a more durable symptomatic
response and higher local control rates than historical controls
using cEBRT23-26
A prospective randomized phase III trial is currently underway
comparing cEBRT to SSRS.27 Although SSRS is still considered by
some to be an experimental treatment,28 the ability to deliver ab-
lative doses to tumor sites has fundamentally changed treat-
ment paradigms,29particularly for solitary and oligometastatic
disease30 (Fig 3). In the last several years, we have witnessed
a transition from treatment with aggressive cytoreductive surgeries, such
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3
2
Fig 2. The Epidural Spinal Cord Com-
pression (ESCC) scale. Adapted with per-
mission from Bilsky et al.8
as en bloc spondylectomy, to definitive oncologic treatment
with radiosurgery. 29
Complications and Limitations
The successful application of SSRS has led to a large growth
in its use and raised awareness of its potential complications.
Currently, major efforts are being directed at defining and pre-
venting SSRS toxicity. Reported structures at risk for radiation-
associated toxicity include the spinal cord, cauda equina, skin,
esophagus, peripheral nerves, paraspinal muscles, and vertebrae.
Fortunately, high-grade toxicity after SSRS occurs infrequently,
and most of the observed complications are mild,31 including
esophagitis, mucositis, dysphagia, diarrhea, paresthesias, tran-
sient laryngitis, and radiculitis.32-37 Dose constraints have been
established for the majority of organs at risk.38,39 Vertebral
compression fractures (VCFs) have recently been described after
SSRS, with a wide range in incidence reported, from 6% to 39%40.
A multi-institutional analysis found that a VCF after SSRS is more
likely to occur after treatment with high-prescription doses for
a solitary spinal metastasis.41 Importantly, the majority of ra-
diographically observed VCFs remain asymptomatic and do not
require stabilization.40
Radiation-induced spinal cord injury from SSRS is rare. One
multicenter publication found only six out of 1,075 cases of
spinal radiosurgery developed radiation-induced myelopathy.42
Although institutional variability in accepted spinal cord dose
exists, one of the commonly used constraints is a cord maximum
dose of 14 Gy.32 An analysis of 476 cervical and thoracic levels
treated with single-fraction SSRS using this spinal cord constraint
resulted in only two patients (0.42%) developing self-limited,
steroid-responsive myelopathy.23 However, it is this spinal cord
constraint that prohibits the use of SSRS in the setting of high-
grade ESCC. In part, the rationale for this is predicated on a study
by Lovelock et al,42a which demonstrated that all local failures
occurred in tumors that received , 15 Gy to any portion of the
planning target volume. Given a 10%/mm falloff of the radiation
dose and a cord maximum dose of 14 Gy, the tumor would either
be underdosed at the margin of the spinal cord, risking epidural
progression, or overdosed, causing myelitis. Delivery of SSRS
© 2017 by American Society of Clinical Oncology 2421
 Barzilai et al

Fig 3. Low-grade metastatic epidural

spinal cord compression can be effectively
treated nonoperatively with spinal ste-
reotactic radiosurgery (SSRS). A 62-year-
old woman with stage IV metastatic colon
cancer. Routine imaging work-up revealed
an L2 lesion. The patient was neurologi-
cally intact, with mild biologic back pain.
A1 A2 Spinal Instability Neoplastic Score 4 (sta-
ble). Computed tomography myelography
and magnetic resonance imaging dem-
onstrated epidural disease, Epidural Spinal
Cord Compression grade 1b. She un-
derwent up-front SSRS, treated with 24 Gy
in a single fraction (maximum dose to the
cauda, 17.60 Gy). At 3-month follow-up
there was improvement of pain and well-
controlled disease with near-complete
resolution of the epidural tumor compo-
nent. Pre- and post-SSRS imaging: (A1)
Computed tomography myelogram (mid-
sagittal) demonstrating a sclerotic L2 le-
sion; and (A2) axial cut demonstrating
the epidural component. (B1) At 2-month
follow-up, magnetic resonance T2 (mid-
sagittal); (B2) T1 with contrast enhancement
demonstrating near-complete resolution of
the epidural component. SSRS treatment
B1 B2 planning: color wash representation of
the treatment dose in (C1) axial and (C2)
sagittal views. A dose of 24 Gy (repre-
sented in orange) was prescribed to the
tumor and delivered in a single fraction.
The maximum dose delivered to the
cauda equina was 17.6 GY (outlined in
pink).

C1 C2

within the spinal cord constraints while delivering the minimal
radiation dose to the tumor volume requires a separation be-
tween the tumor and the spinal cord.43 Therefore, patients with
spinal cord compression (ESCC 2 to 3) secondary to radio-
resistant tumors require surgical decompression of the spinal
cord before SSRS. Currently, the safety of SSRS in the setting of
spinal cord compression is being studied; however, an early
report indicates that a significant risk of neurologic de-
terioration exists in this clinical scenario, especially in radio-
resistant tumors. 44
The Evolving Role of Surgery
The rationale for surgery in patients with metastatic spine
tumors is largely predicated on the study by Patchell et al,45
which provides class 1 evidence in support of direct surgical
decompression for patients with solid tumor metastases resulting
in high-grade ESCC and/or myelopathy.45 In this landmark trial,
patients randomly assigned to direct surgical decompression fol-
lowed by cEBRT had longer overall survival, improved mainte-
nance or recovery of ambulation, better preservation of bowel and
bladder function, and decreased narcotic requirements compared

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Copyright © 2021 American Society of Clinical Oncology. All rights reserved.
 Current Decision Making for Spinal Metastases: NOMS
with cEBRT alone. On the basis of this and a number of other
series, the Spine Oncology Study Group, in a systematic literature
review, made a strong recommendation for surgical stabilization
followed by decompression in patients with radioresistant tumors
in the setting of high-grade compression.29
The integration of SSRS as postoperative adjuvant therapy has
fundamentally changed the goals of surgery and significantly de-
creased the associated morbidity compared with techniques tra-
ditionally used with cEBRT. Patients with high-grade ESCC from
radioresistant tumors require spinal cord decompression for
neurologic salvage and instrumented fusions for spinal stabiliza-
tion; however, the paradigm shift in surgery is reflected in the
extent of tumor resection (Fig 4). Using cEBRT, surgeons pre-
viously relied on invasive procedures to achieve maximal cytor-
eduction. Despite this aggressive surgery, local recurrence rates
were on the order of 60% at 6 months and 96% at 4 years.46 With
the use of SSRS, the surgical goal became simply to create a target
for the safe delivery of SSRS. The term separation surgery was
coined to describe a posterolateral epidural decompression with
posterior instrumented fusion that focused on reconstitution of
spinal fluid space to create a 2-mm margin between the tumor and
spinal cord, but without resection of the vertebral body or para-
spinal tumor. Laufer et al47 evaluated the efficacy of separation
A B1
C D
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surgery followed by SSRS in a retrospective review of 186 patients
and found the strategy to be both safe and effective for establishing
durable local tumor control regardless of tumor histology–specific
radiosensitivity. In this series, the three SSRS dose strategies used
were single fraction (24 Gy), high-dose hypofractionated (24 to
30 Gy in three fractions), or low-dose hypofractionated (18 to
36 Gy in five to six fractions). Overall, the 1-year local rate of
progression was 16.4%. The only significant factor affecting local
tumor progression was the SSRS dose when comparing high-dose
hypofractionated versus low-dose hypofractionated, 4% versus
22%, respectively.47 The 24-Gy single-fraction cohort had a 9% risk
of progression. There was no impact of tumor histology, prior
failed radiation, or the degree of preoperative epidural compres-
sion on recurrence rates, and no patient suffered a neurologic
complication. Rock et al48 also reported a 92% local-control rate in
18 patients treated with radiosurgery after open surgical pro-
cedures, and similar results have been demonstrated in other
smaller series.49 Al-Omair et al50 noted that patients with post-
operative scans that showed continued compression of the spinal
cord (ie, ESCC 2 to 3) had a significantly higher risk of local
recurrence after postoperative SSRS compared with patients with
sufficient separation between the tumor and the spinal cord (ie,
ESCC 0 to 1c). Furthermore, patients with circumferential spinal
Fig 4. Separation surgery with spinal
stereotactic radiosurgery (SSRS) has replaced
more extensive surgeries, such as complete
vertebrectomies in selected patients. A 76-
year-old man with renal cell carcinoma pre-
sented with severe back pain and no signs of
myelopathy. Evaluation including spinal imag-
ing demonstrated a T4 tumor with high-grade
(ie, Epidural Spinal Cord Compression grade 3)
cord compression. Preoperative tumor
embolization was followed by separation
surgery (ie, posterolateral decompression
with pedicle screw fixation). Note the left rib
and vertebral body tumor were not resec-
ted. Postoperatively, the patient remained
neurologically intact and subsequently un-
derwent hypofractionated stereotactic ra-
B2 diosurgery (27 Gy in three fractions) with
well-controlled disease at long-term follow-
up. Pre- and postoperative sagittal imag-
ing: (A) Preoperative magnetic resonance
imaging T2 demonstrating a T4 tumor. (B1)
Postoperative computed tomography
myelography demonstrating the surgical
and reconstituted thecal sac. (B2) upright
x-ray representing the stabilizing construct.
Pre- and postoperative axial imaging: (C)
Preoperative magnetic resonance imaging
T1 with contrast enhancement. (D) Post-
operative computed tomography myelog-
raphy. Note the high-grade cord compression
preoperatively and the CSF-filled thecal sac
and stabilizing construct postoperatively.
This new distance between the tumor and
the spinal cord allows for safe concurrent
radiosurgical treatment.
© 2017 by American Society of Clinical Oncology 2423

cord compression represent challenging postoperative SSRS tar-
gets51 and may benefit from intraoperative brachytherapy using
32 52
P. Intraoperative brachytherapy facilitates improved post-
operative SSRS dosimetry in patients with circumferential tumors
of the spine.53
MECHANICAL INSTABILITY
Mechanical instability serves as an independent surgical indication
regardless of the neurologic or oncologic assessment. Spinal in-
stability, as defined by the Spine Oncology Study Group, is the “loss
of spinal integrity as a result of a neoplastic process that is asso-
ciated with movement-related pain, symptomatic or progressive de-
formity, and/or neural compromise under physiologic loads.”54(pE1226)
The Spinal Instability Neoplastic Score (SINS) was developed to
facilitate the assessment and communication of mechanical sta-
bility.54 SINS incorporates both clinical and radiologic factors
important for maintenance of spinal integrity and includes tumors
location, pain, alignment, lesion character (ie, osteolysis), vertebral
body collapse, and posterior element involvement (Table 1). Be-
cause pain is one of the primary determinants of spinal instability,
differentiating biologic from mechanical pain is crucial for treating
oncologists. Biologic pain increases in severity at night, abates with
glucocorticoid administration, and is not exacerbated by move-
ment. Mechanical pain is generally relieved with rest, exacerbated
by movement, and does not respond to glucocorticoid administration.
Oncolytic therapy reduces biologic pain, whereas mechanical pain is
Table 1. The Spinal Instability Neoplastic Score54
Spinal Instability Neoplastic Score Component Score
Location
Junctional (occiput-C2, C7-T2, T11-L1, L5-S1)
Mobile spine (C3-C6, L2-L4)
Semirigid (T3-T10)
Rigid (S2-S5)
Pain
Yes
Occasional pain but not mechanical
Pain-free lesion
Bone lesion
Lytic
Mixed (lytic/blastic)
Blastic
Radiographic spinal alignment
Subluxation/translation present
De novo deformity (kyphosis/scoliosis)
Normal alignment
Vertebral body collapse
. 50% collapse
, 50% collapse
No collapse with . 50% body involved
None of the above
Posterolateral involvement of spinal elements
Bilateral
Unilateral
None of the above
Total score
Stable 0-6
Indeterminate 7-12
Unstable 13-18
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Barzilai et al
treated with stabilization procedures, such as percutaneous cement
augmentation, pedicle screw fixation, or open surgery (Fig 5). The
Cancer Patient Fracture Evaluation (CAFE) trial provided prospective
randomized data showing significant pain reduction and improve-
ment in disability indexes that persist for up to 6 months when
kyphoplasty was performed compared with the noninterventional
control arm.55
Spinal instability is an independent indication for an inter-
ventional procedure regardless of the radiosensitivity of the tumor or
degree of spinal cord compression. The suspicion of instability
should facilitate referral for early surgical evaluation and the ra-
tionale for routine multidisciplinary evaluation of spine metastases.
SYSTEMIC DISEASE AND MEDICAL COMORBIDITIES
Once the decision has been made regarding treatment on the basis
of assessments of neurologic, oncologic, and mechanical stability,
the remaining question is whether the patient can tolerate the
proposed procedure and whether it makes sense in the clinical
context. Extent of disease, medical comorbidities, and expected
survival all play a critical role in this assessment. Patients most
often undergo magnetic resonance imaging of the entire spinal axis
and histology-specific staging. Medical work-up should be directed
toward known patient comorbidities but often includes pulmonary
function tests, Doppler ultrasounds, and echocardiogram.
Several scoring systems, such as the Tokuhashi revised score,56 the
Tomita score,57 and the Bauer modified score,58,59 have been developed
to estimate expected survival in patients with spinal metastases. The
accuracy of these scores has been questioned, and along with the
current change in survival, the reliability of these methods remains
uncertain.60,61 Currently, the ability of molecular markers to provide
prognostic information is changing cancer treatment schemes. Because
treatment in this population serves a palliative purpose, physicians
3
2 should focus on whether the patients are likely to adequately recover
1 from the indicated procedure and become candidates for systemic
0 therapy. The minimally invasive nature of procedures such as per-
3
cutaneous cement augmentation or pedicle screw fixation can dra-
1 matically improve quality of life even in patients with limited survival.
0 The prevention, diagnosis, treatment, and general manage-
ment of cancer have recently been influenced by major scientific
2
1
advances. Modern technologies allow for the assessment of ge-
0 nomic and proteomic alterations and epigenetic and posttranslational
modifications at the molecular level.62 The understanding of how
4 these influence tumors of the spine is ongoing, and interest is
2
0 growing, predominantly for metastatic melanoma.63,64
Generally, systemic therapy is considered to be more effec-
3 tive for visceral than for osseous disease, yet it may still play a
2
significant role in the treatment of spine metastases, particularly
1
0 when combined with stereotactic radiosurgery (SRS). One strategy
that has demonstrated promising results is the combination of SRS
3 with checkpoint inhibitors inducing the abscopal effect and po-
1
0
tentiating the effects of local radiation. This immune-mediated
effect of SRS with checkpoint inhibitors has been demonstrated in
murine models65 and is believed to be associated with both
hypofractionated and high-dose single-fraction radiation therapy66
but suppressed with conventionally fractionated radiotherapy.67
Postow et al68 reported the abscopal effect in a patient with
JOURNAL OF CLINICAL ONCOLOGY
 Current Decision Making for Spinal Metastases: NOMS
A B
C D
melanoma receiving ipilimumab who received high-dose hypo-
fractionated radiation to a paraspinal lesion with subsequent res-
olution of multiple lung lesions and a 30-fold increase in the titer of
antibodies to a melanoma epitope. Harnessing the abscopal effect
may lead to treatment strategies in which local radiation can sig-
nificantly affect systemic disease control. In addition, vascular
endothelial growth factor has been shown to inhibit the acid
sphingomyelinase pathway that leads to endothelial dysfunction.
Experimental murine models have demonstrated that axitinib, an oral
tyrosine kinase inhibitor–vascular endothelial growth factor inhibitor,
in combination with SRS, can derepress this pathway, potentially
acting as a radiosensitizer.69 From a spine tumor perspective, the
understanding of the effect of these therapies is premature, and as data
accumulate it is likely to continue evolving treatment strategies.
In conclusion, optimal management of spinal metastases
requires a multidisciplinary team effort. The NOMS framework
provides an algorithm for consistent and up-to-date management
that is highly reproducible. The integration of radiosurgery has
completely evolved the way this patient population is being treated,
and overcoming radioresistance has provided a giant leap in the
ability to control these tumors. Surgery still plays a key role in this
paradigm, particularly for those with high-grade ESCC, necessi-
tating separation of the epidural tumor from the spinal cord, but
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Fig 5. Mechanical instability should be
addressed with stabilization. A 66-year-old
woman with newly diagnosed multiple
osseous lesions and lung lesion. She
presented with severe mechanical back
pain with a visual analog score of 9. She
underwent imaging including a chest-
abdomen-pelvis computed tomography
scan, bone scan, and full spinal axis
magnetic resonance imaging (MRI). Im-
aging demonstrated a left lung nodule,
lytic disease at T10, and sclerotic bone
disease at T6. The T10 lesion had a Spinal
Instability Neoplastic Score of 14 but
without spinal cord compression. Given
the presence of mechanical instability, the
patient underwent T9-T11 percutaneous
pedicle screw stabilization with cement-
augmented screws and kyphoplasty at
T10. Needle biopsy obtained during the
kyphoplasty revealed non–small-cell lung
carcinoma. The patient received 24 single-
fraction spinal stereotactic radiosurgery.
She is currently 6 months post spinal
stereotactic radiosurgery with well-
controlled disease, visual analog score
of 1, and neurologically intact. Pre- and
postoperative imaging: (A) Preoperative
sagittal MRI (T1 without contrast en-
hancement) demonstrating the T6 and T10
lesions. (B) Axial T2 MRI at T10 level
demonstrating epidural spinal cord com-
pression. (C) Postoperative sagittal x-ray
with the stabilizing construct and kypho-
plasty. (D) Postoperative anterior-posterior
x-ray with the stabilizing construct and
kyphoplasty.
also for spinal stabilization as facilitated by SINS. The role for
less-invasive surgical options such as separation surgery and
percutaneous stabilization followed by SSRS is growing. These
techniques are largely replacing highly morbid surgical approaches,
such as en bloc spondylectomy or transcavitary vertebrectomy.
Targeted therapies are, at present, redefining cancer treatment, yet
their precise role for spinal tumors is yet to be fully determined.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS
OF INTEREST
Disclosures provided by the authors are available with this article at
jco.org.
AUTHOR CONTRIBUTIONS
Conception and design: Ori Barzilai, Mark H. Bilsky
Collection and assembly of data: Ori Barzilai, Mark H. Bilsky
Data analysis and interpretation: All authors
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
© 2017 by American Society of Clinical Oncology 2425

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JOURNAL OF CLINICAL ONCOLOGY
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Affiliations
Ori Barzilai, Ilya Laufer, Yoshiya Yamada, Daniel S. Higginson, Adam M. Schmitt, Eric Lis, and Mark H. Bilsky, Memorial Sloan
Kettering Cancer Center; Ilya Laufer and Mark H. Bilsky, Weill Cornell Medical College, New York, NY.

nnn

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 Barzilai et al

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Integrating Evidence-Based Medicine for Treatment of Spinal Metastases Into a Decision Framework: Neurologic, Oncologic, Mechanicals Stability,
and Systemic Disease
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are
self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more
information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc.
Ori Barzilai Adam M. Schmitt
No relationship to disclose No relationship to disclose
Ilya Laufer Eric Lis
Consulting or Advisory Role: DePuy Synthes Companies, Globus Consulting or Advisory Role: Medtronic
Medical, Spine Wave, Brainlab, Medtronic Speakers’ Bureau: Medtronic
Yoshiya Yamada Mark H. Bilsky
Consulting or Advisory Role: Varian Medical Systems, Chordoma Honoraria: Globus Medical
Foundation Consulting or Advisory Role: Varian Medical Systems
Speakers’ Bureau: Institute for Medical Education Patents, Royalties, Other Intellectual Property: DePuy Synthes Spine,
Travel, Accommodations, Expenses: National Cancer Center Malaysia Globus Medical
Travel, Accommodations, Expenses: Globus Medical
Daniel S. Higginson
No relationship to disclose

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