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.