SPINE SBRT: The MSKCC Spine ServiceIAEA Singapore SBRT Symposium

Josh Yamada MD FRCPCMark Bilsky MDDepartments of Radiation Oncology and NeurosurgeryMemorial Sloan Kettering Cancer CenterNY NY USA

Disclosures

Varian Medical Systems Consultant

Continuing Medical Education Institute Speakers Bureau

Radiation OncologyJosh Yamada, M.D.

RadiologyEric Lis, M.D.

George Krol, M.D.Sasan Karimi, M.D.Pierre Gobin, M.D.

Athos Patsilides, M.D.

Orthopedic SurgeryPatrick Boland, M.D.

PhysiatryMichael

Stubblefield,M.D.Jonas Sokolof, D.O.Christian Custodio,

M.D.PT/OT

NursingJoan Zatcky, NP

Cynthia Correa, RNRuth Gargan-Klinger,

NPJane Yoffe, NP

Solange Inglis, NPMarie Marte, NP

NeurosurgeryMark Bilsky, M.D.Ilya Laufer, M.D.

NeurologyEdward Avila, D.O.

Xi Chen, M.D.Sonia Sandhu, D.O

PainRoma Tickoo, M.D.

Kenneth Cubert, M.D.Vinay Puttaniah, M.D.Amitabh Gulati, M.D.

MSKCC Spine Service

Goals of TreatmentMulti-disciplinary Approach

• MetastasisMetastasis

• PalliationPalliation

Pain ControlPain Control

NeurologyNeurology

OncologyOncology

Mechanical StabilityMechanical Stability

The Spine Service at MSKCC: Multidisciplinary Care•Spine oncology requires multidisciplinary care

•Spine conference

•All physicians in the hospital bring their spine patient questions for multidisciplinary assessment—meets weekly

•Spine clinic

• Joint clinic with neurosurgery, interventional radiology and radiation oncology

•NOMS assessment

Treatment ConsiderationsNOMS1,2

•Neurologic

•Oncologic

•Mechanical Stability

•Systemic disease

• Systemic Therapy

• Radiation Therapy

• Surgery

vs.

1Bilsky MH, Smith M. Surgical approach to epidural spinal cord compression. Hematology/Oncology Clinics of North America.;20(6):1307-1317, 20062Bilsky MH, Azeem S. The NOMS framework for decision making in metastatic cervical spine tumors.

Current Opinions in Orthopedics 2007;18(3):263-269.

Options for TherapyMulti-disciplinary Approach

• Systemic Therapy• Chemo/Immuno-/Hormonal therapy• Targeted Therapy

• Radiation Therapy• Conventional EBRT (30 Gy in 10

fractions)• Image-guided intensity modulated RT

o Hypofractionated RT (10 Gy x 3)o Single Fraction RT (24 Gy)

• Brachytherapy: p32 plaque

• Surgery– Percutaneous Cement Augmentation • Open: Anterior, Posterolateral,

Combined• En bloc resection for margins

Presentation

•Three Predominant Pain Syndromes:

Biologic

Mechanical

Radiculopathy

•Myelopathy

•Significant treatment implications

Presentation

•Biologic pain

•Indicative of bone pathology

•Predominant pain syndrome (95%)

•Night or morning pain that resolves over the course of the day

•Mechanism: Diurnal variation in endogenous steroid secretion

•Treatment: Steroids/RT

Presentation•Mechanical Pain•Indicative of bone pathology•Movement-related pain•Level dependent

AA: Flexion/extension/rotationSAC: Flexion/extensionThoracic: ExtensionLumbar: Mechanical Radiculopathy

•Radiographic correlates•Treatment: Surgery or Kyphoplasty followed by RT

Presentation

•Radiculopathy

•Indicative of neuroforaminal disease

•Differentiate from the following:Bone lesion (eg. L3 vs. femur fracture)NeuropathyBrachial/Lumbosacral Plexus TumorLeptomeningeal Tumor

•Treatment: Dependent on tumor histology and degree of ESCC, often RT in absence of instability

Presentation •Myelopathy: • Indicative of high-grade ESCCSpinothalamic tracts (Pinprick)Corticospinal tracts (Motor)Posterior Columns (Proprioception)Autonomic (Bowel and Bladder)

Neurogenic vs. other (eg. narcotics)Perineal numbnessConus medullaris or sacrumOther spinal levels: Significant degree of paralysis

Treatment: Dependent on the radiosensitivity of the tumor

NOMS Assessment•Neurologic

•Myelopathy•Functional Radiculopathy•Degree of epidural spinal

cord compression

•Oncologic•Tumor Histology•Radiation or Chemosensitivity

•Mechanical Instability•Systemic Disease and Medical Co-morbidity

NOMS N: ESCC

0

2 3

1Radiation Sensitivity

Tumor Histology

Sensitive Myeloma  LymphomaModerately Sensitive BreastModerately Resistant Colon  NSCLCHighly Resistant Thyroid

RenalSarcomaMelanoma

O: Radiation Sensitivity

NOMS N: ESCC0

2 3

1Radiation Sensitivity

Tumor Histology

Sensitive Myeloma  LymphomaModerately Sensitive BreastModerately Resistant Colon  NSCLCHighly Resistant Thyroid

RenalSarcomaMelanoma

O: Radiation Sensitivity

cEBRT30 Gy in 3 Gy/fraction

NOMS N: ESCC0

2 3

1Radiation Sensitivity

Tumor Histology

Sensitive Myeloma  LymphomaModerately Sensitive BreastModerately Resistant Colon  NSCLCHighly Resistant Thyroid

RenalSarcomaMelanoma

O: Radiation Sensitivity

SRS

NOMS N: ESCC0

2 3

1Radiation Sensitivity

Tumor Histology

Sensitive Myeloma  LymphomaModerately Sensitive BreastModerately Resistant Colon  NSCLCHighly Resistant Thyroid

RenalSarcomaMelanoma

O: Radiation Sensitivity

Surgery + SRS

Histologic ClassificationRadiosensitivity to cEBRT (30 Gy in 10)

LymphomaSeminomaMyeloma

Breast Prostate Sarcoma Melanoma GI NSCLC Renal

Gilbert F F U U U U U UMaranzano F F F U U U U URades F I I I U I U IRades F F F U U U U UKatagiri F F F U U U U UMaranzano F F F U U U U URades F I I I U I U I

Gerszten PC, Mendel E, Yamada Y. Radiotherapy and radiosurgery for metastatic spine disease: What are the options, indications, and

outcomes. Spine 34(22S):S78-92, 2009

Responses: F-Favorable, I-Intermediate, U-Unfavorable

Local Control Histology

Histology3 Yr Local Control

Breast 98%GI 98%H&N 93%Lung 98%Melanoma 90%

Unknown 91%Prostate 98%Renal 89%Sarcoma 96%Thyroid 92%

413 patients

Radiosurgery Recommendations

A strong recommendation can be made with low-quality evidence that radiosurgery should be considered over

conventional fractionated radiotherapy for the treatment of solid tumor spine metastases in the setting of

oligometastatic disease and/or radioresistant histology in which no relative contraindications exist.

Gerszten PC, Mendel E, Yamada Y. Radiotherapy and radiosurgery for metastatic spine disease: What are the options, indications, and

outcomes. Spine 34(22S):S78-92, 2009

CaseSolitary T10 RCC

RCC/MelanomaStereotactic Radiosurgery

•80 patients •2004-2008•SSRS 18 to 24 Gy x 1•Imaging and PE q 4 months•Radiographic/Symptom Control: 92%•Trend towards better control at 24 Gy: 97% vs. 83%

Thiagaragan A, et.al. Stereotactic radiosurgery: A new paradigmFor melanoma and renal cell carcinoma spine metastases. Presented

ASCO, 2010

NOMS Assessment

•Neurologic

•Myelopathy•Functional Radiculopathy

•Degree of epidural spinal cord compression

•Oncologic

•Tumor Histology: RCC

•Radiation or Chemosensitivity

•Mechanical Instability

•Systemic Disease and Medical Co-morbidity

NOMS Assessment

•Neurologic•Myelopathy•Functional Radiculopathy•Degree of epidural spinal cord compression: ESCC 1b

•Oncologic•Tumor Histology: RCC•Radiation: Sensitive to SRS

•Mechanical Stability: Stable•Systemic Disease and Medical Co-morbidity

SRS

RCC

Bilsky M,, et.al. Shifting Paradigms in the Treatment of Metastatic Spine Disease .Spine. 34(22S) Supplement:S101-S107, 2009.

SRS:24 Gy, Cord dMax:14Gy f/u 26 months

RCC

SRS:24 Gy, Cord dMax:14Gy f/u 26

months

A strong recommendation is made that patients with solid

renal cell carcinoma in the absence of epidural disease

may benefit from stereotactic radiosurgery as first line

therapy rather than en bloc excision.

Bilsky M,, et.al. Shifting Paradigms in the Treatment of Metastatic Spine Disease .Spine. 34(22S) Supplement:S101-S107, 2009.

NOMS N: ESCC0

2 3

1Radiation Sensitivity

Tumor Histology

Sensitive Myeloma  LymphomaModerately Sensitive BreastModerately Resistant Colon  NSCLCHighly Resistant Thyroid

RenalSarcomaMelanoma

O: Radiation Sensitivity

Surgery + SRS

Tumor (gross target

volume)

SRS and High-Grade ESCC•7 local failures received <15 Gy to small percentage of PTV•Currently, dMax Cord <14 Gy with 10% per mm falloff:Cytotoxic tumoral dose risks overdosing the spinal cordSubtherapeutic dose that spares spinal cord tolerance risks epidural tumor

progression•Resolution of soft tissue disease can take months: No effective decompression of epidural disease•Caveat: SRS for RT-sensitive disease (Median 16Gy)1

Tumor (gross target

volume)Prescription

isodose

Cord

Under-dosed sub-volume

1Ryu S., et.al Radiosurgical decompression of metastatic epidural compression. Cancer 116(9):

2250, 2010

Neurologic Oncologic Assessment

•Prospective randomized trial•Solid tumors•HG-ESCC with myelopathy•Surgery + cEBRT vs. cEBRT alone

•Exclusion criteria• RT-sensitive tumors ie. Hematologic

malignancies and GCT• Multi-level disease• Systemic contraindications to

surgeryRA Patchell, et al., Direct decompressive surgical resection in the treatment of

spinal cord compression caused by metastatic cancer: a randomized trial. Lancet 366: 643, 2005

ResultsSurgery Radiation Significance

Overall Ambulation

84% (42/50)

57% (29/51) p=.001

Duration 122 days 13 days p=.003

Recover Ambulation

62% (10/16)

19% (3/16) p= .012

Continence 155 days 17 days p=.016

Narcotics (MSO4) .4mgs 4-8 mgs p=.002

Survival Time 126 days 100 days p=.033

RA Patchell, et al., Direct decompressive surgical resection in the treatment of spinal cord compression caused by

metastatic cancer: a randomized trial. Lancet 366: 643, 2005

ResultsSurgery Radiation Significance

Overall Ambulation

84% (42/50)

57% (29/51) p=.001

Duration 122 days 13 days p=.003

Recover Ambulation

62% (10/16)

19% (3/16) p= .012

Continence 155 days 17 days p=.016

Narcotics (MSO4) .4mgs 4-8 mgs p=.002

Survival Time 126 days 100 days p=.033

Evidence-based Recommendations (GRADE methodology) : A strong recommendation is made for patients with high-grade spinal cord compression due to solid tumor malignancy undergo

surgical decompression and stabilization followed by RT.1

Bilsky M,, et.al. Shifting Paradigms in the Treatment of Metastatic Spine Disease. Spine 34(22S): S101-S107,

2009

Radiosurgery Recommendations

A strong recommendation can be made with low-quality evidence that radiosurgery should be considered over

conventional fractionated radiotherapy for the treatment of solid tumor spine metastases in the setting of

oligometastatic disease and/or radioresistant histology in which no relative contraindications exist.

Gerszten PC, Mendel E, Yamada Y. Radiotherapy and radiosurgery for metastatic spine disease: What are the options, indications, and

outcomes. Spine 34(22S):S78-92, 2009

Postoperative Adjuvant Radiation

Klekamp J, Samii. Surgical results for spinal metastases.Acta Neurochir (Wien) 140 (9):957-967, 1998

•101 patients/106 metastases operated between1977 to 1996•Surgery:Posterolateral: 79%Anterior: 12%Combined Anterior/Posterior: 9%Partial (48%) or Complete Resection (43%): 91%•Adjuvant Treatment: 100%•Local Control: 40% @ 6 months 30% @ 1 year 4% @ 4 years•Significant Predictors of Recurrence: Ambulation, Tumor Histology, Completeness of Resection

Postoperative Adjuvant Radiation

Moulding, et.al. Local disease control after decompressive surgery and high-dose single fraction radiation for spine metastases. J Neurosurg Spine 13(1): 87-93, 2010

•MSKCC Data: 21 patients• RT-resistant tumors: 100%Melanoma Renal Cell CarcinomaSarcomaColorectal Carcinoma

•Surgical Indication: High Grade ESCC (Grade 2 or 3): 96%Mechanical Radiculopathy: 4%

•SRS Single Fraction: 18 to 24 Gy GTV contoured to the preoperative tumor volume Myelogram/CT

Local Control Surgery + SRS

HD:94%

LD:40%

Moulding, et.al. Local disease control after decompressive surgery and adjuvant high-dose single fraction radiation for spine metastases.

J Neurosurg Spine 13(1): 87-93, 2010

SRS: 90% Hypo LD:78%

Hypo HD: 95.8%

Local Control Separation Surgery + SRS

192 pts.

“Separation Surgery” + SRS

N: HG ESCCO: RT-resistant

M: StableS: Tolerable

86 year oldPapillary thyroid

ASIA CAbsent

proprioception

“Separation Surgery” + SRS

2Bilsky M, et.al. Shifting Paradigms in the Treatment of Metastatic

Spine Disease .Spine. 34(22S) Supplement:S101-S107, 2009.

• Published literature:• 6 case series:15 patients•Operative times: 8 to 12 hours•Transfusion data: Melcher - PRBC-15.7units/FFP-20units•No complications reported•Recurrences:13%•Median follow-up 16 months

RCCEn bloc excision

• SST post RT/Chemo

• Tumor progression with instability

• T3 vertebral body

• Massive brachial plexus

• N: ESCC 2

Radiculopathy/plexopathy

• O: Resistant

• M: Unstable

• S: Tolerate an operation

“Separation Surgery” + SRS

NOMS Assessment

•Neurologic

•Myelopathy

•Functional Radiculopathy

•Degree of epidural spinal cord compression

•Oncologic

•Tumor Histology: RCC

•Radiation or Chemosensitivity

•Mechanical Stability

•Systemic Disease and Medical Co-morbidity

NOMS Assessment

•Neurologic

•Myelopathy

•Functional Radiculopathy

•Degree of epidural spinal cord compression

•Oncologic

•Tumor Histology: RCC

•Radiation or Chemosensitivity

•Mechanical Stability

•Systemic Disease and Medical Co-morbidity

NOMS Assessment

•Neurologic•Myelopathy•Functional Radiculopathy•Degree of epidural spinal cord

compression

•Oncologic•Tumor Histology: RCC•Radiation or Chemosensitivity

•Mechanical Stability•Systemic Disease and Medical Co-morbidity

High-dose steroidsEmbolization

NOMS Assessment

•Neurologic•Myelopathy•Functional Radiculopathy•Degree of epidural spinal cord

compression

•Oncologic•Tumor Histology: RCC•Radiation or Chemosensitivity

•Mechanical Stability•Systemic Disease and Medical Co-morbidity

Posterolateral decompression

Instrumentation /SRS + /- p32 plaque

NOMS Assessment

•Neurologic•Myelopathy•Functional Radiculopathy•Degree of epidural spinal cord

compression

•Oncologic•Tumor Histology: Lymphoma•Radiation or Chemosensitivity

•Mechanical Stability•Systemic Disease and Medical Co-morbidity

NOMS Assessment

•Neurologic•Myelopathy•Functional Radiculopathy•Degree of epidural spinal cord

compression

•Oncologic•Tumor Histology: Lymphoma•Radiation or Chemosensitivity

•Mechanical Stability•Systemic Disease and Medical Co-morbidity

High-dose steroidscEBRT (30 Gy in 10

fractions)

NOMS Assessment

•Neurologic•Myelopathy•Functional Radiculopathy•Degree of epidural spinal cord

compression

•Oncologic•Tumor Histology: Unknown•Radiation or Chemosensitivity

•Mechanical Stability•Systemic Disease and Medical Co-morbidity

NOMS Assessment

•Neurologic•Myelopathy•Functional Radiculopathy•Degree of epidural spinal cord

compression

•Oncologic•Tumor Histology: Unknown•Radiation or Chemosensitivity

•Mechanical Stability•Systemic Disease and Medical Co-morbidity

High-dose steroidsEstablish RT-sensitive: RT

No Dx: Surgery

NOMechanical InstabilityS

•Recognition of instability as an indication for surgery or percutaneous cement augmentation prior to RT

•Spine Oncology Study Group (SOSG) created a scoring system Spine Instability Neoplastic Score or SINS1

-Integrates systematic literature review with expert opinion

-Reliable: High inter and intra-relater reliability2

-Valid: Substantial agreement between SINS score and expert opinion2

.

1Fisher CG, et al. A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine

Oncology Study Group. Spine. 2010;35(22):E1221-9. 2Fourney DR, et al. Spinal instability neoplastic score: an analysis of reliability

and validity from the spine oncology study group. J Clin Oncol 2011;29(22):3072-71

SINS Component Description Score

Location Junctional (Occ-C2, C7-T2, T11-L1, L5-S)Mobile (C3-6, L2-4)Semirigid (T3-10)Rigid (S2-5)

3210

Pain Yes*Occasional non-mechanical painNo

310

Bone Lesion LyticMixedBlastic

210

Alignment Subluxation / translationDe novo deformityNormal

420

Vertebral Body >50% collapse<50% collapseNo collapse with >50% VB involvedNone of above

3210

Posterolateral Involvement

BilateralUnilateralNone

310

Stable Potentially Unstable

Unstable

0-6 7-12 13-18

Fisher CG, et al. A novel classification system for spinal

instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 35(22):E1221-9,

2010

Spine Instability Neoplastic Score (SINS)

Tallied Score from 6 components

SINS Component Description Score

Location Junctional (Occ-C2, C7-T2, T11-L1, L5-S)Mobile (C3-6, L2-4)Semirigid (T3-10)Rigid (S2-5)

3210

Pain Yes*Occasional non-mechanical painNo

310

Bone Lesion LyticMixedBlastic

210

Alignment Subluxation / translationDe novo deformityNormal

420

Vertebral Body >50% collapse<50% collapseNo collapse with >50% VB involvedNone of above

3210

Posterolateral Involvement

BilateralUnilateralNone

310

Stable Potentially Unstable

Unstable

0-6 7-12 13-18

Fisher CG, et al. A novel classification system for spinal

instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 35(22):E1221-9,

2010

Spine Instability Neoplastic Score (SINS)

Tallied Score from 6 components

SINS Component Description Score

Location Junctional (Occ-C2, C7-T2, T11-L1, L5-S)Mobile (C3-6, L2-4)Semirigid (T3-10)Rigid (S2-5)

3210

Pain Yes*Occasional non-mechanical painNo

310

Bone Lesion LyticMixedBlastic

210

Alignment Subluxation / translationDe novo deformityNormal

420

Vertebral Body >50% collapse<50% collapseNo collapse with >50% VB involvedNone of above

3210

Posterolateral Involvement

BilateralUnilateralNone

310

Stable Potentially Unstable

Unstable

0-6 7-12 13-18

Fisher CG, et al. A novel classification system for spinal

instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 35(22):E1221-9,

2010

Spine Instability Neoplastic Score (SINS)

Tallied Score from 6 components

SINS Component Description Score

Location Junctional (Occ-C2, C7-T2, T11-L1, L5-S)Mobile (C3-6, L2-4)Semirigid (T3-10)Rigid (S2-5)

3210

Pain Yes*Occasional non-mechanical painNo

310

Bone Lesion LyticMixedBlastic

210

Alignment Subluxation / translationDe novo deformityNormal

420

Vertebral Body >50% collapse<50% collapseNo collapse with >50% VB involvedNone of above

3210

Posterolateral Involvement

BilateralUnilateralNone

310

Stable Potentially Unstable

Unstable

0-6 7-12 13-18

Fisher CG, et al. A novel classification system for spinal

instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 35(22):E1221-9,

2010

Spine Instability Neoplastic Score (SINS)

Tallied Score from 6 components

SINS Component Description Score

Location Junctional (Occ-C2, C7-T2, T11-L1, L5-S)Mobile (C3-6, L2-4)Semirigid (T3-10)Rigid (S2-5)

3210

Pain Yes*Occasional non-mechanical painNo

310

Bone Lesion LyticMixedBlastic

210

Alignment Subluxation / translationDe novo deformityNormal

420

Vertebral Body >50% collapse<50% collapseNo collapse with >50% VB involvedNone of above

3210

Posterolateral Involvement

BilateralUnilateralNone

310

Stable Potentially Unstable

Unstable

0-6 7-12 13-18

Fisher CG, et al. A novel classification system for spinal

instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 35(22):E1221-9,

2010

Spine Instability Neoplastic Score (SINS)

Tallied Score from 6 components

SINS Component Description Score

Location Junctional (Occ-C2, C7-T2, T11-L1, L5-S)Mobile (C3-6, L2-4)Semirigid (T3-10)Rigid (S2-5)

3210

Pain Yes*Occasional non-mechanical painNo

310

Bone Lesion LyticMixedBlastic

210

Alignment Subluxation / translationDe novo deformityNormal

420

Vertebral Body >50% collapse<50% collapseNo collapse with >50% VB involvedNone of above

3210

Posterolateral Involvement

BilateralUnilateralNone

310

Stable Potentially Unstable

Unstable

0-6 7-12 13-18

Fisher CG, et al. A novel classification system for spinal

instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 35(22):E1221-9,

2010

Spine Instability Neoplastic Score (SINS)

Tallied Score from 6 components

SINS Component Description Score

Location Junctional (Occ-C2, C7-T2, T11-L1, L5-S)Mobile (C3-6, L2-4)Semirigid (T3-10)Rigid (S2-5)

3210

Pain Yes*Occasional non-mechanical painNo

310

Bone Lesion LyticMixedBlastic

210

Alignment Subluxation / translationDe novo deformityNormal

420

Vertebral Body >50% collapse<50% collapseNo collapse with >50% VB involvedNone of above

3210

Posterolateral Involvement

BilateralUnilateralNone

310

Stable Potentially Unstable

Unstable

0-6 7-12 13-18

Fisher CG, et al. A novel classification system for spinal

instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 35(22):E1221-9,

2010

Spine Instability Neoplastic Score (SINS)

Tallied Score from 6 components

SINS Component Description Score

Location Junctional (Occ-C2, C7-T2, T11-L1, L5-S1)Mobile (C3-6, L2-4)Semirigid (T3-10)Rigid (S2-5)

3210

Pain Yes*Occasional non-mechanical painNo

310

Bone Lesion LyticMixedBlastic

210

Alignment Subluxation / translationDe novo deformityNormal

420

Vertebral Body >50% collapse<50% collapseNo collapse with >50% VB involvedNone of above

3210

Posterolateral Involvement

BilateralUnilateralNone

310

Stable Potentially Unstable

Unstable

0-6 7-12 13-18

Fisher CG, et al. A novel classification system for spinal

instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 35(22):E1221-9,

2010

Spine Instability Neoplastic Score (SINS)

Tallied Score from 6 components

NOMS Algorithm

SRS

Summary

•NOMS provides a comprehensive approach to the multidisciplinary management of spine metastases

•Metastatic cancer patients are a unique cohort

•Integration of new technologies and therapeutic options

•Most effective and low impact = best palliatiion

•NOMS provides a vehicle for surgeons, medical and radiation oncologists to speak a common language