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Management of Metastatic Spinal Cord Compression

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 Review Article
Management of Metastatic Spinal
Cord Compression
Quaovi Sodji, MD, PhD, Joseph Kaminski, MD, Christopher Willey, MD, PhD, Nathan Kim, MD, PhD,
Waleed Mourad, MD, PhD, John Vender, MD, and Byron Dasher, MD
Abstract: Cancer metastasis is a key event in tumor progression asso-
ciated not only with mortality but also significant morbidity. Metastatic
disease can promote end-organ dysfunction and even failure through
mass effect compression of various vital organs including the spinal
cord. In such cases, prompt medical attention is needed to restore neu-
rological function, relieve pain, and prevent permanent damage. The
three therapeutic approaches to managing metastatic spinal cord com-
pression include corticosteroids, surgery, and radiation therapy. Although
each may improve patients’ symptoms, their combination has yielded the
best outcome. In cancer patients with clinical suspicion of spinal cord
compression, dexamethasone should be initiated followed by surgical
decompression, when possible, and radiation. The latter becomes the
preferred treatment in patients with inoperable disease.
Key Words: cancer metastasis, radiation therapy, spinal cord
compression, stereotactic body radiotherapy
P rimary tumors of the spine represent only 5% of all malig-
nancies affecting the spine, thus establishing metastatic lesions
to the spine as the main cause of malignancy-induced spinal cord
compression (SCC).1 A study encompassing 121,435 patients
who succumbed to various malignancies revealed that nearly
3500 experienced at least a single occurrence of metastatic
SCC (MSCC) within the last 5 years.2 Among these patients,
incidence of MSCC resulting from metastatic lesions of prostate,
breast, and lung cancer were 7.24%, 5.52%, and 5.92%, respec-
tively. Only myeloma had a higher incidence rate (Table 1).2
In patients with MSCC, the histology and location of the
primary tumor influence the time between the diagnosis and
occurrence of SCC. Helweg-Larsen et al reported that nearly 48%
From the Departments of Internal Medicine, Radiation Oncology, and Neurosur-
gery, Augusta University, Augusta, Georgia, the Dattoli Cancer Center, Sarasota,
Florida, the Department of Radiation Oncology, University of Alabama at
Birmingham, Birmingham, and the Department of Radiation Oncology,
Texas Oncology, Waco.
Correspondence to Dr Quaovi H. Sodji, Medical College of Georgia at Augusta
University, 1120 15th St, Augusta, GA 30912. E-mail: qsodji@augusta.edu.
To purchase a single copy of this article, visit sma.org/smj-home. To purchase
larger reprint quantities, please contact Reprintsolutions@wolterskluwer.com.
C.W. has received compensation from Varian Medical Systems and North,
Pursell, & Ramos, LLC. The remaining authors did not report any financial
relationships or conflicts of interest.
Accepted March 22, 2017.
Copyright © 2017 by The Southern Medical Association
0038-4348/0–2000/110-586
DOI: 10.14423/SMJ.0000000000000700
586
Copyright © 2017 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.
of patients with lung cancer had ≤6 months between the
diagnosis of their primary tumor and MSCC, whereas in patients
with breast cancer, 57% had their MSCC diagnosed >49 months
after the primary diagnosis.3 MSCC has the highest incidence
among adults aged between 40 and 50 years (4.39%) and declines
steadily during each decade thereafter to 0.54% in individuals
80 years or older.4
Risk Factors and Incidence of MSCC
in Cancer
A retrospective cohort study that analyzed MSCC in 258 patients
with cancer identified several risk factors for MSCC, including
radiographic evidence of vertebral fracture, bony metastasis
diagnosed >1 year earlier, increased deep tendon reflexes,
incapacity to ambulate, and age younger than 60 years. A cor-
relation was established between the number of risk factors present
and the occurrence of MSCC (Table 2). SCC was observed in
only 4% of patients with no risk factor, whereas individuals
with 5 risk factors had an occurrence rate of 87%.5
Not all metastatic lesions are associated with identical risks
of MSCC. Prostate cancer, kidney cancer, and myeloma carry
an estimated lifetime risk of 6.2%, whereas in ovarian cancer,
stomach cancer, and leukemia, the risk drops to 0.4% (Table 3).6
Pathophysiology
Although hematogenous dissemination represents the major route
to achieving such metastases, seeding through the cerebrospinal
Key Points
• When metastatic spinal cord compression is suspected and neuro-
logical symptoms are present, corticosteroids should be started
immediately.
• Magnetic resonance imaging is the gold standard in the diagnosis
of metastatic spinal cord compression.
• To determine the optimal treatment for a patient (surgery alone vs
surgery plus radiation therapy), an algorithm using neurologic,
oncologic, mechanical, and systemic assessments has been devel-
oped and has incorporated the use of novel radiation therapy tech-
niques such as stereotactic body radiotherapy.
© 2017 The Southern Medical Association

Table 1. Cumulative incidence of MSCC in patients
with cancer 5 y before death in Ontario (1990–1995)2
Primary tumor Cumulative incidence, %
Breast 5.52
Prostate 7.24
Lung 5.92
Myeloma 7.91
Nasopharynx 6.50
MSCC, metastatic spinal cord compression.
fluid by intramedullary spinal cord tumors also has been
described.7–9 The expanding mass compresses the thecal sac
and the spinal cord and its surrounding vascular structures.
This is compounded further by the collapse of the vertebral
body secondary to lytic bone destruction.10 Selected tumors
such as lymphoma may induce spinal cord compression by
expanding through the vertebral foramen without lesions to
the vertebral body.11 The compression of the spinal cord and
the venous system result in inflammatory edema that is propa-
gated further by inflammatory cytokines.12,13 Although spinal
cord ischemia may arise gradually through the aforementioned
mechanism, it also can occur suddenly when blood supplies are
compromised as a result of obstruction of the spinal arteries.11,14
Localization and Clinical Presentation
The thoracic spine is the most affected level (60%–80%),
followed by the lumbosacral region (15%–30%) and the cervical
spine (<15%). Multiple levels of the spine can be affected, thus
further complicating a patient’s presentation.4
Pain, the earliest symptom of MSCC, may be of three types:
localized, radicular, and axial.15 It arises from bone damage,
vertebral body collapse, nerve root damage, or compression and
is ubiquitous in MSCC, affecting up to 95% of patients.16–18 A
significant portion of patients with MSCC (75%–85%) also
may present with weakness, which can limit ambulation or, in
extreme cases, lead to paralysis.3 Sensory loss and autonomic
dysfunctions also are observed. In a subset of MSCC involving
Table 2. Correlation between the number of risk
factors and occurrence of SCC in patients with cancer5
No. risk factors Occurrence, %
0 4
1 10
2 21
3 23
4 52
5 87
SCC, spinal cord compression.
Southern Medical Journal • Volume 110, Number 9, September 2017
Copyright © 2017 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.
Review Article
Table 3. Estimated average lifetime risks of malignant
SCC in various primary tumors6
Primary tumor Average lifetime risk, %
Prostate, breast, myeloma, kidney 6.2
Nasopharynx, melanoma, lung 2.5
(SCLC, NSCLC)
Cervix, lymphoma, uterus 1.6
Head/neck, bladder, colorectal 1.0
Ovary, stomach, leukemia, pancreas 0.4
SCLC, small-cell lung cancer; NSCLC, non–small-cell lung cancer; SCC, spinal
cord compression.
the lumbosacral region, compression of the cauda equina results
in decreased sensation over the buttocks and perineal area in a
saddle distribution and loss of bowel and bladder sphincter con-
trol.19,20 Patients often will note symptom exacerbation, with
maneuvers such as the valsalva maneuver increasing the intra-
thoracic pressure. Depending on the onset of symptoms,
changes in reflexia, both hyper- and hyporeflexia, are physical
signs that are suggestive of SCC.
Diagnosis
Timely diagnosis of MSCC is important not only to prevent per-
manent neurologic damages but also to identify the primary
tumor, because in 20% of patients with cancer, SCC represents
the initial presentation of the primary malignancy.21 Magnetic
resonance imaging (MRI) with and without contrast has become
the gold standard for MSCC diagnosis because of a sensitivity
and a specificity of 93% and 97%, respectively, and an accuracy
of diagnosis of 94%.22,23 MRI of the entire spine often is suggested
because metastatic lesions may be present at multiple levels.
Treatments for MSCC
MSCC requires immediate medical attention. Analgesia and
prevention of permanent neurological damage are the paramount
goals of the management of MSCC. Analgesics such as non-
steroidal anti-inflammatory drugs, acetaminophen, and opioids
can provide temporary pain relief, whereas the mainstay of MSCC
therapy for long-term analgesic and symptom management includes
corticosteroids, surgery, and radiation therapy (RT).4,24
Corticosteroids
Corticosteroids such as dexamethasone and methylprednis-
olone have been used to alleviate the inflammation that is associ-
ated with MSCC.12,25 Greenberg et al found that dexamethasone
significantly reduces pain in 64% of patients with MSCC on
the first day of administration.26 Although there is convincing
evidence for the beneficial effects of corticosteroids, the dosing
regimens remain controversial. Various studies used a high intra-
venous (IV) dexamethasone loading dose (96–100 mg) followed
by a few-days’ course of oral or IV dexamethasone; however,
587
Sodji et al • Management of Metastatic Spinal Cord Compression

neurological deficit or a high-grade tumor is present. In a pro-

Table 4. Components of the Spine Instability
spective study, Siegal et al reported that before surgery, 28%
Neoplastic Score28
of patients were ambulatory compared with 85% postsurgery.
Score Paraplegia also was reduced from 21% to 2%.29 As such, sur-
gery is recommended for patients who are medically operable.
Location This becomes the preferred therapeutic approach in patients
Junctional (occiput–C2, C7–T2, T11–L1, L5–S1) 3 with radioresistant tumors or with recurring radiosensitive
Mobile spine (C3–C6, L2–L4) 2 malignancies who have received high radiation doses to the spine.
Semirigid (T3–T10) 1 It also is recommended in individuals with SCC caused by bony
Rigid (S2–S5) 0
fragments and in cases requiring spine stabilization to preserve
Paina
the ability to walk.4,30 The selection of the surgical approach
Yes 3 (ventral vs dorsal) is motivated by the tumor location (eg, ante-
No (occasional but not mechanical) 1 rior vs posterior elements), histology, the agent responsible for
Pain-free lesion 0 SCC (bone or soft tissue), and the need for spinal reconstruc-
Bone lesion tion or stabilization.31 In general, the anterior approach is used
Lytic 2 for tumors compressing the spinal cord anteriorly, whereas
Mixed (lytic/blastic) 1 laminectomy is recommended in patients with posterior com-
Blastic 0
pression of the spinal cord but may lead to more neurological
Radiographic spinal alignment
complications.11,32 The approach also is dictated by the avail-
Subluxation/translocation present 4 ability of surgical specialties. For instance, an anterior thoracic
De novo deformity (kyphosis/scoliosis) 2 lesion can be approached ventrally but requires coordination
Normal alignment 0 with a cardiothoracic surgeon. Nevertheless, emergency surgical
Vertebral body collapse decompression significantly improves mobility and neurological
> 50% collapse 3 functions.33
< 50% collapse 2 Vertebroplasty and kyphoplasty are minimally invasive per-
No collapse with >50% body involved 1
cutaneous vertebral augmentation techniques with an increasing
None of the above 0
role in the management of vertebral body fracture associated
Involvement of posterolateral spinal elementsb with spinal metastases. These procedures seek to augment verte-
Bilateral 3 bral stability and provide analgesia through the application of
Unilateral 1 cement into the spinal column. Whereas vertebroplasty is per-
None of the above 0 formed under local anesthesia, kyphoplasty is performed under
a
Pain relief with recumbency and/or pain with movement of the spine. general anesthesia and also can restore vertebral body height.34
b
Facet, pedicle, or costovertebral joint fracture or replacement with tumor. There is evidence that these interventional procedures can be
effective in providing pain relief for compression fractures while
encouraging faster recovery and lower costs.35 Early results indi-
Vecht et al did not find any beneficial impact on pain and the
cate that these procedures can be combined with radiation, both
ability to walk using such dosing regimens.27 Patients receiving
intraoperatively and sequentially.36 In addition, these interven-
a loading dose of 10 mg IV dexamethasone had a similar
tional procedures can include a computed tomography–guided
outcome.
biopsy that may provide a diagnosis in patients with no cancer
history. It is anticipated that the use of kyphoplasty and
Surgery vertebroplasty will only increase in the coming years; however,
Surgical decompression can provide immediate improve- for optimal results, patient selection is critical.37 Absolute contra-
ment of symptoms and allow vertebral stabilization following indications include asymptomatic vertebral fracture, analgesic
bone collapse. To identify patients who require surgical stabiliza-
tion, the Spine Instability Neoplastic Score (SINS), which ranges
from 0 to 18, is used (Table 4). Parameters encompassing the
Table 5. Metastatic spinal lesion stability based on the
location and type of lesion (lytic vs blastic), pain, vertebral body
Spine Instability Neoplastic Score28
collapse, spinal alignment, and involvement of spinal posterior
elements are used to generate the SINS. Lesions scoring ≤6 Total score
are considered stable, whereas surgical stabilization is recom-
0–6 Stable
mended with SINS ≥13. Although scores between 7 and 12
7–12 Indeterminate (potentially unstable)a
are considered indeterminate, surgical evaluation is warranted
13–18 Unstablea
because instability may be imminent (Table 5).28 Neverthe-
a
less, surgery may still be indicated despite a low SINS if Surgical evaluation recommended.

588 © 2017 The Southern Medical Association

Copyright © 2017 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.

response to medical management, direct cord compression by
the tumor, systemic or local infection, allergy to the cement,
and untreatable coagulopathy.34 Although cement leakage has
been reported by Gangi et al following these percutaneous pro-
cedures, only 0.3% of patients were symptomatic and iatrogenic
cord compression was not observed.38 Nevertheless, percutaneous
vertebral augmentation should be used judiciously in patients
with ≥70% vertebral destruction, ≥5 metastases, and fracture
involving the posterior column.34
RT: Radiation Techniques and Adverse Effects
In the presence of multiple metastatic lesions for which
surgery is not recommended, RT becomes the modality of
choice to alleviate pain and neurological symptoms. Aside from
the palliative use of RT, it also can be used with a curative pur-
pose in patients with localized spinal involvement.
There is no consensus on the dose and fractionation needed
for effective treatment of MSCC. Using conventional RT, doses
and regimens reported to improve the ambulatory status include
30 (10 fractions), 37.5 (15 fractions), 40 (20 fractions), 28 (7
fractions), 16 (2 fractions), and 8 Gy (single dose).39,40 In a
study by Rades et al comparing short-course RT (≤5 fractions)
with long-course RT (≥10 fractions), a better local tumor control
was reported in patients with the long-course RT; however, both
groups had similar functional outcome and survival rates.41
Owing to the potentially deleterious effect of a hypofractionated
radiation dose on the spinal cord and other surrounding organs,
standard fractionation has been preferred in patients with a
favorable survival prognosis because short-course RT does not
provide any additional benefit. Radiation doses of 25 to 36 Gy
given in 10 to 15 fractions are used most often. With most
sarcomas, however, a radiation dose of 60 Gy is needed to
achieve tumor control but such a high dose increases the likeli-
hood of radiation-induced myelopathy (RIM).42–44 The need
for delivering high doses of radiation to the spinal cord and
adjacent vital organs while minimizing radiation has required
the use of other RT techniques. One such technique is intensity-
modulated RT (IMRT), which Milker-Zabel et al used in patients
with recurrent vertebral bones metastases and who previously
received conventional RT. Thirteen of the 16 patients (81%)
experienced pain relief and 42% experienced improvement in
their neurological symptoms following IMRT. Moreover, local
control was observed in all patients after 6 months, and in
84% of patients, further tumor growth was prevented.45 Aside
from IMRT, proton-beam therapy can deliver localized high
doses of radiation while minimally affecting healthy surrounding
tissues. While maintaining the average dose to the spinal cord at
40 Gy, Isacsson and colleagues were able to safely deliver 68 Gy
using protons compared with 57 Gy using photons to a patient
with Ewing sarcoma.46 Among the three aforementioned techniques,
proton-beam therapy may have the highest normal tissue-sparing
ability followed by IMRT.47
Stereotactic body radiotherapy (SBRT) represents an emerging
technique that can maximize the therapeutic window of RT by
Southern Medical Journal • Volume 110, Number 9, September 2017
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Review Article
selectively delivering a higher biological equivalent radiation
dose to malignant tissues while minimizing off-target toxicity.48
Although conventional RT use regimens such as 30 Gy in 10
fractions to achieve local tumor control, SBRT has allowed the
delivery of a higher radiation dose in ≤5 fractions.48 The ensuing
hypofractionation translates into a higher biological equivalent
dose per fraction, resulting in increased tumor cell death
and better local control.49 Tumor death can be potentiated
further by the disruption of its microvasculature.50 Under these
circumstances, SBRT becomes crucial for the treatment of
radioresistant tumors and is well suited to control of recurrent
lesions. Moreover, SBRT may provide faster pain relief than
conventional RT.51 Studies conducted at the MD Anderson
Cancer Center revealed that following SBRT reirradiation of
patients with cancer with spinal metastases, 76% had local control
of the tumor and almost all had no progression of their neurolog-
ical symptoms 1 year later.52
Brachytherapy consisting of the implantation of radioactive
seeds adjacent to the lesion also has been used; however, for
optimum results, as reported by Rogers and colleagues, surgical
resection is needed before the implantation of the radioactive
seeds. Durable local control was achieved in 72.9% of patients
at 3 years. Moreover, ambulatory status was maintained or
improved in 85% of patients while it prevented neurological
deterioration.53
Although theoretically there are risks of radiation-induced
secondary malignancies in treated sites, RIM is the most urgent
concern.54 Even though the risk of RIM always is present,
current techniques have significantly minimized its occurrence.
Maranzano et al reported only 1 case of RIM in a total of
465 patients with MSCC treated with RT in a 10-year span in
their clinical facilities.55
Multidisciplinary Management
Although each of the treatment modalities previously mentioned
has been used alone to manage MSCC, combination therapy has
produced better outcomes. In a study by Greenberg et al, which
used dexamethasone in advance of RT, 64% of subjects experi-
enced pain relief using only dexamethasone; however, after
dexamethasone and RT, 82% experienced relief.26 In a random-
ized study by Sørensen et al, patients receiving dexamethasone
and RT found significant improvement in their ambulatory
status compared with those receiving RT only.56 Surgery and
RT also are used in combination in MSCC, but the order in
which they are used becomes critical in minimizing posttreat-
ment complications. In a retrospective chart review, Ghogawala
and colleagues found that patients who were subjected to pre-
surgical RT had a higher rate of wound complications and had
a worse clinical outcome than individuals who had surgical
decompression followed by RT.57 Patchell and coworkers demon-
strated the superior role of surgical spinal cord decompression
followed by RT over RT alone on the neurological manifesta-
tions of MSCC.58 Patients receiving combination therapy had
better neurological improvement and a lower 30-day mortality
589
Sodji et al • Management of Metastatic Spinal Cord Compression

Fig. NOMS algorithm for the selection optimal treatment in MSCC.62 A, Factors involved in the selection of the optimal treatment. B,
Decision for the treatment selection in low-grade ESCC. C, Decision for treatment selection in high-grade ESCC. *Mechanical stability
based on the SINS. **Based on comorbidities and tumor burden. ‡Low-grade ESCC (grades 0 or 1) and high-grade ESCC (grades 2 or
3) as scored by the Spine Oncology Study Group.63 cEBRT, conventional external beam radiation; ESCC, epidural spinal cord compression;
MSCC, metastatic spinal cord compression; NOMS, neurologic, oncologic, mechanical, and systemic; SINS, Spine Instability Neoplastic
Score; SRS, stereotactic radiosurgery.

590 © 2017 The Southern Medical Association

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 Review Article

as the Karnofsky performance status, the number of extraspinal

Table 6. Survival of patients with cancer with MSCC
bone metastases, the site of primary malignancy, metastases to
following first occurrence2
major internal organs, spinal cord palsy, and the number
Survival rate, % of metastases in the vertebral body to estimate the mean sur-
vival (Table 7).68 The Tomita score is a simplified scoring sys-
Primary tumor Median survival, mo 1y 3y
tem based on three factors including the primary tumor and
Myeloma 6.7 38.7 21.7 visceral and bony metastases (Table 8). It also is used in con-
Lymphoma 6.4 38.3 26.6 junction with the modified Tokuhashi system in evaluation
Breast 5.0 26.9 6.8 for surgery.69 Individuals with moderate or better prognoses
Prostate 4.0 22.1 7.9 based on the modified Tokuhashi and Tomita systems may
Lung 1.5 4.2 1.5

MSCC, metastatic spinal cord compression.

Table 7. Modified Tokuhashi scoring system and selection
of management strategy68
rate. Various algorithms for the treatment of MSCC have been
proposed by different institutions including the Comite de Criteria Score
l’Evolution des Pratiques en Ooncologie. The Comite de Karnofsky performance status
l’Evolution des Pratiques en Oncologie algorithm uses a sur- Poor (10%–40%) 0
vival prognostic scale such as the Tokuhashi score, an evaluation Moderate (50%–70%) 1
of spinal stability, and other evaluation tools to suggest the Good (80%–100%) 2
optimal treatment for each patient.28,59–61 At Memorial Sloan No. extraspinal bone metastases
Kettering Cancer Center, a decision algorithm incorporating ≥3 0
novel technologies such as SBRT has been developed to deter- 1–2 1
mine the optimal treatment for spinal metastases. This algorithm, 0 2
which is based on neurologic, oncologic, mechanical, and systemic No. vertebral body metastases
assessments (Fig.), enables a multidisciplinary team to evaluate ≥3 0
the combination of surgical intervention (decompression and/or 1–2 1
stabilization) and radiation techniques (conventional external beam 0 2
radiation or SBRT) needed for optimal treatment.62 Metastases to major internal organs
Although the multidisciplinary approach has been success- Unremovable 0
ful in managing patients with MSCC, individuals with radio- Removable 1
sensitive tumors such as lymphoma and myeloma can benefit No metastasis 2
from RT alone.64,65 Site of primary cancer
Lung, osteosarcoma, stomach, 0
pancreas, bladder, esophagus
Prognosis Liver, gallbladder, unknown 1
Without treatment, the life expectancy of a patient with MSCC Other 2
is approximately 1 month. The primary tumor histology affected Kidney, uterus 3
not only the time between the diagnosis and the MSCC but also Rectum 4
the patient’s survival time posttherapy.3 According to Loblaw Thyroid, breast, prostate, carcinoid tumor 5
et al, patients with myeloma had the longest median survival Spinal cord palsy
(6.7 months) followed by those with lymphoma (6.4 months), Complete (Frankel A, B) 0
breast cancer (5 months), and prostate cancer (4 months; Table 6).2 Incomplete (Frankel C, D) 1
Among the malignancies evaluated, lung cancer caused patients None (Frankel E) 2
to have the shortest lifespan following their first MSCC episode
Total score Predicted survival, mo Treatment strategy
(1.5 months).2 Histologic types such as small cell, germ cell
tumors, and lymphoma had a more rapid response to treatment.66 0–8 <6 Conservative management:
radiation, chemotherapy,
Optimal local control of MSCC was associated with the lack of hormone therapy, analgesics
visceral metastases before RT and long course of RT treatment. 9–11 ≥6 Palliative surgery: posterior
Survival is contingent on the primary tumor types and the pres- decompression, posterior
ence of visceral and other bone metastases.67 Comprehensive stabilization, laminectomy
scoring systems, including the modified Tokuhashi, Baur, Linden, 12–15 ≥12 Excisional surgery: anterior or
combined curettage or en bloc
and Tomita scores, have been proposed to predict patients’ resection plus stabilization
survival.60 The modified Tokuhashi system uses factors such

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Sodji et al • Management of Metastatic Spinal Cord Compression

2. Loblaw DA, Laperriere NJ, Mackillop WJ. A population-based study of

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