CHAPTER
Ilya Laufer
146
Adjuvant Therapy of Spinal Tumors
INTRODUCTION
Advances in radiation therapy have altered the management of
spinal tumors. This chapter discusses (1) basic considerations
of tissue response to radiation, (2) technology for radiation
delivery, (3) treatment planning, (4) treatment delivery, and
(5) treatment paradigms. While several image-guided radiation
therapy (IGRT) systems are available on the market, including
conventional gantry-based intensity-modulated radiation ther-
apy (IMRT) such as Trilogy (Varian Medical Systems, Palo
Alto, CA), Synergy (Elekta, Stockholm, Sweden), Novalis
(Brainlab, Feldkirchen, Germany), CyberKnife (Accuray,
Sunnyvale, CA), and HiArt (TomoTherapy, Madison, WI),
many basic radiation treatment planning and delivery princi-
ples are universal to all systems. The crucial concepts in the
context of IGRT include three-dimensional (3D) inverse treat-
ment planning, patient immobilization, and image guidance
for patient position and tumor location verification. IGRT,
regardless of which specific system is used, represents a dra-
matic improvement in our ability to treat primary and meta-
static spine tumors and has significantly altered oncologic
treatment paradigms and patient outcomes.
BIOLOGIC BASIS OF TUMOR
RADIATION RESPONSE
DNA represents the main target of radiation therapy. By caus-
ing breaks in the DNA strands through disruption of the chem-
ical bonds between base pairs, radiation triggers a chain of
events that may eventually lead to cell death. These breaks may
involve one or both of the strands. A double-strand break is
more likely to be lethal because there is no template for repair
if both DNA strands are disrupted. A single-strand break may
be repaired under the right conditions and does not guarantee
cell death. These concepts of repairable and nonrepairable cell
injury are incorporated into the linear-quadratic model, which
is based on the empiric observation of cell survival as a function
of radiation dose (D).11 It was observed that the cell survival
curve could be expressed as a function of a first- and second-
order variables. The first-order component (D) reflected the
cells intrinsic radiosensitivity and represents nonrepairable
damage. The second-order component represented the repair-
able damage and is proportionate to the square of the dose
(D2). Thus, the total number of cells killed by each radiation
fraction can be represented as the sum of nonrepairable and
repairable damage to the cells: D D.2
LWBK836_Ch146_p1575-1580.indd 1575
Yoshiya Yamada
Mark H. Bilsky
The cell sensitivity to radiation is tissue-specific and pro-
portionate to the natural proliferation rate of the tissue.
Rapidly dividing tissues have little time to repair the poten-
tially reparable DNA damage and therefore have a large /
ratio. Slowly proliferating tissues have more time to repair the
reversible damage and have a low / ratio. Thus, radiosensi-
tive mucosa or skin cells, both from rapidly proliferating tis-
sues, have an / ratio of 10, indicating the predominant role
of nonrepairable () damage in these tissues. These highly
proliferating tissues, however, are typically also more capable
of replacing cells lost to radiation exposure. On the other
hand, the spinal cord has an / ratio of 2 to 3, reflecting its
slow proliferation rate.2,6,7,17 In the spinal cord, cells lost to
radiation effect may be replaced very slowly or not at all. Data
from animal models suggest that repair of radiation-induced
injury in the spinal cord does occur over time. The effects of
radiation injury are likely multifactorial; radiation may injure
or cause loss of neurons, support cells and demyelination, or
microvascular damage.4,9,14,18
The repairable component of the model (D2) reflects the
response modulation observed as a function of dose-per-frac-
tion and dose rate. The lower the / ratio, the more -signifi-
cantly , which is a coefficient of a second-order variable, will
contribute to the overall response rate, relative to the value.
This is typically the property of slowly dividing tumors, such as
most prostate cancer, as well as normal nonmalignant sur-
rounding tissue. These tissues will be more sensitive to an
increase in fraction dose than tissues with a high / ratio.8
This provides the basis for the conventional fractionation of
radiation therapy, which aims to deliver multiple fractions of
low-dose radiation in order to limit the toxicity to surrounding
healthy tissue by exposing these tissues to such doses of radia-
tion that they are able to repair radiation injury between frac-
tions of radiation. An additive toxic effect is delivered to the
tumor, which is less capable of repairing radiation injury. When
administering high doses of radiation, as in the case of spine
radiosurgery, extreme care must be exercised to minimize the
doses of radiation to surrounding normal tissues to maximize
the probability of recovery from radiation effect. However, very
high-dose radiation has a highly toxic effect on tumor tissue.
This is especially true of tumors that have a low / ratio
because the biologic effect of high-dose radiation is signifi-
cantly higher relative to tissues with a higher / ratio.
Although many radiobiologists feel that the linear-quadratic
model is most relevant between the doses of 1 and 6 Gy, it does
provide a theoretical justification for the current methods of
delivering high-dose focused radiation to low / tumors such
1575
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 1576 Section XIII Tumor and Osteomyelitis
as renal cell carcinoma and melanoma, which conventionally
were deemed radioresistant. Thus, the highly conformal
nature of IMRT and the very precise treatment platforms incor-
porating image-guided technology are able to limit the radia-
tion exposure to nearby normal tissue while safely delivering
tumoricidal doses of radiation to complicated 3D targets.
RADIATION DELIVERY TECHNOLOGY
IGRT is delivered by a gantry-mounted photon beam. The
patient is positioned with the target tumor in the center of the
gantry. The rotation of the gantry in the transverse plane allows
focused delivery of radiation to the tumor bed, thereby mini-
mizing the radiation dose to the surrounding structures. The
radiation is delivered from various angles using beams that con-
verge on the tumor, which maximizes the delivered dose at the
intersection of the beams. The surrounding tissue, however,
receives only a fraction of that dose. Furthermore, the beam is
shaped using a custom collimator, which contours the beam to
fit the target projection in the plane of delivery. The advent of
multileaf collimators has refined this process by providing great
precision in beam contouring and allowing beam modulation
during radiation delivery. Opposing tungsten leaves, as thin as
3 mm, may be placed in the beam to modify or modulate its
intensity at any point. In the case of dynamic multileaf collima-
tion, both beam shape and dose can be continuously modu-
lated during radiation delivery creating a high dose cloud of
radiation that conforms very tightly to the target by directing
multiple beams of modulated radiation to intersect in the
desired volume. This process of specifically modifying each
radiation beam lies at the foundation of IMRT (Fig. 146.1). In
the case of CyberKnife, multiple nonisocentric beams of radia-
tion pass through the target from multiple directions to pro-
vide tightly conformal coverage of the intended target.
Figure 146.1. A photograph of the IMRT suite at the Memorial
Sloan-Kettering Cancer Center.
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TREATMENT PLANNING
The goal of treatment planning is to maximize the radiation
dose delivered to target tissue while minimizing the dose to
normal tissues. The tumor and surrounding normal structures
at risk (i.e., kidneys, esophagus, bowel, and spinal cord) are
manually delineated on a CT scan and a 3D reconstruction is
created. Supplementary information about the target may be
derived from PET or MR imaging and superimposed on the CT
image. Furthermore, patients undergo a CT myelogram in
order to precisely define the subarachnoid space and cord loca-
tion in the vicinity of the tumor. A 10% per mm dose gradient
can be achieved allowing safe delivery of high radiation doses
within 2 to 3 mm of the spinal cord.20
The conventional forward planning approach examines
various combinations of beam directions and apertures without
sophisticated modulation in order to maximize the target vol-
ume that will get the prescribed radiation dose, while minimiz-
ing radiation of the surrounding structures. Doses are calcu-
lated for any given treatment plan, and treatment planners
manually adjust parameters such as the number of beams,
beam angle, and beam energies until a suitable plan that meets
the requirements of the clinical situation -- both to the tumor
and normal tissue structures is accomplished.
On the other hand, inverse treatment planning starts by
defining the end result, the acceptable radiation dose to the
target volume and the surrounding tissue. The permissible lev-
els of radiation for surrounding structures may also be speci-
fied in the dose constraint definition. Normal tissue volumes
may have several different dose constraints based on different
dose levels assigned to different proportions of each volume.
For example, for a lesion at T12/L1 the kidney dose needs to
be considered. The whole kidney should receive less than 10 to
20 Gy in a single fraction to keep the risk of radiation-induced
nephritis to less than 5%. A small volume of the kidney, how-
ever, can receive a significantly higher dose without increasing
the risk of nephritis.
At Memorial Sloan Kettering Cancer Center (MSKCC), the
spinal cord is currently constrained to a maximum dose of
14 Gy in a single fraction, while the mean kidney dose should
be less than 10 Gy. Nearby stomach and bowel are kept lower
than 16 Gy as a maximum dose point. The tumor is prescribed
a dose of 24 Gy. In order to minimize the risk of radiation
myelitis, the dose constraint on the spinal cord is given the
highest penalty and other constraints are assigned penalties
relative to the spinal cord. These constraints represent the
result that computer algorithms then try to achieve, manipulat-
ing beam locations and intensities until an acceptable solution
is found. Because this iterative process starts with the desired
result and then works to find the beam parameters to achieve
it, it is often referred to as an inverse process. Conventional
forward treatment planning, on the other hand, starts with the
beam parameters and then strives to achieve the desired doses
to the volumes of interest.
In addition to assigning radiation dose constraints to nor-
mal structures, inverse treatment planning provides the oppor-
tunity to define dose levels within the target volume based on
biologic rationale. It is thus possible to deliver a very high dose
to the gross tumor volume (GTV), while giving a lower dose to
volumes with suspected microscopic disease (clinical target vol-
ume, CTV). This intentional modulation of dosing within the
target volume is often called dose painting. Furthermore,
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 Chapter 146 Adjuvant Therapy of Spinal Tumors 1577

Figure 146.2. (A) Schematic representation of treatment contours. Gross tumor volume (GTV) repre-
sents radiographically apparent tumor and receives the highest radiation dose. Clinical target volume (CTV)
includes microscopic disease that is assumed to be found in the adjacent bone. Planned target volume (PTV)
is a wider contour that outlines a larger volume that accounts for possible imprecision in treatment delivery.
(B) A representative outline of dose contours on a CT scan showing the expected dose gradient.

planned target volume (PTV) is a wider contour that takes into
account any imprecision in radiation delivery (Fig. 146.2).
Delayed radiation toxicity to the spinal cord, which mani-
fests as an irreversible myelopathy, may occur as a result of spi-
nal radiosurgery. While it is believed to be a dose-dependent
phenomenon, the safe levels of radiation to the spinal cord
have not been established. An upper limit of 45 to 50 Gy in
fractionated therapy and 10 to 14 Gy in single-fraction therapy
are currently used, and are associated with a less than 5% prob-
ability of myelopathy in 5 years. The ALARA (As Low As
Reasonably Achievable) principle is a prudent strategy when
considering cord dosing.13
TREATMENT DELIVERY
During treatment delivery, patient position must be stable at all
times. This is generally achieved with either patient immobiliza-
tion or frequent radiographic position confirmation during the
procedure. Immobilization is achieved using a stereotactic
body frame or a positioning cradle. Both of these modalities
are noninvasive and allow some patient movement. Use of an
immobilization cradle has been shown to provide consistent
precision within 1 mm; the cradle currently used at MSKCC is
shown in Figure 146.3.12 The patients position is further veri-
fied using infrared cameras and reflective markers that are tem-
porarily affixed to the skin. Alternatively, dual in-room kilovolt
radiography units can be used to provide frequent confirma-
tion of the position of bony landmarks and this information
may be used to adjust patient position during treatment
delivery.
The position of the treatment target must be determined
in reference to a stable set of coordinates. These may be bony
landmarks, implanted fiducials, or a stereotactic frame. Wall-
mounted kilovolt sources can be used to confirm the target
position. Alternatively, the kilovolt source may be mounted on
the gantry of the treatment machine and used to obtain
orthogonal localization X-rays. Cone-beam (CB) imaging uses
such a gantry-mounted kilovolt source to make a full rotation
around the patient and to provide a near real-time 3D image,
similar to the one obtained using a conventional CT scanner
(Fig. 146.4). When comparing the 3D image of the patient

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 1578 Section XIII Tumor and Osteomyelitis
Figure 146.3. Immobilization cradle currently used in our institu-
tion. It allows noninvasive precise positioning of the patient.
with the reference CT scan used for treatment planning, nec-
essary adjustments in 3D space can be robustly calculated to
ensure that the tumor is positioned for treatment exactly as
intended. It also provides beams eye view images that can
be compared to prepositioning CT image in order detect any
deviation from the planned beam delivery path. Thus, last-
minute adjustments to the immobilization couch and patient
position can be made in order to maximize treatment preci-
sion. With these safeguards, the PTV margin does not need to
be more than 2 mm.
Figure 146.4. Image obtained with conventional CT (left) com-
pared to the cone-beam image (right) obtained after positioning the
patient in order to ensure accurate target location.
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ALTERNATIVE METHODS OF
RADIATION DELIVERY
Until the advent of IGRT, particle beam radiation such as pro-
ton beam therapy was the only modality able to deliver spinal
radiation at very high doses near the spinal cord. This modal-
ity employs the Bragg peak effect the fact that particles (i.e.,
protons) have a very steep gradient of dose fall-off, allowing
delivery of high doses of focused radiation, and therefore no
exit dose, a phenomenon lacking in photon radiation. It has
been often employed for chordomas and chondrosarcomas.1,15
However, this therapy has not typically been delivered as a
single fraction and has very limited availability due to pro-
hibitive cost and resource requirements. Carbon ion beam
radiation is being developed as a heavy-particle alternative to
proton beam radiation16 with the added effect of variable lin-
ear energy transfer (LET) in addition to the Bragg peak.
Because of the added effect of kinetic energy of ions with sub-
stantial mass, each accelerated carbon ion is more likely to
cause tissue damage along its linear path length, whereas low
mass ions such as protons have a LET similar to photons,
which have no mass.
Brachytherapy is being explored as a treatment adjunct
for tumors where clean margins are crucial for durable con-
trol. It can be especially useful in delivering high-dose radia-
tion to the dural margin while sparing the spinal cord.
90
Yttrium is a -emitting radioisotope that delivers high-dose
radiation with limited penetrance and an effective treatment
distance of less than 5 mm. 90Yttrium plaques may be used
intraoperatively during the resection of sarcomas and chor-
domas, by placing the plaque directly on the dura deemed to
be at risk of recurrence.5
TREATMENT PARADIGMS
While all primary solid spinal tumors require resection, the
treatment of metastatic spinal tumors is not as uniform. We
employ the NOMS assessment in order to determine the appro-
priate treatment of spinal metastases.3 Briefly, the NOMS algo-
rithm considers neurologic (N) and oncologic (O) factors,
mechanical instability (M), and the extent of systemic (S) onco-
logic and medical disease. Generally, patients who exhibit evi-
dence of mechanical instability (Chapter 145) require surgical
stabilization prior to radiation delivery. Furthermore, patients
with considerable degree of neurologic compromise, including
myelopathy or radiculopathy, or high degree of radiographic
cord compression with tumors that are radioresistant to con-
ventional external beam RT undergo surgery in order to
decompress the spinal cord. The extent of systemic disease and
medical comorbidities are considered to determine if the
patient is an appropriate surgical candidate. The patients
oncologic status is considered with the goal of achieving maxi-
mal durable tumor control using a combination of surgery,
radiation therapy, and chemotherapy. Historically, radioresis-
tant tumors have been considered for upfront surgery. The
advent of IGRT, however, and the ability to deliver high-dose
focal radiation to the spine has reduced the number of tumors
that still fall in the radioresistant category. Table 146.1 presents
the traditional grading of tumor radiosensitivity. Currently, the
majority of the traditionally radioresistant tumors can be
treated with upfront radiation therapy achieving excellent
8/26/11 2:23:25 PM
 Chapter 146 Adjuvant Therapy of Spinal Tumors 1579

conventional external beam radiation. All patients were

Traditional Grading of
TABLE 146.1 treated with single fraction radiation therapy, with doses rang-
Tumor Radiosensitivity
ing from 14 to 20 Gy and a maximum spinal cord dose (Dmax
Radiation Sensitivity Tumor cord) of 9.68 Gy. At a median follow-up of 37 months, pain
assessments revealed 95% immediate and 89% durable pain
Sensitive Myeloma improvement. No radiation-induced myelopathy or radicul-
Lymphoma opathy was seen.
Ewings sarcoma Yamada et al reported 103 consecutive tumors treated in
Neuroblastoma 93 patients. Patients were excluded if they had high-grade
Moderately sensitive Breast ESCC or prior radiation to the region of interest. All patients
Moderately resistant Colon received single fraction therapy via IGRT to doses between
NSCLC 18 and 24 Gy (median dose 24 Gy) and the Dmax cord of 14 Gy
Highly resistant Thyroid and Dmax cauda equina of 16 Gy. Radiographic assessments
Renal were performed every 3 months until death. The overall actu-
Melanoma arial local control rate was 90% at a median time of 15-month
Sarcoma
follow-up. The 7 failures occurred at a median of 9 months.
Osteogenic sarcoma
The radiation dose was a significant predictor of local control.
Chondrosarcoma
Chordoma Patients receiving 24 Gy had a 95% local control rate versus
80% in patients receiving less than 24 Gy.20
NSCLC, non-small cell lung cancer.

tumor control. Currently at MSKCC, spinal tumors are treated
using one of three IGRT-based radiation delivery paradigms.
Standard fraction therapy (i.e., 70 Gy in 35 fractions) is used to
treat a subset of primary spine tumors. Hypofractionated
radiation (i.e., 30 Gy in 4 to 5 fractions) is used to retreat recur-
rent metastatic tumors that have already been treated with con-
ventional external beam radiation therapy.19 Single-fraction
radiation (18 to 24 Gy) is used to treat traditionally radioresis-
tant metastatic tumors that have not been previously irradiated
(Fig. 146.5).
OUTCOMES
Two recent studies have shown the potential usefulness of
high-dose single fraction therapy in the management of
radioresistant tumors. Gerszten et al10 reported a series of
60 patients with renal cell carcinoma, of which 42 failed prior
CONCLUSIONS
Advances in our ability to deliver high doses of radiation to a
very precisely defined volume represent a significant addition
to our armamentarium in treating tumors of the spinal column.
Stereotactic radiosurgery allows focused delivery of high-dose
tumoricidal radiation doses to epidural metastatic tumors,
while sparing the spinal cord and adjacent soft tissue organs.
This therapeutic modality provides durable tumor control in
patients with tumors that are resistant to conventional fraction-
ated radiotherapy, such as metastatic melanoma and renal
carcinoma. The accuracy of treatment relies on patient immobi-
lization and image-guided confirmation of the target. Inverse
treatment planning techniques and dose painting when used in
conjunction with IGRT technology provide consistent tumor
control for many patients, obviating or delaying the need for
surgery. Current research in radiation oncology aims to provide
improved control of tumors that still represent radioresistant
targets.

Figure 146.5. A prostate metastasis to the T12 vertebral body with paraspinal extension was treated in its
entirety. The 12-month follow-up image shows resolution of epidural disease.

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 1580 Section XIII Tumor and Osteomyelitis

10. Gerszten PC, Burton SA, Ozhasoglu C, et al. Stereotactic radiosurgery for spinal metastases
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