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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2915_Библиотеки_им_академика_М_И_Перельмана.pdf
Spinal Cord Compression
Malignant spinal cord compression (MSCC) is a common and devasting
neurological complication of cancer.
Due to rapid progression of the neurologic dysfunction, it is considered a
oncologic emergency that demands an early diagnosis and treatment.
More than 95% of MSCC are caused by an epidural compression from a tumour
or a bony fragment from the collapsed vertebra affected by the metastasis.
The most common of the tumours that metastasize to the spinal cord are breast
and lung cancer, followed by lymphoma, myeloma, prostate cancer and
sarcoma.
Pain back is the most common symptom of MSCC, followed by muscular
weakness and autonomic dysfunction.
MRI gives the best information regarding MSCC, thus all patients should have a
MRI initially.
All patients with MSCC should receive corticosteroids immediately, even before
the definitive diagnosis is made.
Other treatment options are surgery with postoperative radiotherapy,
radiotherapy only, specific medical therapies according to the tumour type and
symptomatic therapy, (mainly opiates).
Chapter 17
Abstract
Introduction
Spiller in 1925 was the first to define metastatic epidural spinal cord compression
(MSCC) as "comprehensive indentation, displacement, or encasement of the thecal sac that
surrounds spinal cord or cauda equina by spinal epidural metastases”.
When an epidural mass touches or involves the spinal cord without leading to neurologic
deficits, the situation can be described as impending MESCC. Despite improved treatment
approaches regarding surgical intervention and modern radiation techniques, the treatment of
MSCC remains challenging. In this chapter, we discuss the role of radiotherapy in the
treatment of MSCC.
Gustavo Arruda Viani
252
1. Epidemiology
• It is estimated that up to 5% of cancer patients will develop an episode of metastatic
epidural spinal cord compression (MESCC)
• The incidence of MESCC varies according to the type of primary tumor; for instance,
it occurs in 0.2% of pancreatic cancers and 7.9% of myelomas.
• Incidence decreases with age, and ranges between 5% in patients aged 40-50 years
to 0.5% in patients aged 70-80 years.
• The most common tumors with MESCC are breast, prostate, and lung cancers, which
each account for about 20%, followed by myeloma, which accounts for about 10%.
• The most common site of MESCC is the thoracic spine in 60-80%, followed for the
lumbar spine in 15-30% and cervical spine <10%.
• 10% of patients diagnosed with MESCC may have a second episode.
Reference
Loblaw DA, Laperriere NJ, Mackillop WJ. A population-based study of malignant spinal
cord compression in Ontario. Clin Oncol. 2003;15:211- 217.
2. Anatomy
Spinal cord begins just below foramen magnum of the skull. It lies within protective
covering of vertebral column. Ends opposite 2nd lumbar vertebra. Below of L2 level the spinal
cord continue as a leash of nerve roots known as cauda equina. Prolongation of the pia matter
forms filum terminale (figure-1).
Figure 1. Anatomy of spinal cord.
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253
3. Clinical Features
• Back pain (70-95%) is the most often reported symptom of MESCC followed by
motor deficits (61-90%), sensory deficits (46-90%) and autonomic dysfunction (4060%).
• Generally, pain is localised over the area of tumour due to vertebral destruction. Pain
usually is the initial symptom, which becomes more severe with time and may
change.
• Multiple spinal levels can be affected in up to 30% of patients with more than one
vertebra may be tender on examination.
• Actually about 60% of patients are ambulatory at presentation showing a greater
awareness of physicians and improved diagnostic imaging.
• Weakness is the most obvious and problematic manifestation of MSCC.
Unfortunately, weakness is present in 60–85% of patients at the time of diagnosis
• Sensory deficits are less frequently reported than motor deficits and are much less
noticeable to patients than motor weakness.
• Loss of bladder and bowel control occurs relatively late and is generally associated
with a poor functional outcome after radiotherapy alone.
References
Levack P, Graham J, Collie D, et al. Don’t wait for a sensory level—listen to the symptoms: a
prospective audit of the delays in diagnosis of malignant cord compression. Clin Oncol.
2002;4:472-480.
Abrahm JL. A Physician’s Guide to Pain and Symptom Management in Cancer Patients. 2nd
ed. Baltimore, MD: Johns Hopkins University Press, 2005.
Schiff D, O’Neill BP, Suman VJ. Spinal epidural metastases as the initial manifestation of
malignancy: clinical features and diagnostic approach. Neurology. 1997;49:452-456.
Deyo R, Rainville J, Kent D. What can the history and physical examination tell us about low
back pain. JAMA. 1992;286:760-765.
4. Pathology
More than 95% of MSCC are caused by an epidural compression. It can develop in one
of the following ways:
1. Vertebral bone metastasis grows into the epidural space and compresses the spinal
cord.
2. Para spinal mass grows through the neural foramina.
3. Metastasis in the vertebral body causes its collapse and bone fragments are
displaced in the epidural space.
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All mechanisms cause venous plexus compression, which leads to edema of the spinal
cord (figure-2).
Figure 2. Pathophisiology and sites of spinal cord compression.
Reference
Spinazze S, Caraceni A, Schrjivers D. Epidural spinal cord compression. Crit Rew Oncol
Hematol 2005; 56: 397-406.
5. Diagnosis and Evaluation
• The diagnostic procedures for detection of MESCC include plain x-rays, CT, MRI,
and bone scan.
• Radionuclide bone scanning depends on increased blood flow and new bone
formation to demonstrate bone metastaases. Bone scanning is more sensitive than
plain radiography although less sensitive than MRI for demonstrating bone
metastases.
• Similar to plain radiography, bone scans cannot identify whether epidural tumor is
present
• The diagnostic procedure of choice to detect MSCC is spinal MRI, due to its high
diagnostic accuracy. A sagittal sequence of the all spine is necessary. The rates of
sensitivity and specificity of spinal MRI regarding the differentiation between benign
spondylodiscitis and MSCC are 89% and 90%, respectively.
Spinal Cord Compression
255
• In addition to that, MRI is an excellent method to detect multiple sites of MSCC.
Therefore, a spinal MRI should be performed in every patient presenting with MSCC
before the start of treatment (figure-3).
Figure 3. MRI showing spinal cord compression.
References
Loblaw DA, Perry J, Chambers A, et al. Systematic review of the diagnosis and management
of malignant extradural spinal cord compression: the Cancer Care Ontario Practice
Guidelines Initiative’s NeuroOncology Disease Site Group. J Clin Oncol. 2005;23:2028-
2037.
Ruckdeschel JC. Rapid, cost-effective diagnosis of spinal cord compression due to cancer.
Cancer Control. 1995;2:320-323.
Li KC, Poon PY. Sensitivity and specificity of MRI in detecting malignant spinal cord
compression and in distinguishing malignant from benign compression fractures of
vertebrae. Magn Reson Imaging. 1988;6: 547-556.
6. Prognostic Factors
• The most important predictor of ambulation capacity after treatment are the
pretreatment ambulatory status and time for development of motor deficits.
• In general, for ambulatory patients about 75% remain ambulatory after treatment,
and 50% of those who survive 1 year are still ambulatory.
• Unfortunately only 14% of patients who are paraparetic and 15% of patients who are
paralyzed regain “useful” function after RT.
• Another prognostic fator associated with survival is the histological subtype. Patients
with radiosensitive tumor such as myeloma, breast, or prostate cancer have the
Gustavo Arruda Viani
256
Study
Description
Sørensen S
Et al (1994)
Randomised trial of high-dose dexamethasone as an adjunct to radiotherapy in
patients with MSCC from solid tumours.
57 patients were randomized to treatment with either high-dose dexamethasone or
no steroidal treatment. Dexamethasone was administered as a bolus of 96 mg
intravenously, followed by 96 mg orally for 3 days and then tapered in 10 days.
Gait function after treatment was obtained in 81% of the patients treated with
dexamethasone compared to 63% of the patients receiving no dexamethasone
therapy.
Six months after treatment, 59% of the patients in the dexamethasone group were
still ambulatory compared to 33% in the no dexamethasone group.
Median survival was identical in the two treatment groups.
longest survival, whereas patients with lung, or gastrointestinal cancers have the
shortest.
• Presence of visceral metastases and a low clinical performance status are important
prognostic factors, even in patients with radiosensitive tumors.
References
Rades D, Rudat V, Veninga T et al. A score predicting posttreatment ambulatory status in
patients irradiated for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys.
2008;72(3):905.
Rades D, Fehlauer F, Schulte R et al. Prognostic factors for local control and survival after
radiotherapy of metastatic spinal cord compression. J Clin Oncol. 2006;24(21):3388.
7. Treatment
• The primary goals of treatment for MSCC are to restore spinal cord function, and to
relieve pain and distress.
• A general view of patient and examination will provide the evidence to make the
necessary decisions about treatment.
• Prognostic fators as tumor histology, functional ability, metastatic status of disease
and performance Status (PS) are all importants in treatment selection. Another
important factor of the pretreatment decision making process is an assessment of
spinal instability.
• Corticosteroids are often recommended for MSCC. They are administered in an
attempt to prevent further neurological deterioration and to improve the analgesic
effect. These effects are achieved by decreasing spinal cord edema and a possible
oncolytic effect on some tumours.
• The beneficial actions of glucocorticoids for preventing neurological deterioration
function in patients with MSCC were first reported in the late 1960s (table-1).
Table 1. clinical evidence for dexamethasone as adjunct to radiotherapy
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257
Study
Description
Vecht CJ et al
(1989)
37 patients with MSCC were randomly assigned to dexamethasone in an initial
bolus of 10 mg IV or 100 mg IV followed by 16 mg daily orally.
The average pain score before the start of treatment was 5.2 (SD = 2.8) and
decreased significantly (p less than 0.001) to 3.8 at 3 hrs, 2.8 at 24 hrs, and 1.4
after 1 week.
There were no differences between the conventional and high-dose group on pain,
ambulation, or bladder function.
Study
Description
Patchell et al.
(2005)
Patients with MSCC were randomized to either surgery followed by radiotherapy
(n=50) or radiotherapy alone (n=51).
Radiotherapy dose for both treatment groups was 30 Gy.
101 were randomised. Significantly more patients in the surgery group (42/50, 84%)
than in the radiotherapy group (29/51, 57%) were able to walk after treatment
(p=0.001).
Patients treated with surgery also retained the ability to walk significantly longer than
did those with radiotherapy alone (median 122 days vs 13 days, p=0.003).
32 patients entered the study unable to walk; significantly more patients in the surgery
group regained the ability to walk than patients in the radiation group (p=0.01).
The need for corticosteroids and opioid analgesics was significantly reduced in the
surgical group.
References
Sørensen S, Helweg-Larsen S, Mouridsen H, Hansen HH. Effect of high-dose dexamethasone
in carcinomatous metastatic spinal cord compression treated with radiotherapy: a
randomised trial. Eur J Cancer. 1994;30A(1):22.
Vecht CJ, Haaxma-Reiche H, van Putten WL, de Visser M, Vries EP, Twijnstra A. Initial
bolus of conventional versus high-dose dexamethasone in metastatic spinal cord
compression. Neurology. 1989;39(9):1255.
• Based on the results of these trials (table-2), we indicate for patients with severe
neurologic deficits, high-dose glucocorticoid therapy. On the other hand, for patients
with no severe neurologic symptoms, moderate doses of glucocorticoids should be
used.
• Decompressive resection and fixation followed by radiation therapy rather than
radiotherapy alone is indicated for patients with an unstable spine who have a limited
disease burden and good prognosis. In that clinical situation, a longer course of RT
such as 30Gy in 10 fractions is recommended (table-2).
Table 2. Clinical evidence for surgery followed radiotherapy
Reference
Patchell RA, Tibbs PA, Regine WF, et al. Direct Decompressive Surgical Resection in the
Treatment of Spinal Cord Compression Caused by Metastatic Cancer: A Randomised
Trial. Lancet 2005;366:643-648.
Gustavo Arruda Viani
258
Study
Description
Maranzano et
al. (2005)
300 patients with MSCC were randomly assigned to a short-course RT (8 Gy x 2 days)
or to a split-course RT (5 Gy x 3; 3 Gy x 5). A total of 276 (92%) patients were
assessable; 142 (51%) treated with the short-course and 134 (49%) treated with the
split-course RT regimen.
There was no significant difference in response, duration of response, survival, or
toxicity found between the two arms.
When short- versus split-course regimens were compared, after RT 56% and 59%
patients had back pain relief, 68% and 71% were able to walk, and 90% and 89% had
good bladder function, respectively.
Median survival was 4 months and median duration of improvement was 3.5 months
for both arms.
Rade et al.
(2009)
231 patients who underwent RT were included in this two-arm prospective
nonrandomized study.
Patients received short-course (n = 114) or long-course (n = 117) RT. The primary
endpoint was progression-free survival (PFS). The secondary endpoints were local
control (LC), functional outcome, and overall survival (OS).
The PFS rate at 12 months was 72% after long-course and 55% after short-course RT
(p = 0.034).
The 12-month LC rate was 77% and 61% after long-course and short-course RT,
respectively (p = 0.032).
The corresponding 12-month OS rates were 32% and 25% (p = 0.37). In addition to
radiation schedule, PFS was associated with the interval to developing motor deficits
before RT (relative risk, 1.99; 95% confidence interval, 1.10-3.55; p = 0.024).
Maranzano et
al. (2009)
327 patients with MSCC and short life expectancy were randomly assigned to a short-
course of 8 Gy x 2 or to 8 Gy single-dose RT. Median follow-up was 31 months
(range, 4-58).
No difference in response was found between the two RT schedules adopted.
Median duration of response was 5 and 4.5 months for short-course and single-dose
RT (p=0.4), respectively.
The median overall survival was 4 months for all cases. Light acute toxicity was
registered in a minority of cases. Late toxicity was never recorded.
• RT alone is indicated for patients with extensive metastatic disease and poor
performance status with a short expected survival (months).
• There are several schedules for palliative radiotherapy, a short course of radiation (1x
8 Gy) rather than a more protracted treatment schedule (10x 3 Gy or 20 x 20 Gy)
should be indicated for patients with poorer survival. On the other hand, patients with
good performance and stable spine can be better treated using a more protracted
schedule (10 x 3 Gy).
• Radiotherapy alone can be also indicated for patients with MSCC from radiosensitive
neoplasms (eg, breast cancer, lymphoma, myeloma) and with a stable spine (table-3).
Table 3. Clinical evidence for long or short course radiotherapy
References
Maranzano E, Bellavita R, Rossi R etal. Short-course versus split-course radiotherapy in
metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J
Clin Oncol. 2005;23(15):3358.
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Study
Description
Ryu et al. (2010)
A cohort of 500 cases of spinal metastases underwent radiosurgery. Ages ranged
from 18 to 85 years (mean 56). Lesion location included 73 cervical, 212 thoracic,
112 lumbar, and 103 sacral.
The maximum intratumoral dose ranged from 12.5 to 25 Gy (mean 20).
Long-term pain and control improvement occurred in 86 and 90%, respectivaly.
Long-term tumor control was demonstrated in 90% of lesions treated with SBRT.
84% with a progressive neurologic deficit before treatment experienced at least
some clinical improvement.
Gerszten et al.
(2007)
62 patients with a total of 85 lesions of MSCC were treated. Radiosurgery was
performed to the involved spine segment, including the epidural mass with median
dose of 16 Gy (range 12-20 Gy) in a single session.
The epidural tumor area at the level of the most severe spinal cord compression
was 0.82 +/- 0.08 cm(2) before radiosurgery and 0.41 +/- 0.06 cm(2) after
radiosurgery (P<.001). Thecal sac patency improved from 55 +/- 4% to 76 +/- 3%
(P<.001). Overall, neurological function improved in 81%.
Rades D, Lange M, Veninga T, Rudat V, Bajrovic A, Stalpers LJ, Dunst J, Schild SE.
Preliminary results of spinal cord compression recurrence evaluation (score-1) study
comparing short-course versus long-course radiotherapy for local control of malignant
epidural spinal cord compression. Int J Radiat Oncol Biol Phys. 2009;73(1):228.
Maranzano E, Trippa F, Casale M, Costantini S, Lupattelli M, Bellavita R, Marafioti L,
Pergolizzi S, Santacaterina A, Mignogna M, Silvano G, Fusco V. 8Gy single-dose
radiotherapy is effective in metastatic spinal cord compression: results of a phase III
randomized multicentre Italian trial. Radiother Oncol. 2009;93(2):174.
• SBRT can be indicated for MSCC with stable spine who have relatively
radioresistant tumors such as renal cell cancer, melanoma, and no evidence of highgrade cord compression (table-4).
Table 4. Clinical evidence for SBRT
References
Ryu S, Rock J, Jain R et al. Radiosurgical decompression of metastatic epidural compression.
Cancer. 2010;116(9):2250.
Gerszten PC, Burton SA, Ozhasoglu C, Welch WC. Radiosurgery for spinal metastases:
clinical experience in 500 cases from a single institution. Spine (Phila Pa 1976).
2007;32(2):193.
8. Radiotherapy Techniques
Treatment can be planned using a CT scanner for virtual simulation or a conventional
simulator. Data from clinical examination and the MRI is used to design the target volume.
For conventional radiotherapy , the patient is planned and treated in the prone position using a
direct posterior beam to avoid increased skin dose. But, for some patients the supine position
using an undercouch beam may be easier and more comfortable. CT slices are acquired from
Gustavo Arruda Viani
260
the spine level of interest. The GTV includes vertebral and soft tissue tumour as seen on CT
planning scan and diagnostic MRI. The CTV includes the spinal canal, the width of the
vertebra and one vertebra above and below the MSCC if the planning is based on MRI, or two
vertebrae above and below if based on X-ray or CT to allow for uncertainty about extent of
microscopic disease. The CTV to PTV margin is 1 cm. In patients who were submitted to
surgery previously to he radiotherapy treatment, the CTV will also include any metal that has
been used to stabilise the spine.
For treating the PTV adequately, a direct 6 MV photon beam may be used. For
lumbosacral lesions, a better dose distribution may be obtained with opposing beams (figure-
4).
Figure 4. Beams eye view and isodose distribution for a lumbosacral spine compression.
Conclusion
• Spinal cord compression is a debilitating and devastating condition for cancer
patients.
• Early diagnosis and prompt treatment is the best chance for patients to maintain their
ambulatory status. Agressive treatment combining surgery and radiotherapy in select
patients is the best treatment option in terms of ambulatory status.
• Multiple fractionation radiotherapy is recommedned more than single radiotherapy
for patients with good prognosis or for those submmited to surgery.
• Novel radiotherapy techniques such as SBRT represent a new hope to improve the
results in unfit patients for surgery, or for patients with spinal cord compression due
to radioresistent tumors.