Download Emergency Radiotherapy for Malignant Spinal Cord Compression

Malignant Spinal
Cord Compression
CCPN Round – 15 March 2016
Definition of Malignant spinal cord compression (MSCC)
Comprehensive indentation, displacement, or encasement of the thecal sac
that surrounds spinal cord or cauda equina by spinal epidural metastases
CCON Neuro-Oncology DSG – Loblaw et al – JCO 2005
Compression of the dural sac and its contents (spinal cord and/or
cauda equina) by an epidural tumor mass
Minimum radiologic evidence is indentation of the theca at the level of
clinical features
Subclinical or Impending MSCC: Presence of the radiographic features
in the absence of the clinical features
Malignant spinal cord compression (MSCC)
Occurs in 5-10% of all cancer patients during the course of their disease
In the last 5 years of life, 2.5% of patients dying with cancer will have at least one
Loblaw et al – Clin Oncol - 2003
episode of MSCC
Most common cancers causing MSCC are breast, prostate, and lung cancers,
each account for about 20%, and myeloma, lymphoma, renal cancer 5-10%
In 20% of cancer patients with metastatic disease, MSCC is the initial manifestation of
cancer, 30% of these patients have lung cancer
Sites of MSCC: cervical spine 10% - thoracic spine 60-80% - lumbosacral spine 15-30%
Multi-level compression seen in 10-40% of patients
Epidural cord compression results from
direct extension of bony metastases
Vertebral body (1a) or
posterior elements (1b)
Paraspinal tumor infiltrating through
neural foramina (2)
Subdural (4) and Intramedullary (5) metastases
Soft tissue epidural mass in 75%,
bone collapse with fragments in 25%
Spinal Cord Compression
Cauda Equina Syndrome
MSCC: Compression of the thecal sac by tumor in the epidural space,
either at the level of the spinal cord (above L1-L2) or cauda equina
Pathophysiology: Ischemia and Vasogenic Cord Edema at the Level of Compression
Epidural MSCC most often related to soft tissue metastases causing compression
Direct arterial embolization of cancer cells in to the bone marrow of vertebra
Vertebral body mass impringes on the thecal sac, spinal cord, and epidural venous plexus
Pathologic vertebral body fractures can impringe on the thecal sac
MSCC is vascular in nature: Disrupted blood flow for both venous and arterial circulation
Prostaglandin E2 and Vascular endothelial growth factor (VEGF) release
Cord white-matter edema causing necrosis and gliosis
Venous compression and vasogenic edema of white matter: Slow development of MSCC and
neurologic deficits could be reversible
Arterial flow disruption causing ischemia and spinal cord infarction: Faster development of
MSCC and irreversible neurologic deficits
Pathogenesis of spine metastases and MSCC
Metastases in the bone marrow of vertebra by venous or arterial routes
Cancer cells in the bone marrow invade into the spinal canal through the foramina
of the vertebral veins rather than destroying the cortical bone
Cancer cells growing in an infiltrative fashion posteriorly into spinal canal and soft
tissue mass compresses the cord predominantly from an anterior direction
Disruption of blood flow for venous and/or arterial circulation
Arguello et al – Cancer J - 1990
Clinical Presentation
Back pain : 70-95% incidence
Motor deficits: 60-90% incidence
Sensory deficits: 45-90% incidence
Autonomic (bladder/bowel) dysfunction: 40-55%
Rate of progression of motor deficits and Status of ambulation before
initiation of treatment indicate probability of meaningful neurologic recovery
Clinical Evaluation
Clinical history and detailed neurologic examination
Functional assessment and ambulatory status using Frankel Grading system
MRI of the Entire Length of Spine – Gold Standard
MRI sensitivity 93% - specificity 97% - overall accuracy 95%
Complete MRI study: T1- and T2-weighted sagittal images –
T1- and T2-weighted axial images
A sagittal sequence of the entire spine is necessary
as multi-level compression ~ 10-40%
MRI provides superior resolution of soft tissue structures of
the spine including cord
MRI elucidates the bone-to-soft-tissue interface, providing
accurate anatomical detail of tumor invasion and compression
of bone, neural, and paraspinal structures
MRI can discriminate MSCC from benign conditions like:
Acute osteoporotic compression fracture and Spondylodiscitis
causing cord compression
If MRI facility is not available or in patients with cardiac pacemakers,
high-resolution CT scan or spinal CT myelogram is an alternative option
Prognosis or Outcome Measures
(Abrahm et al – Support Oncol – 2004)
Median survival of patients with MSCC depends on
1. Type of tumor (radio-responsive or radio-resistant)
1-year survival from diagnosis of MSCC:
Lymphoma and myeloma – 40% - Breast – 25% - Prostate – 20% - Lung – 5%
(Loblaw et al – CCON – JCO)
2. Patient’s performance status
3. Pre-treatment ambulatory status is the most important predictor
of ambulation post-treatment and of improved survival
4. Duration of motor deficit development before the onset of RT is
important prognosticator
Predicting overall survival in patients with MSCC treated with RT
Prognostic factors:
1. Tumor type (lymphoma/myeloma – breast ca – prostate ca – other ca)
2. Interval between diagnosis of cancer and MSCC ( < 12 versus > 12 months)
3. Other bone metastases
4. Visceral metastases
5. Ambulatory status before treatment
6. Duration of motor deficits ( < 14 versus > 14 days)
Management of MSCC
Since MSCC is usually associated with inadequate control of the
primary tumor, the goal of treatment is palliative and directed at
maintaining ambulation, decreasing tumor bulk, and relieving pain
(Quinn and DeAngelis – Semin Oncol – 2000)
Treatment Options:
Symptomatic therapy – Steroids – RT – Surgery – Bisphosphonates
Symptomatic therapy: Pain control – Spinal instability – Bladder and bowel function –
Psychological and social distress
Steroid Therapy for MSCC
Steroid should be used in patients with newly diagnosed MSCC causing cord dysfunction
Dexamethasone is most widely used steroid – Optimal dosage is controversial
Recommended regimen of Dexamethasone: 10 mg IV bolus followed by maintenance
16 mg/day IV/PO, tapering over several weeks
Dexamethasone inhibits prostaglandin E2 and VEGF production and activity, which leads
to a decrease of the vasogenic edema
In young patients presenting with an undiagnosed spinal mass with no previous history of
cancer, steroids should be avoided until the diagnosis is made (lymphoma)
Loblaw et al – CCON Neuro-oncology DSG – JCO - 2005
Conventional Radiation Therapy Alone
Indications for RT alone: 1. Expected survival < 6 months
2. Radio-responsive tumors
3. Patient unable to tolerate an operation
4. Duration of neurologic deficit below the level
of cord compression > 24-48 hours
5. Multilevel or diffuse spinal involvement
Radiotherapy Outcome & Dose Fractionation
30 Gy in 10 fractions – 20 Gy in 5 fractions – 8 Gy in 1 fraction
Choice of RT dose fractionation depends on patient’s:
Disease Status and Expected Survival
Pre-treatment Ambulatory Status
Pre-treatment Motor function and Sensory deficit
Different dose-fractionation schedules in pts with MSCC treated with RT alone
Rades et al – JCO supplement 2009
Multicenter nonrandomized study of 265 patients with MSCC comparing short-course RT
(8Gy/1Fx or 20Gy/5Fx) to longer-course RT (30Gy/10Fx – 40Gy/20Fx)
Both regimens were of similar effectiveness regarding post-RT motor function
Improved motor function in 30% of patients after SCRT and LCRT
Further progression of motor deficits was prevented in another 55% of patients in both arms
1-year local control: 80% after LCRT and 60% after SCRT
Better functional outcome associated with: young age - good performance status –
radio-responsive tumors - 1-2 vertebral involvement - being ambulatory before RT –
slow development of MSCC
Effectiveness of SCRT and LCRT have not been evaluated in a prospective phase III
randomized trial
65M – 40 PYS – PS ECOG 2-3
4/12 cough – hemoptysis – dyspnoea – fatigue
2/12 mid and lower back pain
1/52 weakness and numbness in legs
Motor deficits in legs – ambulatory with assistance
No bladder/bowel dysfunction
PET/CT: RUL mass – mediastinal nodes – bone mets – right adrenal mets
Bone scan: multi-level bone mets in axial skeleton
MRI: epidural cord compression at mid T-spine and L-spine
FNAC RUL mass: PD adenocarcinoma
Stage IV NSCLC with bone and adrenal mets (T2 N2 M1)
Selection of appropriate treatment individualized to a specific patient
Stage IV NSCLC with adrenal and multiple bone metastases - MSCC
Ambulatory - with assistance
Time to develop motor deficits - 1 week
Management:
1. Dexamethasone 4 mg QID IV/PO
2. Urgent RT: 8Gy/1 Fx – 20 Gy/ 5 Fx – 30 Gy/10 Fx
3. Consult to Spine Neurosurgery - NO
Surgery for MSCC
Patients with clinical/radiologic evidence of MSCC but no previous diagnosis of
cancer (or remote cancer)
Patient’s life expectancy > 6 months
Radio-resistant tumors
Unstable spine or bony fragment causing cord compression
Previous RT and inability to receive further RT
Surgery should be performed within 24 hours: high probability of improvement
in ambulation – motor function - bladder/bowel function
Anterior approach is preferable: 85% of metastases causing spinal instability or
neurologic deficits arise anteriorly in the vertebral body
Tumor is debulked and bony fragments removed, the void is filled with acrylate
cement, the spine is mechanically stabilized with metal prosthesis
Posterior Decompression Laminectomy
Any neurosurgeon can perform with minimal intraoperative risk to the patient, and
no spinal column reconstruction or stabilization
To establish pathologic diagnosis
15-55% of patients who underwent PDL remained ambulatory post-surgery
Neurologic benefit to the patient is minimal – increases spinal instability – worsen the
pain and neurologic deficits
PDL alone without spine stabilization is not recommended
Anterior Spinal Decompression Surgery
Approaches depends on the location of the tumor: Anterior – Posterolateral
Resection involves: Decompress the cord of any malignant compression
Reconstruction with plate & screw and Stabilization of the spinal column
Anterior Decompression Surgery plus Spine Stabilization is superior to RT alone
Klimo et al – Neuro-Oncology – 2005
24 reports (n-1000) treated with Surgery (anterior decompression & spine stabilization)
and 4 reports (n- 545) treated with RT alone
Post-treatment ambulatory rates: 85% for Surgery – 65% for RT alone
60% of non-ambulatory patients in Surgery group regained the ability to walk compared to
30% patients in RT alone group
Indications for Decompression surgery with spinal stabilization (Klimo et al)
Radio-resistant tumors
Obvious spinal instability
Clinically significant neural compression secondary to bone fragment or spinal deformity
Progression of neurologic deficits during or immediately after RT
55F – No comorbid conditions – PS ECOG 0-1
Left nephrectomy in 2005 for renal cell carcinoma of left kidney
2010: upper back pain for 3/12 - No neurologic deficits - Ambulatory
MRI: Lytic lesions in two upper thoracic vertebras with epidural soft
tissue
mass invading spinal canal and impending cord compression
CT scan chest – abdomen – pelvis: no local recurrence in left renal bed –
no lymphadenopathy or visceral metastases
CT brain clear – Bone scan: metastases in two upper thoracic vertebras
Establish tissue diagnosis from the spine lesion
Left Nephrectomy for RCC
2005
MSCC - 2010
Selection of appropriate treatment individualized to a specific patient
Past history of Renal cell cancer of left kidney treated with nephrectomy (2005)
Solitary bone metastases – no visceral metastases – no local recurrence in left renal bed
Interval from previous cancer diagnosis – 5 years
Ambulatory at presentation of MSCC – yes
No motor deficits at presentation – subclinical MSCC on MRI scan
Management:
1. Consult Spine Neurosurgery: Anterior cord decompression surgery and spine
stabilization - establish pathologic diagnosis
2. May need PORT
3. Lymphoma/Myeloma ?
Direct decompression surgical resection plus PORT versus RT alone in patients
with MSCC: A randomised trial
Patchell et al – Lancet - 2005 (University of Kentucky)
We assessed the efficacy of direct decompression surgery for patients with MSCC
Randomised multi-institutional trial, patients assigned to either surgery followed
by PORT (n=50) or RT alone (n=50)
Surgery involved spinal cord decompression and maximal tumor debulking and
spine stabilization
RT dose for both treatment groups (30 Gy in 10 fractions over 2 weeks)
Primary endpoint was the ability to walk (Ambulation)
Secondary endpoints: Urinary continence - muscle strength - functional status –
need for corticosteroids and opioid analgesics - survival time
Findings: After an interim analysis the study was stopped because the criterion of a
predetermined early stopping rule was met
125 patients were assessed for eligibility before the study closed and 100 were randomised
Significantly more patients in the surgery group (42/50, 84%) than in the RT group (29/50,
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 RT alone (median 122 days versus 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 RT group (10/16 versus 3/16 )
Need for corticosteroids and opioid analgesics was significantly reduced in surgical group
Interpretation: Direct decompression surgery plus PORT is superior to RT alone for
patients with MSCC
Limitations of the Patchell study was the patient selection criteria
Highly radio-sensitive tumors like lymphoma, myeloma, SCLC were excluded from both arms
KM estimates of length of time all pts remained ambulatory after treatment and
pts who were ambulatory at study entry remained ambulatory after treatment
Timing of PORT after Cord Decompression & Spine Stabilization
2 weeks interval between spine surgery and PORT
PORT dose - 30 Gy in 10 fractions over 2 weeks
Detrimental consequences of early initiation of PORT after surgical reconstruction:
-Impaired wound healing
-Impaired bone graft incorporation (arthrodesis)
3-4-week delay in initiation of PORT after surgical decompression and spine stabilization
(Sciubba and Gokaslan – Johns Hopkins Neurosurgery unit – J Neurosurg Spine 2010)
RT alone in patients with MSCC
1. Expected survival < 6 months
2. Radio-responsive tumors
3. Patient unable to tolerate an operation
4. Duration of neurologic deficit below the level of compression > 24-48 hours
5. Diffuse multi-level spinal involvement
B. No significant difference in treatment outcome (improved motor function
and post-RT ambulatory status) with different RT dose fractionation
C. If expected survival < 6 months: 8 Gy/1 Fx or 20 Gy/5 Fx
If expected survival > 6 months: 30 Gy/10 Fx or 40 Gy/16 Fx
D. In-field recurrence less with higher RT dose
E. Pts with good prognostic factors and radio-resistant tumors (melanoma, renal
cell cancer) should be considered for dose-escalation IMRT/SBRT
Surgery + PORT in patients with MSCC
Strict criteria for appropriate patient selection
Patients with clinical/radiologic evidence of MSCC but no previous diagnosis of cancer
Radio-resistant tumors
Unstable spine or bony fragment causing cord compression
Previous RT and inability to receive further RT
If surgery is indicated, should be performed immediately (within 24 hours)
Anterior approach is recommended as 85% of metastases causing spinal instability or
neurologic deficits arise anteriorly from the vertebral body
Using anterior approach, the tumor is debulked and bony fragments removed, the void
is filled with acrylate cement, the spine is mechanically stabilized with metal prosthesis
For posteriorly placed tumors, posterior laminectomy with stabilization is recommended
PORT should be initiated 3-4 weeks after surgical resection and spine reconstruction
High-Precision RT
Young patients with good performance status may be
considered for SBRT
Aim of HPRT is to achieve better sparing of critical normal tissues and/or dose escalation
to the site of metastatic disease in the spine
If the tumor is invading into the spinal canal, fractionated SBRT is preferred to reduce the risk of
radiation-induced myelopathy and vertebral body fracture
Recent reports suggest that HPRT (SBRT) is safe and effective, but has not been compared to
surgery and conventional EBRT
Young patients with good PS and radio-resistant tumors (melanoma, renal cancer) should be
considered for dose-escalation fractionated SBRT
SBRT can be an effective salvage treatment in patients with in-field recurrence after
prior convention EBRT for MSCC
Pros and Cons of HPRT – Spine Neurosurgeon’s prospective
(Sciubba and Gokaslan – John Hopkins University – J Neurosurg Spine 2010)
Convention RT delivers inadequate dose to the target and not recommended if the tumor
histology is radio-resistant
Advent of HPRT (SRS – SBRT) has led to a fundamental change in the treatment paradigm for
spine metastases and MSCC
High dose to the target with maximal sparing of critical neural structures with HPRT provides
superior local disease control – preservation of neurologic function – pain relief
HPRT can not correct spinal instability or deformity causing pain or neurologic dysfunction
HPRT can not correct cord compression caused by pathologic vertebral body fracture and
retropulsion of bone fragment into the spinal canal
Retreatment of MSCC for in-field recurrence after previous EBRT
A second episode of MSCC occurs in up to 15% of patients
Decompression surgery would be first choice of treatment – surgery is possible in 10-15%
of these patients with recurrent MSCC
Re-irradiation may result in an increased risk of radiation-induced myelopathy
For re-irradiation after conventional RT, HPRT like SBRT be considered
Recent HPRT studies report improved motor function in 40-85% of re-irradiated patients
Radiotherapy or Surgery in
Spinal Cord Compression?
The Choice Depends on
Appropriate Patient Selection
Role of radiotherapy for metastatic epidural spinal cord compression (MESCC) – Dirk Rades
RT alone is the most common treatment for metastatic epidural spinal cord compression (MESCC)
Decompressive surgery followed by PORT is generally indicated only in 10–15% of MESCC cases
CT has an unclear role and may be considered for selected patients with lymphoma or myeloma
If RT alone is given, it is important to select the appropriate regimen
Similar functional outcomes can be achieved with short-course and longer-course RT regimens
Longer-course RT is associated with better local control of MESCC than short-course RT
Patients with a more favorable survival prognosis (expected survival of ≥6 months) should receive longer-course RT,
as they may live long enough to develop a recurrence of MESCC
Patients with an expected survival of <6 months should be considered for short-course RT
Recurrence of MESCC in the previously irradiated region after short-course RT may be treated with another shortcourse of RT
After primary administration of longer-course RT, decompressive surgery should be performed if indicated
Alternatively, re-irradiation can be performed using high-precision RT (SBRT) techniques to reduce the cumulative
dose received by the spinal cord
Larger prospective trials are required to better define the appropriate treatment for the individual patient