Spinal Metastases Sohail Bajammal, MBChB, MSc, FRCS(C) October 6, 2008 Spine Fellows Rounds

Spinal Metastases

Sohail Bajammal, MBChB, MSc, FRCS(C)

October 6, 2008Spine Fellows Rounds

Acknowledgement

Aleks Cenic

45 minutes update

Once upon a time…

• Comparison of laminectomy and external beam radiotherapy

Nowadays…..

Total en bloc spondylectomy

Tomita K, Kawahara N, Baba H, Tsuchiya H, Nagata S, Toribatake Y. Total en bloc spondylectomy for solitary spinal metastases. Int Orthop. 1994 Oct;18(5):291-8.

On the other hand, nowadays….

Finn MA, Vrionis FD, Schmidt MH. Spinal radiosurgery for metastatic disease of the spine. Cancer Control. 2007 Oct;14(4):405-11.

Spinal Metastases

• Epidemiology

• Pathophysiology

• Presentation

• Treatment Options

• Decision Making

Epidemiology

• 1.2 million new cancer per year in USA

• 40% of all patients will develop metastatic spinal disease– 10-20% of these patients will develop spinal

cord compression

• Spinal metastasis is the initial presentation of malignancy in 20% of patients

White AP, Kwon BK, Lindskog DM, Friedlaender GE, Grauer JN. Metastatic disease of the spine. J Am Acad Orthop Surg. 2006 Oct;14(11):587-98.

Significance

• The spine is the most common site for skeletal metastases

• Metastatic lesions are the most common tumors of the spine (95-98%)

• Vertebral body affected first

• Approximately 70% of patients who die of cancer have evidence of vertebral metastases on autopsy

Harrington KD. Metastatic disease of the spine. J Bone Joint Surg Am. 1986 Sep;68(7):1110-5.

Future

• Population ages

• Better adjuvant therapy

• Patients surviving longer

• More patients developing metastatic disease

Pathophysiology

• Hematogenous Spread:– Batson’s plexus– Arterial embolization

• Seed and Soil Theory

• Direct invasion

Primary SitesMD Anderson 1984-1994 (n=11,884)

• Breast (30.2%)• Lung (20.3%)• Blood (10.2%)• Prostate (9.6%)• Urinary tract (4%)

• Skin (3.1%)• Unknown 1° (2.9%)• Colon (1.6%)• Other (18.1%)

Gokaslan ZL, York JE, Walsh GL, McCutcheon IE, Lang FF, Putnam JB Jr, Wildrick DM, Swisher SG, Abi-Said D, Sawaya R. Transthoracic vertebrectomy for metastatic spinal tumors. J Neurosurg. 1998 Oct;89(4):599-609.

Level of Metastases

• Thoracic 70%

• Lumbar 20%

• Cervical 10%

Clinical Presentation

• Pain (85%)– Biologic: local release of cytokines, periosteal irritation,

stimulation of intraosseous nerves, increased pressure or mass effect from tumor tissue in the bone

– Mechanical: nerve compression, pathologic fractures, instability

• Weakness (34%)– Spinal cord compression in 20%– Early: edema, venous congestion, and demyelination– Late: secondary vascular injury and spinal infarction

• Mass (13%)

• Constitutional Symptoms

Spine Surgeon’s Role

• 20% of patients, the first presentation of a malignancy is a spinal problem

Schiff D, O’Neill BP, Suman VJ. Spinal epidural metastasis as the initial manifestation of malignancy: clinical features and diagnostic approach. Neurology 1997;49:452–456.

Evaluation

• History• Physical Exam• Laboratory:

– CBC, ESR, CRP, Lytes, BUN, Creatinine– Ca, PO4, Alk Phosph– Urinalysis: routine, Bence-Jones Proteins– Special: PSA, thyroid Fxn, serum and urine protein

electrophoresis, liver function tests, stool guaiac, CEA

• Radiological• Biopsy

Radiological Evaluation

• Local:– X-ray of spine: AP, lateral, oblique

• “winking owl” sign: pedicle destruction• Vertebral body destruction is not visible until 30-

50% of trabeculae are involved• Negative x-ray does not rule out tumor

– Bone Scan: screening, cold in MM– CT: bony architecture– MRI + gadolinium of the whole spine: gold

standard

Radiological Evaluation

• Staging:– CT chest, abdomen and pelvis with oral and

IV contrast– Bone Scan– Mammogram

• Angiogram:– Pre-operative embolization– Renal cell, thyroid

Biopsy• Indicated if diagnosis is unclear after workup:

– Remote history of cancer with long disease-free interval

• Options:– CT-guided: most accessible lesion, minimal morbidity,

tattoo tract for later excision• Accuracy: 93% for lytic lesions, 76% for sclerotic lesions

– Open: cost, delay, definitive for benign tumors

• Culture every tumor and biopsy every infection

Lis E, Bilsky MH, Pisinski L, Boland P, Healey JH, O'malley B, Krol G. Percutaneous CT-guided biopsy of osseous lesion of the spine in patients with known or suspected malignancy. AJNR Am J Neuroradiol 2004;25:1583-1588.

Goal of Management

Maximize quality of life

Curative in certain solitary metastasis

To achieve the goal….

• Provide pain relief

• Improve or maintain neurologic function

• Restore or maintain the structural integrity of the spinal column

Treatment Options• Supportive: Orthotic, Steroids,

Bisphosphonates

• Chemotherapy & Hormonal Therapy

• Radiotherapy

• Surgery

• Combination

Multi-disciplinary approachMulti-disciplinary approach

Pitfall

Aggressive chemotherapeutic regimens for patients with spinal pain not responding to conventional therapy without ruling out subtle mechanical etiology

Severe depression of bone marrow that surgery or radiotherapy are no longer feasible

Steroids• Indicated in cord compression

• Better ambulation and pain control

• Optimal dose is controversial

• Low-dose: 10mg IV blous dexamethasone, followed by 4mg PO q6 hours

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):22-7.

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 Sep;39(9):1255-7.

Bisphosphonates

Efficacy in treatment of hypercalcemia, pain control, reduction in number and time to skeletal events, and improvement of quality of life in patients with multiple myeloma and bone metastases from solid tumors

Pavlakis N, Schmidt RL, Stockler M: Bisphosphonates for breast cancer. Cochrane Database Syst Rev 2005, (3): CD003474.

Penas-Prado M, Loghin ME. Spinal cord compression in cancer patients: review of diagnosis and treatment. Curr Oncol Rep. 2008 Jan;10(1):78-85.

Radiotherapy

• Goal is to debulk, promote calcification or ossification (3 months), relieve pain

• Of patients that are ambulatory at presentation, 70% will remain so

• Can be used when myelopathy due to soft tissue but not if due to bone or deformity (Harrington III)

• Combine with surgery if failure of radiation at that level (deformity or neurological worsening)

External Beam Radiotherapy (EBRT)

• Radiosensitivity– Myeloma & Lymphoma: most radiosensitive– Prostate, Breast, Lung and Colon: moderately– Thyroid, Kidney, Melanoma: not radiosensitive

• Dose– 5,000 cGy in 25 fractions over 5 weeks (C & L-

spine)– 4,500 cGy over 4½ -5 weeks in T-spine


• RCT:– 16 pts underwent laminectomy & radiation– 13 pts underwent radiation alone

• Mean follow-up: 4 months

• No difference in pain relief, improved ambulation, or improved sphincter function

Young RF, Post EM, King GA. Treatment of spinal epidural metastases. Randomized prospective comparison of laminectomy and radiotherapy. J Neurosurg 1980 Dec;53(6):741-8.

Laminectomy is a bad option

• Most of the pathology in the vertebral body is anteriorly

• Insufficient debulking and decompression

• Predisposes to spinal instability

• RCT (n=101)

• Surgery and radiotherapy vs radiotherapy alone

• Primary Endpoint: Ability to walk

• Secondary Endpoints: urinary continence, Frankel functional change, ASIA motor score, functional status, survival time, need for steroids and opioids

Patchell et al, The Lancet 2005


• Post-treatment ability to walk: 84% in the surgery versus 57% in the radiation group (p=0.001)

• Patients retained the ability to walk for 122 days in the surgery group versus 13 days in the radiation group (p=0.003)



However….


• Inclusion Criteria:– > 18 yr, tissue-proven diagnosis of cancer

– MRI evidence of MESCC (metastatic epidural spinal cord compression)

– At least one neurological sign or symptom (e.g., pain)

– Not totally paraplegic for >48 h before study entry

– MESCC restricted to a single area, which could include several contiguous segments


• Exclusion Criteria:– Certain radiosensitive tumors (lymphomas, leukemia,

multiple myeloma, and germ-cell tumors)

– Mass compressed only cauda equina or spinal roots

– Multiple discrete compressive lesions

– Pre-existing neurological problems not related directly to their MESCC (e.g., brain metastases)

– Previous MESCC or previous spinal radiation


• Broad, unfocused energy beam

• Complications: wound healing, infection, fusion delay, bone marrow suppression, myelitis

• Logistics: small fractions over 2 weeks

• More interest in new modalities of radiotherapy


Radiotherapy Modalities

• Conventional External Beam Radiotherapy (EBRT)

• Intensity-modulated radiation therapy (IMRT)

• Stereotactic radiotherapy

• Stereotactic radiosurgery

• Radioisotopes


Indications of Radiotherapy As Primary Treatment

1. Radiosensitive tumor not previously irradiated

2. Widespread spinal metastases with multilevel neural compression

3. Total neurological deficits below the level of compression > 48 hours

4. Patient’s condition (or prognosis) precludes surgery: high surgical risk or short life expectancyPenas-Prado M, Loghin ME. Spinal cord compression in cancer patients: review of diagnosis and treatment. Curr Oncol Rep. 2008 Jan;10(1):78-85.

Adjuvant Radiotherapy

• Done after operative decompression

• Patchell et al study

• Wait 3 weeks for wound healing before starting radiation

• If allograft / autograft bone was used, wait 6/52 for incorporation before starting

Effects of radiation on spinal fusion

• 27 rabbits underwent posterior lumbar fusion with autogenous iliac crest graft, divided into– Group 1 (n = 7): no irradiation – Group 2 (n = 6): preoperative irradiation– Group 3 (n = 7): immediate (day 3) post-op irradiation– Group 4 (n = 7): delayed (day 21) post-op irradiation

• The radiation protocol consisted of 480 cGy/fraction for 5 consecutive days.

Bouchard JA, Koka A, Bensusan JS, Stevenson S, Emery SE. Effects of irradiation on posterior spinal fusions. A rabbit model. Spine. 1994 Aug 15;19(16):1836-41.

Effects of Radiation on Spinal FusionBouchard et al, Spine 1994

• Compared with the control group, – Group 2 (preoperatively irradiated) spines were less stiff in

extension and in compression– Group 3 (immediate postop irradiation) spines were less stiff in

extension, flexion, compression, and left lateral bending

• The control group and the delayed irradiation group had the highest histologic scores and more mature fusion mass

• The immediate postoperative irradiation group had the worst results, with consistent fibrous union of the graft

• Frankel et. al. Paraplegia 1969

• Harrington JBJS(A) 1986

• Tokuhashi et. al. Spine 1990

• Tomita et. al. Spine 2001

Decision Making (Prognostic Decision Rules)

Frankel 1969

• A: Complete sensory & motor loss

• B: Complete motor loss; incomplete sensory loss

• C: Some motor function below level of involvement; incomplete sensory loss

• D: Useful motor function below level of involvement; incomplete sensory loss

• E: Normal motor & sensory function

Harrington K. Metastatic disease of the spine. J Bone Joint Surg Am. 1986 Sep;68(7):1110-5.

I. No significant neurologic compromise

II. Involvement of bone with minimal neurological impairment, but without collapse

III. Major neurologic impairment without significant involvement of bone

IV. Vertebral collapse with pain resulting from mechanical causes or instability, but with no significant neurologic compromise

V. Vertebral collapse or instability with major neurologic compromise

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Tokuhashi et. al. 1990

• Retrospective analysis of 64 patients

• Scoring system for preoperative evaluation of metastatic spine prognosis

• Six parameters employed, each 0-2

• Total score 0-12 predicts the surgical intervention (excisional vs. palliative)

Karnofsky

(Frankel’s)

≥ 9:

• Excision

• Survival > 12 months

≤ 5:

• Palliative

• Survival < 3 months

Tomita et. al. 2001

• Phase 1 (1987-1991):– Retrospective analysis of 67 patients to evaluate

predictors– Hazard ratios were analyzed & standardized

• Phase 2 (1993-1996):– Prospective validation of 61 patients

• Total Score 2-10, based on:– Grade of malignancy of the primary tumor– Visceral Metastases to vital organs– Bone metastases

Tomita et. al. 2001

Predictive value of 7 preoperative prognostic scoring systems for spinal metastases

Leithner et al, Eur Spine J 2008

• Prospective evaluation, 69 patients

• Tokuhashi (original and revised), Sioutos, Tomita, Van der Linden, and Bauer (original and modified) scores

• Of all seven scoring systems, the original Bauer score and a Bauer score without scoring for pathologic fracture had the best association with survival (P<0.001)

Predictive value of 7 preoperative prognostic scoring systems for spinal metastases

Leithner et al, Eur Spine J 2008

Indications for Surgery1. Spinal instability

2. Spinal compression secondary to retropulsed bones or spinal deformity

3. Radiation-resistant tumors (sarcoma, non-small cell lung cancer, colon, renal cell, melanoma)

4. Failure of radiation (progression during treatment or recurrence)

5. Intractable pain unresponsive to medical treatment

6. Unknown primary tumor (histological diagnosis)

7. Rapid progression of neurological deficitsPenas-Prado M, Loghin ME. Spinal cord compression in cancer patients: review of diagnosis and treatment. Curr Oncol Rep. 2008 Jan;10(1):78-85.

Spinal Instability

• White and Punjabi:‘‘the ability of the spine, under physiologic loads, to prevent initial or additional neurologic damage, severe intractable pain, and gross deformity”

• Grubb & Kostuik:–6 columns (3 columns of Denis, right and left):

• if >3 involved unstable

– >20º angulation unstable

Spinal Instability

• Local tumor

• Iatrogenic

• Post-radiation

Spinal Instability Taneichi et. al., Spine 1997

• 100 thoracic & lumbar osteolytic lesions followed

• Suggested that criteria of impending collapse:

– Thoracic Spine (T1-T10)• 50-60% of vertebral body with no destruction of other structures• 25-30% of vertebral body and costovertebral joint destruction

– Thoracolumbar & Thoracic Spine (T10-L5)• 35-40% of vertebral body • 20-25% of vertebral body with posterior element destruction

Principles of Surgical Treatment“Objectives”

• Establish diagnosis, if not done

• Decompression of neural structures

• Debulking of tumor

• Realignment

• Reconstructive stabilization

Boriani-Weinstein-Biagini Staging SystemSpine 1997

Surgical Options

• Approach: anterior, posterior, A+P, or posterolateral, MIS, kyphoplasty

• Reconstruction: bone graft, cement, or cages

• Pre-operative embolization (renal cell ca, thyroid)

• Postoperative radiotherapy: after 3-6 wks

Surgical Approaches

Rothman-Simeone The Spine. 5th Edition. © Elsevier

Posterior Thoracic Approaches

Meta-analysis of Surgery versus Radiotherapy

• 1980 to August 2003

• 24 surgical articles (999 patients)

• 4 radiation articles (543 patients)

• Mostly uncontrolled cohort studies (Class III)

Klimo P Jr, Thompson CJ, Kestle JR, Schmidt MH. A meta-analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease. Neuro Oncol. 2005 Jan;7(1):64-76.

• Surgical patients were 1.3 times more likely to be ambulatory after treatment and twice as likely to regain ambulatory function.

• Concludes that surgery should usually be the primary treatment with radiation given as adjuvant therapy.

Meta-analysis of Surgery versus Radiotherapy

Klimo P Jr, Thompson CJ, Kestle JR, Schmidt MH. A meta-analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease. Neuro Oncol. 2005 Jan;7(1):64-76.

MIS for Spinal Metastases

• Huang TJ, Hsu RW, Li YY, Cheng CC. Minimal access spinal surgery (MASS) in treating thoracic spine metastasis. Spine. 2006 Jul 15;31(16):1860-3.

• Singh K, Samartzis D, Vaccaro AR, Andersson GB, An HS, Heller JG. Current concepts in the management of metastatic spinal disease. The role of minimally-invasive approaches. J Bone Joint Surg Br. 2006 Apr;88(4):434-42.

• Binning MJ, Gottfried ON, Klimo P Jr, Schmidt MH. Minimally invasive treatments for metastatic tumors of the spine. Neurosurg Clin N Am. 2004 Oct;15(4):459-65.

Kyphoplasty for Metastases

• Chi JH, Gokaslan ZL. Vertebroplasty and kyphoplasty for spinal metastases. Curr Opin Support Palliat Care. 2008 Mar;2(1):9-13.

• Bròdano GB, Cappuccio M, Gasbarrini A, Bandiera S, De Salvo F, Cosco F, Boriani S. Vertebroplasty in the treatment of vertebral metastases: clinical cases and review of the literature. Eur Rev Med Pharmacol Sci. 2007 Mar-Apr;11(2):91-100.

• Khanna AJ, Neubauer P, Togawa D, Kay Reinhardt M, Lieberman IH. Kyphoplasty and vertebroplasty for the treatment of spinal metastases. Support Cancer Ther. 2005 Oct 1;3(1):21-5.

Walker MP, Yaszemski MJ, Kim CW, Talac R, Currier BL. Metastatic disease of the spine: evaluation and treatment. Clin Orthop Relat Res. 2003 Oct;(415 Supp):S165-75.

Bartels RH, van der Linden YM, van der Graaf WT. Spinal extradural metastasis: review of current treatment options. CA Cancer J Clin. 2008 Jul-Aug;58(4):245-59.

Bottom Line

Tumor Treatment

Patient• Tumor type• Natural history• Tumor location• Extent of involvement• Number of

metastases

• Neurologic status• Comorbid conditions• Nutritional status• Immune status• Patient & family

wishes• Life expectancy

• Multi-disciplinary• Supportive measures• Surgery: front ± back, MIS, kyphoplasty• Radiotherapy:

external beam, radiosurgery, IMRT• Chemotherapy• Timing

Thank You

Calgary Spine Tumor Day?

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Spinal Metastases Sohail Bajammal, MBChB, MSc, FRCS(C) October 6, 2008 Spine Fellows Rounds