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Spinal metastases

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Proportion of cancer patients affected by spine metastases.
- 40% of all cancer patients develop spinal metastases
- 10-30% of spinal metastases patients will develop spinal cord compression (20K-30K cases/yr)
Distribution of spinal metastases per spine segments
- Thoracic 70%
- Lumbar 20%
- Cervical 10%
Tumors that metastasize to the spine
50% of all spinal mets are from breast, lung, prostate.
The other 50% from kidney, GI, Thyroid, Sarcoma, lymphoma, multiple myeloma
Frequency of spinal mets for specific cancers
- 90.5% of patient with Prostate cancers will have spinal mets
- Breast - 74.3%
- Melanoma - 54.5%
- Lung - 44.9%
Percentage of patients with Spinal mets and unknown primary site
- 10% of patients
What is the primary source of malignancy in a patient presenting first with spinal metastases and no other history of cancer
Lung in 50% of cases
Location of spinal metastases
- Vertebral column 85%
- Paravertebral region 10-15%
- Epidural or subarachnoid space <5%
- Intradural and intramedullary are rare
- Multiple lesions at noncontiguous levels in 10-40%
Presenting symptoms of spinal mets
- Pain (Most frequent). Located at the diseased site.
- Neurological compromise
Pain caused by spinal metastases
- PAIN: Generally proceeds neurological signs.
1- Tumor related: Insidious, progressive, dull, constant and worse at night or early morning.
2- Mechanical: results from destruction of vertebra to the point to create instability. Increased by standing, activity, coughing. Decreased in supine position.
How to explain "Nocturnal pain" in spinal mets
Venous engorgement of tumor with patient in supine position causes increased mass effect on surrounding pain-sensitive structures (Periosteum, dura, nerve roots, etc.)
Neurological Symptoms in spinal mets.
- NEUROLOGICAL COMPROMISE
1- Radicular symptoms
2- Myelopathic symptoms: Gait disturbance, spasticity, sensory or motor deficit, autonomic disturbance (Urinary and bowel symptoms).
Painless urinary retention with incontinence or recurrent UTIs.
Diagnostic Imaging of Spinal Mets
- MRI entire spine (most sensitive and specific modality)
- CT enhanced with myelography
- Bone scan (Detects osteoblastic lesions; Detects osteolytic lesion only if there is significant amount of bone repair)
Metastatic spinal lesions on imaging
- Osteolytic (majority) - 95%
- Osteoblastic - 5%
Plain xray in spinal mets
- Detect osteolytic lesion only when 30-60% of bone has been removed.
When should surgery be considered for spinal metastases
- Radioresistant tumors (sarcoma, lung, colon renal cell, breast)
- Untractable pain
- Spinal instability
- Significant compression of spinal cord
- Radiation failure
Determinants to be considered for the type and goals of surgery in spinal mets
- Patient ability to tolerate the procedure
- Patient life expectancy (base on the extent and aggressiveness of tumor and response to previous therapies)
Harrington classification scheme for spinal mets
1- No significant neurological involvement
2- Involvement of bone without collapse or instability
3- Major neurological involvement without significant bone involvement
4- Vertebral collapse with pain from instability or mechanical causes, but no neurological compromise
5- Vertebral collapse and major neurological compromise
Concepts of instability in spinal tumors
1- [Kostuik]: ANTERIOR COLUMN (vertebral body): Divided in anterior and posterior half and this was divided in left and right halfs (4 columns); POSTERIOR COLUMN: Pedicle and lamina (Divided in left and right- 2 columns). Instability if >3 columns involved.
2- [Tomita]: Instability if: Transitional deformity, Vertebral body collapse >50%, 3 column involvement (Denis 3 column definition: 1) 1/2 ant; 2) 1/2 post VB; 3) pedicle and lamina)
Tokuhashi preoperative prognostic scoring for spinal mets
6 variables (Worse to better: 0-1-2):
1- Karnofsky status (Poor, moderate, Good)
2- No of extraspinal bone mets (>3, 1-2, 0)
3- No of spinal mets (>3, 2, 1)
4- Mets to major internal organs (Unremovable, Removable, none)
5- Primary site (lung and stomach - kidney, liver, uterus, other, unidentified - Thyroid, prostate, breast, rectum)
6- Spinal cord palsy (Complete, Incomplete, None)
Life expectancy prediction based on Tokuhashi score
- 0-8 (<6 months) - Palliative radiation and chemo
- 9-11 (>6 months) - Palliative surgery
- 12-15 (>1 year) - Surgical excision and stabilization
Tomita preoperative prognostic scoring for spinal mets
3 variables (Better to worse: 1-2-4):
1- Primary tumor (Slow 1, moderate 2, rapid growth 4)
2- Visceral mets (Treatable 2, Untreatable 4)
3- Bone mets (Solitary 1, Multiple 2)
Treatment recommendations and life expectancy based on Tomita predictive score
- 2-3: long term local control - wide resection (38.2 mo mean survival)
- 4-5: Middle term local control - Marginal or intralesional excision (21.5 mo)
- 6-7: Short term palliation - Decompression (10.1 mo)
- 8-10: Palliative radiation only (5.3 mo)
Is there evidence to support use of steroid in patients with new spinal mets and neurological deficit?
- Yes!
- RCT: Dexamethasone and XRT vs XRT alone.
83% where ambulatory in treatment group vs 63% in XRT alone group [Sorensen].
- RCT: 100mg Dexamethasone vs 10mg Dexamethasone: No difference in pain relief, ambulation and bladder function [Vecht]. Higher doses are associated with higher risk of complications [Heimdal].
Most appropriate steroid treatment regimen for patient with spinal tumors and neurological involvement
- 10mg Dexamethasone bolus followed by 16mg/day. Tapered over several weeks depending on patient response and other treatments.
Is steroid therapy necessary in patients without clinical evidence of spinal compression?
No.
Steroid theoretical benefits in spinal mets
- Reduces vasogenic edema
- Protects agains lipid peroxidation and hydrolysis
- Enhances blood flow
- Prevent ischemia
- Prevent intracellular accumulation of Ca++,
- Stabilization of lysosomal membranes
- Attenuates inflammatory response
- Supports cellular energy metabolism
Bisphosphonates and spinal mets
2 types: Pyrophosphates and aminobisphosphonates
Inhibit bone resorption by inhibiting osteoclast activity
Direct tumoricidal effect
Is there any evidence in bisphosphonate use in bone mets?
- Yes.
- 18 RCT have showed that they decrease the skeletal related events defined as pathologic fractures, hypercalcemia, etc., in prostate, breast, lung, MM, renal cell cancers, but not spinal cord compression, surgery rates and XRT rates [Ross].
- Benefits were apparent after 6 months.
- Different bisphosphonates act differently in different tumors.
Role of bisphosphonates in cancer therapy
Can reduce the incidence of morbidity related to skeletal mets, but should not be used with intention of preventing spinal cord compression or as a treatment once it develops.
Chemotherapy in spinal mets
- Based on case reports and small case series.
- Successful in lymphoma, breast, prostate, germ cell tumors, hepatoblastoma, neuroblastoma, Ewing Sarcoma
How effective is decompressive laminectomy in spinal mets?
- Alone or in combination with XRT is not more effective than XRT alone in terms of restoring neurological function.
- Used only to establish diagnosis, treat a relapse if patient cannot undergo more XRT, if symptoms progress when undergoing XRT and if tumor is limited to posterior elements of vertebra, or as pure palliative treatment.
How effective is laminectomy and instrumentation in spinal mets?
- [Witham] found that 64% of patients who underwent laminectomy and stabilization had neurological improvement as compared to 36% for those undergoing XRT alone or 42% for those undergoing laminectomy with/without XRT.
- [Sherman]: 92% of 23 patients underwent lami and instrumentation had better posttreatment ambulatory status, sphincter function and pain control vs 57% of 111 patient that underwent lami alone.
What is the role of circumferential decompression and instrumentation in spinal mets?
- [Wang] Anterior decompression and posterior instrumentation: 140 patients, 96% improved postop pain, 75% of nonambulators regained ability to walk. Wound complications in 11.4%.
- [Chaichana] Anterior/Posterior/combined approach:
Negative predictors for regaining ambulatory ability were preop XRT and symptoms duration of >48hrs.
Are there RTC to compare surgery vs XRT in spinal mets?
- [Patchell]: Decompressive surgery (50 patients) followed by XRT and XRT alone (51). Surgical group were more likely to retain ambulatory status 84% vs 57%, retain ambulatory function for longer time (122 days vs 13) and regain ambulatory function if nonambulatory before treatment 62% vs 19% in XRT alone group.
Surgical patients maintained continence, muscle strength, functional ability, survival longer and required less narcotics and steroids than XRT pts.
Complications after surgical decompression in spinal mets.
[Patil]: 26,000 pts: Mortality 5.6% and Morbidity 21.9%
Pulmonary 6.7%, hematomas 5.9%.
Complications were most likely in elderly pts, and those with 2 or more comorbidities.
Strongest factors shown to lead to wound infection after surgery for spinal mets
- Preop XRT
- Nutritional status
- Amount of steroid use
Hence if surgery is being considered needs to be performed before XRT.
Kyphoplasty and vertebroplasty in spinal mets
Used for painful osteolytic mets or minimal pain, but impending vertebral body collapse
Contraindications: disruption of fragmentation of posterior body cortex, severe loss of vertebral height, significant epidural disease.
Indications for XRT in spinal mets
- Radiosensitive tumors (Lymphoma, MM, Small-cell lung carcinoma, seminoma, neuroblastoma, Ewing sarcoma)
- Expected survival <4mo
- Inability to tolerated operation
- Neurological deficit >48hrs
- Multilevel or diffuse spinal involvement
Doses of XRT for spinal mets
Total doses 30 to 40Gy in 10-20 days (Long term XRT)
30Gy in 10d, was similar to 40Gy in 20days [Rades]
1-2 fractions of 8Gy or 5 fractions of 4Gy each (Short term XRT)
Long term given if survival >6mo, Short term if <6mo
MM given long term treatment
Bladder and Lung cancer given short term XRT
Is there a predictive survival score for XRT in spinal mets?
[Rades 2008]:
- Type of primary tumor
- Other bone metastases
- Visceral mets
- Interval from tumor diagnosis to spinal compression
- Ambulatory status pre XRT
- Time to develop motor deficit prior to XRT
Results of XRT for spinal mets
Average pain improvement 77%
Ambulatory success 63%
Neurological rescue 29% [Falkmer]
Suggested treatment for spinal mets
Surgery for those that meet surgical criteria followed by XRT
XRT alone for those that do not meet surgical criteria or have a highly radiosensitive tumor.
Is there a place for Re-Irradiation of first round fails?
[Rades]: 124 patients underwent re-irradiation 77-142Gy, with 92% receiving <120Gy.
Motor function improved in 36% of pts and was stable in 50%.
Post-Treatment motor function was dependent on:
- First course of XRT
- ECOG performance status
- Time to development of motor deficits before XRT
- Presence of visceral metastases
Role of non-conventional XRT
SRS or IMRT:
[Yamada] 93pts with 103 lesions with IMRT 18-24Gy single dose and spinal dose limited to 14Gy.
Median f/u 15mo, local rate control was 90%,
Median time to local failure 9mo
Acute toxicity was mild
Role of non-conventional XRT in pain relief for spinal mets
[Ryu]: Median time to pain relieve was 14d, complete pain relief 46%, partial in 18.9%. Overall pain control in 1 year was 84%.
Optimal patient with spinal mets for radiosurgery
- Well-circumscribed tumor
- Pain as the principal symptom
- lacks severe spinal cord compression
- Lacks progressive neurological deficits
- Poor candidate for open surgery
- Has reached the limit of external-beam XRT
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