1. [Section V Stereotactic Radiosurgery]
Chapter 98 Spinal Neoplasms
Robert E. Lieberson, AKE HANSASUTA, Robert Dodd, STEVEN D. CHANG,
AND JOHN R. ADLER, JR.
INTRODUCTION
The successes of cranial stereotactic radiosurgery (SRS) inspired the development of spinal
SRS.1-4
In little more than a decade, spinal SRS has revolutionized the treatment of spinal tumors and
vascular malformations. The CyberKnife™ allows the delivery of very large doses of radiation to small lesions
while sparing adjacent normal structures. By many measures, CyberKnife™ outcomes are comparable or
superior to those obtained with conventional radiotherapy, frame based stereotactic systems, or conventional
surgery.5-13
Since 1994 the CyberKnife™ has been used to treat over 8000 spinal lesions at more than 180
sites worldwide.
Technology Overview
The CyberKnife system consists of a lightweight, 6 megavolt (MV) linear accelerator (LINAC) mounted on
an industrial robot, a remotely repositionable treatment couch, orthogonally placed digital x-ray cameras, a
treatment delivery computer, and treatment planning stations (Fig. 98-1). During treatment, numerous
images are obtained to optimally locate the target before the delivery of 100 to 150 individual treatment
beams.14
The CyberKnife can deliver individual beams to any part of a tumor from nearly any angle and
provides highly conformal dosing to complex 3-dimensional (3-D) targets.15
Several conventional radiation therapy (RT) systems have recently been modified to provide SRS
using techniques originally developed for the CyberKnife™. The BrainLab Novalis, with floor and
ceiling mounted x-ray detectors, most directly emulates the CyberKnife™ localization system. The
Elekta Synergy, Varian Trilogy, and Novalis TX systems use different combinations of cone-beam CT
scanners and orthogonal x-ray cameras. These RT based systems are constrained by the gimbal design of the
gantry which only allows radiation to be delivered along two-dimensional arcs. Nevertheless, multi-leaf
collimators can compensate for much of the constraints that stem from this gantry design.
TREATMENT DETAILS
Spinal SRS is image guided and completely frameless. Individually moulded masks or cradles are fashioned
before the planning scans are completed. The patient rests in the mask or cradle during computed
tomography (CT) scanning, magnetic resonance imaging (MRI), 3-D angiography or positron emission
tomography (PET) imaging, and again during treatment. The devices are comfortable, limit movement, and
expedite positioning. At Stanford, we use an Aquaplast mask (WFR Corp., Wyckoff, NJ) for upper cervical
lesions (Fig. 98-2A). Lower cervical, thoracic, lumbar, and sacral lesions are treated using an AlphaCradle
(Smithers Medical Products, Inc., Akron, OH) (see Fig. 98-2B). Most patients are treated supine but prone
and lateral decubitus positioning is possible.

2. A high resolution, fine cut CT scan, most often with contrast, is required for all treatment plans. The CT is
essential for its excellent spacial accuracy and is needed to calculate the digitally reconstructed radiographs
(DRRs) used for real time targetting. MRI scans may help with visualization but cannot be utilized alone
because of the need to generate DRRs. Meanwhile, MRI often suffers from inherent limitations in spacial
resolution. In the appropriate clinical situation PET or angiogram images are also obtained. When a
framelses radiosurgical systems is used, the patient does not need to remain in the facility while the treatment
plan is developed.
Bony landmarks are used to target spinal lesions and those in adacent structures. Spinal fusion
hardware does not interfere with treament. The accuracy of CyberKnife approaches ±0.5 mm.7,16
For
lesions not associated with bony landmarks, 3 or more gold seeds or titanium screws are implanted (see Fig.
98-3).13,15
CyberKnife treatment plans use Accuray’s MultiPlan software. BrainLab, Varian, and Elekta systems
employ similar programs. After uploading the CT and other images to the planning station, the surgeon and
radiotherapist “contour” the target and radiation-sensitive structures by tracing their outlines (see fig. 98-4).
The dose and number of sessions, as well as dose limits for adjacent structures, are prescribed by the
physicians (see fig. 98-5). Physicists then use the planning system, the contour data, and the dose
prescriptions to create a 3-dimensional representation of the lesion geometry and define sets of treatment
beams. An ideal treatment includes evenly distributed beams that target the dose uniformly while limiting
exposure to sensitive structures (see fig. 98-6). The neurosurgeon and/or physicist will iteratively perfect the
plan by adding or removing constraints, or re-positioning individual beams. A multidisciplinary team reviews
and accepts each treatment plan before delivery.
During spinal radiosurgery, CyberKnife™ patients are placed on the operating table in their custom mask
or cradle. Images are automatically obtained by the orthogonally placed x-ray cameras and compared with
digitaly reconstructed radiographs (DRRs) which were precalculated by the planning software. The table is
aligned and the computer aims and delivers the first treatment beam. Additional images are obtained,
automatic corrections for movement are made, and all planned treatment beams delivered in order. This
process is automatic; after the intitial targeting verification is performed by the treating neurosurgeon,
radiation delivery is simply monitored by a radiation therapist. Not all commercially systems permit periodic
re-imaging and beam re-targeting. As a result, in the event of patient movement during treatment with such
radiosurgical devices, accuracy may be compromised.
INDICATIONS
It cannot be emphasized enough that the indications for spinal SRS continue to evolve quickly;
spinal SRS is a new subdiscipline within neurosurgery and only now are standarized procedures
for its application being developed. At our institution , we most frequently treat metastases, small benign
tumors, postoperative residuals, lesions that recurr following conventional surgery or radiation, vascular
malformations, inoperable tumors or lesions in those who decline surgery (see tables 98-1 and 98-2).3,7,13
Spinal lesions appropriate for CyberKnife™ radiosurgery should be reasonably well circumscribed, clearly
visible on CT or MRI, and smaller than approximately 5 centimeters in diameter. We do not insist on
obtaining a biopsy in advance of treatment if the diagnosis is clear from pre-radiosurgical imaging studies.
Spinal SRS is contraindicated in the presence of significant spinal cord compression causing a
severe neurologic deficit, especially when the treated lesion is relatively radioresistant.
Radiographic evidence of spinal cord compression is not in itself a contra-indication to spinal
radiosurgery. Spinal SRS can be used as an adjunct if there is evidence of spinal instability. If
the adjacent spinal cord has already received the maximum tolerated radiation dose, then surgery
and/or chemotherapy may be more appropriate.

3. EXTRADURAL METASTASES
The spine is the most common site for bony metastases, accounting for nearly forty percent of
osseus tumor spread.17
Forty percent of cancer patients will develop at least 1 spinal
metastasis.18
Historically, spinal metastases have been managed with chemotherapy,
radiopharmaceuticals, surgery, and external beam irradiation.17,19
Conventional irradiation of
spinal metastatic tumors is useful for palliation but its effectiveness is limited by spinal cord
tolerance20
. Moreover, relapses are common,21-24
and re-treatment with RT is generally
impossible.18
SRS enables much larger biologically effective doses to be delivered by utilizing a
more highly conformal plan that protects the cord. Multiple courses of spinal SRS can control
multiple asynchronous metastases and SRS may be used to sterilize a vertebral body before
vertebroplasty25
or following a debulking procedure. The presence of spinal fusion hardware is
not a contraindication.26
SRS is ideal for those with limited life expectancies or those who need
other treatment. Most SRS treatments are completed in a single one hour session.
Treatment protocols in the published literature vary greatly and there is significant debate
regarding the most appropriate treatment margins.27
For purely bony lesions Amdur, et al.27
recommend treating visible tumor plus a 1 centimeter margin in bone or a 2 millimeter volume
outside the external cortex. For lesions within the canal, the margins are not extended beyond
the visible tumor. Many groups irradiate the entire affected vertebral body including the pedicles.
Chang, et al.18
recommend treating the pedicles for possible tumor extension, pointing out that
18% of recurrences occurred in the pedicles. At Stanford we typically treat the volume of tumor
as seen on CT or MRI.17
There are no studies which show a clear benefit of one approach over
the other, but those who treat smaller volumes argue that the cord dose is decreased and that
recurrences can be retreated. Dose recommendations are variable with single session
prescriptions ranging from 8 to 24 Gy in the published literature.27
At Stanford we have used from
16 to 25 Gy in up to 5 fractions, but usually opt to treat in the fewest possible sessions as dictated
by the length and dose of irradiated spinal cord.17
Overall the efficacy of radiosurgery for spinal metastases appears roughly comparable to that for
brain metastases.2,3,17
Tumor growth is arrested by radiosurgery in up to 100% of cases and
results are independent of histology (see table 98-3).4,28
Pain relief ranged from 43% to 96% and
unlike standard RT, is generally apparent within days of SRS .27
Because of the delay between SRS and the involution of the tumor, radiosurgery is almost never
an alternative to emergency decompression. Neither generalized metastatic involvement of the
axial skeleton nor epidural carcinomatosis are indications for radiosurgery, as SRS cannot cover
such broad areas effectively. In the presence of instability, radiosurgery may be used as an
adjunct to a stabilization procedure such as vertebroplasty. Delayed post SRS spinal instability
can occur but is not common.
INTRADURAL METASTASES
Intramedullary spinal cord metastases, which are rarely seen clinically, are found in 0.9% to 2.1%
of autopsies in cancer patients.33
Such lesions comprise 8.5% of central nervous system
metastases34
and their frequency will likely increase with longer patient survival. Wowra et al.29
review their results and the literature. They report that 96% of spinal metastases were well
controlled with spinal SRS. The risk of myelopathy was less than 1%.
PRIMARY INTRAMEDULARY LESIONS

4. At Stanford, we have treated 92 hemangioblastomas in 31 patients. Sixteen were spinal
intramedullary tumors. Patients were treated with a median radiosurgical dose of 23 Gy, and
after a median of 34 months of follow-up, 15 of the 16 spinal hemangioblastomas in this series
either remained stable or decreased in size. Among all hemangioblastomas, those causing
edema and those associated with cysts did less well. None of the patients developed radiation
myelopathy.35
Some spinal ependymomas prove difficult to resect for reasons of anatomy or associated medical
co-morbidities. Although not common, tumor recurrence also occurs. There is very little
information available regarding SRS. Ependymomas, which may be controlled with conventional
radiation therapy, have responded favorably to spinal SRS in the few cases that have been
published.3,36,37
The Stanford experience with CyberKnife radiosurgery has been quite favorable
with good local control and no complications (unpublished data). We know even less about the
treatment of spinal astrocytomas. For the occasional well-demarcated, biopsy-proven, newly
diagnosed or recurrent spinal cord astrocytoma, spinal SRS may be a theoretical alternative if
surgery is not possible.
INTRADURAL, EXTRAMEDULLARY LESIONS
Meningiomas, schwannomas, neurofibromas, and hemangioblastomas are the benign lesions
most frequently considered for treatment with spinal SRS. However, microsurgical resection
remains the most appropriate intervention for most patients. Surgical resection is generally
curative and in the process, the surgeon both establishes a tissue diagnosis and immediately
decompresses the spinal cord.38
Nevertheless SRS is appropriate for benign lesions that are
inaccessible, when lesions are numerous (as in neurofibromatosis or von Hippel-Lindau disease),
in patients with significant medical co-morbidities, or for patients who decline open surgery.39-41
Moreover, spinal radiosurgery also has the virtue of posing little risk to the parent motor or
sensory nerves in cases of nerve sheath tumors.
Short term control rates for benign lesions intradural, extramedullary spinal tumors appear
comparable to those of similar intracranial lesions. At Stanford we have treated 110 patients with
117 lesions (unpublished data). Greater numbers and longer follow-up periods confirm earlier
published observations.42
Following SRS, 56% of schwannomas and meningiomas stabilized
and 44% percent regressed radiographically. Neurofibromas did less well with 11% enlarging
radiographically, over 50% causing increased pain, and 80% showing a worsening in at least one
examination finding. Even including neurofibromas, most myelopathies and radiculopathies
improved with SRS, whereas bowel and bladder dysfunction did not. Two of our patients
eventually required surgery for tumor enlargement and 3 required surgery for persistent or
progressing symptoms. Only 1 patient developed radiation myelopathy. Others centers have
reported similar results.39-41
Vascular Malformations
Steiner, et al,43
published the first description of SRS for cranial AVM’s in 1972. The successes in
treating the intracranial AVM’s inspired the use of SRS for spinal vascular malformations. Spinal
AVM’s have been described using various systems. Most commonly they have been divided into
4 types.44
Types I and IV are dural and perimedullary fistulas and are better treated with
embolization and resection. Most AVM’s treated with SRS are type II, or glomus AVM’s, with a
well-defined nidus. Some type III, or juvenile AVM’s, may be amenable to SRS when well-focal
and well-defined. SRS causes endothelial damage that leads to the obliteration of the vascular
lumena.45
Low flow lesions, such as cavernous malformations, are rarely candidates for spinal
SRS.46
Of 29 patients treated at Stanford between 1997 and 2009, 22 were followed more than
24 months (unpublished data). Most had glomus AVM’s and 1 had a type III lesion. Sixteen
patients presented with hemorrhage and 8 had more than one bleed. Twelve lesions were
cervical, 8 were thoracic, and 3 were in the conus. The usual treatment dose was 16 Gy in 1

5. session or 20 Gy in 2 sessions (with 10 Gy delivered to adjacent spinal cord). Ten patients (43%)
were previously embolized. All postoperative MRI’s in treated patients showed a reduction in
volume. Of the 8 patients who had post-SRS angiography, 3 had complete obliteration. None of
the treated patients suffered a rebleed, including those where the AVM was not obliterated by
MRI or angiography. There was no mortality. Symptoms improved in over 50% and only 3
patients reported worsening of symptoms. There was only 1 case of radiation myelopathy (3%).
TREATMENT FAILURES AND COMPLICATIONS
Treatment failures fall into several groups. “In-field failures” refer to tumor re-growth within the
treated volume and may be related to inadequate dosing. “Marginal failures” involve re-growth at
the edges of the treated volume and may be related to poor imaging, an underestimate of the
tumor volume, or inaccuracies in position or set-up. “Distant failures” are not complications but
rather involve new lesions in untreated areas. For vertebral metastases, the chance of an
asynchronous metastasis in an adjacent level is only 5%.47
Furthermore, neurological damage
can be divided into 3 groups. (1) Acute complications that occur within 1 month, are usually due
to edema, are transient, and are treated with steroids; (2) subacute complications that occur 3 to
6 months after treatment, may be secondary to demyelination, and usually recover; and 3)
radiation myelopathy, which is the most feared complication and usually occurs after 6 months.
This risk more than any other limits the radiosurgical dose used for most paraspinal lesions.48
In
conventional radiotherapy it is generally believed that treatment with 45 Gy in 22 to 25 fractions is
associated with an incidence of myelopathy of only 0.2%. Meanwhile, among the first 1000
patients treated with CyberKnife for spinal lesions at both Stanford and the University of
Pittsburgh over the past decade, only 6 developed myelopathy (0.6%). In large part due this 10-
year track record with radiosurgery, a re-evaluation of the conventional wisdom and long-standing
radiotherapy guidelines pertaining to spinal cord tolerance is taking place. Nevertheless, at
Stanford we generally seek to avoid exposing more than 1 cubic centimeter of spinal cord to
greater than 10 Gy in single session plans.49
Other complications are rare and, fortunately, less severe. Skin reactions are seen most
commonly when the posterior elements are radiated, nausea pharyngitis,
esophagitis, diarrhea are related to gastrointestinal tract exposure. Renal
complications, occasionally related to Thoraco-lumbar SRS, are rare.
Summary
While the complexity of spinal lesions and their close association with the cord make operative
treatment difficult, it also makes them ideal candidates for spinal SRS. SRS, although a recent
development, is supported by a rapidly expanding literature. For many lesions of the vertebral
bodies, and some intradural, extramedulary lesions, CyberKnife radiosurgery is clearly both safe
and effective. For vascular lesions, the treatment is superior to embolization and surgery for
AVM’s. Early results show that treatment of selected intramedullary lesions is also possible. It is
likely that the indications will expand and the quality of the results will improve as our experience
increases.
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9. Figure 98-1. The CyberKnife frameless stereotactic system includes a modified 6-MV X-band LINAC mounted on a highly
maneuverable robotic manipulator (KUKA Roboter GmbH, Augsburg, Germany) (A). Two high-resolution x-ray cameras
are mounted orthogonally to the headrest (B). One of the two x-ray sources is mounted in the ceiling projecting onto the
camera (C). The treatment couch is mobile, allowing the x-ray sources to image targets at any point along the neuraxis
(D).
Figure 98-2. Simple immobilization devices used during CyberKnife treatment. The Aquaplast mask is used in patients
with upper cervical lesions. (A). AlphaCradle custom body mold is used for those with lesions below the cervical spine (B).
Figure 98-3. Implanted fiducials are marked and numbered. Left: Computed tomography-based digitally reconstructed
images from the perspective of the 2 orthogonal CyberKnife mounted x-ray cameras (A and B). Center: Real time x-ray
images from the two x-ray cameras. Right: Overlay of the reconstructed and actual radiographic images.
Figure 98-4. Contour of L3 metastasis in axial, saggital and coronal projections. The epidural metastasis is in red.
Figure 98-5. Contour of L3 metastasis and spinal roots with superimposed isodose lines from treatment plan in axial, saggital, and
coronal projections. The epidural metastasis is in red, the spinal roots are blue, and the 80% isodose line is represented by the thin
green line.
Figure 98-6. Contour of L3 metastasis and cauda equina with superimposed isodose lines from treatment plan in axial, saggital, and
coronal projections. The epidural metastasis is in red, the spinal roots are blue, and the 80% isodose line is the smaller green line.
Figure 98-7. Left: Spinal cord AVM prior to treatment. Note the compact nidus. Right: Spinal cord AVM 3 years after
SRS. Complete angiographic obliteration noted.
Table 98-1
Indications and Contraindications for Stereotactic Spinal Radiosurgery
Indications Contraindications
Progressive but minimal neurologic deficit
Post-resection or post-RT local irradiation (boost)
Disease progression after surgery and/or irradiation
Inoperable lesions or high risk lesion locations
Medical co-morbidities that preclude surgery
Lesions in patients who decline surgery
Spinal instability (adjunctive treatment only)
Neurologic deficit caused by bony compression
Severe neurologic deficit due to cord compression
Adjacent cord previously radiated to maximum dose
Very rare lesions not responsive to ionizing radiation
TABLE 98-2
Treated/Treatable Lesions with CyberKnife Radiosurgery
Tumors
Benign
Neurofibroma, schwannoma, meningioma, hemangioblastoma,
chordoma, paraganglioma, ependymoma, epidermoid
Malignant/metastatic
Breast, renal, non-small cell lung, colon, gastric and prostate
metastases; squamous cell (laryngeal, esophageal, and lung)
tumors; osteosarcoma; carcinoid; multiple myeloma; clear cell
carcinoma; adenoid cystic carcinoma; malignant nerve sheath
tumor; endometrial carcinoma; malignant neuroendocrine tumor
Vascular Malformations
Arteriovenous malformation (types 2 and 3)

10. Table 98-3
Literature Review, SRS for Spinal Vertebral Metastases
Site
Lesions
/
Patients
Tumor
Type
Modality
Dose /
Fractions
Contouring Complications
Pain
better
Local
control
Overall
Survival
Amdur, et
al., 2009.27
25 / 21 Various LINAC /
IMRT
15 Gy / 1 Lesion with
margin
No neurologic
toxicity
43% 95% 25% at one
year
Wowra, et
al., 2009.29
134 / 102 Various CyberKnife 15 to 24 Gy
/ 1
Not specified No SRS related
neurologic deficits
86% 88% Median
survival 1.4
years
Yamada, et
al., 2008.4
103 / 93 Various LINAC /
IMRT
18 to 24 Gy
/ 1
Entire vertebral
body
No neurologic
toxicity
Not
reported
90% 36% at 3
years
Gibbs, et
al., 2007.17
102 / 74 Various CyberKnife 14 to 25 Gy
/ 1 to 5
Lesion only 3 cases
myelopathy
84% No
symptom
progression
46% at 1 year
Chang, et
al., 2007.18
74 / 63 Various LINAC /
IMRT
27 to 30 Gy
/ 3 to 5
Entire vertebral
body
No neurologic
toxicity
60% 77% 70% at 1 year
Gerszten,
et al,
2007.30
500 / 393 Various CyberKnife 12.5 to 25
Gy / 1
Lesion only No neurological
toxicity
86% 90% Not stated
Ryu, et al.,
2006.31
230 / 177 Various LINAC /
IMRT
8 to 18 Gy /
1
Entire body
with pedicles
1% risk of
myelopathy
85% 96% 49% at 1 year
Milker-
Zabel, et al.,
2003.32
19 / 18 Various LINAC /
IMRT or
FCRT
24 to 45 /
variable
Entire vertebral
body
No neurologic
toxicity
81% 95% 65% at 1 year