metastatic tumors of the spinal column
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Metastatic Tumors of the
Spinal Column: Diagnosis and Management
GEORGE SAPKAS PROFESSOR AT ORTHOPAEDICS
Metropolitan Hospital Athens
Epidemiology
Pneumon’s metastasis
Συχνότητα άνα περιοχή
Metastasis
CA- breast 45-85%
CA- lung 35-60%
CA-kidney 35-40%
CA- prostate 35-85%
CA- thyroid 30-60%
Skull 35%Cervical spine 22%
Humerus 10%Ribs 57%
Thoracic spine 37%Lumbar spine53%Sacrum 6%Pelvis 19%Femur 22%
Gasbarrini A. et al European Review for medical and Pharmacological sciences 2004
Sites of primary tumors
BreastPneumonProstateRenal Thyroid
75%
Pneumon’s metastasis
The most common location for skeletal metastasis:
• Thoracolumbar region ~ 70%
• Lumbar and sacral spine ~ 20%
• Cervical spine ~ 10%
Gilbert R.W. et al. Ann. Neural. 1998 Pneumon’s metastasis
European Review for medical and Pharmacological sciences 2004
Vertebral metastases are the first sign of
malignant disease in 12% to 20% of the cases.
Schick V. et al. Neurosurg. Rev. 2001
Schiff D. et al. Neurology 1997
Pneumon’s metatstasis
Clinical symptoms of
spinal metastasis
PainNeurologic deficit
The spinal pain may be due:
In destruction of the anatomic vertebral elements as a result of metastases Resulting spinal instability
The pain is possible to occur as a result of:
compression or infiltration of the spinal cord – nerves from neoplasmatic masses.
Pain
Pathologic spinal fracture
Spinal pain
Instability Compression of the neural
tissues
Neurologic deficit
Diagnosis of spinal metastases
M.K. F 81
2yrs POP
Thyroid metastasisL3
L3
T12
T12
CT
3-D
Kidney’s metastasis
M.R.I.
Tc 99 MDPSCANNING
Lemphoma
P.E.T.
Graig’s trocar
C.T. – guided percutaneous needle - trocar
Biopsy of the spine
Treatment
Medical treatment ChemotherapyHormone therapy Immunotherapy
Radiotherapy Operative
Medical treatment
ChemotherapyAnti-tumor medicationSteroids Bi-phosphonates
Chemotherapy
Highly sensitiveChildhood cancers like
acute lymphocytic leukemiaWilms tumor Ewing’s tumor Retinoblastoma Rhabdomyosarcoma
Hodgkin’s lymphoma.Carcinoma of the testis.Choriocarcinoma.Burkitts tumor.Acute promyelocytic leukemia.
Costachescu E. et al 2010
Chemotherapy
Moderately sensitiveAdenocarcinoma of breast.Non-Hodgkin’s lymphoma.Lung cancer.Osteosarcoma.Adult myeloid and lymphocytic leukemia.Carcinoma of the prostate.Colorectal carcinoma.Female cancers of the ovary, endometrium, and cervix.
Costachescu E. et al 2010
Chemotherapy
Minimally sensitiveEndocrine gland cancers.Malignant melanoma.Hepatocellular carcinoma.Renal carcinoma.Pancreatic carcinoma.
Costachescu E. et al 2010
Hormonal therapy
Is administered in breast and prostate cancer. In breast cancer
tamoxifen, aromatase inhibitorsfulvestrant
In prostate cancer LHRH-analoges, anti-androgens novel hormonal compounds (abiraterone and enzalutamide)
Targeted therapies
Are used in various tumors and include monoclonal antibodies and TKIs (tyrosine kinase inhibitors). In breast cancer anti-HER2 agents (trastuzumab, pertuzumab, TDM1 and lapatinib) are used, in combination with chemotherapy or hormonal therapy, in patients with HER2-positive disease. In hormone-sensitive breast cancer the mTOR inhibitor everolimus is used in combination with aromatase inhibitors for reversal of the resistance to hormonal therapy. In renal cell carcinoma anti-angiogenic TKIs (sunitib, pazopanib, axitinib) and mTOR inhibitors (temsirolimus and everolimus) are used. In NSCLC anti EGFR TKIs (gefitinib, erlotinib, afatinib) and ALK-inhibitors (crizotinib) are effective agents.
Bi-phosphonates
Tend to inhibit osteoclast re-absortion of bone matrix and decrease bone turnover.There are three generations of bi-phosphonate currently available.
Costachescu E. et al 2010
Bi-phosphonatesBisphosphonates and denosumab are used in combination with other treatments (systemic or radiotherapy or surgery). They reduce skeletal-related events and improve the quality of life of patients. Bisphosphonates are used:
breast, prostate cancerother solid tumors (e.g. NSCLC, renal cell cancer etc).
Denosumab is used: Breast prostate cancer.
The main side effect of the above compounds is osteonecrosis of the jaw.
Radiotherapy
Relevant contraindication : Neurologic deficitAbsolute contraindication : Vertebral collapse
Indications • Palliative • Post-operative
Radiosensitivity of metastatic lesions
Squamous cell carcinomas
Lymphomas
Adenocarcinomas
Sarcomas
Melanoma
• Provide pain relief (in more than 80% of patients)• Improve or maintain neurologic function • Restore or maintain the structural integrity of S.C.
External Beam Radiotherapy for Symptoms
Short course Vs. Long course: Same results in pain relief and functionality More often re-irradiation with short course
Long course more effective for bone re-calcification
Long course is better for patients with longer life expectancy (e.g. Breast or prostate cancer)
Short course 1 × 8 Gy ή 5 × 4 GyLong course 10 × 3 Gy, 15 × 2.5 Gy, ή 20 × 2 Gy
- At diagnosis compression of spinal cord and bone destruction
- 6 months after radiotherapy
2 weeks of radiotherapyBone re-modeling
Intensity Modulated Radiotherapy (IMRT)
Extracranial Body Radiotherapy (SBRT)
Advanced Radiotherapy Techniques
• Oligometastases
• Re-irradiation
Indications for IMRT & SBRT
Protection of spinal cord Option of re-irradiation
Postoperative EBRT with IMRT
Fractions Dose Definition Intications
1-5 12-20 Gy Extracranial Body Stereotactic Radiotherapy(SABRT)
Radical treatment
>5 5 × 5-6 Gy10 × 3 Gy15 × 2.5 Gy 20 × 2 Gy
Fractionated Extracranial Body Stereotactic Radiotherapy(FSBRT)
Lesions near spinal cordRe-irradiation
Extracranial Body Stereotactic Radiotherapy
Breast Prostate Myeloma Lemphoma
• Long survival ship 10x3 Gy vs 1x 8 Gy.
• More effective for re-calcification(Koswig et al. 1999)
10x3 Gy & 20x2 Gy • Lesser local recurrences
Rades et al. JCO 2005
Cortizone versus Placebo & Radiotherapy):• Motor fucntion 81% with cortizone versus 63% without
cortizone Sørensen et al. 1994.
Bone MetastasisRadiotherapy
One metastatic lesion 20 Gy 4 x 5 Gy
(SIB) 25 Gy 5 X 5 Gy
Oligometastatic lesions of S.C. Extracranial Body Stereotactic Radiotherapy
CA Thyroid to 1st lumbar vertebra
Post – Radiotherapy following Kyphoplasty
Radiotherapy of the spine
Radiotherapy
EXPECTED LIFE TIMEQUA
LITY
OF
LIFE
WITHOUT THERAPY
PALLIATIVE THERAPY
Spinal metastasis
Timetable of palliative radiotherapy
Time
Pain
inte
nsit
y
Radiotherapy ???
Radiotherapy
Spinal metastasis
1. Spinal instability2. Pain resistible to conservative
treatment (radiotherapy – chemotherapy)
3. Incomplete neurologic deficit resistible to any type of conservative treatment
4. Rapid deterioration of the neurologic deficit
Indications for operative treatment
5. Recurrence of tumor in an area that has been already submitted in radiotherapy (at the maximum permitted levels)
6. Ambiguous histological diagnosis
The biology of the tumorThe locationThe painThe neurologic deficitThe spinal instabilityLife expectancy Overall condition of the patient
Aboulafia A. Levine A., OKU Spine 2, 2004
Factors for evaluation:
Tokuhashi scoring system
Tomita surgical stagingKarnofsky performance status
scale definitions rating (%) criteria
Methods of evaluation
Tokuhashi’s Evaluation System for prognosis of metastatic spinal tumors
Symptoms 0 1 2General condition performance status
Poor (PS 10% to 40%)
Moderate(50% to 70%)
Good(80% to 100%)
No of extraspinal skeletal metastases
>3 1 to 2 0
Metastases to internal organs
Unremovable Removable No metastases
Primary site of tumor Lung stomach Kidney liver uterus unknown
Thyroid prostate breast rectum
Number of metastases
>3 2 1
Spinal cord palsy Complete Incomplete None
Tokuhashi, Y. et al, Spine 1990
Total score versus survival period:9 to 12 points > 12 months survival0 to 5 points < 3 months survival
Tokuhashi’s criteria allow the definition of a pre-operative strategy and therefore considerable variability in the choice of treatment ranging:
excisional operation should be performed on those who scored above 9 points
a palliative operation should be performed on those who scored under 5 points Tokuhashi Y. et al.
Spine 1990
Simpler system of preoperative evaluation based on only three parameters:
the degree of malignacy
the presence of visceral metastases
the presence of bony metastases.
Tomita K. et al. Spine 2001
Bauer H. et al. Spine 2002
Tomita’s classification systemIntra-compartmental Extra-compartmental Multiple skip
lesion
Type 1
Type 2
Type 3
Type 4
Type 5
Type 6
Type 7
Site (1 or 2 or 3)
Anterior or posteriorLesion in situ
Site (1 +2 or 3 + 2)
Extension to pedicle
Site (1 +2 +r 3)
Anterio-posterior development
(any site + 4)Epidural extension
(any site + 5)Paravertebral development
Involvement toadjacent vertbra
Surgical procedures
Types of operative treatment
Decompression
Decompression– spondylodesia
Debulking
Piecemeal excision
En block excision
(marginal or wide)
Boriani S. et al Spine 1997
1-2 vertebral metastases
Anterior procedure
Gasbarrini A. et al European Review for medical and Pharmacological sciences 2004
Breast’s metastasis
• Vertebrectomy • Vertebral substitution
by cylinderand
• Stabilization
.
Posterior procedure
1. Vertebrae2. Posterior vertebral
elements involvement3. Poor general condition
Posterior decompression ±
stabilization
Gasbarrini A. et al European Review for medical and Pharmacological sciences 2004
Breast’s cancer
A. St.F: 81N(+)
Mastectomies 35 yrs ago
a. Posterior decompression and Occipitocervical stabilization
b. Post-operative adjuvant chemotherapy - radiotherapy
N(-)N(-)
Breast’s metastasis
Posterior decompression ±
stabilization
Thoracic spine
Posterior decompression andstabilization
Combined procedures(anterior – posterior)
Breast metastasis
Breast’s metastasis
Global Spine Tumor Study Group
Gasbarrini A. et al European Review for medical and Pharmacological sciences 2004
Total en block Vertebrectomy
Total vertebrectomyStener 1971
Stener and Johnsen 1971
Sundaresan et al 1988
Roy-Camille et al 1990
Boriani et al 1994
Tomita et al 1994
Total en Bloc spondylectomy (TES) for solitary spinal metastasesInt. Orthopedics, 1994
Total Vertebrectomy according to Tomita
Total en Bloc Spondylectomy (TES)
Harmful
Not useful
Useful
Asymptomatic, Inactive aneurysmal bone cyst T11 , 65 yrs
Primary osteosarcoma L3, 40 yrs
Meta Ca Lung, T4, T7, meta liver, >72 yrs, Karnofsky 20
En Block VertebrectomyIndications
Primary malignant tumors stage Ι - ΙΙ
Aggressive benign tumors stage 3 (GCT)
Isolated metastasis with long life expectancy
Metastatic disease of the Spineindications for En Block total Vertebrectomy
Tomita’s suggestions according to prognostic score2-3 : wide excision4-5 : marginal or intralesional excision6-7 : palliative surgery8-10 : non-surgical supportive care
Tokuhashi’s suggestions according to prognostic score12–15 : excisional 9–11 : palliative surgery <8 : conservative management
Tomita: Spine 26: 2001
Anatomical restrictions
•Anterior longitudinal ligament•Posterior longitudinal ligament•Periosteum of spinal canal•Ligament flavum•Periosteum of lamina•Periosteum of spinal process•Intrespinous ligament•Spinous ligament•End plate •Nucleous polposus
Anatomical restrictions forTotal En Block Vertebrectomy
Total En block Vertebrectomy(TEBV)
operative technique
The two theories need not be mutually exclusive
Total En block Vertebrectomy(TEBV)
surgical approachPosterior – Above L4 vertebra who have no contact wth great vessels (Type 3 – 4) – Straight control of the spinal canal
Combined procedure
Anterior – Posterior Type 5-6– Close contact to great vessels
Posterior – Anterior – For tumors of L5 vertebra (posterior procedure is impossible due to iliac crest and the
anteriorly located great vessels )
Total En block Vertebrectomy(TEBV)
surgical approach
The two theories need not be mutually exclusive
Total En block Vertebrectomy(TEBV)
surgical technique
The two theories need not be mutually exclusive
Total En block Vertebrectomy(TEBV)
surgical technique
Total En block Vertebrectomy(TEBV)
surgical technique
Total En block Vertebrectomy(TEBV)
surgical technique
Total En block Vertebrectomy(TEBV)
surgical technique
Total En block Vertebrectomy(TEBV)
surgical technique
Uncontrollable hemorrhage
Injury of great vessels
Spinal cord injury
Dissemination of cancerous cells
Total instability
Total En block Vertebrectomy(TEBV)
intra-operative complications
Local recurrence due to remaining malignant and dispersion cancerous cells intra-operatively
Talac et al, Relationship between surgical margins and local recurrence in sarcomas of the spine, CORR 397:127 - 132
Tomita et al,J Orthop Sci (2006) 11:3–12
Revision due to local recurrence
Extremely difficult
Postoperative scars with adhisions to nearby sensitive anatomical stractions – meninges – Aorta– vena cava
Therefore the first operation should be and the final
Talac et al, Relationship between surgical margins and local recurrence in sarcomas of the spine, CORR 397:127 - 132
The two theories need not be mutually exclusive
Tomita et al,J Orthop Sci (2006) 11:3–12
Total En block Vertebrectomy
Material(open procedures)
n 2006 - 2012n 45 patients :
28 women and 17 men n Age: 58.8 yrs (range 22-72)n Neurologic deficit 15 pts
Material
The primary tumors were:Breast 12 ptsLung 11 ptsThyroid 4 ptsColon 2 ptsKidney 4 ptsUterus 5 ptsLymphoma 4 ptsGastric 2 ptsHepatocellular 1 pt
The main lesion of the spinal metastases were located in the:
Thoracic spine: 38 pts
Lumbar -//-: 5 pts
Cervical -//-: 2 pts
Material
Breast’s metatstasis
Operative treatment
• Spondylectomy 32 pts• Decompression
& Stabilization 13 pts
Results
Gasbarrini A. et al European Review for medical and Pharmacological sciences 2004
Follow-up:
62 months ( 6 - 115 ).
Operative time:n one session: 13½ h (9 - 21)n two stages: 11 h (9 - 14)
Combined Procedures
blood loss: 1500 ± 500 ml
A. PainB. Neurological
status - paresis C. Gait
Clinical evaluation
Clinical results of prosthetic replacement surgery. The improvement rate was 94% for pain, 82% for motor function and 73% for ambulation.
Prosthetic replacement of spinal metastasis
Posterior stabilization
Clinical results of posterior stabilization. The positive recovery rate was 52% for ambulation, 50% for motor function and 84% for pain.
Neurologic Evaluation:
Improvement in 80% of the patients.
Complications
Intra-operative Early postoperative < 3wksLate postoperative > 3 wks
Major Intra-operative complications
N(-)ve
Early post-operative complications
< 3weeks
Wound dehiscenceNeurologic deteriorationImplants dislodgementinfections
Late post-operative complications
> 3 weeks
Wound dehiscenceNeurologic deteriorationImplants dislodgement or brokeninfections
Late post-operative instability (spinal destabilization)
Breast’s metatstasis
Late post-operative instability (implants failure)
Breast’s metatstasis
Post-operative complementary
treatment
Radiation therapy of spinal metastases
Tombolini Y. et al 1994
Ortho - Athens
Best to start > 3wks post - op
Vertebroplasty - Kyphoplasty
Minimal invasive techniques
Vertebral fractures (compression ± burst)Osteoporotic fractures (compression ± burst)Pathologic fractures of the spinal vertebra (metastasis)Haemangioma of the vertebraMultiple myeloma
Pneumon’s metastasis
Vertebroplasty – KyphoplastyIndications
Destruction of the posterior spinal elementsBurst fractures (±)Neurologic compression syndromes(due to dislocated bony fragments)Destruction of dorsal structures(vertebral arch and facet joints) Vertebra planaSpinal infection Allergy (methylmethacrylate etc)Coagulopathy Untreated cardiovascular disturbances
Thyroid metastasis
Vertebroplasty – KyphoplastyContraindications
18 cases
Vertebroplasty
Kyphoplasty (single level)
kidney’s metastasis10 cases
Kyphoplasty(multiple levels)
11 cases
Pneumon’s metastasis
Conclusions:
Gasbarrini A. et al European Review for medical and Pharmacological sciences 2004
is treated successfully only by operative procedure
Breast’s metatstasis
Spinal instability and
neurologic deficitdue to metastasis
Prosthetic replacement is indicated for
metastasis at one or two consecutive
vertebrae
Pneumon’s metatstasis
Posterior stabilization is recommended:
• For multiple metastases
• Poor general condition
• Short life expectancy
Anterior vertebral replacement and
anterior – posterior stabilization
1. Is indicated in excessively unstable spineand
2. It gives the best overall results
For the metastatic spinal lesions:
The minimal invasive techniques (Verterboplasty – Kyphoplasty)
are recommended methods of treatment.
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